FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Stroncek, DF Yau, YY Oblitas, J Leitman, SF AF Stroncek, DF Yau, YY Oblitas, J Leitman, SF TI Administration of G-CSF plus dexamethasone produces greater granulocyte concentrate yields while causing no more donor toxicity than G-CSF alone SO TRANSFUSION LA English DT Article ID COLONY-STIMULATING FACTOR; STEM-CELL TRANSPLANTATION; PERIPHERAL-BLOOD; NEUTROPHIL TRANSFUSIONS; HEALTHY DONORS; MOBILIZATION; COLLECTION; COUNTS; RECIPIENTS; APHERESIS AB BACKGROUND: G-CSF with or without dexamethasone is becoming the standard agent for mobilizing granulocytes for transfusion. The purpose of this study was to determine if the toxicities of G-CSF with or without dexamethasone are offset by greater collection yields and to define the minimum interval that should separate sequential collections. STUDY DESIGN AND METHODS: Twenty donors were studied on three occasions. They were given either dexamethasone (8 mg, by mouth) plus a placebo injection, G-CSF (5 mug/kg, given subcutaneously) plus placebo capsules, or G-CSF plus dexamethasone. Granulocytes were collected by apheresis. A donor symptom survey was administered, and cell counts and blood chemistries were assessed before collection and 1, 2, 7, 14, 21, 28, and 35 days after collection. RESULTS: More granulocytes were collected when G-CSF was given than when dexamethasone was given (41.1 +/- 20.4 x 10(9) vs. 21.0 +/- 10.0 x 10(9); p < 0.001), but the use of G-CSF plus dexamethasone produced the greatest yields (67.1 +/- 22.0 x 10(9); p < 0.002). When the donors were given dexamethasone alone, 58 percent experienced at least one symptom, compared to 85 percent of those given G-CSF and 75 percent of those given G-CSF plus dexamethasone. In all three regimens, platelet counts fell 19 percent to 24 percent after collection and remained below baseline for 7 to 14 days. Granulocyte counts returned to baseline within 3 to 7 days, but, in all three regimens, a mild granulocytopenia occurred 21 days after collection. With each of the regimens, blood chemistries changed, but the changes were mild and most returned to baseline within 7 days; however, changes in albumin, bilirubin, and AST persisted until 28 days after collection. CONCLUSION: These results support the use of G-CSF plus dexamethasone in granulocyte donors. G-CSF plus dexamethasone resulted in greater granulocyte yields than either agent alone and was associated with donor symptoms and changes in blood cell counts and chemistries similar to those seen with G-CSF alone or dexamethasone alone. Granulocytes can be safely collected a second time after a 7-day interval; however, for regular donors, it may be best to separate collections by 4 weeks. C1 NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. RP Stroncek, DF (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, 10 Ctr Dr,MSC 1184,Bldg 10,Room 1C711, Bethesda, MD 20892 USA. NR 21 TC 42 Z9 44 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD AUG PY 2001 VL 41 IS 8 BP 1037 EP 1044 DI 10.1046/j.1537-2995.2001.41081037.x PG 8 WC Hematology SC Hematology GA 459JP UT WOS:000170247500012 PM 11493736 ER PT J AU Wolf, YI Koonin, EV AF Wolf, YI Koonin, EV TI Origin of an animal mitochondrial DNA polymerase subunit via lineage-specific acquisition of a glycyl-tRNA synthetase from bacteria of the Thermus-Deinococcus group SO TRENDS IN GENETICS LA English DT Editorial Material ID ACCESSORY SUBUNIT; PROTEIN SEQUENCES; PHYLOGENETIC TREES; GENE-TRANSFER; EVOLUTION; GENOMES; GAMMA; PROCESSIVITY; DIVERGENCE; GENERATION AB Phylogenetic tree analysis shows that the accessory subunit animal mitochondrial DNA polymerase emerges as a result of horizontal transfer of the gene encoding glycyl-tRNA synthetase from a bacterium of the Thermus-Deinococcus group into the animal nuclear genome. This acquisition by a distinct eukaryotic lineage of a gene encoding a mitochondrial protein from a nonmitochondrial bacterial source underscores the contribution of different types of horizontal transfer event to the evolution of eukaryotes. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Wolf, YI (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov NR 27 TC 15 Z9 16 U1 0 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD AUG PY 2001 VL 17 IS 8 BP 431 EP 433 DI 10.1016/S0168-9525(01)02370-8 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 457GB UT WOS:000170127800004 PM 11485800 ER PT J AU Jankovic, D Liu, ZG Gause, WC AF Jankovic, D Liu, ZG Gause, WC TI Th1-and Th2-cell commitment during infectious disease: asymmetry in divergent pathways SO TRENDS IN IMMUNOLOGY LA English DT Review ID T-HELPER CELL; CYTOKINE GENE-EXPRESSION; LEISHMANIA-MAJOR INFECTION; RESPONSES IN-VIVO; DENDRITIC CELLS; IFN-GAMMA; IMMUNE-RESPONSES; IL-4 PRODUCTION; CUTTING EDGE; COSTIMULATORY MOLECULES AB The development of T helper 1 (Th1) versus Th2 cells is a major branch point in the immune response. It is an important determinant of whether the response to an infectious pathogen will lead to protection of the host or dissemination of the disease. Recent studies have suggested that this process is governed by distinct sets of signals provided by dendritic cells upon interactions with specific infectious agents. A model is proposed that links together the pathogen,the innate response and Th-cell polarization. C1 Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Gause, WC (reprint author), Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bldg B,Rm 3106,4301 Jones Bridge Rd, Bethesda, MD 20814 USA. FU NIAID NIH HHS [R01 AI47478, R01 AI31678, R01 AI46551] NR 87 TC 158 Z9 176 U1 0 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 J9 TRENDS IMMUNOL JI Trends Immunol. PD AUG PY 2001 VL 22 IS 8 BP 450 EP 457 DI 10.1016/S1471-4906(01)01975-5 PG 10 WC Immunology SC Immunology GA 461KP UT WOS:000170363700010 PM 11473835 ER PT J AU Kopecko, DJ Hu, L Zaal, KJM AF Kopecko, DJ Hu, L Zaal, KJM TI Campylobacter jejuni - microtubule-dependent invasion SO TRENDS IN MICROBIOLOGY LA English DT Review ID EPITHELIAL-CELL CULTURES; INTRACELLULAR SURVIVAL; CHLAMYDIA-TRACHOMATIS; INTESTINAL-CELLS; HEP-2 CELLS; INTERNALIZATION; INFECTION; CAMPYLOBACTER-JEJUNI-81-176; TRANSLOCATION; PHAGOCYTOSIS AB Campylobacter jejuni is the leading bacterial cause of food-borne illness worldwide and a major cause of Guillain-Barre paralysis. Recent molecular and cellular studies of one well-characterized C. jejuni strain have begun to unravel the details of an unusual microtubule-dependent (actin-filament-independent) gut-invasion mechanism, through which at least some C. jejuni initiate disease. Although responsible for causing a human dysenteric syndrome remarkably similar to that triggered by Shigella spp., current evidence suggests that C. jejuni use some markedly different molecular mechanisms of pathogenesis compared with shigellae. C1 US FDA, Ctr Biol Evaluat & Res, Lab Enter & Sexually Transmitted Dis, Bethesda, MD 20892 USA. NINDS, Cellular Org Unit, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Kopecko, DJ (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Enter & Sexually Transmitted Dis, Bldg 29-420,NIH Campus, Bethesda, MD 20892 USA. NR 48 TC 58 Z9 59 U1 1 U2 4 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD AUG PY 2001 VL 9 IS 8 BP 389 EP 396 DI 10.1016/S0966-842X(01)02107-2 PG 8 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 463DV UT WOS:000170462300010 PM 11514222 ER PT J AU Lee, W Blanckaert, K Bronsteen, RA Huang, R Romero, R AF Lee, W Blanckaert, K Bronsteen, RA Huang, R Romero, R TI Fetal iliac angle measurements by three-dimensional sonography SO ULTRASOUND IN OBSTETRICS & GYNECOLOGY LA English DT Article DE 3D sonography; Down syndrome; fetus; iliac angle; prenatal diagnosis ID DOWN-SYNDROME; 2ND-TRIMESTER FETUSES; GENETIC SONOGRAM; TRISOMY-21; MARKER; RISK AB Objective To determine the technical reliability of fetal iliac angle measurements by three-dimensional sonography as a prenatal marker for Down syndrome. Methods Three-dimensional multiplanar views of the fetal pelvis were used to standardize iliac angle measurements from 35 normal second-trimester pregnancies. Measurement reliability for a single examiner and between two different examiners were analyzed by intraclass correlation. Normal iliac angle measurements were compared to those obtained from 16 fetuses with trisomy 21. Results The mean axial angle for normal fetuses was 79 +/-5.5 degrees, which was significantly less than that observed in fetuses with trisomy 21 (87.7 +/-4.9 degrees) (P < 0.001). Iliac angles did not correlate with gestational age. Axial angles were reproducible between two examiners who measured the same multiplanar view of the pelvis. Inter- and intraobserver reliability were also acceptable after a standardized multiplanar view was independently obtained by each examiner (intraclass correlation = 0.91 for both). Coronal angles were unreliable because of difficulties with finding a reproducible measurement plane. For a false-positive rate of 5%, an axial angle threshold of 87 correctly identified 56% of fetuses with trisomy 21. Conclusion Axial iliac angle measurements are reliable by standardized three-dimensional multiplanar views of the pelvis and can be used to identify some fetuses at increased risk for trisomy 21. C1 William Beaumont Hosp, Dept Obstet & Gynecol, Div Fetal Imaging, Royal Oak, MI 48073 USA. William Beaumont Hosp, Div Biostat, Royal Oak, MI 48073 USA. Wayne State Univ, Hutzel Hosp, NICHHD, Perinatol Res Branch, Detroit, MI USA. RP Lee, W (reprint author), William Beaumont Hosp, Dept Obstet & Gynecol, Div Fetal Imaging, 3601 W 13 Mile Rd, Royal Oak, MI 48073 USA. NR 19 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0960-7692 J9 ULTRASOUND OBST GYN JI Ultrasound Obstet. Gynecol. PD AUG PY 2001 VL 18 IS 2 BP 150 EP 154 DI 10.1046/j.1469-0705.2001.00447.x PG 5 WC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging GA 464TH UT WOS:000170547500013 PM 11529996 ER PT J AU Carroll, PR Fair, WR Grossfeld, GD Heston, WDW Lieberman, R Malkowicz, SB Stricker, HJ Sylvester, J Peehl, DM Meyer, F Hart, C AF Carroll, PR Fair, WR Grossfeld, GD Heston, WDW Lieberman, R Malkowicz, SB Stricker, HJ Sylvester, J Peehl, DM Meyer, F Hart, C TI Overview consensus statement SO UROLOGY LA English DT Editorial Material C1 Univ Calif San Francisco, Sch Med, Med Ctr, Dept Urol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Mt Zion Comprehens Care Ctr, Program Urol Onocl, San Francisco, CA 94143 USA. Haelth LLC, New York, NY USA. Cleveland Clin Fdn, Lerner Res Inst, Dept Canc Biol, George M OBrien Urol Res Ctr, Cleveland, OH 44195 USA. NCI, Div Canc Prevent, Prostate & Urol Canc Res Grp, Rockville, MD USA. Univ Penn, Med Ctr, Dept Surg, Div Urol, Philadelphia, PA 19104 USA. Philadelphia Vet Adm Med Ctr, Philadelphia, PA USA. Henry Ford Hosp, Dept Urol, Detroit, MI USA. Seattle Prostate Inst, Seattle, WA USA. Stanford Univ, Sch Med, Dept Urol, Stanford, CA 94305 USA. Univ Laval, CHU Quebec, Hotel Dieu, Canc Res Ctr, Quebec City, PQ, Canada. InforMED Inc, Narberth, PA USA. RP Carroll, PR (reprint author), Univ Calif San Francisco, Sch Med, Med Ctr, Dept Urol, 533 Parnassus Ave, San Francisco, CA 94143 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD AUG PY 2001 VL 58 IS 2A SU S BP 1 EP 4 DI 10.1016/S0090-4295(01)01234-1 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 462LV UT WOS:000170422300001 PM 11502434 ER PT J AU Lieberman, R AF Lieberman, R TI Androgen deprivation therapy for prostate cancer chemoprevention: Current status and future directions for agent development SO UROLOGY LA English DT Article; Proceedings Paper CT 1st International Conference on Newer Approaches to Androgen Deprivation Therapy in Prostate Cancer CY NOV 09-11, 2000 CL SARASOTA, FLORIDA ID INTRAEPITHELIAL NEOPLASIA; ORNITHINE DECARBOXYLASE; PREVENTION TRIAL; EXPRESSION; CELLS; PROGRESSION; CARCINOMA; RECEPTOR; GENE; CYCLOOXYGENASE-2 AB Prostate cancer chemoprevention is defined as the administration of natural and synthetic agents that inhibit greater than or equal to 1 steps in the natural history of prostate carcinogenesis. The goal is to find agents that modulate the progression from normal epithelium to dysplasia to high-grade prostatic intraepithelial neoplasia (HGPIN) to locally invasive cancer and systemic disease. Another important goal for chemoprevention is the maintenance of an androgen-sensitive clinical state and delay of the emergence of androgen independence. There is a strong rationale for androgen deprivation therapy (ADT) as a chemoprevention strategy for prostate cancer based on evidence from epidemiologic, experimental, molecular pathophysiologic, and randomized, controlled clinical trials. This includes the fact that HGPIN, the most likely precursor of invasive cancer, is androgen dependent and responds to ADT. Although the large, phase-3 Prostate Cancer Prevention Trial (PCPT) of finasteride versus placebo has established the feasibility and role of ADT for primary prevention, nevertheless, limitations of the anticipated treatment-effect size (eg, 25% reduction) and the potential for selection of androgen resistance provide incentive for finding other effective chemopreventive agents. The availability of novel noncytotoxic pharmaceutical and natural products in clinical development create opportunities for improving the therapeutic index through the principles of combination therapy. The emergence of new powerful tools, such as gene chip complementary DNA microarrays for multiplex gene expression profiling, will accelerate the identification of new molecular targets and the design of rational combinations. Several agent classes have a strong basis for combination with ADT, including antiproliferatives, antioxidant micronutrients (selenium), antiestrogens, and nonsteroidal anti-inflammatory drugs (selective cyclooxygenase-2 inhibitors). (C) 2001, Elsevier Science Inc. C1 NCI, Prostate & Urol Canc Res Grp, Div Canc Prevent, Rockville, MD 20852 USA. RP Lieberman, R (reprint author), NCI, Prostate & Urol Canc Res Grp, Div Canc Prevent, 6130 Execut Blvd,Suite EPN 2105, Rockville, MD 20852 USA. NR 48 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD AUG PY 2001 VL 58 IS 2A SU S BP 83 EP 90 DI 10.1016/S0090-4295(01)01247-X PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 462LV UT WOS:000170422300024 PM 11502457 ER PT J AU Prikhod'ko, GG Prikhod'ko, EA Cohen, JI Pletnev, AG AF Prikhod'ko, GG Prikhod'ko, EA Cohen, JI Pletnev, AG TI Infection with Langat flavivirus or expression of the envelope protein induces apoptotic cell death SO VIROLOGY LA English DT Article DE flaviviruses; Langat virus and envelope glycoprotein E; apoptosis; DEVDase activity; Neuro-2a and Vero cells; caspases and inhibitors ID JAPANESE ENCEPHALITIS-VIRUS; CENTRAL-NERVOUS-SYSTEM; TICK-BORNE FLAVIVIRUS; DENGUE TYPE-1 VIRUS; NF-KAPPA-B; NEUROBLASTOMA-CELLS; CULTURED-CELLS; HUMAN BCL-2; VIRULENCE; PATHWAY AB Langat (LGT) flavivirus, derived from infectious full-length cDNA clone 636, was investigated for its apoptotic activities in mouse neuroblastoma (Neuro-2a) and simian kidney (Vero and LLC-MK2) cells. The hallmark of apoptosis, cleavage of cellular DNA, was observed 48 h after infection of Vero, LLC-MK2, and Neuro-2a cells by electrophoresis analysis. Apoptosis in infected cells was also confirmed by TUNEL assay. LGT-infected Neuro-2a cells showed an increase in caspase-3-like protease (DEVDase) activity. Expression of the major envelope glycoprotein (E) alone reduced cell viability in both Vero and Neuro-2a cells, and the baculovirus P35 protein, which inhibits multiple caspases, completely blocked this effect Cleavage of cellular DNA was observed in E gene-transfected Vero cells by TUNEL assay, Expression of E protein or caspase-9 resulted in activation of caspase-3-like proteases in Neuro-2a cells. The caspase-3-like protease specific inhibitor, Ac-DEVD-CHO peptide, partially inhibited E protein- or caspase-9-induced apoptosis in Neuro-2a cells. These observations indicate that infection of cells with LGT virus or expression of LGT virus E protein induces apoptosis through a caspase-3-like protease pathway. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Prikhod'ko, GG (reprint author), Amer Red Cross, Jerome H Holland Lab, Plasma Derivat Dept, 15601 Crabbs Branch Way, Rockville, MD 20855 USA. NR 34 TC 27 Z9 27 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD AUG 1 PY 2001 VL 286 IS 2 BP 328 EP 335 DI 10.1006/viro.2001.0980 PG 8 WC Virology SC Virology GA 460GX UT WOS:000170300800008 PM 11485400 ER PT J AU Pletneva, MA Sosnovtsev, SV Green, KY AF Pletneva, MA Sosnovtsev, SV Green, KY TI The genome of Hawaii virus and its relationship with other members of the Caliciviridae SO VIRUS GENES LA English DT Article DE Hawaii virus; Norwalk-like virus; calicivirus; epidemic gastroenteritis ID HEMORRHAGIC-DISEASE VIRUS; NORWALK-LIKE VIRUSES; HEPATITIS-C VIRUS; DEPENDENT RNA-POLYMERASE; FELINE CALICIVIRUS; CAPSID PROTEIN; NUCLEOTIDE-SEQUENCE; 3C-LIKE PROTEASE; CLEAVAGE SITES; MOLECULAR CHARACTERIZATION AB Hawaii virus (Hu/NLV/GII/Hawaii virus/1971/US), a member of the genus 'Norwalk-like viruses' (NLVs) in the family Caliciviridae, has served as one of the reference strains for the fastidious caliciviruses associated with epidemic gastroenteritis in humans. The consensus sequence of the RNA genome of Hawaii virus was determined in order to establish its relatedness with other members of the family. The RNA genome is 7,513 nucleotides (nts) in length, excluding the 3'-end poly (A) tract, and is organized into three major open reading frames (ORF1, nts 5-5,104; ORF2, nts 5,085-6,692; and ORF3, nts 6,692-7,471). Phylogenetic analysis showed the closest relatedness of Hawaii virus throughout its genome to Lordsdale virus, a Genogroup II NLV. Analysis of the predicted secondary structure of the RNA from the 5'-end of the genome and the putative beginning of the subgenomic RNA showed the presence of two hairpin structures at both ends that are similar to each other and to those of other NLVs. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Green, KY (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. NR 63 TC 25 Z9 26 U1 0 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0920-8569 J9 VIRUS GENES JI Virus Genes PD AUG PY 2001 VL 23 IS 1 BP 5 EP 16 DI 10.1023/A:1011138125317 PG 12 WC Genetics & Heredity; Virology SC Genetics & Heredity; Virology GA 452PN UT WOS:000169867200001 PM 11556401 ER PT J AU Costa, C Barber, DF Long, EO Fodor, WL AF Costa, C Barber, DF Long, EO Fodor, WL TI Inhibition of human NK cell-mediated cytotoxicity towards porcine cells by CD86 blockade and carbohydrate remodeling SO XENOTRANSPLANTATION LA English DT Meeting Abstract C1 NIH, NIAID, Rockville, MD USA. Alex Pharmaceut, Cheshire, CT USA. RI Barber, Domingo/G-1257-2010 OI Barber, Domingo/0000-0001-8824-5405 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD AUG PY 2001 VL 8 SU 1 MA 178 BP 59 EP 59 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 477XD UT WOS:000171308800157 ER PT J AU Achilli, A Pavlov, YI Morpurgo, G Babudri, N AF Achilli, A Pavlov, YI Morpurgo, G Babudri, N TI Influence of adenine starvation on the ade5-1 reversion in proofreading exonuclease deficient S.cerevisiae strains. SO YEAST LA English DT Meeting Abstract C1 Univ Perugia, Dept Cell & Mol Biol, I-06100 Perugia, Italy. St Petersburg State Univ, Dept Genet, St Petersburg 199034, Russia. NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RI Achilli, Alessandro/I-9236-2012 OI Achilli, Alessandro/0000-0001-6871-3451 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0749-503X J9 YEAST JI Yeast PD AUG PY 2001 VL 18 SU 1 BP S36 EP S36 PG 1 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology GA 462WE UT WOS:000170442100047 ER PT J AU Babudri, N Pavlov, YI Matmati, N Achilli, A AF Babudri, N Pavlov, YI Matmati, N Achilli, A TI Suppression of frameshift mutations arising in polymerase eta deficient S.cerevisiae strain by deletion of the RAD30 gene. SO YEAST LA English DT Meeting Abstract C1 Univ Perugia, Dept Cell & Mol Biol, I-06100 Perugia, Italy. St Petersburg State Univ, Dept Genet, St Petersburg 199034, Russia. NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RI Achilli, Alessandro/I-9236-2012 OI Achilli, Alessandro/0000-0001-6871-3451 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0749-503X J9 YEAST JI Yeast PD AUG PY 2001 VL 18 SU 1 BP S36 EP S36 PG 1 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology GA 462WE UT WOS:000170442100048 ER PT J AU Sattlegger, E Swanson, M Hinnebusch, A AF Sattlegger, E Swanson, M Hinnebusch, A TI Binding of GCN1 near the ribosomal A-site and to the N-terminus of GCN2 is required for activation of the kinase GCN2 in amino acid starved cells. SO YEAST LA English DT Meeting Abstract C1 NICHHD, LGRD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0749-503X J9 YEAST JI Yeast PD AUG PY 2001 VL 18 SU 1 BP S193 EP S193 PG 1 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology GA 462WE UT WOS:000170442100334 ER PT J AU Storici, F Lewis, LK Resnick, MA AF Storici, F Lewis, LK Resnick, MA TI In vivo site-directed mutagenesis using oligonucleotides: a versatile system for functional genomics. SO YEAST LA English DT Meeting Abstract C1 NIEHS, LMG, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0749-503X J9 YEAST JI Yeast PD AUG PY 2001 VL 18 SU 1 BP S109 EP S109 PG 1 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology GA 462WE UT WOS:000170442100180 ER PT J AU Valasek, L Hasek, J Nielsen, KH Hinnebusch, AG AF Valasek, L Hasek, J Nielsen, KH Hinnebusch, AG TI HCR1 functions at a late step of the 40S ribosome biogenesis besides its role in translation initiation. SO YEAST LA English DT Meeting Abstract C1 NIH, NICHHD, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA. Acad Sci Czech Republ, Inst Microbiol, Prague, Czech Republic. RI Hasek, Jiri/H-2427-2014 NR 0 TC 0 Z9 0 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0749-503X J9 YEAST JI Yeast PD AUG PY 2001 VL 18 SU 1 BP S68 EP S68 PG 1 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology GA 462WE UT WOS:000170442100102 ER PT J AU Zakalskiy, A Luschnig, D Zisser, G Ishikawa, T Steven, A Ebner, B Bergler, H Hogenauer, G AF Zakalskiy, A Luschnig, D Zisser, G Ishikawa, T Steven, A Ebner, B Bergler, H Hogenauer, G TI Generation and characterisation of temperature sensitive AFG2 mutants. SO YEAST LA English DT Meeting Abstract C1 Karl Franzens Univ Graz, Inst Molekularbiol, A-8010 Graz, Austria. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0749-503X J9 YEAST JI Yeast PD AUG PY 2001 VL 18 SU 1 BP S248 EP S248 PG 1 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology GA 462WE UT WOS:000170442100431 ER PT J AU Chung, MC Kim, HK Kawamoto, S AF Chung, MC Kim, HK Kawamoto, S TI TFEC can function as a transcriptional activator of the nonmuscle myosin II heavy chain-A gene in transfected cells SO BIOCHEMISTRY LA English DT Article ID LOOP-HELIX PROTEIN; FACTOR USF; MESSENGER-RNA; NUCLEAR-LOCALIZATION; REGULATORY PROTEINS; CELLULAR MYOSIN; DNA-BINDING; MYOD FAMILY; CLONING; DOMAINS AB Transcription of the human nonmuscle myosin II heavy chain-A (NMHC-A) gene is regulated via multiple elements located in intron I, including element F which contains an E-box. In this study we have identified and characterized the factors that are capable of binding to element F. Yeast one-hybrid screening using element F allowed isolation of cDNAs encoding transcriptional factors TFEC, TFE3, and USF2, each of which contains basic helix-loop-helix and leucine zipper motifs. Furthermore, cDNA cloning by polymerase chain reaction yielded cDNAs for two TFEC isoforms, designated TFEC-1 and TFEC-s, which are generated by alternative pre-mRNA splicing. In addition to these four factors, USF1, which is known to share the same DNA binding elements with USF2, was isolated for comparison. Electrophoretic mobility shift assays and cotransfection studies of the expression constructs with reporter gene constructs revealed that the above five factors have different binding activities for element F with different transactivation potencies. USF1 and USF2 demonstrate the highest binding activity to element F, yet show the lowest element F-dependent transactivation. TFE3 has a high transactivation potency but the lowest binding activity. TFEC-1 demonstrates a high binding activity with the highest transactivation potency, whereas TFEC-s has the same binding activity as TFEC-1 with intermediate transactivation. We also demonstrate that an N-terminal activation domain exists only in TFEC-1, whereas a C-terminal activation domain is common to both the 1 and s isoforms. This study provides the first evidence of TFEC being an activator of transcription, with two separate activation domains. C1 NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. RP Kawamoto, S (reprint author), NHLBI, Mol Cardiol Lab, NIH, Bldg 10,Room 8N202,10 Ctr Dr,MSC 1762, Bethesda, MD 20892 USA. NR 48 TC 9 Z9 10 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUL 31 PY 2001 VL 40 IS 30 BP 8887 EP 8897 DI 10.1021/bi002847d PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 458BQ UT WOS:000170173700026 PM 11467950 ER PT J AU Liu, X Osherov, N Yamashita, R Brzeska, H Korn, ED May, GS AF Liu, X Osherov, N Yamashita, R Brzeska, H Korn, ED May, GS TI Myosin I mutants with only 1% of wild-type actin-activated MgATase activity retain essential in vivo function(s) SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SITE-DIRECTED MUTAGENESIS; ASPERGILLUS-NIDULANS; ACANTHAMOEBA MYOSIN; PHOSPHORYLATION SITE; CORTICAL TENSION; ARP2/3 COMPLEX; TAIL DOMAINS; YEAST; MOTOR; GENE AB The single class I myosin (MYOA) of Aspergillus nidulans is essential for hyphal growth. It is generally assumed that the functions of all myosins depend on their actin-activated MgATPase activity. Here we show that MYOA mutants with no more than 1 % of the actin-activated MgATPase activity of wild-type MYOA in vitro and no detectable in vitro motility activity can support fungal cell growth, albeit with a delay in germination time and a reduction in hyphal elongation. From these and other data, we conclude that the essential roles) of myosin I in A. nidulans is probably structural, requiring little, if any, actin-activated MgATPase or motor activity, which have long been considered the defining characteristics of the myosin family. C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Div Pathol & Lab Med, Houston, TX 77030 USA. RP Korn, ED (reprint author), NHLBI, Cell Biol Lab, NIH, Bldg 50,Room 2517, Bethesda, MD 20892 USA. RI Korn, Edward/F-9929-2012 NR 44 TC 26 Z9 27 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 31 PY 2001 VL 98 IS 16 BP 9122 EP 9127 DI 10.1073/pnas.161285698 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 458VV UT WOS:000170216900038 PM 11459943 ER PT J AU Sutterlin, C Lin, CY Feng, Y Ferris, DK Erikson, RL Malhotra, V AF Sutterlin, C Lin, CY Feng, Y Ferris, DK Erikson, RL Malhotra, V TI Polo-like kinase is required for the fragmentation of pericentriolar Golgi stacks during mitosis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CELL-DIVISION; CISTERNAE; GRASP65; MEK1; CDC2; PLK AB The pericentriolar stacks of Golgi cisternae undergo extensive reorganization during mitosis in mammalian cells. GM130 and GRASP65 (Golgi reassembly stacking protein of 65 kDa) are Golgi-associated proteins that are targets of mitotic kinases, and they have also been implicated in the reorganization of the Golgi structure during cell division. Previous studies have reported that mitogen-activated protein kinase kinase-1 (MEK1} and Cdc2 protein kinases are involved in these dynamic changes in the Golgi structure. More recently, the mitotic polo-like kinase (Plk} has been shown to interact with and phosphorylate GRASP65. Here, we provide evidence that Plk is involved in the mitosis-specific fragmentation of the Golgi apparatus. The addition of kinase-defective Plk or immunodepletion of Plk disrupts the fragmentation process. Furthermore, Golgi fragmentation is inhibited by the addition of either full-length or truncated GRASP65. These findings suggest that phospharylation of GRASP65 by Plk may be a critical event in the reorganization of the Golgi structure during mitosis. C1 Univ Calif San Diego, Dept Biol, La Jolla, CA 92093 USA. NCI, Frederick, MD 21702 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RP Malhotra, V (reprint author), Univ Calif San Diego, Dept Biol, 9500 Gilman Dr, La Jolla, CA 92093 USA. RI Malhotra, Vivek/O-9811-2014 OI Malhotra, Vivek/0000-0001-6198-7943 FU NCI NIH HHS [CA62580]; NIGMS NIH HHS [GM59172, R01 GM059172] NR 16 TC 86 Z9 88 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 31 PY 2001 VL 98 IS 16 BP 9128 EP 9132 DI 10.1073/pnas.161283998 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 458VV UT WOS:000170216900039 PM 11447294 ER PT J AU Liu, X Alexander, V Vijayachandra, K Bhogte, E Diamond, I Glick, A AF Liu, X Alexander, V Vijayachandra, K Bhogte, E Diamond, I Glick, A TI Conditional epidermal expression of TGF beta 1 blocks neonatal lethality but causes a reversible hyperplasia and alopecia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GROWTH-FACTOR-BETA; FOLLICLE REGRESSION CATAGEN; TRANSGENIC MICE; TRANSFORMING GROWTH-FACTOR-BETA-1; GENE-EXPRESSION; KERATIN-5 GENE; MESSENGER-RNA; IN-VIVO; SKIN; CELLS AB To study the role of transforming growth factor type beta1 (TGF beta1) in epidermal growth control and disease, we have generated a conditional expression system by using the bovine keratin 5 promoter to drive expression of the tetracycline-regulated transactivators tTA and rTA, and a constitutively active mutant of TGF beta1 linked to the tetO target sequence for the transactivator. This model allows for induction or suppression of exogenous TGF beta1 with oral doxycycline. Maximal expression of TGF beta1 during gestation caused embryonic lethality, whereas partial suppression allowed full-term development with neonatal lethality characterized by runting, epidermal hypoproliferation, and blocked hair follicle growth. With complete suppression, phenotypically normal double transgenic (DT) mice were born. Acute induction of TGF beta1 in the epidermis of adult mice inhibited basal and follicular keratinocyte proliferation and reentry of telogen hair follicles into anagen. However, chronic expression of TGF beta1 in adult DTs caused severe alopecia characterized by epidermal and follicular hyperproliferation, apoptosis, as well as dermal fibrosis and inflammation. Readministration of doxycycline to tTA DT mice caused hair regrowth within 14 days. The mRNA and protein for Smad7, an inhibitor of TGF beta signaling, were up-regulated in the epidermis and hair follicles of alopecic skin and rapidly induced in rTA mice in parallel with the TGF/31 transgene, suggesting that the hyperproliferative phenotype may result in part from development of a sustained negative feedback loop. Thus, this conditional expression system provides an important model for understanding the role of TGF beta1 during development, in normal skin biology, and in disease. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, Bethesda, MD 20892 USA. RP Glick, A (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, Bldg 37 3B26, Bethesda, MD 20892 USA. NR 39 TC 53 Z9 58 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 31 PY 2001 VL 98 IS 16 BP 9139 EP 9144 DI 10.1073/pnas.161016098 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 458VV UT WOS:000170216900041 PM 11481479 ER PT J AU Iwashiro, M Messer, RJ Peterson, KE Stromnes, IM Sugie, T Hasenkrug, KJ AF Iwashiro, M Messer, RJ Peterson, KE Stromnes, IM Sugie, T Hasenkrug, KJ TI Immunosuppression by CD4(+) regulatory T cells induced by chronic retroviral infection SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID IMMUNOLOGICAL SELF-TOLERANCE; IMMUNODEFICIENCY-VIRUS INFECTION; LYMPHOCYTE-ASSOCIATED ANTIGEN-4; GROWTH-FACTOR-BETA; AUTOIMMUNE ENCEPHALOMYELITIS; INTESTINAL INFLAMMATION; TRANSGENIC MICE; HOMOSEXUAL MEN; HIV-INFECTION; TUMOR-CELLS AB Normal levels of CD4(+) regulatory T cells are critical for the maintenance of immunological homeostasis and the prevention of autoimmune diseases. However, we now show that the expansion of CD4(+) regulatory T cells in response to a chronic viral infection can lead to immunosuppression. Mice persistently infected with Friend retrovirus develop approximately twice the normal percentage of splenic CD4(+) regulatory T cells and lose their ability to reject certain tumor transplants. The role of CD4(+) regulatory T cells was demonstrated by the transmission of immunosuppression to uninfected mice by adoptive transfers of CD4(+) T cells. CD4(+) T cells from chronically infected mice were also immunosuppressive in vitro, inhibiting the generation of cytolytic T lymphocytes in mixed lymphocyte cultures. Inhibition occurred at the level of blast-cell formation through a mechanism or mechanisms involving transforming growth factor-beta and the cell surface molecule CTLA-4 (CD152). These results suggest a possible explanation for HIV- and human T cell leukemia virus-I-induced immunosuppression in the absence of T cell depletion. C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. Stanford Univ, Ctr Blood, Palo Alto, CA 94304 USA. RP Hasenkrug, KJ (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, 903 S 4th St, Hamilton, MT 59840 USA. RI Peterson, Karin/D-1492-2016 OI Peterson, Karin/0000-0003-4177-7249 NR 60 TC 141 Z9 155 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 31 PY 2001 VL 98 IS 16 BP 9226 EP 9230 DI 10.1073/pnas.151174198 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 458VV UT WOS:000170216900057 PM 11459933 ER PT J AU Ribeiro, RC Sandrini, F Figueiredo, B Zambetti, GP Michalkiewicz, E Lafferty, AR DeLacerda, L Rabin, M Cadwell, C Sampaio, G Cat, I Stratakis, CA Sandrini, R AF Ribeiro, RC Sandrini, F Figueiredo, B Zambetti, GP Michalkiewicz, E Lafferty, AR DeLacerda, L Rabin, M Cadwell, C Sampaio, G Cat, I Stratakis, CA Sandrini, R TI A inherited p53 mutation that contributes in a tissue-specific manner to pediatric adrenal cortical carcinoma SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CHILDHOOD ADRENOCORTICAL TUMORS; LI-FRAUMENI-SYNDROME; OLIGOMERIZATION DOMAIN; GENE-EXPRESSION; MUTANT P53; CANCER; FAMILIES; TP53; TETRAMERIZATION; ACTIVATION AB The incidence of pediatric adrenal cortical carcinoma (ACC) in southern Brazil is 10-15 times higher than that of pediatric ACC worldwide. Because childhood ACC is associated with Li-Fraumeni syndrome, we examined the cancer history and p53 status of 36 Brazilian patients and their families. Remarkably, 35 of 36 patients had an identical germ-line point mutation of p53 encoding an R337H amino acid substitution. Differences within intragenic polymorphic markers demonstrated that at least some mutant alleles arose independently, thus eliminating a founder effect. In tumor cells, the wild-type allele was deleted, and mutant p53 protein accumulated within the nuclei. Although these features are consistent with Li-Fraumeni syndrome-associated adrenal tumors, there was no history of increased cancer incidence among family members. Therefore, this inherited R337H p53 mutation represents a low-penetrance p53 allele that contributes in a tissue-specific manner to the development of pediatric ACC. C1 St Jude Childrens Res Hosp, Dept Hematol Oncol, Memphis, TN 38105 USA. St Jude Childrens Res Hosp, Dept Biochem, Memphis, TN 38105 USA. St Jude Childrens Res Hosp, Int OutreachProgram, Memphis, TN 38105 USA. Univ Tennessee, Coll Med, Dept Pediat, Memphis, TN 38101 USA. Univ Tennessee, Coll Med, Dept Biochem, Memphis, TN 38101 USA. Gene Log Inc, DNA Profiling Lab, Gaithersburg, MD 20878 USA. NICHHD, Dev Endocrinol Branch, Unit Genet & Endocrinol, Bethesda, MD 20892 USA. Univ Fed Parana, Dept Pediat, BR-8006090 Curitiba, Parana, Brazil. Univ Fed Parana, Dept Pathol, BR-8006090 Curitiba, Parana, Brazil. Univ Fed Parana, Clin Hosp, Div Endocrinol, BR-8006090 Curitiba, Parana, Brazil. RP Ribeiro, RC (reprint author), St Jude Childrens Res Hosp, Dept Hematol Oncol, 332 N Lauderdale St, Memphis, TN 38105 USA. EM raul.ribeiro@stjude.org FU NCI NIH HHS [R01 CA063230, P30 CA021765, P30-CA-21765, P01-CA-20180, R01-CA63230] NR 36 TC 264 Z9 275 U1 0 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 31 PY 2001 VL 98 IS 16 BP 9330 EP 9335 DI 10.1073/pnas.161479898 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 458VV UT WOS:000170216900075 PM 11481490 ER PT J AU Abashkin, YG Collins, JR Burt, SK AF Abashkin, YG Collins, JR Burt, SK TI (Salen)Mn(III)-catalyzed epoxidation reaction as a multichannel process with different spin states. Electronic tuning of asymmetric catalysis: A theoretical study SO INORGANIC CHEMISTRY LA English DT Article ID JACOBSEN-KATSUKI EPOXIDATION; DENSITY-FUNCTIONAL THEORY; COMPLEXES; APPROXIMATION; GEOMETRIES; MECHANISM; ENERGIES; EXCHANGE; OLEFINS; ALKENES AB The (salen)Mn(III)-catalyzed epoxidation reaction mechanism has been investigated using density functional theory (DFT). There is considerable interest in and controversy over the mechanism of this reaction. The results of experimental studies have offered some support for three different reaction mechanisms: concerted, stepwise radical, and metallooxetane mediated. In this paper, a theoretical examination of the reaction suggests a novel mechanism that describes the reaction as a multichannel process combining both concerted and stepwise radical pathways. The competing channels have different spin states: the singlet, the triplet, and the quintet. The singlet reaction pathway corresponds to a concerted mechanism and leads exclusively to a cis epoxide product. In contrast, the triplet and quintet reactions follow a stepwise mechanism and lead to a product mixture of cis and trans epoxides. We show that the experimentally observed dependence of isomer product ratios on electronic effects connected with the substitution of the catalyst ligands is due to changing the relative position and, hence, the relative activities of the channels with different cis-trans yields. Because the results and conclusions of the present work dramatically differ from the results and conclusion of the recent DFT theoretical investigation (Linde, C.; Akermark, B; Norrby, P.-O.; Svensson, M. J. Am. Chem. Soc. 1999, 121, 5083.), we studied possible sources for the deep contradictions between the two works. The choice of the DFT functional and a model has been shown to be crucial for accurate results. Using high level ab initio calculations (coupled cluster-CCSD(T)), we show that the computational procedure employed in this study generates significantly more reliable numerical results. It is also shown that the smaller cationic model without a chlorine ligand that was used by Linde et al. is too oversimplified with respect to our larger neutral model. For this reason, using the cationic model led to a qualitatively wrong quintet reaction profile that played a key role in theoretical postulates in the earlier work. C1 NCI, SAIC Frederick, Adv Biomed Comp Ctr, Ft Detrick, MD 21702 USA. RP Abashkin, YG (reprint author), NCI, SAIC Frederick, Adv Biomed Comp Ctr, POB B, Ft Detrick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 33 TC 72 Z9 73 U1 3 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0020-1669 J9 INORG CHEM JI Inorg. Chem. PD JUL 30 PY 2001 VL 40 IS 16 BP 4040 EP 4048 DI 10.1021/ic0012221 PG 9 WC Chemistry, Inorganic & Nuclear SC Chemistry GA 458MX UT WOS:000170199100029 PM 11466066 ER PT J AU Sei, S Boler, AM Nguyen, GT Stewart, SK Yang, QE Edgerly, M Wood, LV Brouwers, P Venzon, DJ AF Sei, S Boler, AM Nguyen, GT Stewart, SK Yang, QE Edgerly, M Wood, LV Brouwers, P Venzon, DJ TI Protective effect of CCR5 Delta 32 heterozygosity is restricted by SDF-1 genotype in children with HIV-1 infection SO AIDS LA English DT Article DE children; HIV-1; CCR5 Delta 32 heterozygosity; SDF1-3 ' A polymorphism; disease progression; AIDS; genetic restrictions ID CHEMOKINE RECEPTOR GENE; VIRUS TYPE-1 INFECTION; POLYMERASE-CHAIN-REACTION; MACROPHAGE-TROPIC HIV-1; PLASMA VIRAL LOAD; DISEASE PROGRESSION; CEREBROSPINAL-FLUID; T-CELL; PERIPHERAL-BLOOD; CLINICAL-COURSE AB Objective To determine the influences on pediatric AIDS of a heterozygous 32 base pair deletion in the CC-chemokine receptor 5 gene (CCR5 wt/Delta 32) and a common polymorphism in the 3' untranslated region of stromal cell-derived factor-1 beta gene transcript (SDF1-3'A). Design The rate of HIV-1 disease progression and viral burden were compared according to the CCR5 and SDF-1 genotypes in 127 (58 Caucasians, 60 African-Americans and nine Hispanics) perinatally HIV-1-infected children. Results Regardless of ethnic background, the CCR5 wt/Delta 32 genotype was associated with a delayed onset of AIDS-defining infectious complications during the first 5 years of infection [relative hazard (RH) = 0.22; 95% confidence interval (CI), 0.012-1.02; P = 0.053]. Similarly, CCR5 wt/Delta 32 conferred an early protection against severe immune suppression and HIV-1 encephalopathy, but only in those without SDF1-3'A (RH = 0; 95% CI, 0-0.70; P = 0.020, and RH = 0; 95% CI, 0-0.71; P = 0.021, respectively). When examined before 5 years of age (n = 81), the children with CCR5 wt/Delta 32 had significantly lower levels of cell-associated HIV-1 DNA than wild-type homozygotes (P = 0.016, adjusted by race), while SDF1-3'A carriers had relatively higher levels (P = 0.047, adjusted by race). Although the disease-retarding effect of CCR5 wt/Delta 32 subsequently disappeared, time to death was still significantly delayed in the CCR5 Delta 32 heterozygotes without SDF1-3'A (RH = 0; 95% CI, 0-0.53; P = 0.008). Conclusion In pediatric AIDS, the protective effect of CCR5 wt/Delta 32 is more pronounced in early years of infection and appears to be abrogated by the SDF1-3'A genotype. (C) 2001 Lippincott Williams & Wilkins. C1 NCI Frederick, SAIC Frederick, HIV Clin Interface Lab, Frederick, MD 21702 USA. NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. RP NCI Frederick, SAIC Frederick, HIV Clin Interface Lab, Bldg 469,Room 105, Frederick, MD 21702 USA. RI Venzon, David/B-3078-2008 FU NCI NIH HHS [N01-CO-56000] NR 68 TC 29 Z9 30 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD JUL 27 PY 2001 VL 15 IS 11 BP 1343 EP 1352 DI 10.1097/00002030-200107270-00003 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 455YN UT WOS:000170055500005 PM 11504955 ER PT J AU Stevceva, L Tryniszewska, E Hel, Z Nacsa, J Kelsall, B Parks, RW Franchini, G AF Stevceva, L Tryniszewska, E Hel, Z Nacsa, J Kelsall, B Parks, RW Franchini, G TI Differences in time of virus appearance in the blood and virus-specific immune responses in intravenous and intrarectal primary SIVmac251 infection of rhesus macaques; a pilot study SO BMC INFECTIOUS DISEASES LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; CYTOTOXIC T-LYMPHOCYTES; CELL DEPLETION; SIV INFECTION; SEXUAL TRANSMISSION; TYPE-1 INFECTION; ESCAPE VARIANTS; HIV INFECTION; LYMPH-NODES; MONKEYS AB Background: HIV-1 can be transmitted by intravenous inoculation of contaminated blood or blood product or sexually through mucosal surfaces. Here we performed a pilot study in the SIVmac251 macaque model to address whether the route of viral entry influences the kinetics of the appearance and the size of virus-specific immune in different tissue compartments. Methods: For this purpose, of 2 genetically defined Mamu-A*01-positive macaques, 1 was exposed intravenously and the other intrarectally to the same SIVmac251 viral stock and virus-specific CD8+ T-cells were measured within the first 12 days of infection in the blood and at day 12 in several tissues following euthanasia. Results: Virus-specific CD8+ T-cell responses to Gag, Env, and particularly Tat appeared earlier in the blood of the animal exposed by the mucosal route than in the animal exposed intravenously. The magnitude of these virus-specific responses was consistently higher in the systemic tissues and GALT of the macaque exposed by the intravenous route, suggesting a higher viral burden in the tissues as reflected by the faster appearance of virus in plasma. Differences in the ability of the virus-specific CD8+ T-cells to respond in vitro to specific peptide stimulation were also observed and the greatest proliferative ability was found in the GALT of the animal infected by the intrarectal route. Conclusions: These data may suggest that the natural mucosal barrier may delay viral spreading. The consequences of this observation, if confirmed in studies with a larger number of animals, may have implications in vaccine development. C1 NCI, Basic Res Lab, Bethesda, MD 20892 USA. NIAID, Clin Invest Lab, Bethesda, MD 20892 USA. RP Franchini, G (reprint author), NCI, Basic Res Lab, 41-D804, Bethesda, MD 20892 USA. NR 43 TC 9 Z9 9 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2334 J9 BMC INFECT DIS JI BMC Infect. Dis. PD JUL 27 PY 2001 VL 1 BP art. no. EP 9 DI 10.1186/1471-2334-1-9 PG 10 WC Infectious Diseases SC Infectious Diseases GA 501QM UT WOS:000172697600001 PM 11504564 ER PT J AU Cohen-Fix, O AF Cohen-Fix, O TI The making and breaking of sister chromatid cohesion SO CELL LA English DT Review ID DNA-REPLICATION; YEAST COHESIN; ANAPHASE; PROTEOLYSIS; SEPARATION; MITOSIS; COMPLEX C1 NIDDKD, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. RP Cohen-Fix, O (reprint author), NIDDKD, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. NR 19 TC 30 Z9 30 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JUL 27 PY 2001 VL 106 IS 2 BP 137 EP 140 DI 10.1016/S0092-8674(01)00439-1 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 458KG UT WOS:000170193100003 PM 11511341 ER PT J AU Galmozzi, E Tomassetti, A Sforzini, S Mangiarotti, F Mazzi, M Nachmanoff, K Elwood, PC Canevari, S AF Galmozzi, E Tomassetti, A Sforzini, S Mangiarotti, F Mazzi, M Nachmanoff, K Elwood, PC Canevari, S TI Exon 3 of the alpha folate receptor gene contains a 5 ' splice site which confers enhanced ovarian carcinoma specific expression SO FEBS LETTERS LA English DT Article DE transcription regulation; alternative splicing; alpha folate receptor; ovarian carcinoma; gene therapy ID OPEN READING FRAMES; BINDING-PROTEIN; MESSENGER-RNA; TRANSLATIONAL CONTROL; CANCER; OVEREXPRESSION; ANTIBODIES AB The human folate receptor (FR) is overexpressed in ovarian carcinoma. FR transcripts are heterogeneous due to the use of two promoters, P1 and P4, and alternative splicing of exon 3. RNase protection assay and RT-PCR revealed higher levels of the transcripts that include exon 3 in lines and specimens from ovarian carcinoma. A P1-chloramphenicol acetyltransferase (CAT) construct containing exon 3 demonstrated efficient reporter expression only in ovarian carcinoma. 5' and 3' deleted variants of the P1-CAT construct were analyzed by RT-PCR of the exogenous transcripts and reporter activity. A 5' splice site and 35 bp downstream intronic region of exon 3 appeared to regulate enhanced FR expression in ovarian carcinoma. (C) 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies. C1 Ist Nazl Tumori, Dept Expt Oncol, Unit Mol Therapies, I-20133 Milan, Italy. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. RP Tomassetti, A (reprint author), Ist Nazl Tumori, Dept Expt Oncol, Unit Mol Therapies, Via Venezian 1, I-20133 Milan, Italy. RI Tomassetti, Antonella/G-7906-2015 OI Tomassetti, Antonella/0000-0001-6772-9937 NR 22 TC 10 Z9 10 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 27 PY 2001 VL 502 IS 1-2 BP 31 EP 34 DI 10.1016/S0014-5793(01)02659-X PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 459QZ UT WOS:000170263500007 PM 11478943 ER PT J AU Rodrigues, RG Guo, NH Zhou, LG Sipes, JM Williams, SB Templeton, NS Gralnick, HR Roberts, DD AF Rodrigues, RG Guo, NH Zhou, LG Sipes, JM Williams, SB Templeton, NS Gralnick, HR Roberts, DD TI Conformational regulation of the fibronectin binding and alpha(3)beta(1) integrin-mediated adhesive activities of thrombospondin-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN DISULFIDE-ISOMERASE; CELL LUNG-CARCINOMA; GROWTH-FACTOR; MONOCLONAL-ANTIBODIES; PLATELET THROMBOSPONDIN; PLASMA FIBRONECTIN; ENDOTHELIAL-CELLS; TUMOR-GROWTH; GPIIB-IIIA; I REPEAT AB The recognition of extracellular matrix components can be regulated by conformational changes that alter the activity of cell surface integrins. We now demonstrate that conformational regulation of the matrix glycoprotein thrombospondin-1 (TSP1) can also modulate its binding to an integrin receptor. F18 1G8 is a conformation-sensitive TSP1 antibody that binds weakly to soluble TSP1 in the presence of divalent cations. However, binding of the antibody to melanoma cells was strongly stimulated by adding exogenous TSP1 in the presence of calcium, suggesting that TSP1 undergoes a conformational change following its binding to the cell surface. This conformation was not induced by known cell surface TSP1 receptors, whereas binding of F18 was stimulated when TSP1 bound to fibronectin but not to heparin or fibrinogen. Conversely, binding of F18 to TSP1 enhanced TSP1 binding to fibronectin. Exogenous fibronectin also stimulated TSP1-dependent binding of F18 to melanoma cells. Binding of the fibronectin-TSP1 complex to melanoma cells was mediated by alpha (4)beta (1) and alpha (5)beta (1) integrins. Furthermore, binding to F18 or fibronectin strongly enhanced the adhesive activity of immobilized TSP1 for some cell types. This enhancement of adhesion was mediated by alpha (3)beta (1) integrin and required that the alpha (3)beta (1) integrin be in an active state. Fibronectin also enhanced TSP1 binding to purified alpha (3)beta (1) integrin. Therefore, both fibronectin and the F18 antibody induce conformational changes in TSP1 that enhance the ability of TSP1 to be recognized by alpha (3)beta (1) integrin. The conformational and functional regulation of TSP1 activity by fibronectin represents a novel mechanism for extracellular signal transduction. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NIH, Hematol Serv, Ctr Clin, Bethesda, MD 20892 USA. Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. RP Roberts, DD (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Rm 2A33,10 Ctr DR,MSC 1500, Bethesda, MD 20892 USA. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 65 TC 20 Z9 21 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 27 PY 2001 VL 276 IS 30 BP 27913 EP 27922 DI 10.1074/jbc.M009518200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 456QH UT WOS:000170093400024 PM 11358957 ER PT J AU Callahan, NA Xiong, LW Caughey, B AF Callahan, NA Xiong, LW Caughey, B TI Reversibility of scrapie-associated prion protein aggregation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; BETA-AMYLOID PROTOFIBRILS; CELL-FREE FORMATION; ALZHEIMERS-DISEASE; RESISTANT STATE; INFRARED-SPECTROSCOPY; FIBRILS SAF; PRP 27-30; CONVERSION; FORM AB During the course of the transmissible spongiform encephalopathy diseases, a protease-resistant ordered aggregate of scrapie prion protein (PrPSc) accumulates in affected animals. From mechanistic and therapeutic points of view, it is relevant to determine the extent to which PrPSc formation and aggregation are reversible. PrPSc solubilized with 5 M guanidine hydrochloride (GdnHCl) was unfolded to a predominantly random coil conformation. Upon dilution of GdnHCl, PrP refolded into a conformation that was high in a-helix as measured by CD spectroscopy, similar to the normal cellular isoform. of PrP (PrPC). This provided evidence that PrPSc can be induced to revert to a PrPC-like conformation with a strong denaturant. To examine the reversibility of PrPSc formation and aggregation under more physiological conditions, PrPSc aggregates were washed and resuspended in buffers lacking GdnHCl and monitored over time for the appearance of soluble PrP. No dissociation of PrP from the PrPSc aggregates was detected in aqueous buffers at pH 6 and 7.5. The effective solubility of PrP was <0.7 nM. Treatment of PrPSc with proteinase K (PK) before the analysis did not enhance the dissociation of PrP from the PrPSc aggregates. Treatment with 2.5 M GdnHCl, which partially and reversibly unfolds PrPSc, caused only limited dissociation of PrP from the aggregates. The PrP that dissociated from the aggregates over time was entirely PK-sensitive, like PrPC, whereas all of the aggregated PrP was partially PK-resistant. PrP also dissociated from aggregates of protease-resistant PrP generated in a cell-free conversion reaction, but only if treated with GdnHCl. Overall, the results suggest that PrP aggregation is not appreciably reversible under physiological conditions' but dissociation and refolding can be enhanced by treatments with GdnHCl. C1 NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Caughey, B (reprint author), NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. EM beaughey@niaid.nih.gov NR 60 TC 13 Z9 13 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 27 PY 2001 VL 276 IS 30 BP 28022 EP 28028 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 456QH UT WOS:000170093400038 ER PT J AU Hong, SH Park, SJ Kong, HJ Shuman, JD Cheong, JH AF Hong, SH Park, SJ Kong, HJ Shuman, JD Cheong, JH TI Functional interaction of bZIP proteins and the large subunit of replication factor C in liver and adipose cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ENHANCER-BINDING-PROTEIN; C/EBP-ALPHA GENE; TERMINAL ADIPOCYTE DIFFERENTIATION; EUKARYOTIC DNA-REPLICATION; ACTIVATED RECEPTOR-GAMMA; RETINOBLASTOMA PROTEIN; TRANSCRIPTION FACTORS; NUCLEAR ANTIGEN; LEUCINE-ZIPPER; EXPRESSION AB The transcription factor CCAAT/enhancer-binding protein-vt (C/EBP alpha) has a vital role in cell growth and differentiation. To delineate further a mechanism for C/EBP alpha -mediated differentiation, we screened C/EBP alpha -interacting proteins through far-Western screening. One of the strongest interactions was with RFC140, the large subunit of the replication factor C complex. C/EBPa specifically interacted with RFC140 from rat liver nuclear extract as determined by a combination of affinity chromatography and co-immunoprecipitation. Subsequent far-Western blotting showed that the bZIP domain of C/EBPa interacted with the DNA-binding region of RFC140. Overexpression of RFC140 in mammalian cells increased the transactivation activity of C/EBPa on both minimal and native promoters. Consistent with the enhanced transactivation, a complex of C/EBP alpha and RFC140 proteins with the cognate DNA element was detected in vitro. The specific interaction between C/EBP alpha and RFC140 was detected in the terminal differentiation of 3T3-LI preadipocytes to adipocytes. The synergistic transcription effect of these two proteins increased the promoter activity and protein expression of peroxisome proliferator-activated receptor-gamma, which is a main regulator of adipocyte differentiation. Our results demonstrate that the specific transcription factor C/EBPa and the general DNA replication factor RFC140 interact functionally and physically. This observation highlights a unique mechanism by which the levels of the general replication factor can strongly modulate the functional activity of the specific transcription factor as a coactivator. C1 Chonnam Natl Univ, Hormone Res Ctr, Kwangju 500757, South Korea. NCI, Regulat Cell Growth Lab, Frederick Canc Res & Dev Ctr, NIH, Frederick, MD 21701 USA. RP Cheong, JH (reprint author), Chonnam Natl Univ, Hormone Res Ctr, Kwangju 500757, South Korea. NR 42 TC 19 Z9 19 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 27 PY 2001 VL 276 IS 30 BP 28098 EP 28105 DI 10.1074/jbc.M010912200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 456QH UT WOS:000170093400048 PM 11356826 ER PT J AU Furumura, M Potter, SB Toyofuku, K Matsunaga, J Muller, J Hearing, VJ AF Furumura, M Potter, SB Toyofuku, K Matsunaga, J Muller, J Hearing, VJ TI Involvement of ITF2 in the transcriptional regulation of melanogenic genes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AGOUTI-RELATED PROTEIN; MELANOCYTE-SPECIFIC TRANSCRIPTION; WAARDENBURG SYNDROME; IN-VITRO; SIGNAL PROTEIN; MELANOCORTIN RECEPTORS; TYROSINASE GENE; SPLICE VARIANT; CYCLIC-AMP; E-BOX AB In response to agouti signal protein, melanocytes switch from producing eumelanin to pheomelanin concomitant with the down-regulation of melanogenic gene transcription. We previously reported that a ubiquitous basic helix-loop-helix transcription factor, known as ITF2, is up-regulated during this switch, and we now report that treatment of melanocytes with melanocyte-stimulating hormone down-regulates expression of ITF2. To more fully characterize the involvement of ITF2 in regulating melanogenic gene transcription, ITF2 sense or antisense constructs were introduced into melan-a melanocytes. Gene and protein expression analyses and luciferase reporter assays using promoters from melanogenic genes showed that up-regulation of ITF2 suppressed melanogenic gene expression as well as the expression of Mitf, a melanocyte-specific transcription factor. In addition, stable ITF2 sense transfectants had significant reductions in pigmentation and a less dendritic phenotype compared with mock transfectants. In contrast, ITF2 antisense-transfected melanocytes were more pigmented and more dendritic. These results demonstrate that up-regulation of ITF2 during the pheomelanin switch is functionally significant and reveal that differential expression of a ubiquitous basic helix-loop-helix transcription factor can modulate expression of melanogenic genes and the differentiation of melanocytes. C1 NCI, Pigment Cell Biol Sect, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Div Virol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Hearing, VJ (reprint author), NCI, Pigment Cell Biol Sect, Cell Biol Lab, NIH, Bldg 37,Rm 1B25, Bethesda, MD 20892 USA. NR 53 TC 30 Z9 31 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 27 PY 2001 VL 276 IS 30 BP 28147 EP 28154 DI 10.1074/jbc.M101626200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 456QH UT WOS:000170093400055 PM 11382753 ER PT J AU Leng, Y Chase, TN Bennett, MC AF Leng, Y Chase, TN Bennett, MC TI Muscarinic receptor stimulation induces translocation of an alpha-synuclein oligomer from plasma membrane to a light vesicle fraction in cytoplasm SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SPORADIC PARKINSONS-DISEASE; NUCLEAR TRANSLOCATION; ALZHEIMERS-DISEASE; PHOSPHOLIPASE D2; NERVOUS-SYSTEM; LEWY BODIES; PROTEIN; BINDING; BRAIN; ENDOCYTOSIS AB The close correspondence between the distribution of brain alpha -synuclein and that of muscarinic M-1 and M-3 receptors suggests a role for this protein in cholinergic transmission. We thus examined the effect of muscarinic stimulation on alpha -synuclein in SH-SY5Y, a human dopaminergic cell line that expresses this protein. Under basal conditions, alpha -synuclein was detected in all subcellular compartments isolated as follows: plasma membrane, cytoplasm, nucleus, and two vesicle fractions. The lipid fractions contained only a 45-kDa alpha -synuclein oligomer, whereas the cytoplasmic and nuclear fractions contained both the oligomer and the monomer. This finding suggests alpha -synuclein exists physiologically as a lipid-bound oligomer and a soluble monomer. Muscarinic stimulation by carbachol reduced the alpha -synuclein oligomer in plasma membrane over a 30-min period, with a concomitant increase of both the oligomer and the monomer in the cytoplasmic fraction. The oligomer was associated with a light vesicle fraction in cytoplasm that contains uncoated endocytotic vesicles. The carbachol-induced alteration of alpha -synuclein was blocked by atropine. Translocation of the alpha -synuclein oligomer in response to carbachol, stimulation corresponds closely with the time course of ligand-stimulated muscarinic receptor endocytosis. The data suggest that the muscarine receptor stimulated release of the alpha -synuclein oligomer from plasma membrane, and its subsequent association with the endocytotic vesicle fraction may have a role in muscarine receptor endocytosis. We propose that its function may be a transient release of membrane-bound phospholipase D-2 from alpha -synuclein inhibition, thus allowing this lipase to participate in muscarinic receptor endocytosis. C1 NINDS, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Chase, TN (reprint author), NINDS, Expt Therapeut Branch, NIH, Bldg 10,Rm 5C-103, Bethesda, MD 20892 USA. EM chaset@ninds.nih.gov NR 42 TC 51 Z9 52 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 27 PY 2001 VL 276 IS 30 BP 28212 EP 28218 DI 10.1074/jbc.M011121200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 456QH UT WOS:000170093400064 PM 11337491 ER PT J AU Schofield, MJ Nayak, S Scott, TH Du, CW Hsieh, P AF Schofield, MJ Nayak, S Scott, TH Du, CW Hsieh, P TI Interaction of Escherichia coli MutS and MutL at a DNA mismatch SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID REPAIR PROTEIN MUTS; HETERODUPLEX DNA; ATP-HYDROLYSIS; TRANSLOCATION MECHANISM; CRYSTAL-STRUCTURE; MOLECULAR SWITCH; BINDING; COMPLEX; YEAST; RECOMBINATION AB MutS and MutL are both required to activate downstream events in DNA mismatch repair. We examined the rate of dissociation of MutS from a mismatch using linear heteroduplex DNAs or heteroduplexes blocked at one or both ends by four-way DNA junctions in the presence and absence of MutL. In the presence of ATP, dissociation of MutS from linear heteroduplexes or heteroduplexes blocked at only one end occurs within 15 s. When both duplex ends are blocked, MutS remains associated with the DNA in complexes with half-lives of 30 min. DNase I footprinting of MutS complexes is consistent with migration of MutS throughout the DNA duplex region. When MutL is present, it associates with MutS and prevents ATP-dependent migration away from the mismatch in a manner that is dependent on the length of the heteroduplex. The rate and extent of mismatch-provoked cleavage at hemimethylated GATC sites by MutH in the presence of MutS, MutL, and ATP are the same whether the mismatch and GATC sites are in cis or in trans. These results suggest that a MutS-MutL complex in the vicinity of a mismatch is involved in activating MutH. C1 NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. RP Hsieh, P (reprint author), NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. NR 40 TC 105 Z9 106 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 27 PY 2001 VL 276 IS 30 BP 28291 EP 28299 DI 10.1074/jbc.M103148200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 456QH UT WOS:000170093400074 PM 11371566 ER PT J AU Wang, XT McCullough, KD Wang, XJ Carpenter, G Holbrook, NJ AF Wang, XT McCullough, KD Wang, XJ Carpenter, G Holbrook, NJ TI Oxidative stress-induced phospholipase C-gamma l activation enhances cell survival SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; TYROSINE KINASE; FACTOR RECEPTOR; HYDROGEN-PEROXIDE; PROTEIN-KINASE; SIGNALING PATHWAYS; INDUCED APOPTOSIS; PHOSPHORYLATION; SRC; C-GAMMA-1 AB Phospholipase C-gamma1 (PLC-gamma1) is rapidly activated in response to growth factor stimulation and plays an important role in regulating cell proliferation and differentiation through the generation of the second messengers diacylglycerol and inositol 1,4,5-trisphosphate, leading to the activation of protein kinase C (PKC) and increased levels of intracellular calcium, respectively. Given the existing overlap between signaling pathways that are activated in response to oxidant injury and those involved in responding to proliferative stimuli, we investigated the role of PLC-gamma1 during the cellular response to oxidative stress. Treatment of normal mouse embryonic fibroblasts (MEF) with H2O2 resulted in time- and concentration-dependent tyrosine phosphorylation of PLC-gamma1. Phosphorylation could be blocked by pharmacological inhibitors of Src family tyrosine kinases or the epidermal growth factor receptor tyrosine kinase, but not by inhibitors of the platelet-derived growth factor receptor or phosphatidylinositol 3-kinase. To investigate the physiologic relevance of H2O2-induced tyrosine phosphorylation of PLC-gamma1, we compared survival of normal MEF and PLC-gamma1-deficient MEF following exposure to H2O2. Treatment of PLC-gamma1-deficient MEF with H2O2 resulted in rapid cell death, whereas normal MEF were resistant to the stress. Pretreatment of normal MEF with a selective pharmacological inhibitor of PLC-gamma1, or inhibitors of inositol trisphosphate receptors and PKC, increased their sensitivity to H2O2, whereas treatment of PLC-gamma1-deficient MEF with agents capable of directly activating PKC and enhancing calcium mobilization significantly improved their survival. Finally, reconstitution of PLC-gamma1 protein expression in PLC-gamma1-deficient MEF restored cell survival following H2O2 treatment. These findings suggest an important protective function for PLC-gamma1 activation during the cellular response to oxidative stress. C1 NIA, Cell Stress & Aging Sect, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37232 USA. RP Holbrook, NJ (reprint author), NIA, Cell Stress & Aging Sect, Cellular & Mol Biol Lab, NIH, Box 12,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. FU NCI NIH HHS [CA75195] NR 40 TC 106 Z9 108 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 27 PY 2001 VL 276 IS 30 BP 28364 EP 28371 DI 10.1074/jbc.M102693200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 456QH UT WOS:000170093400083 PM 11350969 ER PT J AU Bhagwat, M Nossal, NG AF Bhagwat, M Nossal, NG TI Bacteriophage T4 RNase H removes both RNA primers and adjacent DNA from the 5 ' end of lagging strand fragments SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ESCHERICHIA-COLI; OKAZAKI FRAGMENT; REPLICATION FORK; SACCHAROMYCES-CEREVISIAE; POLYMERASE HOLOENZYME; SLIDING CLAMPS; PROTEINS; 5'-EXONUCLEASE; ENDONUCLEASE; HELICASE AB Bacteriophage T4 RNase H belongs to a family of prokaryotic and eukaryotic nucleases that remove RNA primers from lagging strand fragments during DNA replication. Each enzyme has a flap endonuclease activity, cutting at or near the junction between single- and double-stranded DNA, and a 5'- to 3-exonuclease, degrading both RNA-DNA and DNA-DNA duplexes. On model substrates for lagging strand synthesis, T4 RNase H functions as an exonuclease removing short oligonucleotides, rather than as an endonuclease removing longer flaps created by the advancing polymerase. The combined length of the DNA oligonucleotides released from each fragment ranges from 3 to 30 nucleotides, which corresponds to one round of processive degradation by T4 RNase H with 32 single-stranded DNA-binding protein present. Approximately 30 nucleotides are removed from each fragment during coupled leading and lagging strand synthesis with the complete T4 replication system. We conclude that the presence of 32 protein on the single-stranded DNA between lagging strand fragments guarantees that the nuclease will degrade processively, removing adjacent DNA as well as the RNA primers, and that the difference in the relative rates of synthesis and hydrolysis ensures that there is usually only a single round of degradation during each lagging strand cycle. C1 NIDDKD, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. RP Nossal, NG (reprint author), NIDDKD, Mol & Cellular Biol Lab, NIH, Bldg 8,Rm 2A19, Bethesda, MD 20892 USA. NR 42 TC 20 Z9 21 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 27 PY 2001 VL 276 IS 30 BP 28516 EP 28524 DI 10.1074/jbc.M103914200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 456QH UT WOS:000170093400103 PM 11376000 ER PT J AU Potapova, O Basu, S Mercola, D Holbrook, NJ AF Potapova, O Basu, S Mercola, D Holbrook, NJ TI Protective role for c-Jun in the cellular response to DNA damage SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNAL-TRANSDUCTION; ACTIVATION DOMAIN; CYCLE PROGRESSION; INDUCED APOPTOSIS; PROTEIN-KINASE; MEK KINASE-1; PHOSPHORYLATION; INDUCTION; AP-1; JNK AB c-Jun, a member of the activation protein 1 (AP-1) family of transcription factors, has been implicated in the regulation of many important biological processes including cell cycle progression, transformation, differentiation, and apoptosis. Accordingly, its expression and function are upregulated in response to diverse stimuli including mitogens and a wide range of stresses. Transcriptional activation of the e-Jun protein is dependent on its phosphorylation at Ser-63 and Ser-73, process mediated by c-Jun N-terminal kinase. Active c-Jun is required for AP-1 transactivation and c-Jun-mediated transformation, but its role during stress remains unclear as both pro-apoptotic and pro-survival effects of e-Jun have been observed. Here we investigated the importance of c-Jun N-terminal phosphorylation in influencing the sensitivity of human T98G glioblastoma cells to a variety of cytotoxic agents. Stable expression of a nonphosphorylatable dominant negative protein c-Jun(S63A,S73A) markedly inhibited the activation of AP-1-driven transcription and greatly increased the cytotoxic effects of DNA-damaging agents associated with enhanced apoptosis. However, the same cells expressing the mutant Jun protein did not differ from parental cells in their sensitivity to several non-DNA-damaging cytotoxic agents. Our results suggest that activated e-Jun has a selective role in protecting human tumor cells from apoptosis induced by DNA damage. C1 NIA, Cell Stress & Aging Sect, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. Sidney Kimmel Canc Ctr, San Diego, CA 92121 USA. RP Holbrook, NJ (reprint author), NIA, Cell Stress & Aging Sect, Cellular & Mol Biol Lab, Box 12,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 32 TC 83 Z9 86 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 27 PY 2001 VL 276 IS 30 BP 28546 EP 28553 DI 10.1074/jbc.M102075200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 456QH UT WOS:000170093400107 PM 11352915 ER PT J AU Kawaguchi, T Veech, RL Uyeda, K AF Kawaguchi, T Veech, RL Uyeda, K TI Regulation of energy metabolism in macrophages during hypoxia - Roles of fructose 2,6-bisphosphate and ribose 1,5-bisphosphate SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; RAT-LIVER; KINETIC-PROPERTIES; PHOSPHOLIPASE-C; PATHWAY; ACTIVATION; 6-PHOSPHOFRUCTO-2-KINASE/FRUCTOSE-2,6-BISPHOSPHATASE; PHOSPHOFRUCTOKINASES; HEPATOCYTES; GLYCOLYSIS AB Macrophages can adapt to the absence of oxygen by switching to anaerobic glycolysis. In this study, we investigated (a) the roles of fructose 2,6-bisphosphate (Fru-2,6-P-2) and ribose 1,5-bisphosphate (Rib-1,5-P-2), Potent activators of phosphofructokinase, (b) the enzymes responsible for the synthesis of Rib-1,5-P-2, and (c) the mechanisms of regulation of these enzymes in H36.12j macrophages during the initial phase of hypoxia. Within I min after initiating hypoxia, glycolysis was activated through activation of phosphofructokinase. Over the same period, Fru-2,6-P-2 decreased 50% and recovered completely upon reoxygenation. Similar changes in cAMP levels were observed. In contrast, the Rib-1,5-P-2 concentration rapidly increased to a maximum level of 8.0 +/- 0.9 nmol/g cell 30 s after hypoxia. Thus, Rib-1,5-P-2 was the major factor increasing the rate of glycolysis during the initial phase of hypoxia. Moreover, we found that Rib-1,5-P-2 was synthesized by two steps: the ribose-phosphate pyrophosphokinase (5-phosphoribosyl-1-pyrophosphate synthetase; PRPP synthetase) reaction (EC 2.7.6.1) catalyzing the reaction, Rib-5-P + ATP --> PRPP + AMP and a new enzyme, "PRPP pyrophosphatase" catalyzing the reaction, PRPP --> Rib-1,5-P-2 + P-i. Both PRPP synthetase and PRPP pyrophosphatase were significantly activated 30 s after hypoxia. Pretreatment with 1-octadecyl-2-methyl-rac-glycero-3-phosphocholine and calphostin C prevented the activation of ribose PRPP synthetase and PRPP pyrophosphatase as well as increase in Rib-1,5-P-2 and activation of phosphofructokinase 30 s after hypoxia. These data suggest that the activation of the above enzymes was mediated by protein kinase C acting via activation of phosphatidylinositol specific phospholipase C in the macrophages during hypoxia. C1 Dallas Vet Affairs Med Ctr, Dept Biochem, Dallas, TX 75216 USA. Univ Texas, SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75223 USA. NIAAA, Rockville, MD 20852 USA. RP Uyeda, K (reprint author), Dallas Vet Affairs Med Ctr, Dept Biochem, 4500 S Lancaster Rd, Dallas, TX 75216 USA. FU NIDDK NIH HHS [DK16194] NR 31 TC 46 Z9 49 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 27 PY 2001 VL 276 IS 30 BP 28554 EP 28561 DI 10.1074/jbc.M101396200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 456QH UT WOS:000170093400108 PM 11373280 ER PT J AU Kedei, N Szabo, T Lile, JD Treanor, JJ Olah, Z Iadarola, MJ Blumberg, PM AF Kedei, N Szabo, T Lile, JD Treanor, JJ Olah, Z Iadarola, MJ Blumberg, PM TI Analysis of the native quaternary structure of vanilloid receptor 1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ROOT GANGLION NEURONS; CAPSAICIN-RECEPTOR; OLIGOMERIC STRUCTURE; CHANNELS; PROTEINS; CALCIUM; BINDING; TARGET; HEAT; TRP AB Vanilloid receptor subtype I (VRI) is a ligand-gated channel that can be activated by capsaicin and other vanilloids as well as by protons and heat. In the present study, we have analyzed the oligomeric state of VR1. Co-immunoprecipitation of differently tagged VRI molecules indicated that VRI can form oligomers. Using two different heterologous VR1 expression systems as well as endogenous VRI expressed in dorsal root ganglion cells, we analyzed oligomer formation using perfluorooctanoic acid polyacrylamide gel electrophoresis. Results were confirmed both with chemical cross-linking agents as well as through endogenous cross-linking mediated by transglutaminase. Our results clearly show that VRI forms multimers in each of the expression systems with a homotetramer as a predominant form. The oligomeric structure of VR1 may contribute to the complexity of VRI pharmacology. Finally, differences in glycosylation between the systems were observed, indicating the need for caution in the use of the heterologous expression systems for analysis of VRI properties. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. NIDCR, Neuronal Gene Express Unit, Pain & Neurosensory Mech Branch, NIH, Bethesda, MD 20892 USA. Amgen Corp, Thousand Oaks, CA 91320 USA. RP Blumberg, PM (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bldg 37,Rm 3A01,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 44 TC 227 Z9 239 U1 4 U2 10 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 27 PY 2001 VL 276 IS 30 BP 28613 EP 28619 DI 10.1074/jbc.M103272200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 456QH UT WOS:000170093400115 PM 11358970 ER PT J AU Janini, GM Metral, CJ Issaq, HJ AF Janini, GM Metral, CJ Issaq, HJ TI Peptide mapping by capillary zone electrophoresis: How close is theoretical simulation to experimental determination SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 14th International Symposium on Microscale Separations and Analysis CY JAN 13-18, 2001 CL BOSTON, MASSACHUSETTS DE peptide mapping; electrophoretic mobility; computer simulation; glucagon; cytochromes; proteins ID FLIGHT MASS-SPECTROMETRY; PHYSICOCHEMICAL PROPERTIES; MOBILITY; PROTEINS; CHROMATOGRAPHY; OLIGOGLYCINES; OLIGOALANINES; OPTIMIZATION; PREDICTION; SEPARATION AB A multi-variable computer model is presented for the prediction of the electrophoretic mobilities of peptides at pH 2.5 from known physico-chemical constants of their amino acid residues. The model is empirical and does not claim any theoretical dependencies; however, the results suggest that, at least at this pH, peptides may be theoretically represented as classical polymers of freely joined amino acid residues of unequal sizes. The model assumes that the electrophoretic mobility can be represented by a product of three functions that return the contributions of peptide charge, length and width, respectively to the mobility. The model relies on accurate experimental determination of the electrophoretic mobilities of a diverse set of peptides, by capillary zone electrophoresis (CZE), at 22 degreesC, with a 50 mM phosphate buffer, at pH 2.5. The electrophoretic mobilities of a basis set of 102 peptides that varied in charge from 0.65 to 16 and in size from two to 42 amino acid residues were accurately measured at these fixed experimental conditions using a stable 10% linear polyacrylamide-coated column. Data from this basis set was used to derive the peptide charge, length, and width functions respectively. The main purpose of this endeavor is to use the model for the prediction of peptide mobilities at pH 2.5, and for simulation of CZE peptide maps of protein digests. Excellent agreement was obtained between predicted and experimental electrophoretic mobilities for all categories of peptides, including the highly charged and the hydrophobic. To illustrate the utility of this model in protein studies it was used to simulate theoretical peptide maps of the digests of glucagon and horse cytochrome c. The resulting maps were compared and contrasted with their experimental counterparts. The potential of this approach and its limitations are discussed. Published by Elsevier Science B.V. C1 NCI, SAIC Frederick, Frederick, MD 21702 USA. RP Janini, GM (reprint author), NCI, SAIC Frederick, POB B, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 35 TC 33 Z9 34 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD JUL 27 PY 2001 VL 924 IS 1-2 BP 291 EP 306 DI 10.1016/S0021-9673(01)00919-0 PG 16 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 461HQ UT WOS:000170359200029 PM 11521876 ER PT J AU Ng, PWP Iha, H Iwanaga, Y Bittner, M Chen, YD Jiang, Y Gooden, G Trent, JM Meltzer, P Jeang, KT Zeichner, SL AF Ng, PWP Iha, H Iwanaga, Y Bittner, M Chen, YD Jiang, Y Gooden, G Trent, JM Meltzer, P Jeang, KT Zeichner, SL TI Genome-wide expression changes induced by HTLV-1 Tax: evidence for MLK-3 mixed lineage kinase involvement in Tax-mediated NF-kappa B activation SO ONCOGENE LA English DT Article DE HTLV-1; Tax; microarray; gene expression; MLK-3; JPX-9 ID T-CELL LEUKEMIA; VIRUS TYPE-I; VIRAL TRANSACTIVATOR TAX; HEPATOCYTE GROWTH-FACTOR; GENE-EXPRESSION; PROTEIN-KINASE; TYPE-1 TAX; MOLECULAR-MECHANISMS; CYCLE PROGRESSION; 1-INFECTED CELLS AB The Tax protein of human T-lymphotropic virus type 1 (HTLV-1), an oncoprotein that transactivates viral and cellular genes, plays a key role in HTLV-1 replication and pathogenesis. We used cDNA microarrays to examine Tax-mediated transcriptional changes in the human Jurkat T-cell lines JPX-9 and JPX-M which express Tax and Tax-mutant protein, respectively, under the control of an inducible promoter. Approximately 300 of the over 2000 genes examined were differentially expressed in the presence of Tax. These genes were grouped according to their function and are discussed in the context of existing findings in the literature. There was strong agreement between our results and genes previously reported as being Tax-responsive. Genes that were differentially expressed in the presence of Tax included those related to apoptosis, the cell cycle and DNA repair, signaling factors, immune modulators, cytokines and growth factors, and adhesion molecules. Functionally, we provide evidence that one of these genes, the mixed-lineage kinase MLK-3, is involved in Tax-mediated NF-kappaB signaling. Our current results provide additional insights into Tax-mediated signaling. C1 NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Zeichner, SL (reprint author), NCI, HIV & AIDS Malignancy Branch, NIH, Bldg 10,Room 10S255, Bethesda, MD 20892 USA. EM kj7e@nih.gov; zeichner@nih.gov RI Jeang, Kuan-Teh/A-2424-2008 NR 75 TC 84 Z9 85 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL 27 PY 2001 VL 20 IS 33 BP 4484 EP 4496 DI 10.1038/sj.onc.1204513 PG 13 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 456GN UT WOS:000170074900006 PM 11494144 ER PT J AU Gottesman, S Maurizi, MR AF Gottesman, S Maurizi, MR TI Cell biology - Surviving starvation SO SCIENCE LA English DT Editorial Material ID INORGANIC POLYPHOSPHATE; PROTEIN-DEGRADATION; ESCHERICHIA-COLI C1 NCI, Mol Biol Lab, Bethesda, MD 20892 USA. NCI, Cell Biol Lab, Bethesda, MD 20892 USA. RP Gottesman, S (reprint author), NCI, Mol Biol Lab, Bldg 37, Bethesda, MD 20892 USA. NR 9 TC 20 Z9 20 U1 2 U2 7 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUL 27 PY 2001 VL 293 IS 5530 BP 614 EP 615 DI 10.1126/science.1063371 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 458PW UT WOS:000170204600030 PM 11474088 ER PT J AU Modan, B Hartge, P Hirsh-Yechezkel, G Chetrit, A Lubin, F Beller, U Ben-Baruch, G Fishman, A Menczer, J Struewing, JP Tucker, MA Wacholder, S Ebbers, SM Friedman, E Piura, B AF Modan, B Hartge, P Hirsh-Yechezkel, G Chetrit, A Lubin, F Beller, U Ben-Baruch, G Fishman, A Menczer, J Struewing, JP Tucker, MA Wacholder, S Ebbers, SM Friedman, E Piura, B CA Natl Israel Ovarian Canc Study Grp TI Parity, oral contraceptives, and the risk of ovarian cancer among carriers and noncarriers of a BRCA1 or BRCA2 mutation SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BREAST-CANCER; DETERMINANTS; POPULATION; OVULATION; ISRAEL; WOMEN AB Background Multiparity and the use of oral contraceptives reduce the risk of ovarian cancer, but their effects on this risk in women with a BRCA1 or BRCA2 mutation are unclear. Methods We conducted a population-based case control study of ovarian cancer among Jewish women in Israel. Women were tested for the two founder mutations in BRCA1 and the one founder mutation in BRCA2 that are known to be common among Jews. We estimated the effects of parity and oral-contraceptive use on the risk of ovarian cancer in carriers and noncarriers in separate analyses that included all control women, who did not have ovarian cancer. Results Of 751 controls who underwent mutation analysis, 13 (1.7 percent) had a BRCA1 or BRCA2 mutation, whereas 244 of 840 women with ovarian cancer (29.0 percent) had a BRCA1 or BRCA2 mutation. Overall, each additional birth and each additional year of use of oral contraceptives were found to lower the risk of ovarian cancer, as expected. Additional births were protective in separate analyses of carriers and non-carriers, but oral-contraceptive use appeared to reduce the risk only in noncarriers; among carriers, the reduction in the odds of ovarian cancer was 12 percent per birth (95 percent confidence interval, 2.3 to 21 percent) and 0..2 percent per year of oral-contraceptive use (-4.9 to 5.0 percent). Conclusions The risk of ovarian cancer among carriers of a BRCA1 or BRCA2 mutation decreases with each birth but not with increased duration of use of oral contraceptives. These data suggest that it is premature to use oral contraceptives for the chemoprevention of ovarian cancer in carriers of such mutations. (N Engl J Med 2001;345:235-40.) Copyright (C) 2001 Massachusetts Medical Society. C1 Chaim Sheba Med Ctr, Dept Clin Epidemiol, IL-52621 Tel Hashomer, Israel. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Shaare Zedek Med Ctr, Jerusalem, Israel. Sapir Med Ctr, Kfar Saba, Israel. Edith Wolfson Med Ctr, Holon, Israel. RP Modan, B (reprint author), Chaim Sheba Med Ctr, Dept Clin Epidemiol, IL-52621 Tel Hashomer, Israel. RI Struewing, Jeffery/C-3221-2008; Tucker, Margaret/B-4297-2015; Struewing, Jeffery/I-7502-2013 OI Struewing, Jeffery/0000-0002-4848-3334 FU NCI NIH HHS [MS N02-CP-81005, N02-CP-60534, N02-CP-91026, R01 CA61126-01-03] NR 29 TC 202 Z9 204 U1 1 U2 8 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 26 PY 2001 VL 345 IS 4 BP 235 EP 240 DI 10.1056/NEJM200107263450401 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 455XZ UT WOS:000170054200001 PM 11474660 ER PT J AU Kreitman, RJ Wilson, WH Bergeron, K Raggio, M Stetler-Stevenson, M FitzGerald, DJ Pastan, I AF Kreitman, RJ Wilson, WH Bergeron, K Raggio, M Stetler-Stevenson, M FitzGerald, DJ Pastan, I TI Efficacy of the anti-CD22 recombinant immunotoxin BL22 in chemotherapy-resistant hairy-cell leukemia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MINIMAL RESIDUAL DISEASE; VASCULAR LEAK SYNDROME; A CHAIN IMMUNOTOXIN; PHASE-I TRIAL; FOLLOW-UP; CONTINUOUS-INFUSION; COMPLETE REMISSION; ENDOTHELIAL-CELLS; 2-CHLORODEOXYADENOSINE; LYMPHOMA AB Background Hairy-cell leukemia that is resistant to treatment with purine analogues, including cladribine, has a poor prognosis. We tested the safety and efficacy of an immunotoxin directed against a surface antigen that is strongly expressed by leukemic hairy cells. Methods RFB4(dsFv)-PE38 (BL22), a recombinant immunotoxin containing an anti-CD22 variable domain (Fv) fused to truncated pseudomonas exotoxin, was administered in a dose-escalation trial by intravenous infusion every other day for a total of three doses. Results Of 16 patients who were resistant to cladribine, 11 had a complete remission and 2 had a partial remission with BL22. The three patients who did not have a response received low doses of BL22 or had preexisting toxin-neutralizing antibodies. Of the 11 patients in complete remission, 2 had minimal residual disease in the bone marrow or blood. During a median follow-up of 16 months ( range, 10 to 23), 3 of the 11 patients who had a complete response relapsed and were retreated; all of these patients had a second complete remission. In 2 of the 16 patients, a serious but completely reversible hemolytic uremic syndrome developed during the second cycle of treatment with BL22. Common toxic effects included transient hypoalbuminemia and elevated aminotransferase levels. Conclusions BL22 can induce complete remissions in patients with hairy-cell leukemia that is resistant to treatment with purine analogues. (N Engl J Med 2001; 345: 241-7.) Copyright (C) 2001 Massachusetts Medical Society. C1 NCI, Mol Biol Lab, Bethesda, MD 20892 USA. NCI, Med Branch, Bethesda, MD 20892 USA. NCI, Clin Pathol Lab, Bethesda, MD 20892 USA. RP Kreitman, RJ (reprint author), NCI, Mol Biol Lab, Bldg 37,Rm 4B27,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 44 TC 376 Z9 395 U1 0 U2 5 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 26 PY 2001 VL 345 IS 4 BP 241 EP 247 DI 10.1056/NEJM200107263450402 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 455XZ UT WOS:000170054200002 PM 11474661 ER PT J AU Srinivasan, A Kraus, CN DeShazer, D Becker, PM Dick, JD Spacek, L Bartlett, JG Byrne, WR Thomas, DL AF Srinivasan, A Kraus, CN DeShazer, D Becker, PM Dick, JD Spacek, L Bartlett, JG Byrne, WR Thomas, DL TI Glanders in a military research microbiologist SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article C1 Johns Hopkins Med Inst, Div Infect Dis, Bethesda, MD USA. Johns Hopkins Med Inst, Div Pulm & Crit Care Med, Bethesda, MD USA. Johns Hopkins Med Inst, Dept Pathol, Bethesda, MD USA. NIAID, NIH, Bethesda, MD 20892 USA. USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. RP Thomas, DL (reprint author), 424 N Bond St, Baltimore, MD 21231 USA. NR 11 TC 124 Z9 128 U1 1 U2 6 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 26 PY 2001 VL 345 IS 4 BP 256 EP 258 DI 10.1056/NEJM200107263450404 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 455XZ UT WOS:000170054200004 PM 11474663 ER PT J AU Moss, RA Fede, JM Yan, SQ AF Moss, RA Fede, JM Yan, SQ TI SbF5-mediated reactions of oxafluorodiazirines SO ORGANIC LETTERS LA English DT Article ID EXCHANGE-REACTIONS; HALODIAZIRINES; FRAGMENTATION; MECHANISM; AZIDE AB [GRAPHICS] The reaction of benzyloxyfluorodiazirine (3) with SbF5 in benzene gives PhCH2OCF, which undergoes SbF5-mediated fragmentation to PhCH2+, CO, and SbF6-; the benzyl cation alkylates benzene to yield diphenylmethane. Phenoxyfluorodiazirine (4) reacts with SbF5 in benzene to give PhOCF and (ultimately) triphenylmethane by a pathway that avoids fragmentation. C1 Rutgers State Univ, Dept Chem, New Brunswick, NJ 08903 USA. NCI, Med Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. RP Moss, RA (reprint author), Rutgers State Univ, Dept Chem, New Brunswick, NJ 08903 USA. NR 19 TC 9 Z9 9 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1523-7060 J9 ORG LETT JI Org. Lett. PD JUL 26 PY 2001 VL 3 IS 15 BP 2305 EP 2308 DI 10.1021/ol010091k PG 4 WC Chemistry, Organic SC Chemistry GA 456AB UT WOS:000170059000013 PM 11463302 ER PT J AU Tammur, J Prades, C Arnould, I Rzhetsky, A Hutchinson, A Adachi, M Schuetz, JD Swoboda, KJ Ptacek, LJ Rosier, M Dean, M Allikmets, R AF Tammur, J Prades, C Arnould, I Rzhetsky, A Hutchinson, A Adachi, M Schuetz, JD Swoboda, KJ Ptacek, LJ Rosier, M Dean, M Allikmets, R TI Two new genes from the human ATP-binding cassette transporter superfamily, ABCC11 and ABCC12, tandemly duplicated on chromosome 16q12 SO GENE LA English DT Article DE ATP-binding cassette transporters; mapping; paroxysmal kinesigenic choreoathetosis ID MULTIDRUG-RESISTANCE PROTEIN; PAROXYSMAL KINESIGENIC DYSKINESIA; CAUSE PSEUDOXANTHOMA ELASTICUM; INFANTILE CONVULSIONS; CYSTIC-FIBROSIS; MUTATIONS; LOCUS; 9-(2-PHOSPHONYLMETHOXYETHYL)ADENINE; IDENTIFICATION; LINKAGE AB Several years ago, we initiated a long-term project of cloning new human ATP-binding cassette (ABC) transporters and linking them to various disease phenotypes. As one of the results of this project, we present two new members of the human ABCC subfamily, ABCC11 and ABCC12. These two new human ABC transporters were fully characterized and mapped to the human chromosome 16q12. With the addition of these two genes, the complete human ABCC subfamily has 12 identified members (ABCC1-12), nine from the multidrug resistance-like subgroup, two from the sulfonylurea receptor subgroup, and the CFTR gene. Phylogenetic analysis determined that ABCC11 and ABCC12 are derived by duplication. and are most closely related to the ABCC5 gene. Genetic variation in some ABCC subfamily members is associated with human inherited diseases, including cystic fibrosis (CFTR/ABCC7), Dubin-Johnson syndrome (ABCC2). pseudoxanthoma elasticum (ABCC6) and familial persistent hyperinsulinemic hypoglycemia of infancy (ABCC8). Since ABCC11 and ABCC12 were mapped to a region harboring gene(s) for paroxysmal kinesigenic choreoathetosis, the two genes represent positional candidates for this disorder. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Columbia Univ, Dept Ophthalmol, New York, NY 10032 USA. Univ Tartu, Inst Mol & Cell Biol, Dept Biotechnol, EE-50090 Tartu, Estonia. Aventis Pharma, Funct Genom Dept, Paris, France. Columbia Univ, Columbia Genome Ctr, New York, NY 10032 USA. St Jude Childrens Res Hosp, Dept Pharmacol Sci, Memphis, TN 38105 USA. Univ Utah, Sch Med, Dept Neurol, Salt Lake City, UT USA. Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT USA. Univ Utah, Sch Med, Dept Human Genet, Salt Lake City, UT USA. Univ Utah, Sch Med, Howard Hughes Med Inst, Salt Lake City, UT USA. NCI, Lab Genom Divers, FCRDC, Frederick, MD USA. Columbia Univ, Dept Pathol, New York, NY 10032 USA. RP Allikmets, R (reprint author), Columbia Univ, Dept Ophthalmol, Eye Res Addit,Room 715,630 W 168th St, New York, NY 10032 USA. EM rla22@columbia.edu RI rzhetsky, andrey/B-6118-2012; Dean, Michael/G-8172-2012; OI Dean, Michael/0000-0003-2234-0631; Rzhetsky, Andrey/0000-0001-6959-7405 NR 30 TC 107 Z9 114 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JUL 25 PY 2001 VL 273 IS 1 BP 89 EP 96 DI 10.1016/S0378-1119(01)00572-8 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 473MP UT WOS:000171048300010 PM 11483364 ER PT J AU Folkers, GK Fauci, AS AF Folkers, GK Fauci, AS TI The AIDS research model - Implications for other infectious diseases of global health importance SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID CHALLENGES; PREVENTION; HIV/AIDS C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Fauci, AS (reprint author), NIAID, NIH, Bldg 31,Room 7A03,31 Ctr Dr,MSC 2520, Bethesda, MD 20892 USA. EM afauci@nih.gov NR 28 TC 13 Z9 13 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 25 PY 2001 VL 286 IS 4 BP 458 EP 461 DI 10.1001/jama.286.4.458 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 456DZ UT WOS:000170069000019 PM 11466126 ER PT J AU Farb, A Heller, PF Shroff, S Cheng, L Kolodgie, FD Carter, AJ Scott, DS Froehlich, J Virmani, R AF Farb, A Heller, PF Shroff, S Cheng, L Kolodgie, FD Carter, AJ Scott, DS Froehlich, J Virmani, R TI Pathological analysis of local delivery of paclitaxel via a polymer-coated stent SO CIRCULATION LA English DT Article DE stents; restenosis; pathology ID MUSCLE CELL-PROLIFERATION; IN-VIVO; TAXOL; RESTENOSIS; INJURY; ACCUMULATION; PREVENTION; GROWTH; ARREST; MODEL AB Background-Paclitaxel can inhibit vascular smooth muscle proliferation in vitro, and early studies suggest that paclitaxel may be useful in preventing restenosis. Early and late intimal. growth and local vascular pathological changes associated with paclitaxel delivered via stents have not been fully explored. Methods and Results-Localized drug delivery was accomplished with balloon-expandable stainless steel stents coated with a cross-linked biodegradable polymer, chondroitin sulfate and gelatin (CSG), containing various doses of paclitaxel. CSG-coated stents with paclitaxel (42.0, 20.2, 8.6, or 1.5 mug of paclitaxel per stent), CSG-coated stents without paclitaxel, and uncoated stents (without paclitaxel or CSG) were deployed in the iliac arteries of New Zealand White rabbits, which were killed 28 days after implant. Mean neointimal thickness at stent strut sites was reduced 49% (P<0.0003) and 36% (P<0.007) with stents containing 42.0 and 20.2 mug of paclitaxel per stent, respectively, versus CSG-coated stents without paclitaxel. However, histological findings suggested incomplete healing in the higher-dose (42.0 and 20.2 mug) paclitaxel-containing stents consisting of persistent intimal fibrin deposition, intraintimal hemorrhage, and increased intimal and adventitial inflammation. Stents coated with CSG alone (without paclitaxel) had similar neointimal growth as uncoated stents. In a separate group of rabbits killed at 90 days, neointimal growth was no longer suppressed by CSG-coated stents containing 42.0 or 21.0 mug of paclitaxel Conclusions-coating appears to be a promising medium for localized drug delivery. Paclitaxel polymer-coated stents reduce neointima formation but are associated with evidence of incomplete healing at 28 days. However, neointimal suppression was not maintained at 90 days. C1 Armed Forces Inst Pathol, Dept Cardiovasc Pathol, Washington, DC 20306 USA. NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. RP Virmani, R (reprint author), Armed Forces Inst Pathol, Dept Cardiovasc Pathol, Washington, DC 20306 USA. NR 21 TC 287 Z9 321 U1 1 U2 29 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL 24 PY 2001 VL 104 IS 4 BP 473 EP 479 DI 10.1161/hc3001.092037 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 457BA UT WOS:000170116200019 PM 11468212 ER PT J AU Grundy, SM D'Agostino, RB Mosca, L Burke, GL Wilson, PWF Rader, DJ Cleeman, JI Roccella, EJ Cutler, JA Friedman, LM AF Grundy, SM D'Agostino, RB Mosca, L Burke, GL Wilson, PWF Rader, DJ Cleeman, JI Roccella, EJ Cutler, JA Friedman, LM TI Cardiovascular risk assessment based on US cohort studies - Findings from a National Heart, Lung, and Blood Institute workshop SO CIRCULATION LA English DT Article DE cardiovascular diseases; coronary disease; risk factors; epidemiology ID ROC ANALYSIS; DISEASE; PREDICTION; THICKNESS C1 NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. NHLBI, Off Director, Bethesda, MD 20892 USA. NHLBI, Off Prevent Educ & Control, Bethesda, MD 20892 USA. Univ Penn Hlth Syst, Prevent Cardiol & Lipid Res Ctr, Philadelphia, PA USA. Wake Forest Sch Med, Winston Salem, NC USA. Cornell Univ, New York, NY USA. Columbia Univ, New York, NY USA. Boston Univ, Framington Heart Study, Boston, MA 02215 USA. Univ Texas, SW Med Ctr, Ctr Human Nutr, Dallas, TX 75235 USA. RP Cutler, JA (reprint author), NHLBI, Div Epidemiol & Clin Applicat, 6701 Rockledge Dr, Bethesda, MD 20892 USA. NR 18 TC 92 Z9 101 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL 24 PY 2001 VL 104 IS 4 BP 491 EP 496 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 457BA UT WOS:000170116200022 PM 11468215 ER PT J AU Holmgren, C Kanduri, C Dell, G Ward, A Mukhopadhya, R Kanduri, M Lobanenkov, V Ohlsson, R AF Holmgren, C Kanduri, C Dell, G Ward, A Mukhopadhya, R Kanduri, M Lobanenkov, V Ohlsson, R TI CpG methylation regulates the Igf2/H19 insulator SO CURRENT BIOLOGY LA English DT Article ID H19/IGF2 LOCUS; MOUSE H19; CTCF; GENE AB The differentially methylated 5'-flank of the mouse H19 gene unidirectionally regulates the communication between enhancer elements and gene promoters and presumably represses maternal lgf2 expression in vivo [1-6]. The specific activation of the paternally inherited lgf2 allele has been proposed to involve methylation-mediated inactivation of the H19 insulator function during male germline development [[1 -4, 6]. Here, we addressed the role of methylation by inserting a methylated fragment of the H19-imprinting control region (ICR) into a nonmethylated episomal H19 minigene construct, followed by the transfection of ligation mixture into Hep3B cells. Individual clones were expanded and analyzed for genotype, methylation status, chromatin conformation, and insulator function. The results show that the methylated status of the H19 ICR could be propagated for several passages without spreading into the episomal vector. Moreover, the nuclease hypersensitive sites, which are typical for the maternally inherited H19 ICR allele [1], were absent on the methylated ICR, underscoring the suggestion that the methylation mark dictates parent of origin-specific chromatin conformations [1] that involve CTCF [2]. Finally, the insulator function was strongly attenuated in stably maintained episomes. Collectively, these results provide the first experimental support that the H19 insulator function is regulated by CpG methylation. C1 Uppsala Univ, Dept Genet & Dev, S-75236 Uppsala, Sweden. Univ Bath, Dept Biol & Biochem, Bath BA2 7AY, Avon, England. NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. RP Ohlsson, R (reprint author), Uppsala Univ, Dept Genet & Dev, Norbyvagen 18A, S-75236 Uppsala, Sweden. OI Lobanenkov, Victor/0000-0001-6665-3635 NR 10 TC 68 Z9 72 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JUL 24 PY 2001 VL 11 IS 14 BP 1128 EP 1130 DI 10.1016/S0960-9822(01)00314-1 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 456QL UT WOS:000170093700024 PM 11509237 ER PT J AU Del Brutto, OH Rajshekhar, V White, AC Tsang, VCW Nash, TE Takayanagui, OM Schantz, PM Evans, CAW Flisser, A Correa, D Botero, D Allan, JC Sarti, E Gonzalez, AE Gilman, RH Garcia, HH AF Del Brutto, OH Rajshekhar, V White, AC Tsang, VCW Nash, TE Takayanagui, OM Schantz, PM Evans, CAW Flisser, A Correa, D Botero, D Allan, JC Sarti, E Gonzalez, AE Gilman, RH Garcia, HH TI Proposed diagnostic criteria for neurocysticercosis SO NEUROLOGY LA English DT Review ID TAENIA-SOLIUM CYSTICERCOSIS; DOUBLE-BLIND TRIAL; CEREBRAL CYSTICERCOSIS; ALBENDAZOLE THERAPY; CEREBROSPINAL-FLUID; MAJOR CAUSE; IMMUNODIAGNOSIS; SEIZURES; EPILEPSY; ELISA AB Neurocysticercosis is the most common helminthic infection of the CNS but its diagnosis remains difficult. Clinical manifestations are nonspecific, most neuroimaging findings are not pathognomonic, and some serologic tests have low sensitivity and specificity. The authors provide diagnostic criteria for neurocysticercosis based on objective clinical, imaging, immunologic, and epidemiologic data. These include four categories of criteria stratified on the basis of their diagnostic strength, including the following: 1) absolute-histologic demonstration of the parasite from biopsy of a brain or spinal cord lesion, cystic lesions showing the scolex on CT or MRI, and direct visualization of subretinal parasites by funduscopic examination; 2) major-lesions highly suggestive of neurocysticercosis on neuroimaging studies, positive serum enzyme-linked immunoelectrotransfer blot for the detection of anticysticercal antibodies, resolution of intracranial cystic lesions after therapy with albendazole or praziquantel, and spontaneous resolution of small single enhancing lesions; 3) minor-lesions compatible with neurocysticercosis on neuroimaging studies, clinical manifestations suggestive of neurocysticercosis, positive CSF enzyme-linked immunosorbent assay for detection of anticysticercal antibodies or cysticercal antigens, and cysticercosis outside the CNS; and 4) epidemiologic-evidence of a household contact with Taenia solium infection, individuals coming from or living in an area where cysticercosis is endemic, and history of frequent travel to disease-endemic areas. Interpretation of these criteria permits two degrees of diagnostic certainty: 1) definitive diagnosis, in patients who have one absolute criterion or in those who have two major plus one minor and one epidemiologic criterion; and 2) probable diagnosis, in patients who have one major plus two minor criteria, in those who have one major plus one minor and one epidemiologic criterion, and in those who have three minor plus one epidemiologic criterion. C1 Hosp Clin Kennedy, Dept Neurol Sci, Guayaquil, Ecuador. Christian Med Coll & Hosp, Dept Neurol Sci, Vellore 632004, Tamil Nadu, India. Baylor Coll Med, Dept Med, Infect Dis Sect, Houston, TX 77030 USA. Ctr Dis Control, Div Parasit Dis, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Neurol, BR-05508 Sao Paulo, Brazil. Univ Cambridge, Sch Clin, Cambridge, England. Secretaria Salud, Inst Diagnost & Referencia Epidemiol, Mexico City, DF, Mexico. Secretaria Salud, Direcc Gen Epidemiol, Mexico City, DF, Mexico. Inst Colombiano Med Trop, Medellin, Colombia. Pfizer Global Res & Dev, Sandwich, Kent, England. Univ Nacl Mayor San Marcos, Lima 14, Peru. Asociac Benefica Proyectos Informat Salud Med & A, Lima, Peru. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Int Hlth, Baltimore, MD USA. Inst Nacl Ciencias Neurol, Cysticercosis Unit, Lima, Peru. Univ Peruana Cayetano Heredia, Dept Microbiol, Lima, Peru. Univ Peruana Cayetano Heredia, Dept Pathol, Lima, Peru. RP Del Brutto, OH (reprint author), Air Ctr 3542, POB 522970, Miami, FL 33152 USA. RI Takayanagui, Osvaldo/C-8159-2013; OI Takayanagui, Osvaldo/0000-0002-8190-0275; White, A Clinton/0000-0002-9668-4632 FU Wellcome Trust [057434] NR 63 TC 386 Z9 400 U1 0 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL 24 PY 2001 VL 57 IS 2 BP 177 EP 183 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 454WG UT WOS:000169994300005 PM 11480424 ER PT J AU Petrovitch, H White, LR Ross, GW Steinhorn, SC Li, CY Masaki, KH Davis, DG Nelson, J Hardman, J Curb, JD Blanchette, PL Launer, LJ Yano, K Markesbery, WR AF Petrovitch, H White, LR Ross, GW Steinhorn, SC Li, CY Masaki, KH Davis, DG Nelson, J Hardman, J Curb, JD Blanchette, PL Launer, LJ Yano, K Markesbery, WR TI Accuracy of clinical criteria for AD in the Honolulu-Asia Aging Study, a population-based study SO NEUROLOGY LA English DT Article ID ALZHEIMERS-DISEASE CERAD; JAPANESE-AMERICAN MEN; ADRDA WORK GROUP; DIAGNOSTIC-CRITERIA; NEUROFIBRILLARY TANGLES; SENILE PLAQUES; AUTOPSY POPULATION; VASCULAR DEMENTIA; CONSORTIUM; PREVALENCE AB Objective: To determine diagnostic accuracy for AD in a population-based study of Japanese-American men. AD is neuropathologically confirmed for more than 80% of cases at major referral centers (primarily Caucasians); however, information on diagnostic accuracy in population-based studies and studies of different ethnic groups is limited. Methods: There were 3,734 men who participated in the Honolulu-Asia Aging Study 1991 through 1993 dementia examination and 2,603 in the 1994 through 1996 examination. Diagnoses were based on published criteria. Neuropathologists blinded to clinical data quantified neurofibrillary tangles (NFT) and neuritic plaques (NP). Results: Of 220 autopsied subjects, clinical evaluation revealed 68 with normal cognition, 73 intermediate, and 79 with dementia: 20 AD, 27 vascular dementia, 19 AD + other, and 13 other dementia. Among 20 cases with pure AD, the median value for maximum neocortical NFT density was 6.9/mm(2) and for neocortical NP density was 8.0/mm(2). Corresponding densities for other groups were <3.0/mm(2), Using established neuropathologic criteria, 25% (5/20) of clinical AD cases had enough NP to meet definite AD criteria, whereas 65% (13/20) had sufficient NP to meet neuropathologic definite or probable AD criteria. Among nine AD cases with moderately severe dementia, only two (22%) had NP densities great enough to meet definite neuropathologic criteria, whereas seven (78%) met neuropathologic criteria for probable AD. Conclusions: Neuropathologic confirmation and NP density among decedents with clinical AD in this population-based study were lower than reported by referral centers and similar to reports from two other community studies. Ethnic differences in propensity for amyloid deposition as well as differences in clinical severity and representativeness of cases might contribute to these findings. C1 Pacific Hlth Res Inst, Honolulu, HI 96813 USA. Dept Vet Affairs, Honolulu, HI USA. Kuakini Med Ctr, Asia Aging Study, Honolulu, HI USA. Univ Hawaii, John A Burns Sch Med, Dept Med, Honolulu, HI 96822 USA. Univ Hawaii, John A Burns Sch Med, Dept Pathol, Honolulu, HI 96822 USA. Univ Kentucky, Med Ctr, Sanders Brown Ctr Aging, Lexington, KY USA. Univ Kentucky, Med Ctr, Dept Pathol, Lexington, KY 40536 USA. Univ Kentucky, Med Ctr, Dept Neurol, Lexington, KY USA. Louisiana State Univ, Dept Pathol, New Orleans, LA USA. NIA, Epidemiol Demog & Biometry Program, NIH, Bethesda, MD 20892 USA. RP Petrovitch, H (reprint author), Pacific Hlth Res Inst, Suite 307,846 S Hotel St, Honolulu, HI 96813 USA. FU NHLBI NIH HHS [N01-HC-05102]; NIA NIH HHS [N01-AG-4-2149] NR 56 TC 92 Z9 94 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL 24 PY 2001 VL 57 IS 2 BP 226 EP 234 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 454WG UT WOS:000169994300012 PM 11468306 ER PT J AU Gao, Y Voigt, J Wu, JX Yang, DJ Burke, TR AF Gao, Y Voigt, J Wu, JX Yang, DJ Burke, TR TI Macrocyclization in the design of a conformationally constrained Grb2 SH2 domain inhibitor SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID PHOSPHATE-CONTAINING LIGANDS; BINDING AB Grubbs' olefin metathesis reaction was utilized to prepare a macrocyclic variant of a linear Grb7 SH2 domain antagonist in an attempt to induce a beta -bend conformation known to be required for high affinity binding. In extracellular Grb2 SH2 domain binding assays, the macrocyclic analogue exhibited an approximate 100-fold enhancement in binding potency relative to its linear counterpart. The macrocycle was not as effective in whole cell binding assays as would be expected based on its extracellular binding potency. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 NCI, Frederick Canc Res & Dev Ctr, Med Chem Lab, NIH, Frederick, MD 21702 USA. Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Washington, DC 20007 USA. RP Burke, TR (reprint author), NCI, Frederick Canc Res & Dev Ctr, Med Chem Lab, NIH, Frederick, MD 21702 USA. RI Burke, Terrence/N-2601-2014 NR 11 TC 35 Z9 36 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD JUL 23 PY 2001 VL 11 IS 14 BP 1889 EP 1892 DI 10.1016/S0960-894X(01)00316-X PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 451MJ UT WOS:000169805600021 PM 11459654 ER PT J AU Arteaga-Solis, E Gayraud, B Lee, SY Shum, L Sakai, L Ramirez, F AF Arteaga-Solis, E Gayraud, B Lee, SY Shum, L Sakai, L Ramirez, F TI Regulation of limb patterning by extracellular microfibrils SO JOURNAL OF CELL BIOLOGY LA English DT Article DE BMP; fibrillin; limb patterning; morphogenesis; syndactyly ID PROGRAMMED CELL-DEATH; DEVELOPING CHICK LIMB; TGF-BETA-S; MARFAN-SYNDROME; FIBRILLIN; BMP; DIGITS; MOUSE; CHONDROGENESIS; CHROMOSOME-18 AB To elucidate the contribution of the extracellular microfibril-elastic fiber network to vertebrate organogenesis, we generated fibrillin 2 (Fbn2)-null mice by gene targeting and identified a limb-patterning defect in the form of bilateral syndactyly. Digit fusion involves both soft and hard tissues, and is associated with reduced apoptosis at affected sites. Two lines of evidence suggest that syndactily is primarily due to defective mesenchyme differentiation, rather than reduced apoptosis of interdigital tissue. First, fusion occurs before appearance of interdigital cell death; second, interdigital tissues having incomplete separation fail to respond to apoptotic clues from im-planted BMP-4 beads. Syndactyly is associated with a disorganized matrix, but with normal BMP gene expression. On the other hand, mice double heterozygous for null Fbn2 and Bmp7 alleles display the combined digit phenotype of both nullizygotes. Together, these results imply functional interaction between Fbn2-rich microfibrils and BMP-7 signaling. As such, they uncover an unexpected relationship between the insoluble matrix and soluble factors during limb patterning. We also demonstrate that the Fbn2-null mutation is allelic to the recessive shaker-with-syndactyly (sy) locus on chromosome 18. C1 CUNY Mt Sinai Sch Med, Dept Biochem & Mol Biol, Brookdale Ctr, New York, NY 10029 USA. NIAMSD, Craniofacial Dev Sect, NIH, Bethesda, MD 20892 USA. Shriners Hosp Children, Portland, OR 97201 USA. RP Ramirez, F (reprint author), CUNY Mt Sinai Sch Med, Dept Biochem & Mol Biol, Brookdale Ctr, 1 Gustav L Levy Pl,Box 1020, New York, NY 10029 USA. FU NIAMS NIH HHS [AR42044, R01 AR042044]; NIGMS NIH HHS [F31 GM018511, GM18511] NR 35 TC 140 Z9 148 U1 1 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUL 23 PY 2001 VL 154 IS 2 BP 275 EP 281 DI 10.1083/jcb.200105046 PG 7 WC Cell Biology SC Cell Biology GA 457KL UT WOS:000170136100008 PM 11470817 ER PT J AU Nanni, L Ming, JE Du, YZ Hall, RK Aldred, M Bankier, A Muenke, M AF Nanni, L Ming, JE Du, YZ Hall, RK Aldred, M Bankier, A Muenke, M TI SHH mutation is associated with solitary median maxillary central incisor: A study of 13 patients and review of the literature SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE solitary median maxillary central incisor (SMMCI); single central incisor; midline defects; HPE; short stature; Sonic Hedgehog (SHH); SIX3; review ID PYRIFORM APERTURE STENOSIS; SINGLE CENTRAL INCISOR; 7Q TERMINAL DELETION; SONIC-HEDGEHOG GENE; DEVELOPMENTAL FIELD; HYPOPITUITARISM; MALFORMATION; EXPRESSION; MONOSOMY; SPECTRUM AB Solitary median maxillary central incisor (SMMCI) or single central incisor is a rare dental anomaly. It has been reported in holoprosencephaly (HPE) cases with severe facial anomalies or as a microform in autosomal dominant HPE (ADHPE). In our review of the literature, we note that SMMCI may also occur as an isolated finding or in association with other systemic abnormalities. These anomalies include short stature, pituitary insufficiency, microcephaly, choanal atresia, midnasal stenosis, and congenital nasal pyriform aperture stenosis, SMMCI can also be a feature of recognized syndromes or associations or a finding in patients with specific chromosomal abnormalities. We performed a molecular study on a cohort of 13 SMMCI patients who did not have HPE, We studied two genes, Sonic Hedgehog (SHH) and SIX3, in which mutations have been reported in patients showing SMMCI as part of the HPE spectrum. A new missense mutation in SHH (I111F), segregating in one SMMCI family, was identified. Our results suggest that this mutation may be specific for the SMMCI phenotype since it has not been found in the HPE population or in normal controls. Published 2001 Wiley-Liss, Inc.(dagger). C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Childrens Hosp Philadelphia, Dept Genet, Philadelphia, PA 19104 USA. Royal Childrens Hosp, Murdoch Inst, Victorian Clin Genet Serv, Melbourne, Vic, Australia. Royal Childrens Hosp, Dept Dent, Melbourne, Vic, Australia. RP Muenke, M (reprint author), NHGRI, Med Genet Branch, NIH, 10 Ctr Dr,MSC 1852,Bldg 10,10C101, Bethesda, MD 20892 USA. FU NICHD NIH HHS [HD28732, HD01218, HD29862] NR 76 TC 83 Z9 88 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD JUL 22 PY 2001 VL 102 IS 1 BP 1 EP 10 DI 10.1002/1096-8628(20010722)102:1<1::AID-AJMG1336>3.0.CO;2-U PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 449UW UT WOS:000169706400001 PM 11471164 ER PT J AU Nowaczyk, MJM McCaughey, D Whelan, DT Porter, FD AF Nowaczyk, MJM McCaughey, D Whelan, DT Porter, FD TI Incidence of Smith-Lemli-Opitz syndrome in Ontario, Canada SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE Smith-Lemli-Opitz syndrome; 7-dehydrocholesterol; prenatal diagnosis; DHCR7 mutations; incidence ID REDUCTASE GENE; 7-DEHYDROCHOLESTEROL; METABOLISM; DIAGNOSIS; PHENOTYPE; MUTATIONS; SPECTRUM AB Smith-Lemli-Opitz syndrome (OMIM 270400) (SLOS) is caused by inherited enzymatic deficiency of 3 beta -hydroxysterol-Delta (7)-reductase (7-dehydrocholesterol-Delta (7)-reductase, DHCR7). SLOS is diagnosed clinically by the demonstration of elevated levels of 7-dehydrocholesterol (7DHC) in body fluids or tissues. SLOS is associated with mental retardation of variable degree and severe behavior abnormalities. The physical abnormalities range from minor facial anomalies to lethal malformations of the central nervous system, heart, kidneys, and other organs. The exact incidence of SLOS is not known. Although there exist estimates of the incidence of SLOS ranging from 1 in 20,000 to 1 in 60,000, no prospective studies of the incidence of SLOS, based on the clinical data and biochemical diagnosis of SLOS, have been performed. Five unrelated cases of SLOS were diagnosed in Ontario during a 12-month period. The diagnoses were made based on the demonstration of elevated 7DHC in plasma or amniotic fluid. The birth rate for Ontario for that period was 132,000 births, The incidence of SLOS in Ontario was at least 1 in 26,500 pregnancies in 1999-2000. Given that 86% of the population of Ontario is of European origin, the incidence of SLOS in the Ontario population of European origin was at least 1 in 22,700. As infants with mild forms of SLOS born during this period may remain undiagnosed, these numbers likely are underestimates. This observation has implications for prenatal and newborn screening for this potentially treatable inherited disorder. (C) 2001 Wiley-Liss, Inc. C1 McMaster Univ, Med Ctr, Dept Pathol & Mol Med, Hamilton, ON L8S 4J9, Canada. McMaster Univ, Dept Paediat, Hamilton, ON, Canada. Hamilton Reg Lab, Program Med, Hamilton, ON, Canada. NICHHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Nowaczyk, MJM (reprint author), McMaster Univ, Med Ctr, Dept Pathol & Mol Med, Rm 3N16,1200 Main St W, Hamilton, ON L8S 4J9, Canada. NR 22 TC 28 Z9 30 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD JUL 22 PY 2001 VL 102 IS 1 BP 18 EP 20 DI 10.1002/1096-8628(20010722)102:1<18::AID-AJMG1376>3.0.CO;2-E PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 449UW UT WOS:000169706400003 PM 11471166 ER PT J AU Wong, LJC Dai, P Tan, DJ Lipson, M Grix, A Sifry-Platt, M Gropman, A Chen, TJ AF Wong, LJC Dai, P Tan, DJ Lipson, M Grix, A Sifry-Platt, M Gropman, A Chen, TJ TI Severe lactic acidosis caused by a novel frame-shift mutation in mitochondrial-encoded cytochrome c oxidase subunit II SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE mtDNA mutation; COXII mutation; mitochondrial disorder; complex IV deficiency ID PYRUVATE-DEHYDROGENASE COMPLEX; GRADIENT GEL-ELECTROPHORESIS; RAGGED-RED FIBERS; MYOCLONIC EPILEPSY; GENOME DATABASE; MTDNA MUTATION; DNA; DEFICIENCY; CODON; GENE AB We report the first frame-shift truncation mutation in a mitochondrial DNA (mtDNA)-encoded subunit II of cytochrome c oxidase (COXII). The mutation was identified by temporal temperature gradient gel electrophoresis (TTGE) followed by direct DNA sequencing in an infant who died at 12 days of age following a course of apnea, bradycardia, and severe lactic acidosis. The patient had a twin brother who died at two days of age of similar course. The mutation, 8042delAT, produced a truncated protein that was 72 amino acids shorter than the wild type protein. The mutant protein, missing one third of the amino acid residues at the C-terminal essential for hydrophilic interaction with cytochrome c, ligand binding to Cu-A and Mg, and the formation of proton and water channels, apparently has devastating effects on mitochondrial respiratory function. Published 2001 Wiley-Liss, Inc.(dagger). C1 Georgetown Univ, Med Ctr, Inst Mol & Human Genet, Washington, DC 20007 USA. Kaiser Permanente, Dept Genet, Sacramento, CA USA. NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. RP Wong, LJC (reprint author), Georgetown Univ, Med Ctr, Inst Mol & Human Genet, M4000,3800 Reservoir Rd NW, Washington, DC 20007 USA. NR 30 TC 20 Z9 20 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD JUL 22 PY 2001 VL 102 IS 1 BP 95 EP 99 DI 10.1002/1096-8628(20010722)102:1<95::AID-AJMG1412>3.0.CO;2-U PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 449UW UT WOS:000169706400017 PM 11471180 ER PT J AU Podgornik, R Dobnikar, J AF Podgornik, R Dobnikar, J TI Casimir and pseudo-Casimir interactions in confined polyelectrolytes SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID FLUCTUATION-INDUCED FORCES; LIQUID-CRYSTALS; WALLS; CHAIN AB We investigate the pseudo-Casimir force acting between two charged surfaces confining a single polyelectrolyte chain with opposite charge. We expand the exact free energy to the second order in the local electrostatic field as well as the replicated polymer density field around the mean-field (saddle-point) solution. The quadratic terms lead to a fluctuation interaction that is partly due to the (thermal) Casimir effect for the confined electrostatic field and partly due to the pseudo-Casimir effect due to the confined replicated polymer density field. We study the intersurface separation dependence of both effects and show that the pseudo-Casimir effect leads to a long range attraction between the surfaces that decays with an anomalous algebraic exponent of similar to1.7, smaller than the standard exponent of 2 in the case of Casimir interactions. (C) 2001 American Institute of Physics. C1 NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. Univ Ljubljana, Fac Math & Phys, Dept Phys, Ljubljana 1000, Slovenia. Jozef Stefan Inst, Dept Theoret Phys, Ljubljana 1000, Slovenia. Univ Konstanz, Fak Phys, D-78457 Constance, Germany. RP Podgornik, R (reprint author), NICHD, Lab Phys & Struct Biol, NIH, Bldg 12A,Room 2041, Bethesda, MD 20892 USA. RI dobnikar, jure/A-4835-2008; Dobnikar, Jure/C-8765-2011; Podgornik, Rudolf/C-6209-2008 OI Dobnikar, Jure/0000-0002-1169-6619; Podgornik, Rudolf/0000-0002-3855-4637 NR 33 TC 4 Z9 4 U1 0 U2 2 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD JUL 22 PY 2001 VL 115 IS 4 BP 1951 EP 1959 DI 10.1063/1.1383052 PG 9 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 451JY UT WOS:000169800000036 ER PT J AU Gonzalez, CE Lyman, CA Lee, S Del Guercio, C Roilides, E Bacher, J Gehrt, A Feuerstein, E Tsokos, M Walsh, TJ AF Gonzalez, CE Lyman, CA Lee, S Del Guercio, C Roilides, E Bacher, J Gehrt, A Feuerstein, E Tsokos, M Walsh, TJ TI Recombinant human macrophage colony-stimulating factor augments pulmonary host defences against Aspergillus fumigatus SO CYTOKINE LA English DT Article DE Aspergillus; host defense; macrophage-colony stimulating factor; pulmonary ID HUMAN MONOCYTE FUNCTION; FACTOR M-CSF; MURINE MACROPHAGES; CANDIDA-ALBICANS; GRANULOCYTE-MACROPHAGE; ANTIFUNGAL ACTIVITY; FUNGAL-INFECTIONS; INVIVO; MONONUCLEAR; INDUCTION AB The in vivo and ex vivo effects of macrophage colony-stimulating factor (M-CSF) were studied in a profoundly neutropenic rabbit model in order to determine its potential to augment pulmonary host defence against Aspergillus., M-CSF (100-600 mug/kg/d) was administered prophylactically to neutropenic rabbits with pulmonary aspergillosis starting three days pre-inoculation and then throughout neutropenia. Rabbits receiving M-CSF had significantly increased survival (P = 0.01) and decreased pulmonary injury, as measured by decreased pulmonary infarction (P = 0.004), when compared with untreated controls. Microscopic studies demonstrated greater numbers of activated pulmonary alveolar macrophages (PAMs) in lung tissue of rabbits receiving M-CSF, in comparison to controls (P < 0.001). PAMs harvested from rabbits treated with M-CSF had a significantly greater percent phagocytosis of Aspergillus fumigatus conidia than did PAMs from controls (P = 0.04). These data indicate that prophylactic administration of M-CSF augments pulmonary host defence against A. fumigatus and suggest a potential role for this cytokine as adjunctive therapy in the treatment of pulmonary aspergillosis in the setting of profound neutropenia. (C) 2001 Academic Press. C1 NCI, Immunocompromised Hosp Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. Univ Thessaloniki, Dept Pediat, Hippokrat Hosp, GR-54006 Salonika, Greece. NIH, Surg Serv, Vet Resource Program, Bethesda, MD 20892 USA. Warren Grant Magnuson Clin Ctr, Dept Radiol, Bethesda, MD USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. RP Lyman, CA (reprint author), NCI, Immunocompromised Hosp Sect, Pediat Oncol Branch, Bldg 10,Room 13N-240, Bethesda, MD 20892 USA. NR 51 TC 26 Z9 27 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1043-4666 J9 CYTOKINE JI Cytokine PD JUL 21 PY 2001 VL 15 IS 2 BP 87 EP 95 DI 10.1006/cyto.2001.00889 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 465JV UT WOS:000170586600005 PM 11500084 ER PT J AU Singh, JP Larson, MG O'Donnell, CJ Levy, D AF Singh, JP Larson, MG O'Donnell, CJ Levy, D TI Genetic factors contribute to the variance in frequency domain measures of heart rate variability SO AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL LA English DT Review DE heart rate variability; genetics ID RESPIRATORY SINUS ARRHYTHMIA; HERITABILITY; MORTALITY; LOCUS; RISK AB Power spectral analysis of heart rate variability (HRV) provides quantitative phenotypic markers of autonomic nervous system activity. Reported determinants of HRV only partially explain its variability in the population. The purpose of this study was to estimate the contribution of genetic factors to the variance in HRV measures and assess the heritability of HRV. Subjects who underwent Halter recordings at a routine examination were eligible, excluding subjects with congestive heart failure, coronary artery disease, diabetes mellitus and those taking cardioactive medications. We analyzed the low-frequency power (LF), high-frequency power (HF), LF/HF ratio,. very low-frequency power (VLF) and total power (TP). Heritability analysis was done by studying correlations between siblings (n = 682, in 291 sibships, 517 pairs) and between spouse pairs (n = 206 pairs). Adjustments were made for sex, age, systolic and diastolic blood pressure, heart rate, coffee and alcohol intake. SAS procedure MIXED was used to estimate and test significance of correlation within sibling pairs and within spouse pairs. Results from separate models were combined to estimate the components of variance of each phenotype, i.e. variance attributable to measured covariates, additive genetic effects (heritability) and household effects. After adjusting for covariates, the correlations were consistently higher among siblings (0.21-0.26) compared to spouses (0.01-0.19)The measured covariates in general accounted for 13-40% of the total phenotypic variance, whereas genes accounted for 13-23% of the variation among HRV measures. Genetic factors contribute towards a substantial proportion of the variance in heart rate and HRV. Recognition of the genetic determinants of HRV may provide additional insight into the pathophysiology of the autonomic nervous system and offer clues toward its modulation. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Div Cardiol, Boston, MA 02114 USA. NHLBI, Framingham Heart Study, Boston, MA USA. NHLBI, Bethesda, MD 20892 USA. Beth Israel Hosp, Div Cardiol, Boston, MA USA. Beth Israel Hosp, Div Clin Epidemiol, Boston, MA USA. RP Singh, JP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Div Cardiol, Bullfinch Basement 001, Boston, MA 02114 USA. NR 23 TC 25 Z9 26 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1566-0702 J9 AUTON NEUROSCI-BASIC JI Auton. Neurosci-Basic Clin. PD JUL 20 PY 2001 VL 90 IS 1-2 SI SI BP 122 EP 126 DI 10.1016/S1566-0702(01)00277-6 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 450YW UT WOS:000169773300018 PM 11485278 ER PT J AU Patterson, LJ Aberdeen, A Kone, J Haben, M Raymond, M Berkower, I AF Patterson, LJ Aberdeen, A Kone, J Haben, M Raymond, M Berkower, I TI Formation of HIV-1 envelope-hepatitis B core antigen hybrids with high affinity for CD4 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE HIV vaccine; immunogenicity; gp120; particle assembly ID HUMAN MONOCLONAL-ANTIBODY; VIRUS CORE; NEUTRALIZING ANTIBODIES; GP120; GLYCOPROTEIN; PROTEIN; EPITOPE; DOMAIN; IMMUNOGENICITY; PARTICLES AB We have identified an acceptor site on HIV gp120, where foreign protein sequences can be inserted while retaining the native conformation of gp120. The resulting hybrids showed dual antigenicity, normal glycosylation, and high affinity binding of the CD4 receptor. This site allows insertion of highly immunogenic proteins such as core antigen of hepatitis B virus. By combining the immunogenicity of the carrier protein with the antigenicity of gp120, these hybrids may lead to modified HIV-1 antigens with enhanced immunogenicity. (C) 2001 Academic Press. C1 NIH, Immunoregulat Lab, DVP, Off Vaccine Res & Review,Ctr Biol,US FDA, Bethesda, MD 20892 USA. NCI, Basic Res Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Berkower, I (reprint author), NIH, Immunoregulat Lab, DVP, Off Vaccine Res & Review,Ctr Biol,US FDA, Bldg 29,Room 523,NIH Campus, Bethesda, MD 20892 USA. NR 30 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 20 PY 2001 VL 285 IS 3 BP 639 EP 643 DI 10.1006/bbrc.2001.5227 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 457HP UT WOS:000170131400011 PM 11453640 ER PT J AU Sellitti, DF Suzuki, K Doi, SQ LaGranha, C Machado, M Matos, T Kohn, LD AF Sellitti, DF Suzuki, K Doi, SQ LaGranha, C Machado, M Matos, T Kohn, LD TI Thyroglobulin increases cell proliferation and suppresses Pax-8 in mesangial cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE thyroglobulin; mesangial cells; Pax-8; bcl-2 apoptosis suppressor; cell proliferation ID ASIALOGLYCOPROTEIN RECEPTOR; GENE; EXPRESSION; TRANSCRIPTION; ACTIVATION; TG AB Thyroglobulin (Tg), has recently been identified as a transcriptional regulator of thyroid-restricted genes. The extrathyroidal expression of several of these genes (including the transcription factor Pax-8) together with the occurrence of specific Tg binding sites suggests a secondary role for Tg as a circulating hormone. In this study, we demonstrate using Northern analysis that Pax-8 is expressed in the mouse mesangial cell, and that its transcript levels are suppressed by Tg. These cells also express an asialoglycoprotein receptor, a receptor involved in Tg endocytosis in the thyroid, and a Tg transcript smaller than the 8.3-kb thyroidal form. Reverse transcriptase PCR showed that suppression of Pax-8 by Tg is correlated with reduced expression of bcl-2 apoptosis suppressor. Tg, but not triiodothyronine (T-3) significantly increased MC proliferation above control as determined by DNA content of MC cultures. The effect of Tg on proliferation was not duplicated by either bovine serum albumin, gamma -globulins, lactoferrin, or the ASGPR-specific ligand, orosomucoid. These results suggest a possible endocrine role for Tg in regulating both Pax-8 related gene transcription and cell division in the mesangial cell. (C) 2001 Academic Press. C1 Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20814 USA. NIDDK, NIH, Bethesda, MD USA. Washington Hosp Ctr, Washington, DC 20010 USA. Univ Sao Paulo, Sao Paulo, Brazil. RP Sellitti, DF (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. NR 18 TC 15 Z9 15 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 20 PY 2001 VL 285 IS 3 BP 795 EP 799 DI 10.1006/bbrc.2001.5238 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 457HP UT WOS:000170131400033 PM 11453662 ER PT J AU Ozaki, K Enomoto, T Yoshino, K Fujita, M Buzard, GS Kawano, K Yamasaki, M Murata, Y AF Ozaki, K Enomoto, T Yoshino, K Fujita, M Buzard, GS Kawano, K Yamasaki, M Murata, Y TI Impaired FHIT expression characterizes serous ovarian carcinoma SO BRITISH JOURNAL OF CANCER LA English DT Article DE FHIT (fragile histidine triad) gene; ovarian tumour; serous carcinoma ID TUMOR-SUPPRESSOR GENE; K-RAS ACTIVATION; COMMON EPITHELIAL TUMORS; CHROMOSOME 3P; CELL-LINES; DCC GENE; CANCER; TRANSCRIPTS; ADENOCARCINOMAS; APOPTOSIS AB The FHIT (fragile histidine triad) gene on chromosome 3p14.2 is a candidate tumour suppressor gene. To define the role of the FHIT gene in the development of ovarian cancer, we have examined 33 ovarian carcinomas, 2 borderline tumours and 10 benign adenomas for the presence of FHIT gene alterations. FHIT transcripts were analysed by RT-PCR and sequencing. Aberrant FHIT transcripts were observed in 5/33 carcinomas (15%) and in 1 of 2 borderline tumours. Loss of normal FHIT transcript was observed in 5/33 carcinomas (15%) but not in 2 borderline tumours or 10 benign adenomas. Allelic losses at D3S1300 and D3S4103, both located within intron 5 of FHIT, were detected in 5/24 (21%) and 5/25 (20%) informative ovarian carcinomas, respectively. Expression of Fhit protein was analysed by immunohistochemistry in 44 carcinomas, 19 borderline tumours and 16 benign adenomas. Loss or significantly reduced expression of Fhit protein was observed in 6/44 (14%) ovarian carcinomas but not in any of 19 borderline tumours or 16 benign adenomas. The impaired Fhit protein expression was significantly correlated with the loss of normal FHIT transcription. Most notably, loss of normal FHIT transcript and impaired expression of Fhit protein occurred only in serous adenocarcinomas of grade 2 and 3 (5/15; 33% and 6/19; 32%, respectively). The present data suggest that inactivation of the FHIT gene by loss of expression is one of the important molecular events associated with the genesis of ovarian carcinoma, especially of high-grade serous carcinoma. (C) 2001 Cancer Research Campaign. C1 Osaka Univ, Fac Med, Dept Obstet & Gynecol, Osaka, Japan. Osaka Rosai Hosp, Dept Obstet & Gynecol, Osaka, Japan. NCI, SAIC, Intramural Res Support Program, Frederick, MD 21701 USA. RP Enomoto, T (reprint author), Osaka Univ, Fac Med, Dept Obstet & Gynecol, Osaka, Japan. FU NCI NIH HHS [N01-CO-56000] NR 30 TC 8 Z9 9 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JUL 20 PY 2001 VL 85 IS 2 BP 247 EP 254 DI 10.1054/bjoc.2001.1886 PG 8 WC Oncology SC Oncology GA 457TG UT WOS:000170152500019 PM 11461085 ER PT J AU Nowicki, PT Flavahan, S Hassanain, H Mitra, S Holland, S Goldschmidt-Clermont, PJ Flavahan, NA AF Nowicki, PT Flavahan, S Hassanain, H Mitra, S Holland, S Goldschmidt-Clermont, PJ Flavahan, NA TI Redox signaling of the arteriolar myogenic response SO CIRCULATION RESEARCH LA English DT Article ID OXIDASE; H2O2; CYTOSKELETON; DISEASE AB Arteriolar vascular smooth muscle cells (VSMCs) are mechanosensitive, constricting to elevations in transmural pressure (P-TM). The goal of the present study was to determine using mouse isolated tail arterioles and arteries whether oxidant signaling regulates this myogenic response. In response to P-TM elevation, VSMCs of arterioles but not arteries generated constriction and increased reactive oxygen species (ROS) activity (using the H2O2-sensitive probe dichlorodihydrofluorescein). Arterioles had increased expression of NADPH oxidase components compared with arteries. Inhibition of NADPH oxidase, using mice with targeted impairment of enzyme components (p47(phox) or rac1) or diphenyleneiodonium, prevented the pressure-induced generation of ROS. When ROS activity was inhibited, either by inhibiting NADPH oxidase or with N-acetylcysteine, the myogenic constriction was abolished. The myogenic. constriction was also inhibited by catalase, which inactivates H2O2, but was unaffected by a cell-permeant mimic of superoxide dismutase (MnTMPyP). alpha (1)-Adrenergic constriction was not associated with altered ROS activity and was not affected by inhibition of NADPH oxidase or ROS. Exogenous H2O2 constricted VSMCs of arterioles but not arteries. Thus, NADPH oxidase and ROS, in particular H2O2 contribute to the myogenic: response of arteriolar VSMCs. C1 Ohio State Univ, Heart & Lung Res Inst, Columbus, OH 43210 USA. NIAID, Bethesda, MD 20892 USA. Duke Univ, Durham, NC USA. RP Flavahan, NA (reprint author), Ohio State Univ, Heart & Lung Res Inst, 473 W 12th Ave,Room 110E, Columbus, OH 43210 USA. FU NHLBI NIH HHS [HL56091, HL67331]; NIAMS NIH HHS [AR46126] NR 15 TC 81 Z9 81 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD JUL 20 PY 2001 VL 89 IS 2 BP 114 EP 116 DI 10.1161/hh1401.094367 PG 3 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 456ZB UT WOS:000170111700006 PM 11463716 ER PT J AU Ni, YS McPhie, P Deacon, A Ealick, S Coleman, WG AF Ni, YS McPhie, P Deacon, A Ealick, S Coleman, WG TI Evidence that NADP(+) is the physiological cofactor of ADP-L-glycero-D-mannoheptose 6-epimerase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ESCHERICHIA-COLI K-12; DEPENDENT GLUTAMATE-DEHYDROGENASE; AMINO-ACID-SEQUENCE; COENZYME SPECIFICITY; NUCLEOTIDE-SEQUENCE; RFAD GENE; BINDING; PURIFICATION; PROTEINS AB ADP-L-glycero-D-mannoheptose 6-epimerase is required for lipopolysaccharide inner core biosynthesis in several genera of Gram-negative bacteria. The enzyme contains both fingerprint sequences Gly-X-Gly-X-X-Gly and Gly-X-X-Gly-X-X-Gly near its N terminus, which is indicative of an ADP binding fold. Previous studies of this ADP-L-glycero-D-mannoheptose 6-epimerase (ADP-hep 6-epimerase) were consistent with an NAD(+) cofactor. However, the crystal structure of this ADP-hep 6-epimerase showed bound NADP (Deacon, A. M., Ni, Y. S., Coleman, W. G., Jr., and Ealick, S. E. (2000) Structure 5, 453-462). In present studies, apo-ADP-hep 6-epimerase was reconstituted with NAD(+), NADP(+), and FAD. In this report we provide data that shows NAD(+) and NADP(+) both restored enzymatic activity, but FAD could not. Furthermore, ADP-hep 6-epimerase exhibited a preference for binding of NADP(+) over NAD(+). The K-d value for NADP(+) was 26 muM whereas that for NAD(+) was 45 muM. Ultraviolet circular dichroism spectra showed that apo-ADP-hep 6-epimerase reconstituted with NADP(+) had more secondary structure than apo-ADP-hep 6-epimerase reconstituted with NAD(+). Perchloric acid extracts of the purified enzyme were assayed with NAD(+)-specific alcohol dehydrogenase and NADP(+)- specific isocitric dehydrogenase. A sample of the same perchloric acid extract was analyzed in chromatographic studies, which demonstrated that ADP-hep 6-epimerase binds NADP(+) in vivo. A structural comparison of ADP-hep 6-epimerase with UDP-galactose 4-epimerase, which utilizes an NAD(+) cofactor, has identified the regions of ADP-hep 6-epimerase, which defines its specificity for NADP(+). C1 NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. Stanford Univ, Stanford Linear Accelerator Ctr, Stanford, CA 94309 USA. Cornell Univ, Dept Chem & Chem Biol, Ithaca, NY 14853 USA. RP Coleman, WG (reprint author), NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. NR 21 TC 16 Z9 17 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 20 PY 2001 VL 276 IS 29 BP 27329 EP 27334 DI 10.1074/jbc.M102258200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 454HJ UT WOS:000169966900080 PM 11313358 ER PT J AU Chang, CS Mooser, A Pluckthun, A Wlodawer, A AF Chang, CS Mooser, A Pluckthun, A Wlodawer, A TI Crystal structure of the dimeric C-terminal domain of TonB reveals a novel fold SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ESCHERICHIA-COLI TONB; OUTER-MEMBRANE; ENERGY TRANSDUCTION; VITAMIN-B12 TRANSPORT; CYTOPLASMIC MEMBRANE; LIGAND-BINDING; PROTEIN TONB; BTUB AFFECT; IN-VIVO; RECEPTOR AB The TonB-dependent complex of Gram-negative bacteria couples the inner membrane proton motive force to the active transport of iron siderophore and vitamin B-12 across the outer membrane. The structural basis of that process has not been described so far in full detail. The crystal structure of the C-terminal domain of TonB from Escherichia coli has now been solved by multi-wavelength anomalous diffraction and refined at 1.55-Angstrom resolution, providing the first evidence that this region of TonB (residues 164-239) dimerizes. Moreover, the structure shows a novel architecture that has no structural homologs among any known proteins. The dimer of the C-terminal domain of TonB is cylinder-shaped with a length of 65 Angstrom and a diameter of 25 Angstrom. Each monomer contains three beta strands and a single alpha helix. The two monomers are intertwined with each other, and all six beta -strands of the dimer make a large antiparallel beta -sheet. We propose a plausible model of binding of TonB to FhuA and FepA, two TonB-dependent outer-membrane receptors. C1 Univ Zurich, Inst Biochem, CH-8057 Zurich, Switzerland. NCI, Mol Crystallog Lab, NIH, Frederick, MD 21702 USA. RP Pluckthun, A (reprint author), Univ Zurich, Inst Biochem, Winterthurerstr 190, CH-8057 Zurich, Switzerland. RI Pluckthun, Andreas/C-2746-2009 OI Pluckthun, Andreas/0000-0003-4191-5306 NR 60 TC 93 Z9 94 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 20 PY 2001 VL 276 IS 29 BP 27535 EP 27540 DI 10.1074/jbc.M102778200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 454HJ UT WOS:000169966900105 PM 11328822 ER PT J AU Neufeld, EB Remaley, AT Demosky, SJ Stonik, JA Cooney, AM Comly, M Dwyer, NK Zhang, M Blanchette-Mackie, J Santamarina-Fojo, S Brewer, HB AF Neufeld, EB Remaley, AT Demosky, SJ Stonik, JA Cooney, AM Comly, M Dwyer, NK Zhang, M Blanchette-Mackie, J Santamarina-Fojo, S Brewer, HB TI Cellular localization and trafficking of the human ABCA1 transporter SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BINDING CASSETTE TRANSPORTER-1; LOW-DENSITY-LIPOPROTEIN; APOLIPOPROTEIN-A-I; TANGIER-DISEASE; CHOLESTEROL EFFLUX; PLASMA-MEMBRANE; BREFELDIN-A; CELLS; REMOVAL; FIBROBLASTS AB ABCA1, the ATP-binding cassette protein,mutated in Tangier disease, mediates the efflux of,excess cellular sterol to apoA-I and thereby the formation of high density lipoprotein. The intracellular localization and trafficking of ABCA1 was examined in stably and transiently transfected HeLa cells expressing a functional human ABCA1-green fluorescent protein (GFP) fusion protein. The fluorescent chimeric ABCA1 transporter was found to reside on the cell surface and on intracellular vesicles that include a novel subset of early endosomes, as well as late endosomes and lysosomes, Studies of the localization and trafficking of ABCA1-GFP in the presence of brefeldin A or monensin, agents known to block intracellular vesicular trafficking as well as apoA-I-mediated cellular lipid efflux, showed that: (i) ABCA1 functions in lipid efflux at the cell surface, and (ii) delivery of ABCA1 to lysosomes for degradation may serve as a mechanism to modulate its surface expression. Time-lapse fluorescence microscopy revealed that ABCA1-GFP-containing early endosomes undergo fusion, fission,: and tubulation and transiently interact with one another, late endocytic vesicles, and the cell surface, These studies establish a complex intracellular trafficking pathway for human ABCA1 that may play important roles in modulating ABCA1 transporter activity and cellular cholesterol homeostasis. C1 NHLBI, NIH, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD 20892 USA. RP Neufeld, EB (reprint author), NHLBI, NIH, 10-7N115,10 Ctr Dr, Bethesda, MD 20892 USA. NR 36 TC 222 Z9 225 U1 3 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 20 PY 2001 VL 276 IS 29 BP 27584 EP 27590 DI 10.1074/jbc.M103264200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 454HJ UT WOS:000169966900112 PM 11349133 ER PT J AU Butscher, WG Haggerty, CM Chaudhry, S Gardner, K AF Butscher, WG Haggerty, CM Chaudhry, S Gardner, K TI Targeting of p300 to the interleukin-2 promoter via CREB-Rel cross-talk during mitogen and oncogenic molecular signaling in activated T-cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; UBIQUITOUS TRANSCRIPTION FACTORS; CYTOKINE GENE-EXPRESSION; DNA-BINDING ACTIVITY; LEUKEMIA-VIRUS; I TAX; COACTIVATOR CBP; IL-2 GENE; PROTEIN; RECEPTOR AB In this report, we explore the mechanisms of targeting of p300 to the interleukin-2 (IL-2) promoter in response to mitogenic and oncogenic molecular signals. Recruitment of p300 by cAMP-responsive element-binding protein-Rel cross-talk at the composite CD28 response element (CD28RE)-TRE element of the IL-2 promoter is essential for promoter inducibility during T-cell activation, and CD28RE-TRE is the exclusive target of the human T-cell lymphotropic virus type I oncoprotein Tax. The intrinsic histone acetyltransferase activity of p300 is dispensable for activation of the IL-2 promoter, and the N-terminal 743 residues contain the minimal structural requirements for synergistic transactivation of the CD28RE-TRE, the IL-2 promoter, and endogenous IL-2 gene expression. Mutational analysis of p300 reveals differential structural requirements for the N-terminal p300 module by individual cis-elements within the IL-2 promoter. These findings provide evidence that p300 assembles at the IL-2 promoter to form an enhanceosome-like signal transduction target that is centrally integrated at the CD28RE-TRE element of the IL-2 promoter through specific protein module-targeted associations in activated T-cells. C1 NCI, Ctr Adv Technol, Pathol Lab, NIH, Bethesda, MD 20892 USA. Howard Univ, Coll Med, Dept Microbiol, Washington, DC 20059 USA. RP Gardner, K (reprint author), NCI, Ctr Adv Technol, Pathol Lab, NIH, Rm 134C,8717 Grovemont Circle, Bethesda, MD 20892 USA. NR 49 TC 21 Z9 21 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 20 PY 2001 VL 276 IS 29 BP 27647 EP 27656 DI 10.1074/jbc.M009614200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 454HJ UT WOS:000169966900120 PM 11313336 ER PT J AU Ettenberg, SA Magnifico, A Cuello, M Nau, MM Rubinstein, YR Yarden, Y Weissman, AM Lipkowitz, S AF Ettenberg, SA Magnifico, A Cuello, M Nau, MM Rubinstein, YR Yarden, Y Weissman, AM Lipkowitz, S TI Cbl-b-dependent coordinated degradation of the epidermal growth factor receptor signaling complex SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID UBIQUITIN-PROTEIN LIGASES; PROTOONCOGENE C-CBL; RING FINGER; TYROSINE KINASE; NEGATIVE REGULATOR; HORMONE RECEPTOR; CSF-1 RECEPTOR; EGF RECEPTOR; FAMILY; PHOSPHORYLATION AB Cbl proteins function as ubiquitin protein ligases for the activated epidermal growth factor receptor and, thus, negatively regulate its activity. Here we show that Cbl-b is ubiquitinated and degraded upon activation of the receptor. Epidermal growth factor (EGF)-induced Cbl-b degradation requires intact RING finger and tyrosine kinase binding domains and requires binding of the Cbl-b protein to the activated EGF receptor (EGFR), Degradation of both the EGFR and the Cbl-b protein is blocked by lysosomal and proteasomal inhibitors, Other components of the EGFR-signaling complex (i.e. Grb2 and Shc) are also degraded in an EGF-induced Cbl-b-dependent fashion. Our results suggest that the ubiquitin protein ligase function of Cbl-b is regulated by coordinated degradation of the Cbl-b protein along with its substrate. Furthermore, the data demonstrate that Cbl-b mediates degradation of multiple proteins in the EGFR-signaling complex. C1 NCI, Dept Genet, Med Branch, Natl Naval Med Ctr,NIH, Bethesda, MD 20889 USA. NCI, Lab Immune Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20889 USA. Uniformed Serv Univ Hlth Sci, Cell & Mol Biol Program, Bethesda, MD 20889 USA. Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel. RP Lipkowitz, S (reprint author), NCI, Dept Genet, Med Branch, Natl Naval Med Ctr,NIH, Bldg 8,Rm 5101, Bethesda, MD 20889 USA. RI YARDEN, YOSEF/K-1467-2012 NR 60 TC 104 Z9 108 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 20 PY 2001 VL 276 IS 29 BP 27677 EP 27684 DI 10.1074/jbc.M102641200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 454HJ UT WOS:000169966900124 PM 11375397 ER PT J AU Miller, JT Ehresmann, B Hubscher, U Le Grice, SFJ AF Miller, JT Ehresmann, B Hubscher, U Le Grice, SFJ TI A novel interaction of tRNA(Lys,3) with the feline immunodeficiency virus RNA genome governs initiation of minus strand DNA synthesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HIV-1 REVERSE TRANSCRIPTION; PRIMER-BINDING-SITE; EFFICIENT INITIATION; SECONDARY STRUCTURE; POSTTRANSCRIPTIONAL MODIFICATIONS; TY1 RETROTRANSPOSON; GENETIC-ANALYSIS; TYPE-1; COMPLEMENTARY; TRNA(3)(LYS) AB Complementarity between nucleotides at the 5' terminus of tRNA(Lys,3) and the U5-IR loop of the feline immunodeficiency virus RNA genome suggests a novel intermolecular interaction controls initiation of minus strand synthesis in a manner analogous to other retroviral systems. Base pairing of this tRNA-viral RNA duplex was confirmed by nuclease mapping of the RNA genome containing full-length or 5'-deleted variants of tRNA(Lys,3) hybridized to the primer-binding site. A major pause in RNA-dependent DNA synthesis occurred 14 nucleotides ahead of the primer-binding site with natural and synthetic tRNA(Lys,3) primers, indicating it was not a consequence of tRNA base modifications. The majority of the paused complexes resulted in dissociation of the reverse transcriptase from the template/primer, as demonstrated by an assay limited to a single binding event. Hybridization of a tRNA mutant whose 5' nucleotides are deleted relieved pausing at this position and subsequently allowed high level DNA synthesis. Additional experiments with tRNA-DNA chimeric primers were used to localize the stage of minus strand synthesis at which the tRNA-viral RNA interaction was disrupted. Finally, replacing nucleotides of the feline immunodeficiency virus US-IR loop with the (A), sequence of its human immunodeficiency virus (HIV)-1 counterpart also relieved pausing, but did not induce pausing immediately downstream of the primer-binding site previously noted during initiation of HIV-1 DNA synthesis. These combined observations provide further evidence of cis-acting sequences immediately adjacent to the primer-binding site controlling initiation of minus strand DNA synthesis in retroviruses and retrotransposons. C1 NCI, HIV Drug Resistance Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. CNRS, Inst Biol Mol & Cellulaire, F-67084 Strasbourg, France. Univ Zurich Irchel, Inst Vet Biochem, CH-8057 Zurich, Switzerland. RP Le Grice, SFJ (reprint author), NCI, HIV Drug Resistance Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. EM slegrice@mail.ncifcrf.gov NR 56 TC 15 Z9 15 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 20 PY 2001 VL 276 IS 29 BP 27721 EP 27730 DI 10.1074/jbc.M100513200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 454HJ UT WOS:000169966900130 PM 11353768 ER PT J AU Weisz, A Mazzola, EP Matusik, JE Ito, Y AF Weisz, A Mazzola, EP Matusik, JE Ito, Y TI Preparative separation of isomeric 2-(2-quinolinyl)-1H-indene-1,3(2H)-dione monosulfonic acids of the color additive D&C Yellow No. 10 (Quinoline Yellow) by pH-zone-refining counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE counter-current chromatography; positional isomers; D&C yellow no. 10; Quinoline Yellow; monosulfonic acids; sulfonic acids; dyes ID PHLOXINE-B; PURIFICATION; COMPONENTS AB The main components of the color additive D&C Yellow No. 10 (Quinoline Yellow, Color Index No. 47005), 2-(2-quinolinyl)-1H-indene-1,3(2H)-dione-6 ' -sulfonic acid (6SA) and 2-(2-quinolinyl)-1H-indene-1,3(2H)-dione-8 ' -sulfonic acid (8SA), were isolated from the dye mixture by pH-zone-refining counter-current chromatography (CCC) in the ion-exchange mode. These positional isomers were separated from a portion of dye using sulfuric acid as the retainer acid and dodecylamine as the ligand (ion exchanger). The added ligand enhanced the partitioning of the hydrophilic components in the organic stationary phase of the two-phase solvent system that consisted of isoamyl alcohol-methyl tert-butyl ether-acetonitrile-water (3:1:1:5). Thus, separation of 1.8 g of D&C Yellow No. 10 using the above method resulted in 0.6 g of 6SA and 0.18 g of 8SA of over 99% purity. The isolated compounds were characterized by mass spectrometry and proton nuclear magnetic resonance with correlated spectroscopy assignments. The study exemplifies a new field of applications for pH-zone-refining CCC, to the separation of positional isomers of strongly hydrophylic compounds containing sulfonic acid groups. Published by Elsevier Science B.V. C1 US FDA, Off Cosmet & Colors, Washington, DC 20204 USA. US FDA, Off Sci Anal & Support, Washington, DC 20204 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Weisz, A (reprint author), US FDA, Off Cosmet & Colors, Washington, DC 20204 USA. NR 22 TC 26 Z9 28 U1 2 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD JUL 20 PY 2001 VL 923 IS 1-2 BP 87 EP 96 DI 10.1016/S0021-9673(01)00984-0 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 458PM UT WOS:000170203800011 PM 11510564 ER PT J AU Du, QZ Li, ZH Ito, Y AF Du, QZ Li, ZH Ito, Y TI Preparative separation of isoflavone components in soybeans using high-speed counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE counter-current chromatography; preparative chromatography; soybean; isoflavones AB Four isoflavone components were purified from soybean extract by high-speed counter-current chromatography (HSCCC). Two types of multilayer coil separation columns were used: a small column made of standard 2.6-mm I.D. PTFE (polytetrafluoroethylene) tubing with a 260-ml capacity and a large column of convoluted PTFE tubing of 5.7-mm average I.D. with a 1200-ml capacity. Separation was performed with a two-phase solvent system composed of hexane-ethyl acetate-1-butanol-methanol-acetic acid-water (1:2:1:1:5:1, v/v) by eluting the lower aqueous phase at 2 ml/min (small column) and 5 ml/min (large column) at a revolution speed of 700 rpm. From 500 mg of crude sample the small column yielded 33 mg of daidzin, 41 mg of genistin, 27 mg of 6 " -O-malonyldaidzin and 24 mg of 6 " -O-malonylgenistin. The large convoluted column separated, from 3 g of crude sample, 203 mg of daidzin., 241 mg of genistin, 158 mg of 6 "O-malonyldaidzin and 135 mg of 6 " -O-malonylgenistin all at over 90% purity. The convoluted tubing facilitated preparation of a large multilayer coil due to its high flexibility. (C) 2001 Elsevier Science B.V. All rights reserved. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. Hunan Agr Univ, Coll Food Sci & Technol, Changsha 410008, Peoples R China. Hangzhou Univ Commerce, Inst Food & Biol Engn, Hangzhou 310035, Peoples R China. RP Ito, Y (reprint author), NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. NR 7 TC 35 Z9 52 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD JUL 20 PY 2001 VL 923 IS 1-2 BP 271 EP 274 DI 10.1016/S0021-9673(01)01031-7 PG 4 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 458PM UT WOS:000170203800029 PM 11510551 ER PT J AU Yang, FQ Ito, Y AF Yang, FQ Ito, Y TI pH-zone-refining counter-current chromatography of lappaconitine from Aconitum sinomontanum Nakai I. Separation of prepurified extract SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE counter-current chromatography; Aconitum sinomontanum; preparative chromatography; pharmaceutical analysis; lappaconitine; alkaloids; terpenoids; ranaconitine ID PREPARATIVE SEPARATION; ALKALOIDS; PURIFICATION; COMPONENTS AB pH-Zone-refining counter-current chromatography was applied to the separation of diterpenoid alkaloids from a crude sample from a crude prepurified sample containing lappaconitine at about 90% purity using a multilayer coil planet centrifuge. The experiment was performed with a two-phase solvent system composed of methyl tert-butyl ether-tetrahydrofuran-distilled water (2:2:3, v/v) where triethylamine (10 mM) was added to the upper organic stationary phase as a retainer and hydrochloric acid (10 mM) to the aqueous mobile phase as an eluter. The separation of 10.5 g of the sample yielded 9.0 g of lappaconitine at a high purity of over 99% as determined by HPLC. (C) 2001 Elsevier Science B.V. rights reserved. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Ito, Y (reprint author), NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. NR 22 TC 44 Z9 48 U1 3 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD JUL 20 PY 2001 VL 923 IS 1-2 BP 281 EP 285 DI 10.1016/S0021-9673(01)01032-9 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 458PM UT WOS:000170203800031 PM 11510553 ER PT J AU Sidorova, NY Rau, DC AF Sidorova, NY Rau, DC TI Linkage of EcoRI dissociation from its specific DNA recognition site to water activity, salt concentration, and pH: Separating their roles in specific and non-specific binding SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE protein-DNA interactions; osmotic stress; EcoRI restriction endonuclease; dissociation rate; bound water ID OSMOTIC-STRESS; RESTRICTION ENDONUCLEASES; LINEAR DIFFUSION; RI ENDONUCLEASE; PROTEIN; CLEAVAGE; SEQUENCES; COMPLEX AB We have measured the dependencies of both the dissociation rate of specifically bound EcoRI endonuclease and the ratio of non-specific and specific association constants on water activity, salt concentration, and pH in order to distinguish the contributions of these solution components to specific and non-specific binding. For proteins such as EcoRI that locate their specific recognition site efficiently by diffusing along nonspecific DNA, the specific site dissociation rate can be separated into two steps: an equilibrium between non-specific and specific binding of the enzyme to DNA, and the dissociation of non-specifically bound protein. We demonstrated previously that the osmotic dependence of the dissociation rate is dominated by the equilibrium between specific and nonspecific binding that is independent of the osmolyte nature. The remaining osmotic sensitivity linked to the dissociation of non-specifically bound protein depends significantly on the particular osmolyte used, indicating a change in solute-accessible surface area. In contrast, the dissociation of non-specifically bound enzyme accounts for almost all the pH and salt-dependencies. We observed virtually no pH-dependence of the equilibrium between specific and non-specific binding measured by the competition assay. The observed weak salt-sensitivity of the ratio of specific and non-specific association constants is consistent with an osmotic, rather than electrostatic, action. The seeming lack of a dependence on viscosity suggests the rate-limiting step in dissociation of non-specifically bound protein is a discrete conformational change rather than a general diffusion of the protein away from the DNA. C1 NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. RP Rau, DC (reprint author), NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. NR 35 TC 29 Z9 29 U1 3 U2 6 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUL 20 PY 2001 VL 310 IS 4 BP 801 EP 816 DI 10.1006/jmbi.2001.4781 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 454RJ UT WOS:000169985300010 PM 11453689 ER PT J AU Ashur-Fabian, O Giladi, E Furman, S Steingart, RA Wollman, Y Fridkin, M Brenneman, DE Gozes, I AF Ashur-Fabian, O Giladi, E Furman, S Steingart, RA Wollman, Y Fridkin, M Brenneman, DE Gozes, I TI Vasoactive intestinal peptide and related molecules induce nitrite accumulation in the extracellular milieu of rat cerebral cortical cultures SO NEUROSCIENCE LETTERS LA English DT Article DE vasoactive intestinal peptide; stearyl-norleucine17-vasoactive intestinal peptide; activity-dependent neuroprotective protein; nitric oxide; cyclic guanosine monophosphate; cortical cultures ID DEPENDENT NEUROTROPHIC FACTOR; OXIDE SYNTHASE; NEUROPROTECTIVE PEPTIDE; ASTROCYTES; PROTEIN; DISEASE; CGMP; NO AB Nanomolar concentrations of vasoactive intestinal peptide (VIP), picomolar concentrations of stearyl-norleucine17-VIP (SNV) and femtomolar concentrations of NAPVSIPQ (NAP), an 8-amino-acid peptide derived from the VIP-responsive activity-dependent neuroprotective protein, provide broad neuroprotection. In rat cerebral cortical cultures, 10(-16)-10(-7) M NAP increased intracellular cyclic guanosine monophosphate (cGMP) (2.5-4-fold) and 10(-10) M NAP increased extracellular nitric oxide (NO) by 60%. In the same culture system, VIP and SNV (at micromolar concentrations) increased extracellular NO by 45-55%. The NAP dose required for cGMP increases correlated with the dose providing neuroprotection. However, the concentrations of NAP, SNV and VIP affecting NO production did not match the neuro-protective doses. Thus, NO may mediate part of the cell-cell interaction and natural maintenance activity of VIP/SNV/NAP, while cGMP may mediate neuroprotection. (C) 2001 Published by Elsevier Science Ireland Ltd. C1 Tel Aviv Univ, Sackler Fac Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israel. Tel Aviv Med Ctr, Dept Nephrol, IL-64239 Tel Aviv, Israel. Weizmann Inst Sci, Dept Organ Chem, IL-76100 Rehovot, Israel. NICHHD, Sec Dev & Mol Pharmacol, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Gozes, I (reprint author), Tel Aviv Univ, Sackler Fac Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israel. NR 20 TC 34 Z9 36 U1 2 U2 5 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 20 PY 2001 VL 307 IS 3 BP 167 EP 170 DI 10.1016/S0304-3940(01)01954-1 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 451NQ UT WOS:000169808500009 PM 11438390 ER PT J AU Rogan, WJ Ware, JH Dietrich, KN Radcliffe, J Rhoads, GG AF Rogan, WJ Ware, JH Dietrich, KN Radcliffe, J Rhoads, GG TI Effects of lead exposure - Response SO SCIENCE LA English DT Letter C1 NIEHS, Res Triangle Pk, NC 27709 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Cincinnati, Cincinnati, OH 45267 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Univ Med & Dent New Jersey, Environm & Occupat Hlth Sci Inst, Piscataway, NJ 08854 USA. RP Rogan, WJ (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. RI Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUL 20 PY 2001 VL 293 IS 5529 BP 427 EP 428 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 454HG UT WOS:000169966700022 ER PT J AU Zwanzig, R AF Zwanzig, R TI A chemical Langevin equation with non-Gaussian noise SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article; Proceedings Paper CT Symposium on Molecular Dynamics - The Next Millennium CY JUN 02-03, 2000 CL COLUMBIA UNIV, NEW YORK, NEW YORK HO COLUMBIA UNIV AB The noise that appears in the Langevin equation for "well-stirred" chemical reactions is found by considering how one would do a "gedanken" computer simulation of the reaction. The noise is not Gaussian. C1 NIH, Chem Phys Lab, Bethesda, MD 20892 USA. RP Zwanzig, R (reprint author), NIH, Chem Phys Lab, Bldg 10, Bethesda, MD 20892 USA. NR 2 TC 7 Z9 7 U1 0 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1089-5647 J9 J PHYS CHEM B JI J. Phys. Chem. B PD JUL 19 PY 2001 VL 105 IS 28 BP 6472 EP 6473 DI 10.1021/jp0034630 PG 2 WC Chemistry, Physical SC Chemistry GA 456YN UT WOS:000170110500003 ER PT J AU Frisch, M Biggar, RJ AF Frisch, M Biggar, RJ TI Appendectomy and protection against ulcerative colitis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Statens Serum Inst, DK-2300 Copenhagen, Denmark. NCI, Rockville, MD 20852 USA. RP Frisch, M (reprint author), Statens Serum Inst, DK-2300 Copenhagen, Denmark. RI Frisch, Morten/E-9206-2016 OI Frisch, Morten/0000-0002-3864-8860 NR 3 TC 6 Z9 6 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 19 PY 2001 VL 345 IS 3 BP 222 EP 223 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 453JM UT WOS:000169912800023 PM 11463028 ER PT J AU Archer, T Baylin, S Hansen, J Hayes, J Pelicci, PG Robertson, K Stunnenberg, H Urnov, F Wade, P AF Archer, T Baylin, S Hansen, J Hayes, J Pelicci, PG Robertson, K Stunnenberg, H Urnov, F Wade, P TI Dr Alan P Wolffe 1959-2000 - Obituary SO ONCOGENE LA English DT Biographical-Item C1 NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD USA. Univ Rochester, Rochester, NY USA. European Inst Oncol, Milan, Italy. Catholic Univ Nijmegen, Nijmegen, Netherlands. Emory Univ, Atlanta, GA 30322 USA. RP Archer, T (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. RI Stunnenberg, Hendrik/D-6875-2012 NR 1 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL 19 PY 2001 VL 20 IS 32 BP 4439 EP 4439 DI 10.1038/sj.onc.1204716 PG 1 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 453JK UT WOS:000169912600021 ER PT J AU Doan, LX Lin, B Yagi, H Jerina, DM Whalen, DL AF Doan, LX Lin, B Yagi, H Jerina, DM Whalen, DL TI New insights on the mechanisms of the pH-independent reactions of benzo[a]pyrene 7,8-diol 9,10-epoxides SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID ACID-CATALYZED HYDROLYSIS; POLYCYCLIC AROMATIC-HYDROCARBONS; ANION COMBINATION REACTIONS; REGION DIOL EPOXIDES; CARCINOGEN BENZOPYRENE; PRODUCT DISTRIBUTIONS; ANETHOLE OXIDES; CIS-ANETHOLE; INTERMEDIATE; CARBOCATION AB The rates and products of the reactions of (+/-)-7 beta ,8 alpha -dihydroxy-9 beta ,10 beta -epoxy-7,8,9, drobenzo[a]pyrene (1) and (+/-)-7 beta ,8 alpha -dihydroxy-9 alpha ,10 alpha -epoxy 7,8,9,10-tetrahydrobenzo[a]pyrene (2) in water and dioxane-water mixtures have been determined over a pH range wider than that of earlier studies. This study provides additional insight on the mechanisms of the pH-independent reactions of I and 2. The rate profile for reaction of 1 shows acid-catalyzed hydrolysis at pH <5, a rate plateau at pH 5-9.5, a negative inflection at pH 10-11.5, and a rate increase at pH > 11.5. The rate decrease between pH 10 and pH 11.5 is accompanied by a decrease in the yield of tetrols from 60% (pH 8) to 29% (pH 11.2) and is interpreted to be the result of a partial change in mechanism brought about by attack of hydroxide ion acting as a base to deprotonate a carbocation intermediate and regenerate I at pH > 10, thus reducing the contribution of the pathway for tetrol formation in which water attacks the carbocation. The rate profile for the reaction of 2 exhibits only a single rate plateau at intermediate pH, along with increases in rate at low and high pH because of second-order reactions of 2 with H+ acid HO-, respectively. The lack of a rate depression at pH > 10 and the product studies for the reaction of 2 in dilute sodium azide solutions suggest that the tetrol-forming reactions of the pH-independent reaction of 2 are concerted or near-concerted. C1 Univ Maryland Baltimore Cty, Dept Chem & Biochem, Baltimore, MD 21250 USA. NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Whalen, DL (reprint author), Univ Maryland Baltimore Cty, Dept Chem & Biochem, Baltimore, MD 21250 USA. NR 28 TC 9 Z9 9 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JUL 18 PY 2001 VL 123 IS 28 BP 6785 EP 6791 DI 10.1021/ja004359z PG 7 WC Chemistry, Multidisciplinary SC Chemistry GA 451LF UT WOS:000169803000006 PM 11448182 ER PT J AU Szabo, E AF Szabo, E TI Lung epithelial proliferation: a biomarker for chemoprevention trials? SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID CELL-PROLIFERATION; NUCLEAR ANTIGEN; VITAMIN-A; CANCER; PREVENTION; HEAD; NECK C1 NCI, Div Canc Prevent, Lung & Upper Aerodigest Canc Res Grp, Bethesda, MD USA. RP Szabo, E (reprint author), NIH, 6130 Execut Blvd,Rm 2132, Bethesda, MD 20892 USA. NR 21 TC 14 Z9 14 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUL 18 PY 2001 VL 93 IS 14 BP 1042 EP 1043 DI 10.1093/jnci/93.14.1042 PG 2 WC Oncology SC Oncology GA 451XX UT WOS:000169829000002 PM 11459858 ER PT J AU Mehta, RG Bhat, KPL Hawthorne, ME Kopelovich, L Mehta, RR Christov, K Kelloff, GJ Steele, VE Pezzuto, JM AF Mehta, RG Bhat, KPL Hawthorne, ME Kopelovich, L Mehta, RR Christov, K Kelloff, GJ Steele, VE Pezzuto, JM TI Induction of atypical ductal hyperplasia in mouse mammary gland organ culture SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID VITAMIN-D ANALOG; 1-ALPHA-HYDROXYVITAMIN D-5; BREAST; CELLS; CARCINOGENESIS; PREVENTION; CARCINOMA; CANCER C1 Univ Illinois, Coll Pharm MC 877, Dept Med Chem & Pharmacognosy, Chicago, IL 60612 USA. Univ Illinois, Coll Med, Dept Surg Oncol, Chicago, IL 60612 USA. NCI, Div Canc Prevent & Control, Chemoprevent Agent Dev Grp, Bethesda, MD 20892 USA. RP Pezzuto, JM (reprint author), Univ Illinois, Coll Pharm MC 877, Dept Med Chem & Pharmacognosy, 833 S Wood St, Chicago, IL 60612 USA. FU NCI NIH HHS [CN65114, CN55135, P01CA48112] NR 16 TC 20 Z9 21 U1 0 U2 4 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUL 18 PY 2001 VL 93 IS 14 BP 1103 EP 1106 DI 10.1093/jnci/93.14.1103 PG 4 WC Oncology SC Oncology GA 451XX UT WOS:000169829000015 PM 11459872 ER PT J AU Kervinen, J Jaffe, EK Stauffer, F Neier, R Wlodawer, A Zdanov, A AF Kervinen, J Jaffe, EK Stauffer, F Neier, R Wlodawer, A Zdanov, A TI Mechanistic basis for suicide inactivation of porphobilinogen synthase by 4,7-dioxosebacic acid, an inhibitor that shows dramatic species selectivity SO BIOCHEMISTRY LA English DT Article ID X-RAY STRUCTURE; ESCHERICHIA-COLI; BRADYRHIZOBIUM-JAPONICUM; PSEUDOMONAS-AERUGINOSA; HEME-BIOSYNTHESIS; ARTIFICIAL GENE; DEHYDRATASE; BINDING; ENZYME; PEA AB 4,7-Dioxosebacic acid (4,7-DOSA) is an active site-directed irreversible inhibitor of porphobilinogen synthase (PBGS). PBGS catalyzes the first common step in the biosynthesis of the tetrapyrrole cofactors such as heme, vitamin Bit, and chlorophyll. 4,7-DOSA was designed as an analogue of a proposed reaction intermediate in the physiological PBGS-catalyzed condensation of two molecules of 5-amino-levulinic acid. As shown here, 4,7-DOSA exhibits time-dependent and dramatic species-specific inhibition of PBGS enzymes. IC50 values vary from 1 muM to 2.4 mM for human, Escherichia coli, Bradyrhizobium japonicum, Pseudomonas aeruginosa, and pea enzymes. Those PBGS utilizing a catalytic Zn2+ are more sensitive to 4,7-DOSA than those that do not. Weak inhibition of a human mutant PBGS establishes that the inactivation by 4,7-DOSA requires formation of a Schiff base to a lysine that normally forms a Schiff base intermediate to one substrate molecule. A 1.9 Angstrom resolution crystal structure of E. coli PBGS complexed with 4,7-DOSA (PDE code 1I8J) shows one dimer per asymmetric unit and reveals that the inhibitor forms two Schiff base linkages with each monomer, one to the normal Schiff base-forming Lys-246 and the other to a universally conserved "perturbing" Lys-194 (E. coli numbering). This is the first structure to show inhibitor binding at the second of two substrate-binding sites. C1 Fox Chase Canc Ctr, Inst Canc Res, Philadelphia, PA 19111 USA. NCI, Macromol Struct Lab, Ft Detrick, MD 21702 USA. Univ Neuchatel, Dept Chem, CH-2007 Neuchatel, Switzerland. RP Jaffe, EK (reprint author), Fox Chase Canc Ctr, Inst Canc Res, 7701 Burholme Ave, Philadelphia, PA 19111 USA. FU NCI NIH HHS [CA06927]; NIEHS NIH HHS [ES03654] NR 36 TC 39 Z9 42 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUL 17 PY 2001 VL 40 IS 28 BP 8227 EP 8236 DI 10.1021/bi010656k PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 451ZW UT WOS:000169833500006 PM 11444968 ER PT J AU Leikina, E LeDuc, DL Macosko, JC Epand, R Epand, R Shin, YK Chernomordik, LV AF Leikina, E LeDuc, DL Macosko, JC Epand, R Epand, R Shin, YK Chernomordik, LV TI The 1-127 HA2 construct of influenza virus hemagglutinin induces cell-cell hemifusion SO BIOCHEMISTRY LA English DT Article ID MEDIATED MEMBRANE-FUSION; PHOSPHOLIPID-VESICLES; PORE FORMATION; CONFORMATIONAL CHANGE; TRANSMEMBRANE DOMAIN; UNILAMELLAR VESICLES; RECEPTOR-BINDING; PH CONFORMATION; HA(2) SUBUNIT; EARLY-STAGE AB Conformational changes in the HA2 subunit of influenza hemagglutinin (HA) are coupled to membrane fusion. We investigated the fusogenic activity of the polypeptide FHA2 representing 127 aminoterminal residues of the ectodomain of HA2. While the conformation of FHA2 both at neutral and at low pH is nearly identical to the final low-pH conformation of HA2, FHA2 still induces lipid mixing between liposomes in a low-pH-dependent manner. Here, we found that FHA2 induces lipid mixing between bound cells, indicating that the "spring-loaded" energy is not required for FHA2-mediated membrane merger. Although, unlike HA, FHA2 did not form an expanding fusion pore, both acidic pH and membrane concentrations of FHA2, required for lipid mixing, have been close to those required for HA-mediated fusion. Similar to what is observed for HA, FHA2-induced lipid mixing was reversibly blocked by lysophosphatidylcholine and low temperature, 4 degreesC. The same genetic modification of the fusion peptide inhibits both HA- and FHA2-fusogenic activities. The kink region of FHA2, critical for FHA2-mediated lipid mixing, was exposed in the low-pH conformation of the whole HA prior to fusion. The ability of FHA2 to mediate lipid mixing very similar to HA-mediated lipid mixing is consistent with the hypothesis that hemifusion requires just a portion of the energy released in the conformational change of HA at acidic pH. C1 NICHD, Sect Membrane Biol, LCMB, NIH, Bethesda, MD 20892 USA. Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA. McMaster Univ, Dept Biochem, Hamilton, ON L8N 3Z5, Canada. Iowa State Univ, Dept Biochem & Biophys, Ames, IA 50011 USA. RP Chernomordik, LV (reprint author), NICHD, Sect Membrane Biol, LCMB, NIH, Bldg 10,Room 10D04,10 Ctr Dr, Bethesda, MD 20892 USA. NR 66 TC 38 Z9 40 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUL 17 PY 2001 VL 40 IS 28 BP 8378 EP 8386 DI 10.1021/bi010466+ PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 451ZW UT WOS:000169833500023 PM 11444985 ER PT J AU Lipshultz, SE Easley, KA Orav, J Kaplan, S Starc, TJ Bricker, JT Lai, WW Moodie, DS Sopko, G Schluchter, MD Colan, SD AF Lipshultz, SE Easley, KA Orav, J Kaplan, S Starc, TJ Bricker, JT Lai, WW Moodie, DS Sopko, G Schluchter, MD Colan, SD CA Pediat Pulm Cardiac Complication V TI Reliability of multicenter pediatric echocardiographic measurements of left ventricular structure and function - The prospective (PCHIV)-C-2-H-2 study SO CIRCULATION LA English DT Article DE echocardiography; pediatrics; AIDS ID AGREEMENT; CHILDREN AB Background - To assess the reliability of pediatric echocardiographic measurements, we compared local measurements with those made at a central facility. Methods and Results - The comparison was based on the first echocardiographic recording obtained on 735 children of HIV-infected mothers at 10 clinical sites focusing on measurements of left ventricular (LV) dimension, wall thicknesses, and fractional shortening. The recordings were measured locally and then remeasured at a central facility. The highest agreement expressed as an intraclass correlation coefficient (ICC=0.97) was noted for LV dimension, with much lower agreement for posterior wall thickness (ICC=0.65), fractional shortening (ICC=0.64), and septal wall thickness (ICC=0.50). The mean dimension was 0.03 cm smaller in central measurements (95% prediction interval [PI], -0.32 to 0.25 cm) for which 95% PI reflects the magnitude of differences between local and central measurements. Mean posterior wall thickness was 0.02 cm larger in central measurements (95% PI, -0.18 to 0.22 cm). Mean fractional shortening was 1% smaller in central measurements. However, the 95% PI was -10% to 8%, indicating that a fractional shortening of 32% measured centrally could be anywhere between 22% and 40% when measured locally. Central measurements of mean septal thickness were approximate to0.1 cm thicker than local ones (95% PI, -0.18 to 0.34 cm). Centrally measured wall thickness was more closely related to mortality and possibly was more valid than local measurements. Conclusions - Although LV dimension was reliably measured, local measurements of LV wall thickness and fractional shortening differed from central measurements. C1 Univ Rochester, Med Ctr, Div Pediat Cardiol, Rochester, NY 14642 USA. Childrens Hosp, Rochester, NY 14642 USA. Univ Rochester, Sch Med & Dent, Dept Pediat, Rochester, NY USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA USA. Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Boston Med Ctr, Dept Pediat, Boston, MA USA. Cleveland Clin Fdn, Dept Biostat & Epidemiol, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Pediat, Div Pediat Cardiol, Cleveland, OH 44195 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Univ Calif Los Angeles, Med Ctr, Dept Pediat, Div Pediat Cardiol, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Mt Sinai Sch Med, Div Pediat Cardiol, Dept Pediat, New York, NY USA. Columbia Univ Coll Phys & Surg, Dept Pediat, Div Pediat Cardiol, Presbyterian Hosp, New York, NY 10032 USA. Baylor Coll Med, Dept Pediat, Div Pediat Cardiol, Houston, TX 77030 USA. Natl Heart & Lung Inst, Bethesda, MD USA. RP Lipshultz, SE (reprint author), Univ Rochester, Med Ctr, Div Pediat Cardiol, 601 Elmwood Ave,Box 631, Rochester, NY 14642 USA. RI Easley, Kirk/K-6910-2015 OI Easley, Kirk/0000-0003-4419-2617 FU NCRR NIH HHS [M01 RR000645, M01 RR002172, RR-00645, RR-02172, K01 RR000188, M01 RR000071, M01 RR000188, M01 RR000533, RR-00071, RR-00188, RR-00533, M01 RR000043, M01 RR000865, RR-00865, RR-00043, RR-00685]; NHLBI NIH HHS [N01-HR-96040, N01 HR096037, N01 HR096043, N01-HR-96039, N01-HR-96042, N01-HR-96038, N01-HR-96041] NR 9 TC 56 Z9 56 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL 17 PY 2001 VL 104 IS 3 BP 310 EP 316 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 455AH UT WOS:000170005000015 PM 11457750 ER PT J AU Jones, CE Mueser, TC Dudas, KC Kreuzer, KN Nossal, NG AF Jones, CE Mueser, TC Dudas, KC Kreuzer, KN Nossal, NG TI Bacteriophage T4 gene 41 helicase and gene 59 helicase-loading protein: A versatile couple with roles in replication and recombination SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Proceedings Paper CT Colloquium on Links Between Recombination and Replication - Vital Roles of Recombination CY NOV 10-12, 2000 CL IRVINE, CALIFORNIA SP Natl Acad Sci ID DEPENDENT DNA-REPLICATION; POLAR BRANCH MIGRATION; 4-WAY JUNCTION DNA; ESCHERICHIA-COLI; ASSEMBLY PROTEIN; LAMBDA-P; BINDING; PRIA; FORK; PHAGE-T4 AB Bacteriophage T4 uses two modes of replication initiation: origin-dependent replication early in infection and recombination-dependent replication at later times. The same relatively simple complex of T4 replication proteins is responsible for both modes of DNA synthesis. Thus the mechanism for loading the T4 41 helicase must be versatile enough to allow it to be loaded on 9 loops created by transcription at several origins, on D loops created by recombination, and on stalled replication forks. T4 59 helicase-loading protein is a small, basic, almost completely alpha -helical protein whose N-terminal domain has structural similarity to high mobility group family proteins. In this paper we review recent evidence that 59 protein recognizes specific structures rather than specific sequences. It binds and loads the helicase on replication forks and on three- and four-stranded (Holliday junction) recombination structures, without sequence specificity. We summarize our experiments showing that purified T4 enzymes catalyze complete unidirectional replication of a plasmid containing the T4 ori(uvsY) origin, with a preformed 9 loop at the position of the 9 loop identified at this origin in vivo. This replication depends on the 41 helicase and is strongly stimulated by 59 protein. Moreover, the helicase-loading protein helps to coordinate leading and lagging strand synthesis by blocking replication on the ori(uvsY) R loop plasmid until the helicase is loaded. The T4 enzymes also can replicate plasmids with 9 loops that do not have a T4 origin sequence, but only if the 9 loops are within an easily unwound DNA sequence. C1 NIDDKD, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Toledo, Dept Chem, Toledo, OH 43606 USA. Duke Univ, Med Ctr, Dept Microbiol, Durham, NC 27710 USA. RP Nossal, NG (reprint author), NIDDKD, Mol & Cellular Biol Lab, NIH, Bldg 8,Room 2A19, Bethesda, MD 20892 USA. FU NIGMS NIH HHS [R01 GM034622, F32 GM19000, F32 GM019000, GM34622, R37 GM034622] NR 57 TC 31 Z9 31 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 17 PY 2001 VL 98 IS 15 BP 8312 EP 8318 DI 10.1073/pnas.121009398 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 454HK UT WOS:000169967000027 PM 11459969 ER PT J AU Pham, P Rangarajan, S Woodgate, R Goodman, MF AF Pham, P Rangarajan, S Woodgate, R Goodman, MF TI Roles of DNA polymerases V and II in SOS-induced error-prone and error-free repair in Escherichia coli SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Proceedings Paper CT Colloquium on Links Between Recombination and Replication - Vital Roles of Recombination CY NOV 10-12, 2000 CL IRVINE, CALIFORNIA SP Natl Acad Sci ID RECA PROTEIN; POL-II; ADAPTIVE MUTATION; MUTAGENESIS; REPLICATION; DAMAGE; GENE; PURIFICATION; INHIBITION; COMPLEX AB DNA polymerase V, composed of a heterotrimer of the DNA damage-inducible UmuC and UmuD(2)' proteins, working in conjunction with RecA, single-stranded DNA (ssDNA)-binding protein (SSB), beta sliding clamp, and gamma clamp loading complex, are responsible for most SOS lesion-targeted mutations in Escherichia coli, by catalyzing translesion synthesis (TLS). DNA polymerase II, the product of the damage-inducible polB (dinA) gene plays a pivotal role in replication-restart, a process that bypasses DNA damage in an error-free manner. Replication-restart takes place almost immediately after the DNA is damaged (approximate to min post-UV irradiation), whereas TLS occurs after pol V is induced approximate to 50 min later. We discuss recent data for pol V-catalyzed TLS and pol II-catalyzed replication-restart. Specific roles during TLS for pol V and each of its accessory factors have been recently determined. Although the precise molecular mechanism of pol II-dependent replication-restart remains to be elucidated, it has recently been shown to operate in conjunction with RecFOR and PriA proteins. C1 Univ So Calif, Dept Biol Sci, Los Angeles, CA 90089 USA. Univ So Calif, Dept Chem, Hedco Mol Biol Labs, Los Angeles, CA 90089 USA. NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bethesda, MD 20892 USA. RP Goodman, MF (reprint author), Univ So Calif, Dept Biol Sci, Los Angeles, CA 90089 USA. FU NIGMS NIH HHS [GM21422, GM42554, R01 GM021422, R37 GM021422] NR 54 TC 66 Z9 67 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 17 PY 2001 VL 98 IS 15 BP 8350 EP 8354 DI 10.1073/pnas.111007198 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 454HK UT WOS:000169967000032 PM 11459974 ER PT J AU Cheng, JG Chen, JR Hernandez, L Alvord, WG Stewart, CL AF Cheng, JG Chen, JR Hernandez, L Alvord, WG Stewart, CL TI Dual control of LIF expression and LIF receptor function regulate Stat3 activation at the onset of uterine receptivity and embryo implantation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LEUKEMIA-INHIBITORY FACTOR; EPIDERMAL GROWTH-FACTOR; EARLY-PREGNANCY; BLASTOCYST IMPLANTATION; GENE-EXPRESSION; MICE LACKING; STEM-CELLS; UTERUS; MOUSE; INTERLEUKIN-6 AB Leukemia inhibitory factor (LIF) expression in the uterus is essential for embryo implantation in mice. Here we describe the spatial and temporal regulation of LIF signaling in vivo by using tissues isolated from uteri on different days over the implantation period. During this time, LIF receptors are expressed predominantly in the luminal epithelium (LE) of the uterus. Isolated epithelium responds to LIF by phosphorylation and nuclear translocation of signal transducer and activator of transcription (Stat) 3, but not by an increase in mitogen-activated protein kinase levels. The related cytokines II-6, ciliary neurotrophic factor, as well as epidermal growth factor, do not activate Stat3, although epidermal growth factor stimulates mitogen-activated protein kinase. In vivo Stat3 activation is induced by LIF alone, resulting in the localization of Stat3 specifically to the nuclei of the LE coinciding with the onset of uterine receptivity. The responsiveness of the LE to LIF is regulated temporally, with Stat activation being restricted to day 4 of pregnancy despite the presence of constant levels of LIF receptor throughout the preimplantation period. Uterine receptivity is therefore under dual control and is regulated by both the onset of LIF expression in the endometrial glands and the release from inhibition of receptor function in the LE. C1 NCI, Div Basic Sci, Lab Expt & Computat Biol, Comp & Stat Serv,Data Mangement Serv, Frederick, MD 21702 USA. NCI, Canc & Dev Biol Lab, Frederick, MD 21702 USA. RP Stewart, CL (reprint author), NCI, Div Basic Sci, Lab Expt & Computat Biol, Comp & Stat Serv,Data Mangement Serv, Bldg 539,Room 121, Frederick, MD 21702 USA. NR 44 TC 79 Z9 88 U1 2 U2 12 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 17 PY 2001 VL 98 IS 15 BP 8680 EP 8685 DI 10.1073/pnas.151180898 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 454HK UT WOS:000169967000085 PM 11438698 ER PT J AU Wada, T Schurman, SH Otsu, M Garabedian, EK Ochs, HD Nelson, DL Candotti, F AF Wada, T Schurman, SH Otsu, M Garabedian, EK Ochs, HD Nelson, DL Candotti, F TI Somatic mosaicism in Wiskott-Aldrich syndrome suggests in vivo reversion by a DNA slippage mechanism SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SYNDROME PROTEIN WASP; T-CELL REPERTOIRE; REVERTANT MOSAICISM; HEMATOPOIETIC-CELLS; GENETIC-DEFECT; CARRIER STATUS; IN-VIVO; EXPRESSION; MUTATIONS; IDENTIFICATION AB Somatic mosaicism caused by in vivo reversion of inherited mutations has been described in several human genetic disorders. Back mutations resulting in restoration of wild-type sequences and second-site mutations leading to compensatory changes have been shown in mosaic individuals. in most cases, however, the precise genetic mechanisms underlying the reversion events have remained unclear, except for the few instances where crossing over or gene conversion have been demonstrated. Here, we report a patient affected with Wiskott-Aldrich syndrome (WAS) caused by a 6-bp insertion (ACGAGG) in the WAS protein gene, which abrogates protein expression. Somatic mosaicism was documented in this patient whose majority of T lymphocytes expressed nearly normal levels of WAS protein. These lymphocytes were found to lack the deleterious mutation and showed a selective growth advantage in vivo. Analysis of the sequence surrounding the mutation site showed that the 6-bp insertion followed a tandem repeat of the same six nucleotides. These findings strongly suggest that DNA polymerase slippage was the cause of the original germ-line insertion mutation in this family and that the same mechanism was responsible for its deletion in one of the propositus T cell progenitors, thus leading to reversion mosaicism. C1 NHGRI, Disorders Immun Sect, Genet & Mol BIol Branch, NIH, Bethesda, MD 20892 USA. Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA. NCI, Immunophysiol Sect, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Candotti, F (reprint author), NHGRI, Disorders Immun Sect, Genet & Mol BIol Branch, NIH, Bethesda, MD 20892 USA. OI Otsu, Makoto/0000-0002-9769-0217; Schurman, Shepherd/0000-0002-9133-7906 FU NICHD NIH HHS [HD17427, R37 HD017427] NR 33 TC 101 Z9 104 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 17 PY 2001 VL 98 IS 15 BP 8697 EP 8702 DI 10.1073/pnas.151260498 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 454HK UT WOS:000169967000088 PM 11447283 ER PT J AU Shuto, T Xu, HD Wang, BN Han, JH Kai, HF Gu, XX Murphy, TF Lim, DJ Li, JD AF Shuto, T Xu, HD Wang, BN Han, JH Kai, HF Gu, XX Murphy, TF Lim, DJ Li, JD TI Activation of NF-kappa B by nontypeable Hemophilus influenzae is mediated by toll-like receptor 2-TAK1-dependent NIK-IKK alpha/beta-I kappa B alpha and MKK3/6-p38 MAP kinase signaling pathways in epithelial cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NONTYPABLE HAEMOPHILUS-INFLUENZAE; INNATE IMMUNE-RESPONSE; OUTER-MEMBRANE PROTEIN; PSEUDOMONAS-AERUGINOSA; OTITIS-MEDIA; GENE-EXPRESSION; LIPOPOLYSACCHARIDE; PATHOGENESIS; DETERMINANTS; CHILDREN AB Nontypeable Hemophilus influenzae (NTHi) is an important human pathogen in both children and adults. In children, it causes otitis media, the most common childhood infection and the leading cause of conductive hearing loss in the United States. In adults, it causes lower respiratory tract infections in the setting of chronic obstructive pulmonary disease, the fourth leading cause of death in the United States. The molecular mechanisms underlying the pathogenesis of NTHi-induced infections remain undefined, but they may involve activation of NF-kappaB, a transcriptional activator of multiple host defense genes involved in immune and inflammatory responses. Here, we show that NTHi strongly activates NF-KB in human epithelial cells via two distinct signaling pathways, NF-kappaB translocation-dependent and -independent pathways. The NF-K kappaB translocation-dependent pathway involves activation of NF-kappaB inducing kinase (NIK)-IKK alpha/beta complex leading to I kappaB alpha phosphorylation and degradation, whereas the NF-kappaB translocation-independent pathway involves activation of MKK3/6-p38 mitogen-activated protein (MAP) kinase pathway. Bifurcation of NTHi-induced NIK-IKK alpha/beta -I kappaB alpha and MKK3/6-p38 MAP kinase pathways may occur at transforming growth factor-beta activated kinase 1 (TAK1). Furthermore, we show that toll-like receptor 2 (TLR2) is required for NTHi-induced NF-kappaB activation. In addition, several key inflammatory mediators including IL-1 beta, IL-8, and tumor necrosis factor-cu are up-regulated by NTHi. Finally, P6, a 16-kDa lipoprotein highly conserved in the outer membrane of all NTHi and H. influenzae type b strains, appears to also activate NF-kappaB via similar signaling pathways. Taken together, our results demonstrate that NTHi activates NF-kappaB via TLRZ-TAK1-dependent NIK-IKK alpha/beta -I kappaB alpha and MKK3/6-p38 MAP kinase signaling pathways. These studies may bring new insights into molecular pathogenesis of NTHi-induced infections and open up new therapeutic targets for these diseases. C1 Univ So Calif, Gonda Dept Cell & Mol Biol, House Ear Inst, Los Angeles, CA 90057 USA. Univ So Calif, Dept Otolaryngol, Los Angeles, CA 90057 USA. Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. Kumamoto Univ, Dept Pharmacol Sci, Kumamoto 8620973, Japan. Natl Inst Deafnes & Other Commun Disorders, Immunol Lab, Rockville, MD 20850 USA. SUNY Buffalo, Div Infect Dis, Buffalo, NY 14215 USA. RP Li, JD (reprint author), Univ So Calif, Gonda Dept Cell & Mol Biol, House Ear Inst, Los Angeles, CA 90057 USA. RI Han, J/G-4671-2010 FU NIAID NIH HHS [AI41637, AI19641, R01 AI019641, R01 AI041637]; NIDCD NIH HHS [DC04562, R01 DC004562, R01 DC005025] NR 39 TC 197 Z9 201 U1 0 U2 11 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 17 PY 2001 VL 98 IS 15 BP 8774 EP 8779 DI 10.1073/pnas.151236098 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 454HK UT WOS:000169967000101 PM 11438700 ER PT J AU Fitzgerald, JR Sturdevant, DE Mackie, SM Gill, SR Musser, JM AF Fitzgerald, JR Sturdevant, DE Mackie, SM Gill, SR Musser, JM TI Evolutionary genomics of Staphylococcus aureus: Insights into the origin of methicillin-resistant strains and the toxic shock syndrome epidemic SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DNA microarray; evolution ID COWS; GENE; BCG; DNA AB An emerging theme in medical microbiology is that extensive variation exists in gene content among strains of many pathogenic bacterial species. However, this topic has not been investigated on a genome scare with strains recovered from patients with well-defined clinical conditions. Staphylococcus aureus is a major human pathogen and also causes economically important infections in cows and sheep. A DNA microarray representing > 90% of the S. aureus genome was used to characterize genomic diversity, evolutionary relationships, and virulence gene distribution among 36 strains of divergent clonal lineages, including methicillin-resistant strains and organisms causing toxic shock syndrome. Genetic variation in 5, aureus is Very extensive, with approximate to 22% of the genome comprised of dispensable genetic material. Eighteen large regions of difference were identified, and 10 of these regions have genes that encode putative Virulence factors or proteins mediating antibiotic resistance. We find that lateral gene transfer has played a fundamental role in the evolution of 5, aureus. The mec gene has been horizontally transferred into distinct 5. aureus chromosomal backgrounds at least five times, demonstrating that methicillin-resistant strains have evolved multiple independent times, rather than from a single ancestral strain. This finding resolves a longstanding controversy in 5. aureus research. The epidemic of toxic shock syndrome that occurred in the 1970s was caused by a change in the host environment, rather than rapid geographic dissemination of a new hypervirulent strain, DNA microarray analysis of large samples of clinically characterized strains provides broad insights into evolution, pathogenesis, and disease emergence. C1 NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. Inst Genom Res, Rockville, MD 20850 USA. RP Musser, JM (reprint author), NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, 903 S 4th St, Hamilton, MT 59840 USA. NR 18 TC 273 Z9 294 U1 6 U2 28 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 17 PY 2001 VL 98 IS 15 BP 8821 EP 8826 DI 10.1073/pnas.161098098 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 454HK UT WOS:000169967000109 PM 11447287 ER PT J AU Ung, TL Cao, C Lu, JM Ozato, K Dever, TE AF Ung, TL Cao, C Lu, JM Ozato, K Dever, TE TI Heterologous dimerization domains functionally substitute for the double-stranded RNA binding domains of the kinase PKR SO EMBO JOURNAL LA English DT Article DE dimerization; eIF2; PKR; protein kinase; Xlim-1 ID DEPENDENT PROTEIN-KINASE; GLUTATHIONE-S-TRANSFERASE; TRANSLATIONAL CONTROL; IN-VIVO; INITIATION FACTOR-2-ALPHA; 3-DIMENSIONAL STRUCTURE; ENDOPLASMIC-RETICULUM; MOLECULAR MECHANISMS; SIGNAL-TRANSDUCTION; INTERFERON ACTION AB The protein kinase PKR (dsRNA-dependent protein kinase) phosphorylates the eukaryotic translation initiation factor eIF2 alpha to downregulate protein synthesis in virus-infected cells. Two double-stranded RNA binding domains (dsRBDs) in the N-terminal half of PKR are thought to bind the activator double-stranded RNA, mediate dimerization of the protein and target PKR to the ribosome. To investigate further the importance of dimerization for PKR activity, fusion proteins were generated linking the PKR kinase domain to heterologous dimerization domains. Whereas the isolated PKR kinase domain (KD) was non-functional in vivo, expression of a glutathione S-transferase-KD fusion, or co-expression of KD fusions containing the heterodimerization domains of the Xlim-1 and Ldb1 proteins, restored PKR activity in yeast cells. Finally, coumermycin-mediated dimerization of a GyrB-KD fusion protein increased eIF2 alpha phosphorylation and inhibited reporter gene translation in mammalian cells. These results demonstrate the critical importance of dimerization for PKR activity in vivo, and suggest that a primary function of double-stranded RNA binding to the dsRBDs of native PKR is to promote dimerization and activation of the kinase domain. C1 NICHHD, Labs Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. NICHHD, Labs Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RP Dever, TE (reprint author), NICHHD, Labs Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. NR 50 TC 77 Z9 78 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD JUL 16 PY 2001 VL 20 IS 14 BP 3728 EP 3737 DI 10.1093/emboj/20.14.3728 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 457RA UT WOS:000170149500014 PM 11447114 ER PT J AU Kontoyiannis, D Kotlyarov, A Carballo, E Alexopoulou, L Blackshear, PJ Gaestel, M Davis, R Flavell, R Kollias, G AF Kontoyiannis, D Kotlyarov, A Carballo, E Alexopoulou, L Blackshear, PJ Gaestel, M Davis, R Flavell, R Kollias, G TI Interleukin-10 targets p38 MAPK to modulate ARE-dependent TNF mRNA translation and limit intestinal pathology SO EMBO JOURNAL LA English DT Article DE animal model; anti-inflammatory; Crohn's disease; gene expression; knockout ID TUMOR-NECROSIS-FACTOR; ALPHA MESSENGER-RNA; AU-RICH ELEMENTS; SIGNAL-TRANSDUCTION PATHWAY; NF-KAPPA-B; C-JUN; EXPERIMENTAL ENDOTOXEMIA; CHRONIC ENTEROCOLITIS; GENE-EXPRESSION; HUMAN MONOCYTES AB Interleukin-10 (IL-10) is a key inhibitory signal of inflammatory responses that regulates the production of potentially pathogenic cytokines like tumor necrosis factor (TNF). We show here that the development of chronic intestinal inflammation in IL-10-deficient mice requires the function of TNF, indicating that the IL-10/TNF axis regulates mucosal immunity. We further show that IL-10 targets the 3 ' AU-rich elements (ARE) of TNF mRNA to inhibit its translation. Moreover, IL-10 does not alter TNF mRNA stability, and its action does not require the presence of the stability-regulating ARE binding factor tristetraprolin, indicating a differential assembly of stability and translation determinants on the TNF ARE. Inhibition of TNF translation by IL-10 is exerted mainly by inhibition of the activating p38/MAPK-activated protein kinase-2 pathway. These results demonstrate a physiologically significant cross-talk between the IL-10 receptor and the stress-activated protein kinase modules targeting TNF mRNA translation. This crosstalk is necessary for optimal TNF production and for the maintenance of immune homeostasis in the gut. C1 BSRC Alexander Fleming, Inst Immunol, Vari 16672, Greece. Univ Halle Wittenberg, Innovationskolleg Zellspezialisierung, D-06120 Halle, Germany. NIH, Lab Signal Transduct, NIEHS, Res Triangle Pk, NC 27709 USA. Yale Univ, Sch Med, Immunobiol Sect, New Haven, CT 06520 USA. Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06520 USA. Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Program Mol Med,Dept Biochem & Mol Biol, Worcester, MA 01605 USA. RP Kollias, G (reprint author), BSRC Alexander Fleming, Inst Immunol, Vari 16672, Greece. RI Kollias, George/A-7079-2012; Alexopoulou, Lena/A-5041-2017; OI Kollias, George/0000-0003-1867-3150; Alexopoulou, Lena/0000-0003-4619-697X; Gaestel, Matthias/0000-0002-4944-4652 NR 52 TC 196 Z9 204 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD JUL 16 PY 2001 VL 20 IS 14 BP 3760 EP 3770 DI 10.1093/emboj/20.14.3760 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 457RA UT WOS:000170149500017 PM 11447117 ER PT J AU Sommers, CL Menon, RK Grinberg, A Zhang, WG Samelson, LE Love, PE AF Sommers, CL Menon, RK Grinberg, A Zhang, WG Samelson, LE Love, PE TI Knock-in mutation of the distal four tyrosines of linker for activation of T cells blocks murine T cell development SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE thymocyte; development; signal transduction; adapter; gene targeting ID SIGNALING PATHWAYS; LAT; RECEPTOR; MICE; TCR; CD3-EPSILON; ASSOCIATION; COMPLEXES; SURFACE; PROTEIN AB The integral membrane adapter protein linker for activation of T cells (LAT) performs a critical function in T cell antigen receptor (TCR) signal transduction by coupling the TCR to downstream signaling pathways. After TCR engagement, LAT is tyrosine phosphorylated by ZAP-70 creating docking sites for multiple src homology 2-containing effector proteins. In the Jurkat T cell line, the distal four tyrosines of LAT bind PLC gamma -1, Grb2, and Gads. Mutation of these four tyrosine residues to phenylalanine (4YF) blocked TCR-mediated calcium mobilization, Erk activation, and nuclear factor (NF)-AT activation. In this study, we examined whether these four tyrosine residues were essential for T cell development by generating LAT "knock-in" mutant mice that express the;4YF mutant protein under the control of endogenous LAT regulatory sequences. Significantly, the phenotype of 4YF knock-in mice was identical to LAT(-/-) (null) mice; thymocyte: development was arrested at the immature CB4(-)CD8(-) stage and no mature T cells were present. Knock-in mice expressing wild-type LAT protein, generated by a similar strategy, displayed a normal T cell developmental profile. These results demonstrate that the distal four tyrosine residues of LAT are essential for preTCR signaling and T cell development in vivo. C1 NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA. RP Sommers, CL (reprint author), NCI, Cellular & Mol Biol Lab, NIH, Bldg 37,Rm 1E24,37 Convent Dr, Bethesda, MD 20892 USA. NR 27 TC 66 Z9 68 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUL 16 PY 2001 VL 194 IS 2 BP 135 EP 142 DI 10.1084/jem.194.2.135 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 454KH UT WOS:000169971400003 PM 11457888 ER PT J AU Smeltz, RB Chen, J Hu-Li, J Shevach, EM AF Smeltz, RB Chen, J Hu-Li, J Shevach, EM TI Regulation of interleukin (IL)-18 receptor alpha chain expression on CD4(+) T cells during T helper (Th)1/Th2 differentiation: Critical downregulatory role of IL-4 SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE IFN-gamma-inducing factor; IL-12; IL-1R-related protein; Stat; IFN-gamma ID IFN-GAMMA PRODUCTION; TH2 CELLS; UP-REGULATION; CYTOKINE; INTERFERON; ACTIVATION; BINDING; INDUCE; MICE; NK AB Interleukin (IL)-18 has been well characterized as a costimulatory factor for the induction of IL-12-mediated interferon (IFN)-gamma production by T helper (Th)1 cells, but also can induce IL-4 production and thus facilitate the differentiation of Th2 cells. To determine the mechanisms by which IL-18 might regulate these diametrically distinct immune responses, we have analyzed the role of cytokines in the regulation of IL-18 receptor cc chain (IL-18R alpha) expression. The majority of peripheral CD4(+) T cells constitutively expressed the IL-18R alpha. Upon antigen stimulation in the presence of IL-12, marked enhancement of IL-18R alpha expression was observed. IL-12-mediated upregulation of IL-18R alpha required IFN-gamma. Activated CD4(+) T cells that expressed low levels of IL-18R alpha could produce IFN-gamma when stimulated with the combination of IL-12. and IL-18, while CD4(+) cells which expressed high levels of IL-18R alpha could respond to IL-18 alone. Tn contrast, T cell stimulation in the presence of IL-4 resulted in a downregulation of IL-18Ra expression. Both IL-4(-/-) and signal transducer and activator of transcription (Stat)6(-/-) T cells ex-pressed higher levels of IL-18R alpha after TCR stimulation. Furthermore, activated T cells from Stat6(-/-) mice produced more IFN-gamma in response to IL-18 than wild-type controls. Thus, positive/negative regulation of the IL-18R alpha by the major inductive cytokines (IL-12 and IL-4) determines the capacity of IL-18 to polarize an immune response. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Natl Inst Hlth Res Scholars Program, Howard Hughes Med Inst, Bethesda, MD 20814 USA. RP Shevach, EM (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Rm 11N315, Bethesda, MD 20892 USA. NR 35 TC 75 Z9 78 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUL 16 PY 2001 VL 194 IS 2 BP 143 EP 153 DI 10.1084/jem.194.2.143 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 454KH UT WOS:000169971400004 PM 11457889 ER PT J AU Zhang, YK Apilado, R Coleman, J Ben-Sasson, S Tsang, S Hu-Li, J Paul, WE Huang, H AF Zhang, YK Apilado, R Coleman, J Ben-Sasson, S Tsang, S Hu-Li, J Paul, WE Huang, H TI Interferon gamma stabilizes the T helper cell type 1 phenotype SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE IL-4; IL-12; differentiation; commitment; cell cloning ID RECEPTOR-BETA CHAIN; JAK-3 JANUS KINASE; IFN-GAMMA; TRANSCRIPTION FACTOR; C-MAF; GENE-EXPRESSION; TH2 CELLS; INTERLEUKIN-4; MICE; IL-12 AB T helper cell (Th)1-primed CD4 T cells from wild-type donors make little interleukin (IL)-4 when restimulated under Th2 conditions. However, such restimulation of Th1-primed cells from interferon (IFN)-gamma (-/-) or IFN-gamma receptor (IFN-gammaR)(-/-) mice resulted in substantial production of IL-4 and other Th2 cytokines. Adding IFN-gamma to the priming culture markedly diminished the capacity of Th1-primed IFN-gamma (-/-) cells to express IL-4. Even IFN-gamma -producing cells from IFN-gammaR(-/-) mice could acquire IL-4-producing capacity. Thus, IFN-gamma is not required for the development of IFN-gamma -producing capacity, but it plays a critical role in suppressing the IL-4-producing potential of Th1 cells. C1 Loyola Univ, Stritch Sch Med, Dept Cell Biol Neurobiol & Anat, Maywood, IL 60153 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Hebrew Univ Jerusalem, Sch Med, Lautenberg Ctr Gen & Tumor Immunol, IL-91120 Jerusalem, Israel. RP Huang, H (reprint author), Loyola Univ, Stritch Sch Med, Dept Cell Biol Neurobiol & Anat, Bldg 102,Rm 5657,2160 S 1st Ave, Maywood, IL 60153 USA. FU NIAID NIH HHS [K22 AI01663-02] NR 37 TC 53 Z9 56 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUL 16 PY 2001 VL 194 IS 2 BP 165 EP 172 DI 10.1084/jem.194.2.165 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 454KH UT WOS:000169971400006 PM 11457891 ER PT J AU Collazo, CM Yap, GS Sempowski, GD Lusby, KC Tessarollo, L Woude, GFV Sher, A Taylor, GA AF Collazo, CM Yap, GS Sempowski, GD Lusby, KC Tessarollo, L Woude, GFV Sher, A Taylor, GA TI Inactivation of LRG-47 and IRG-47 reveals a family of interferon gamma-inducible genes with essential, pathogen-specific roles in resistance to infection SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE interferon; GTPase; protozoa; bacteria; virus ID MURINE CYTOMEGALOVIRUS-INFECTION; IFN-GAMMA; GTP-BINDING; TOXOPLASMA-GONDII; EXPRESSED GTPASE; PROTEIN; CELLS; IDENTIFICATION; MICE; CDNA AB The cytokine interferon (IFN)-gamma regulates immune clearance of parasitic, bacterial, and viral infections, however, the underlying mechanisms are poorly understood. Recently, a family of IFN-gamma -induced genes has been identified that encode 48-kD GTP-binding proteins that localize to the endoplasmic reticulum of cells. The prototype of this family, IGTP, has been shown to be required for host defense against acute infections with the protozoan parasite Toxoplasma gondii, but not for normal clearance of the bacterium Lister ia monocytogenes and murine cytomegalovirus (MCMV). To determine whether other members of the gene family also play important roles in immune defense, we generated mice that lacked expression of the genes LRG-47 and IRG-47, and examined their responses to representative pathogens. After infection with T, gondii, LRG-47-deficient mice succumbed uniformly and rapidly during the acute phase of the infection; in contrast, IRG-47-deficient mice displayed only partially decreased resistance that was not manifested until the chronic phase. After infection with L. monocytogenes, LRG-47-deficient mice exhibited a profound loss of resistance, whereas IRG-47-deficient mice exhibited completely normal resistance. In addition, both strains displayed normal clearance of MCMV. Thus, LRG-47 and IRG-47 have vital, but distinct roles in immune defense against protozoan and bacterial infections. C1 Duke Univ, Med Ctr, Dept Med, Div Rheumatol Allergy & Clin Immunol, Durham, NC 27710 USA. NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Brown Univ, Dept Mol Microbiol & Immunol, Div Biol & Med, Providence, RI 02912 USA. Duke Univ, Dept Med, Durham, NC 27710 USA. Duke Univ, Dept Immunol, Div Geriatr, Durham, NC 27710 USA. Duke Univ, Ctr Study Aging & Human Dev, Durham, NC 27710 USA. Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Durham, NC 27705 USA. NCI, Div Basic Sci, Frederick, MD 21702 USA. Van Andel Res Inst, Grand Rapids, MI 49503 USA. RP Taylor, GA (reprint author), Duke Univ, Med Ctr, Dept Med, Div Rheumatol Allergy & Clin Immunol, POB 3003, Durham, NC 27710 USA. FU NIA NIH HHS [AG11268, P60 AG011268] NR 26 TC 213 Z9 224 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUL 16 PY 2001 VL 194 IS 2 BP 181 EP 187 DI 10.1084/jem.194.2.181 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 454KH UT WOS:000169971400008 PM 11457893 ER PT J AU Hanlon, CA DeMattos, CA DeMattos, CC Niezgoda, M Hooper, DC Koprowski, H Notkins, A Rupprecht, CE AF Hanlon, CA DeMattos, CA DeMattos, CC Niezgoda, M Hooper, DC Koprowski, H Notkins, A Rupprecht, CE TI Experimental utility of rabies virus-neutralizing human monoclonal antibodies in post-exposure prophylaxis SO VACCINE LA English DT Article DE rabies; human monoclonal antibodies; lyssaviruses ID POSTEXPOSURE TREATMENT; IMMUNE GLOBULIN; VACCINE; FAILURE; GLYCOPROTEIN; LYSSAVIRUS; INFECTION; AUSTRALIA; THAILAND; BATS AB Rabies immune globulin (RIG) is essential for post-exposure prophylaxis but is expensive and not widely available. Rabies virus-neutralizing human monoclonal antibodies (Mabs) were evaluated in vitro and in a Syrian hamster model as a potential future alternative. Seven Mabs neutralized representative rabies virus variants. However, a European bat lyssavirus was not neutralized by either Mabs or RIG. Moreover. Duvenhage virus was neutralized by RIG, but not by Mabs, and Lagos bat and Mokola viruses were neutralized by one Mab but not by RIG. In hamsters, one Mab resulted in protection that was comparable to human RIG. These results suggest that Mabs may provide a promising alternative to RIG. 2001 Published by Elsevier Science Ltd. C1 Ctr Dis Control & Prevent, Rabies Sect MSG33, Atlanta, GA 30333 USA. Thomas Jefferson Univ, Ctr Neurovirol, Philadelphia, PA 19107 USA. NIDR, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Hanlon, CA (reprint author), Ctr Dis Control & Prevent, Rabies Sect MSG33, 1600 Clifton Rd NE, Atlanta, GA 30333 USA. OI Hooper, Douglas/0000-0002-8578-5104 FU PHS HHS [NIDR-2-95-6R] NR 60 TC 44 Z9 45 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JUL 16 PY 2001 VL 19 IS 28-29 BP 3834 EP 3842 DI 10.1016/S0264-410X(01)00135-9 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 450WE UT WOS:000169767200005 PM 11427255 ER PT J AU Rautaharju, PM Nelson, JC Kronmal, RA Zhang, ZM Robbins, J Gottdiener, JS Furberg, CD Manolio, T Fried, L AF Rautaharju, PM Nelson, JC Kronmal, RA Zhang, ZM Robbins, J Gottdiener, JS Furberg, CD Manolio, T Fried, L TI Usefulness of T-axis deviation as an independent risk indicator for incident cardiac events in older men and women free from coronary heart disease (The Cardiovascular Health Study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ELECTROCARDIOGRAPHIC ABNORMALITIES; ECG AB T-axis shift has been reported to be an indicator of increased mortality risk. We evaluated the association of spatial T-axis deviation with incident coronary heart disease (CHD) events in older men and women h ee from clinically overt CHD. Spatial T-axis deviation was measured from the standard 12-lead electrocardiogram of a subgroup of 4,173 subjects considered free of CHD at baseline in the Cardiovascular Health Study, a prospective cohort study of risk factors for CHD and stroke in older men and women. Cox regression analysis was used to evaluate the associations of altered repolarization with the risk of incident CHD events. The prevalence of marked T-axis deviation (greater than or equal to 45 degrees) was 12%. During the median follow-up of 7.4 years, there were 161 CHD deaths, 743 deaths from all causes, and 679 incident CHD events. Adjusting for demographic and clinical risk factors, including other electrocardiographic abnormalities, there was a nearly twofold excess risk of CHD death, and approximately a 50% excess risk of incident CHD and all-cause mortality for those with marked Taxis deviation. From other electrocardiographic abnormalities, only QT prolongation was associated with excess risk for incident CHD comparable to that for abnormal T-axis deviation. These results suggest that T-axis deviation is an easily quantified marker for subclinical disease and an independent indicator for the risk of incident CHD events in older men and women free of CHD. (C) 2001 by Excerpta Medica, Inc. C1 Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. Univ Washington, CHS Coordinating Ctr, Seattle, WA 98195 USA. Univ Calif Davis, Dept Med, Sacramento, CA 95817 USA. St Francis Hosp, Dept Cardiol, Roslyn, NY USA. NHLBI, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. RP Rautaharju, PM (reprint author), EPICARE Ctr, Suite 505,Piedmont Plaza 2,2000 W 1st St, Winston Salem, NC 27104 USA. FU NHLBI NIH HHS [N01-HC-85086, N01-HC-85079] NR 18 TC 60 Z9 60 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUL 15 PY 2001 VL 88 IS 2 BP 118 EP 123 DI 10.1016/S0002-9149(01)01604-6 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 451XL UT WOS:000169827800004 PM 11448406 ER PT J AU Rao, MR Naficy, AB Savarino, SJ Abu-Elyazeed, R Wierzba, TF Peruski, LF Abdel-Messih, I Frenck, R Clemens, JD AF Rao, MR Naficy, AB Savarino, SJ Abu-Elyazeed, R Wierzba, TF Peruski, LF Abdel-Messih, I Frenck, R Clemens, JD TI Pathogenicity and convalescent excretion of Campylobacter in rural Egyptian children SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Campylobacter; cohort studies; convalescence; diarrhea ID JEJUNI INFECTION; IMMUNOSORBENT-ASSAY; ENTERITIS; DIARRHEA; COHORT; COLI; PERU; ENTEROPATHOGENS; TRANSMISSION; EPIDEMIOLOGY AB Campylobacter infection in developing countries has not received much public health attention because of the observation that infections are not associated with disease beyond the first 6 months of life. A cohort of 397 Egyptian children aged less than 3 years, who were observed twice weekly during 1995-1998, experienced an incidence of 0.6 episodes of Campylobacter diarrhea per child-year. A total of 13% of the Campylobacter diarrheal episodes were characterized by severe dehydration. Age-specific incidence rates (episodes per year) were 0.9 in infants aged less than 6 months, 1.5 in those 6-12 months, and 0.4 and 0.2 in the second and third years of life, respectively. Convalescent excretion of Campylobacter after a diarrheal episode might be enhancing transmission and contributing to this high incidence. Observed risk factors for Campylobacter diarrhea were poor hygienic conditions and the presence of animals in the house. Regardless of the child's age, a first infection by Campylobacter was associated with diarrhea (odds ratio = 2.45; 95% confidence interval: 1.61, 3.71); however, subsequent infections were associated with diarrhea only in children aged less than 6 months. This observation that natural infection did not confer protection during the first 6 months of life poses a challenge to vaccine development. C1 NICHHD, Epidemiol Branch, Bethesda, MD 20892 USA. USN, Med Res Unit 3, Cairo, Egypt. Int Vaccine Inst, Seoul, South Korea. RP Rao, MR (reprint author), NICHHD, Epidemiol Branch, Room 7B03,6100 Execut Blvd, Bethesda, MD 20892 USA. FU NICHD NIH HHS [Y1-HD-0026-01] NR 40 TC 53 Z9 54 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUL 15 PY 2001 VL 154 IS 2 BP 166 EP 173 DI 10.1093/aje/154.2.166 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 453FT UT WOS:000169906400011 PM 11447051 ER PT J AU Freeman, BD Danner, RL Banks, SM Natanson, C AF Freeman, BD Danner, RL Banks, SM Natanson, C TI Safeguarding patients in clinical trials with high mortality rates SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID CROSS-LINKED HEMOGLOBIN; OXIDE SYNTHASE INHIBITOR; CRITICALLY ILL PATIENTS; GROWTH-HORMONE THERAPY; NITRIC-OXIDE; SEPTIC SHOCK; HYDROCHLORIDE; INJURY; ADULTS C1 Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Freeman, BD (reprint author), Washington Univ, Sch Med, Dept Surg, Suite 6104,Box 8109, St Louis, MO 63110 USA. FU NIGMS NIH HHS [GM00691-01] NR 21 TC 51 Z9 52 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JUL 15 PY 2001 VL 164 IS 2 BP 190 EP 192 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 459WW UT WOS:000170275300004 PM 11463585 ER PT J AU Lee, J Jung, ID Nam, SW Clair, T Jeong, EM Hong, SY Han, JW Lee, HW Stracke, ML Lee, HY AF Lee, J Jung, ID Nam, SW Clair, T Jeong, EM Hong, SY Han, JW Lee, HW Stracke, ML Lee, HY TI Enzymatic activation of autotaxin by divalent cations without EF-hand loop region involvement SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE autotaxin (ATX); tumor cell motility; type I phosphodiesterase (PDE); EF-hand loop; mutagenesis ID ALKALINE PHOSPHODIESTERASE-I; MOTILITY-STIMULATING PROTEIN; CALCIUM-BINDING; CDNA CLONING; PYROPHOSPHATASE; SEQUENCE; CELLS; PC-1; DIFFERENTIATION; IDENTIFICATION AB Autotaxin (ATX) is a recently described member of the nucleotide pyrophosphatase/phosphodiesterase (NPP) family of proteins with potent tumor cell motility-stimulating activity. Like other NPPs, ATX is a glycoprotein with peptide sequences homologous to the catalytic site of bovine intestinal alkaline phosphodiesterase (PDE) and the loop region of an EF-hand motif. The PDE active site of ATX has been associated with the motility-stimulating activity of ATX. In this study, we examined the roles of the EF-hand loop region and of divalent cations on the enzymatic activities of ATX. Ca2+ or Mg2+ was each demonstrated to increase the PDE activity of ATX in a concentration-dependent manner, whereas incubation of ATX with chelating agents abolished this activity, indicating a requirement for divalent cations. Non-linear regression analysis of enzyme kinetic data indicated that addition of these divalent cations increases reaction velocity predominantly through an effect on V-max. Three mutant proteins, Ala(740)-, Ala(742)-, and Ala(751)-ATX, in the EF-hand loop region of ATX had enzymatic activity comparable to that of the wild-type protein. A deletion mutation of the entire loop region resulted in slightly reduced PDE activity but normal motility-stimulating activity. However, the PDE activity of this same deletion mutant remained sensitive to augmentation by cations, strongly implying that cations exert their effect by interactions outside of the EF-hand loop region. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Konyang Univ, Coll Med, Nonsan 320711, South Korea. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Sungkyunkwan Univ, Coll Life Sci & Nat Resources, Suwon 440746, South Korea. Sungkyunkwan Univ, Coll Pharm, Suwon 440746, South Korea. RP Lee, HY (reprint author), Konyang Univ, Coll Med, Nonsan 320711, South Korea. EM hoi@kytis.konyang.ac.kr NR 22 TC 21 Z9 22 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JUL 15 PY 2001 VL 62 IS 2 BP 219 EP 224 DI 10.1016/S0006-2952(01)00658-X PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 440EW UT WOS:000169163800010 PM 11389881 ER PT J AU Egan, MF Goldberg, TE Gscheidle, T Weirich, M Rawlings, R Hyde, TM Bigelow, L Weinberger, DR AF Egan, MF Goldberg, TE Gscheidle, T Weirich, M Rawlings, R Hyde, TM Bigelow, L Weinberger, DR TI Relative risk for cognitive impairments in siblings of patients with schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE schizophrenia; genetics; intermediate phenotype; cognition; working memory; verbal memory ID MONOZYGOTIC TWINS DISCORDANT; GENETICALLY COMPLEX TRAITS; CARD SORTING TEST; NONPSYCHOTIC RELATIVES; VULNERABILITY LOCUS; LINKAGE STRATEGIES; HETEROGENEITY; INDICATORS; ATTENTION; DEFICIT AB Background: Patients with schizophrenia have impairments in several domains of cognition, including working memory/executive function, verbal memory, language, oculomotor scanning/psychomotor speed, and general intelligence. Impairments have also been found in unaffected siblings, suggesting they could be heritable. To assess the suitability of cognitive dysfunction for use in genetic studies, we estimated relative risk (lambda) in a large cohort of siblings. Methods: One hundred forty-seven patients with schizophrenia, 193 of their siblings, and 47 control subjects were studied using a neuropsychological test batters,, which included intelligence quotient (IQ), Wide Range Achievement Test, Wisconsin Card Sort, Wechsler Memory Scale (revised), California Verbal List Test, Trails A and B, and Letter and Category Fluency. Relative risk was estimated using a cutoff score of 1 SD below the control mean. Results: As expected, patients performed markedly worse than control subjects on all tests except the Wide Range Achievement Test. Siblings had impaired performance on the Wisconsin Card Sort and Trails B, with trends for reduction (p = .01-.05) on the California Verbal List Test and Letter Fluency. Relative risk to siblings was elevated on the Trails B (lambda = 4.0) and California Verbal List Test (lambda = 2.8). Trends (p = .01-.05) for increased lambda were also seen for Wisconsin Card Sort, Letter Fluency, Wechsler Memory Scale and decline in IQ (lambda = 1.74-2.4). Correlations between tests of different cognitive junctions were weak, indicating they measure relatively independent processes. Conclusion: Unselected siblings of patients with schizophrenia have impairments in several cognitive domains. Relative risk scores were in the moderate range, suggesting a significant genetic component. Impairments on one test only weakly predicted impairments on other tests. Thus, cognitive phenotypes identify distinct, familial traits associated with schizophrenia. Using this dimensional approach to subdividing schizophrenia may reduce the clinical and genetic heterogeneity of schizophrenia and improve the power of genetic studies, (C) 2001 Society of Biological Psychiatry. C1 NIMH, Clin Brain Disorders Branch, Intramural Res Program, Bethesda, MD 20892 USA. NIAAA, NIH, Bethesda, MD USA. RP Egan, MF (reprint author), NIMH, Clin Brain Disorders Branch, Intramural Res Program, Bldg 10,4S 241 Ctr Dr,9000 Rockville Pike,MSC1377, Bethesda, MD 20892 USA. NR 55 TC 203 Z9 211 U1 4 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUL 15 PY 2001 VL 50 IS 2 BP 98 EP 107 DI 10.1016/S0006-3223(01)01133-7 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 459KL UT WOS:000170249500003 PM 11527000 ER PT J AU Khaldoyanidi, S Sikora, L Orlovskaya, I Matrosova, V Kozlov, V Sriramarao, P AF Khaldoyanidi, S Sikora, L Orlovskaya, I Matrosova, V Kozlov, V Sriramarao, P TI Correlation between nicotine-induced inhibition of hematopoiesis and decreased CD44 expression on bone marrow stromal cells SO BLOOD LA English DT Article ID HUMAN GINGIVAL FIBROBLASTS; COLONY-FORMING CELLS; SMOOTH-MUSCLE CELLS; GROWTH-FACTOR; ADHESION MOLECULES; PROGENITOR CELLS; EXTRACELLULAR-MATRIX; CIGARETTE-SMOKE; STEM-CELLS; ENDOTHELIAL-CELLS AB This study demonstrates that in vivo exposure to cigarette smoke (CS) and in vitro treatment of long-term bone marrow cultures (LTBMCs) with nicotine, a major constituent of CS, result in inhibition of hematopoiesis, Nicotine treatment significantly delayed the onset of hematopoietic foci and reduced their size, Furthermore, the number of long-term culture-initiating cells (LTC-ICs) within an adherent layer of LTBMCs was significantly reduced in cultures treated with nicotine. Although the production of nonadherent mature cells and their progenitors in nicotine treated LTBMCs was inhibited, this treatment failed to influence the proliferation of Introduction committed hematopoietic progenitors when added into methylcellulose cultures. Bone marrow stromal cells are an integral component of the hematopoietic microenvironment and play a critical role in the regulation of hematopoietic stem cell proliferation and self-renewal. Exposure to nicotine decreased CD44 surface expression on primary bone marrow-derived fibroblastlike stromal cells and MS-5 stromal cell line, but not on hematopoietic cells. In addition, mainstream CS altered the trafficking of hematopoietic stem/progenitor cells (HSPC) in vivo. Exposure of mice to CS resulted in the inhibition of HSPC homing into bone marrow. Nicotine and cotinine treatment resulted in reduction of CD44 surface expression on lung microvascular endothelial cell line (LEISVO) and bone marrow-derived (STR-12) endothelial cell line. Nicotine treatment increased E-selectin expression on LEISVO cells, but not on STR-12 cells. These findings demonstrate that nicotine can modulate hematopoiesis by affecting the functions of the hematopoiesis-supportive stromal microenvironment, resulting in the inhibition of bone marrow seeding by LTC-ICs and interfering with stem cell homing by targeting microvascular endothelial cells. (C) 2001 by The American Society of Hematology. C1 La Jolla Inst Mol Med, Div Vasc Biol, San Diego, CA 92121 USA. Inst Clin Immunol, Novosibirsk, Russia. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. RP Sriramarao, P (reprint author), La Jolla Inst Mol Med, Div Vasc Biol, 4570 Execut Dr, San Diego, CA 92121 USA. RI Kozlov, Vladimir/K-2634-2014 OI Kozlov, Vladimir/0000-0002-1756-1782 FU NIAID NIH HHS [AI35796] NR 69 TC 28 Z9 28 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 15 PY 2001 VL 98 IS 2 BP 303 EP 312 DI 10.1182/blood.V98.2.303 PG 10 WC Hematology SC Hematology GA 450AY UT WOS:000169720400008 PM 11435297 ER PT J AU O'Laughlin-Bunner, B Radosevic, N Taylor, ML Shivakrupa DeBerry, C Metcalfe, DD Zhou, MJ Lowell, C Linnekin, D AF O'Laughlin-Bunner, B Radosevic, N Taylor, ML Shivakrupa DeBerry, C Metcalfe, DD Zhou, MJ Lowell, C Linnekin, D TI Lyn is required for normal stem cell factor-induced proliferation and chemotaxis of primary hematopoietic cells SO BLOOD LA English DT Article ID SRC FAMILY KINASES; RECEPTOR C-KIT; DEFICIENT MICE; MAST-CELLS; AUTOIMMUNE-DISEASE; NEGATIVE REGULATOR; SIGNALING PATHWAYS; POINT MUTATION; B-CELLS; ACTIVATION AB Stem cell factor (SCF) binds to c-Kit and is an important mediator of survival, growth, and function of hematopoietic progenitor cells and mast cells. Lyn and other Src family members are activated by SCF and associate with phosphorylated tyrosine residues in the c-Kit juxtamembrane region. However, studies using c-Kit mutants incapable of directly recruiting Src family members suggest this kinase family plays a minimal role in c-Kit stimulus-response coupling mechanisms, The objective of this study was to specifically target Lyn and subsequently address its role in SCF-mediated responses of primary hematopoietic progenitor cells and mast cells, To this end, a dominant-inhibitory Lyn mutant and Lyn-deficient mice were used. Transfection of normal murine mast cells with kinase-inactive Lyn impaired SCF-induced growth. Further, SCF-induced proliferation and chemotaxis of Lyn-deficient mast cells were less than for wild-type mast cells. SCF-induced growth of progenitor cells lacking Lyn was also reduced compared with that bf wild-type progenitor cells. Impairment of SCF-mediated responses of Lyn-deficient mast cells and progenitor cells did not result from reductions in surface expression of c-Kit, These studies demonstrate that Lyn is required for normal SCF-mediated responses of primary progenitors and for a differentiated lineage. (C) 2001 by The American Society of Hematology. C1 NCI, Div Basic Sci, Basic Res Lab, Frederick, MD 21702 USA. NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Sch Med, Dept Lab Med, San Francisco, CA 94143 USA. RP Linnekin, D (reprint author), NCI, Div Basic Sci, Basic Res Lab, Bldg 567,Rm 226, Frederick, MD 21702 USA. FU NHLBI NIH HHS [HL54476] NR 38 TC 71 Z9 73 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 15 PY 2001 VL 98 IS 2 BP 343 EP 350 DI 10.1182/blood.V98.2.343 PG 8 WC Hematology SC Hematology GA 450AY UT WOS:000169720400013 PM 11435302 ER PT J AU Yu, XB Lin, CS Costantini, F Noguchi, CT AF Yu, XB Lin, CS Costantini, F Noguchi, CT TI The human erythropoietin receptor gene rescues erythropoiesis and developmental defects in the erythropoietin receptor null mouse SO BLOOD LA English DT Article ID ENDOTHELIAL-CELLS; IN-VIVO; MESSENGER-RNA; BRAIN; TRANSCRIPTION; DIFFERENTIATION; PROGENITORS; EXPRESSION; ACTIVATION; NEURONS AB Erythropoietin and its receptor are required for definitive erythropoiesis and maturation of erythroid progenitor cells. Mice lacking the erythropoietin receptor exhibit severe anemia and die at about embryonic day 13.5. This phenotype can be rescued by the human erythropoietin receptor transgene. Animals expressing only the human erythropoietin receptor survived through adulthood with normal hematologic parameters and appeared to respond appropriately to induced anemic stress. In addition to restoration of erythropoiesis during development, the cardiac defect associated with embryos lacking the erythropoietin receptor was corrected and the increased apoptosis in fetal liver, heart, and brain in the erythropoietin receptor null phenotype was markedly reduced. These studies indicate that no species barrier exists between mouse and human erythropoietin receptor and that the human erythropoietin receptor transgene is able to provide specific expression in hematopoietic and other selected tissues to rescue erythropoiesis and other organ defects observed in the erythropoietin receptor null mouse. (C) 2001 by The American Society of Hematology. C1 Natl Inst Diabet & Digest & Kidney Disorders, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. Columbia Univ, Dept Genet & Dev, New York, NY USA. RP Noguchi, CT (reprint author), Inst Diabet & Digest & Kidney Disorders, NIH, Bethesda, MD 20892 USA. NR 25 TC 53 Z9 58 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 15 PY 2001 VL 98 IS 2 BP 475 EP 477 DI 10.1182/blood.V98.2.475 PG 3 WC Hematology SC Hematology GA 450AY UT WOS:000169720400030 PM 11435319 ER PT J AU Damadzic, R Bigelow, LB Krimer, LS Goldenson, DA Saunders, RC Kleinman, JE Herman, MM AF Damadzic, R Bigelow, LB Krimer, LS Goldenson, DA Saunders, RC Kleinman, JE Herman, MM TI A quantitative immunohistochemical study of astrocytes in the entorhinal cortex in schizophrenia, bipolar disorder and major depression: Absence of significant astrocytosis SO BRAIN RESEARCH BULLETIN LA English DT Article DE mesial temporal cortex; GFAP; mental illness ID TEMPORAL-LOBE; ALZHEIMERS-DISEASE; PROGRESS REPORT; HUMAN-BRAIN; NEUROPATHOLOGY; POSTMORTEM; GLIOSIS; PATHOLOGY; PROTEIN; GFAP AB A number of macroscopic changes have been reported in the temporal lobe in schizophrenia. We have evaluated the density of glial fibrillary acidic protein (GFAP)-positive astrocytes in cortical layers 2 through 6 in the intermediate subarea of entorhinal cortex in two cohorts: the first, 15 cases, made up of schizophrenic (n = 7) and normal nonpsychiatric control subjects (n = 8), and the second, 56 cases, composed of schizophrenic (n = 14), bipolar disorder (n = 13), major depressive (n = 14) and normal control subjects (n 15). No significant difference in density of GFAP-positive astrocytes was detected between the psychiatric diagnostic groups and the normal controls in either of the two cohorts. In both cohorts there was a positive correlation between increasing age and astrocytic density which reached statistical significance in only the larger cohort (r = 0.38, p = 0.004). Our results find no evidence for astrocytosis in the entorhinal cortex in several mental illnesses. Although other studies have reported macroscopic and other structural abnormalities in this region, we have not detected astrocytic proliferation, which is a typical hallmark of atrophy and/or progressive neuronal loss. (C) 2001 Elsevier Science Inc. C1 NIMH, Clin Brain Disorders Branch, Neuropathol Sect, Intramural Res Program,NIH, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Neurobiol Sect, New Haven, CT 06510 USA. RP Herman, MM (reprint author), NIMH, Clin Brain Disorders Branch, Neuropathol Sect, Intramural Res Program,NIH, 36-3A24,36 Convent Dr,MSC 4091, Bethesda, MD 20892 USA. NR 53 TC 44 Z9 45 U1 3 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD JUL 15 PY 2001 VL 55 IS 5 BP 611 EP 618 DI 10.1016/S0361-9230(01)00529-9 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 477CP UT WOS:000171265800006 PM 11576757 ER PT J AU Vawter, MP Barrett, T Cheadle, C Sokolov, BP Wood, WH Donovan, DM Webster, M Freed, WJ Becker, KG AF Vawter, MP Barrett, T Cheadle, C Sokolov, BP Wood, WH Donovan, DM Webster, M Freed, WJ Becker, KG TI Application of cDNA microarrays to examine gene expression differences in schizophrenia SO BRAIN RESEARCH BULLETIN LA English DT Article DE schizophrenia; gene expression; prefrontal cortex; cerebellum; microarray ID RECEPTOR MESSENGER-RNA; 14-3-3 PROTEIN; PREFRONTAL CORTEX; BRAIN; CALMODULIN; ASSIGNMENT; PREMORTEM; ACTIVATOR; SUBUNITS; TYROSINE AB Using cDNA microarrays we have investigated gene expression patterns in brain regions of patients with schizophrenia. A cDNA neuroarray, comprised of genes related to brain function, was used to screen pools of samples from the cerebellum and prefrontal cortex from a matched set of subjects, and middle temporal gyrus, from a separate subject cohort. Samples of cerebellum and prefrontal cortex from neuroleptic naive patients were also included. Genes that passed a 3% reproducibility criterion for differential expression in independent experiments included 21 genes for drug-treated patients and 5 genes for drug-naive patients. Of these 26 genes, 10 genes were increased and 16 were decreased. Many of the differentially expressed genes were related to synaptic signaling and proteolytic functions. A smaller number of these genes were also differentially expressed in the middle temporal gyrus. The five genes that were differentially expressed in two brain regions from separate cohorts are: tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, eta polypeptide; sialyltransferase; proteasome subunit, alpha type 1; ubiquitin carboxyl-terminal esterase LI; and solute carrier family 10, member 1. Identification of patterns of changes in gene expression may lead to a better understanding of the pathophysiology of schizophrenia disorders. (C) 2001 Elsevier Science Inc. C1 NIDA, Sect Plast & Dev, Cellular Neurobiol Res Branch, Baltimore, MD USA. NIA, Gerontol Res Ctr, Transgen & Knockout Facil Sect, Baltimore, MD 21224 USA. NIDA, Mol Neurobiol Branch, Baltimore, MD USA. NIA, DNA Array Unit, Res Resources Branch, Baltimore, MD 21224 USA. Uniformed Serv Univ Hlth Sci, Dept Psychiat, Stanley Lab Brain Res, Bethesda, MD 20814 USA. RP Vawter, MP (reprint author), Univ Calif Irvine, Coll Med, Dept Psychiat & Human Behav, Med Sci D433, Irvine, CA 92697 USA. OI Becker, Kevin/0000-0002-6794-6656 NR 29 TC 185 Z9 192 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD JUL 15 PY 2001 VL 55 IS 5 BP 641 EP 650 DI 10.1016/S0361-9230(01)00522-6 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 477CP UT WOS:000171265800010 PM 11576761 ER PT J AU de Souza-Pinto, NC Eide, L Hogue, BA Thybo, T Stevnsner, T Seeberg, E Klungland, A Bohr, VA AF de Souza-Pinto, NC Eide, L Hogue, BA Thybo, T Stevnsner, T Seeberg, E Klungland, A Bohr, VA TI Repair of 8-oxodeoxyguanosine lesions in mitochondrial DNA depends on the oxoguanine DNA glycosylase (OGG1) gene and 8-oxoguanine accumulates in the mitochondrial DNA of OGG1-defective mice SO CANCER RESEARCH LA English DT Article ID BASE EXCISION-REPAIR; OXIDATIVE DAMAGE; EXTRACTS; PROTEIN; SITES; CELLS AB Mitochondria are not only the major site for generation of reactive oxygen species, but also one of the main targets of oxidative damage. One of the major products of DNA oxidation, 8-oxodeoxyguanosine (8-oxodC), accumulates in mitochondrial DNA (mtDNA) at levels three times higher than in nuclear DNA, The main pathway for the repair of 8-oxodG is the base excision repair pathway initiated by oxoguanine DNA glycosylase (OGG1), We previously demonstrated that mammalian mitochondria from mice efficiently remove 8-oxodG from their genomes and isolated a protein from rat liver mitochondria with 8-oxoguanine (8-oxodG) DNA glycosylase/apurinic DNA lyase activity. In the present study, we demonstrated that the mitochondrial 8-oxodG DNA glycosylase/apurinic DNA lyase activity is the mitochondrial isoform of OGG1, Using mouse liver mitochondria isolated from ogg1(-/-) mice, we showed that the OGG1 gene encodes for the mitochondrial 8-oxodG glycosylase because these extracts have no incision activity toward an oligonucleotide containing a single 8-oxodG DNA base lesion, Consistent with an important role for the OGG1 protein in the removal of 8-oxodC from the mitochondrial genome, we found that mtDNA isolated from liver from OGG1-null mutant animals contained 20-fold more 8-oxodC than mtDNA From wild-type animals. C1 NIA, Gerontol Res Ctr, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. Univ Oslo, Natl Hosp, Dept Mol Biol, N-0027 Oslo, Norway. Aarhus Univ, Danish Ctr Mol Gerontol, DK-8000 Aarhus, Denmark. Tech Univ Denmark, BioCentrum, DK-2800 Lyngby, Denmark. RP Bohr, VA (reprint author), NIA, Gerontol Res Ctr, Lab Mol Gerontol, NIH, Box 1,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Souza-Pinto, Nadja/C-3462-2013 OI Souza-Pinto, Nadja/0000-0003-4206-964X NR 17 TC 174 Z9 176 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 2001 VL 61 IS 14 BP 5378 EP 5381 PG 4 WC Oncology SC Oncology GA 451YN UT WOS:000169830500011 PM 11454679 ER PT J AU Palli, D Russo, A Ottini, L Masala, G Saieva, C Amorosi, A Cama, A D'Amico, C Falchetti, M Palmirotta, R Decarli, A Costantini, RM Fraumeni, JF AF Palli, D Russo, A Ottini, L Masala, G Saieva, C Amorosi, A Cama, A D'Amico, C Falchetti, M Palmirotta, R Decarli, A Costantini, RM Fraumeni, JF TI Red meat, family history, and increased risk of gastric cancer with microsatellite instability SO CANCER RESEARCH LA English DT Article ID REPEATED SEQUENCES REVEAL; MISMATCH REPAIR; COLORECTAL-CANCER; MUTATOR PHENOTYPE; SOMATIC MUTATIONS; COLON-CANCER; DIET; PROMOTER; STOMACH; HMLH1 AB Microsateliite instability (MSI) occurs frequently in sporadic gastric cancer (GC) and may define a distinctive molecular pathway of carcinogenesis. We evaluated the role of dietary risk factors in GC according to MSI status. A large series of 382 GC cases and 561 controls were originally identified in a population-based case-control study carried out in the high-risk area around Florence, Italy; 126 GC patients were typed for MSI status. A MSI+ phenotype was detected in 43 of 126 cases (34.1%), whereas 83 cases were classified as MSI-. A multinomial logistic regression model was used to compare the two subgroups of GC classified according to MSI status in the same analysis, with all of the available population controls. A case-case approach was also used. The risk of MSI+ tumors was positively associated with high consumption of red meat and meat sauce and negatively associated with consumption of white meat. A positive association was also seen with total protein and nitrite intake, whereas no relation was found with micronutrient intake. Risk was especially high among subjects reporting both a positive GC family history and a high consumption of red meat (odds ratio, 25.7; 958 confidence interval, 6.4-102.8), For MSI- tumors, a significant protective effect was associated with frequent consumption of citrus and other fresh fruit, garlic, legumes, vegetables, and olive oil and with high intake of p-carotene and other antioxidants and sugar, whereas positive associations were seen with protein and sodium intake. In summary, a specific dietary pattern emerged for MSI+ gastric tumors, suggesting that factors related to red meat consumption are involved in this pathway, particularly among individuals with a positive family history. In contrast, the risk of MSI- tumors was strongly reduced by the frequent consumption of fresh fruit and vegetables. C1 Ctr Studio & Prevenz Oncol, Epidemiol Unit, I-50135 Florence, Italy. Univ Gabriele DAnnunzio, Dept Oncol & Neurosci, Chieti, Italy. Univ Rome La Sapienza, Dept Expt Med & Pathol, Rome, Italy. Univ Florence, Dept Pathol, Florence, Italy. Univ Brescia, Sez Stat Med & Biometr, Brescia, Italy. NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. RP Palli, D (reprint author), Ctr Studio & Prevenz Oncol, Epidemiol Unit, Via San Salvi 12, I-50135 Florence, Italy. RI Decarli, Adriano/C-3129-2017; palmirotta, raffaele/E-3286-2017; OI Decarli, Adriano/0000-0003-1451-8292; palmirotta, raffaele/0000-0002-9401-7377; saieva, calogero/0000-0002-0117-1608; PALLI, Domenico/0000-0002-5558-2437; Russo, Antonio Giampiero/0000-0002-5681-5861; Masala, Giovanna/0000-0002-5758-9069 NR 40 TC 57 Z9 63 U1 2 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 2001 VL 61 IS 14 BP 5415 EP 5419 PG 5 WC Oncology SC Oncology GA 451YN UT WOS:000169830500017 PM 11454685 ER PT J AU Hanada, K Perry-Lalley, DM Ohnmacht, GA Bettinotti, MP Yang, JC AF Hanada, K Perry-Lalley, DM Ohnmacht, GA Bettinotti, MP Yang, JC TI Identification of fibroblast growth factor-5 as an overexpressed antigen in multiple human adenocarcinomas SO CANCER RESEARCH LA English DT Article ID RENAL-CELL CARCINOMA; TUMOR-INFILTRATING LYMPHOCYTES; CYTOLYTIC T-LYMPHOCYTES; GENE; MELANOMA; CTL; RECOGNITION; EXPRESSION; CANCER; PEPTIDE AB Methodology for identifying tumor-associated antigens recognized by T cells has been successfully used to clone antigens from melanoma cells. Similar efforts for nonmelanoma tumors have had limited success with few antigens identified. To identify potentially relevant tumor-associated antigens expressed in renal cell carcinoma cell lines, a tamer-specific CTL done was established from tumor-infiltrating lymphocytes from a regressing pulmonary lesion, This CTL recognized nonmutated fibroblast growth factor-5 (FGF-5), Quantitative real-time reverse transcription PCR revealed that FGF-5 was overexpressed in the majority of renal cell carcinomas, as well as in some prostate carcinoma and breast carcinoma lines, FGF-5 expression by quantitative real-time reverse transcription PCR in normal tissues was below the recognition threshold for this CTL, As a normal protein with significant overexpression by multiple adenocarcinomas and little normal tissue expression, FGF-5 represents an immunotherapy target with potential utility against a broad array of nonmelanoma cancers. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Yang, JC (reprint author), NCI, Surg Branch, NIH, 9000 Rockville Pike,Bldg 10,Room 2B37, Bethesda, MD 20892 USA. RI Hanada, Ken-ichi/A-4642-2008; Hanada, Ken-ichi/L-2481-2013 OI Hanada, Ken-ichi/0000-0003-2959-1257 NR 42 TC 40 Z9 42 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 2001 VL 61 IS 14 BP 5511 EP 5516 PG 6 WC Oncology SC Oncology GA 451YN UT WOS:000169830500032 PM 11454700 ER PT J AU Reali, E Greiner, JW Corti, A Gould, HJ Bottazzoli, F Paganelli, G Schlom, J Siccardi, AG AF Reali, E Greiner, JW Corti, A Gould, HJ Bottazzoli, F Paganelli, G Schlom, J Siccardi, AG TI IgEs targeted on tumor cells: Therapeutic activity and potential in the design of tumor vaccines SO CANCER RESEARCH LA English DT Article ID COLONY-STIMULATING FACTOR; FC-EPSILON-RI; NECROSIS-FACTOR-ALPHA; LASTING ANTITUMOR IMMUNITY; GAMMA-INTERFERON GENE; DENDRITIC CELLS; ANTIGEN PRESENTATION; IN-VITRO; T-CELLS; CANCER AB Surface-bound IgE play a central role in antiparasite immunity; to exploit IgE-driven immune mechanisms in tumor prevention and control, monoclonal IgEs of irrelevant specificity were loaded through biotin-avidin bridging onto tumor cells, either by systemic administration to tumor-bearing mice or pre-loading of tumor cells before inoculation. Here we show that systemic administration of biotinylated IgEs to mice bearing tumors pre-targeted with biotinylated antibodies and avidin significantly decreased tumor growth rate. In addition, as compared with IgC-loaded control cells, inoculation of suboptimal doses of IgE-loaded tumor cells suppressed tumor formation in a fraction of animals and induced protective host immunity by eliciting tumor-specific T-cell responses, Similarly, tumor vaccination experiments showed that irradiated tumor cells (IgE loaded by biotin-avidin bridging) conferred protective immunity at doses 100-fold lower than the corresponding control cells without IgE, Finally, in vivo depletion of eosinophils or T cells abrogated IgE-driven tumor growth inhibition. These results demonstrate that IgEs targeted on tumor cells not only possess a curative potential but also confer long-term antitumor immunity and that IgE-driven antitumor activity is not restricted to the activation of innate immunity effector mechanisms but also results from eosinophil-dependent priming of a T-cell-mediated adaptive immune response. This suggests a potential role for IgEs in the design of new cell-based tumor vaccines. C1 NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. Ist Sci San Raffaele, I-20132 Milan, Italy. Kings Coll London, Randall Inst, London WC2R 2LS, England. Univ Milan, Ist Europeo Oncol, Milan, Italy. Univ Milan, Dept Biol & Genet, Milan, Italy. RP Reali, E (reprint author), NCI, Tumor Immunol & Biol Lab, NIH, 10 Ctr Dr,Room 8B04, Bethesda, MD 20892 USA. EM realie@mail.nih.gov RI Corti, Angelo/F-7046-2012; Reali, Eva/Q-1161-2016 OI Corti, Angelo/0000-0002-0893-6191; Reali, Eva/0000-0003-1900-1356 NR 49 TC 33 Z9 36 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 2001 VL 61 IS 14 BP 5517 EP 5522 PG 6 WC Oncology SC Oncology GA 451YN UT WOS:000169830500033 PM 11454701 ER PT J AU Nicholson, SA Okby, NT Khan, MA Welsh, JA McMenamin, MG Travis, WD Jett, JR Tazelaar, HD Trastek, V Pairolero, PC Corn, PG Herman, JG Liotta, LA Caporaso, NE Harris, CC AF Nicholson, SA Okby, NT Khan, MA Welsh, JA McMenamin, MG Travis, WD Jett, JR Tazelaar, HD Trastek, V Pairolero, PC Corn, PG Herman, JG Liotta, LA Caporaso, NE Harris, CC TI Alterations of p14(ARF), p53, and p73 genes involved in the E2F-1-mediated apoptotic pathways in non-small cell lung carcinoma SO CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR GENE; NON-HODGKINS-LYMPHOMAS; HUMAN CANCER-CELLS; INK4A/ARF LOCUS; PROTEIN EXPRESSION; P16(INK4A) EXPRESSION; MUTATIONAL ANALYSIS; ISLAND METHYLATION; STABILIZES P53; CYCLE CONTROL AB Overexpression of E2F-1 induces apoptosis by both a p14(ARF)-p53- and a p73-mediated pathway. p14(ARF) is the alternate tumor suppressor product of the INK4a/ARF locus that is inactivated frequently in lung carrinogenesis, Because p14(ARF) stabilizes p53, it has been proposed that the loss of p14(ARF) is functionally equivalent to a p53 mutation. We have tested this hypothesis by examining the genomic status of the unique exon Ip of p14(ARF) in 53 human cell lines and 86 primary non-small cell lung carcinomas and correlated this with previously characterized alterations of p53, Homozygous deletions of p14(ARF) were detected in 12 of 53 (23%) cell lines and 16 of 86 (19%) primary tumors. A single cell line, but no primary tumors, harbored an intragenic mutation. The deletion of p14(ARF) was inversely correlated with the loss of p53 in the majority of cell lines (P = 0.02), but this relationship was not maintained among primary tumors (P = 0.5). E2F-1 can also induce p73 via a p53-independent apoptotic pathway, Although we did not observe inactivation of p73 by either mutation or DNA methylation, haploinsufficiency of p73 correlated positively with either p14(ARF) Or p53 mutation or both (P = 0.01) in primary non-small cell lung carcinomas. These data are consistent with the current model of p14(ARF) and p53 interaction as a complex network rather than a simple linear pathway and indicate a possible role for an E2F-1-mediated failsafe, p53-independent, apoptotic pathway involving p73 in human lung carcinogenesis. C1 NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Orange Pathol Associates, Middleton, NY 10940 USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. Mayo Clin, Rochester, MN 55905 USA. Johns Hopkins Oncol Ctr, Baltimore, MD 21231 USA. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, NIH, Bldg 37,Room 2C05,37 Convent Dr, Bethesda, MD 20892 USA. NR 81 TC 40 Z9 44 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 2001 VL 61 IS 14 BP 5636 EP 5643 PG 8 WC Oncology SC Oncology GA 451YN UT WOS:000169830500050 PM 11454718 ER PT J AU Sereti, I Holland, SM AF Sereti, I Holland, SM TI Disseminated nocardiosis in a patient with X-linked chronic granulomatous disease and human immunodeficiency virus infection SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID SUPEROXIDE PRODUCTION; CLINICAL-FEATURES; AIDS PATIENT; NEUTROPHIL; BRASILIENSIS; ACTIVATION; ABSCESSES AB We report the first case of HIV infection in a patient with underlying X-linked chronic granulomatous disease (CGD) who presented with hepatopulmonary nocardiosis. Despite the coexistence of CGD and HIV, the response to therapy was normal, and no unusual sequelae were noted. The patient's high virus burden was successfully repressed with antiretroviral therapy, suggesting that the nicotinamide adenine dinucleotide phosphate oxidase system is not essential for active viral replication or response to antiretroviral agents. C1 NIAID, Immunopathogenesis Unit, Clin Pathophysiol Sect, Lab Host Def,NIH, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Holland, SM (reprint author), NIAID, Immunopathogenesis Unit, Clin Pathophysiol Sect, Lab Host Def,NIH, 10 Ctr Dr MSC 1886,Bldg 10-11N-103, Bethesda, MD 20892 USA. NR 27 TC 5 Z9 5 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL 15 PY 2001 VL 33 IS 2 BP 235 EP 239 DI 10.1086/321818 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 444FD UT WOS:000169387700014 PM 11418884 ER PT J AU Mocellin, S Ohnmacht, GA Wang, E Marincola, FM AF Mocellin, S Ohnmacht, GA Wang, E Marincola, FM TI Kinetics of cytokine expression in melanoma metastases classifies immune responsiveness SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE cytokine; melanoma; metastasis; immune response; fine-needle aspiration ID GROWTH-FACTOR; HODGKINS-DISEASE; BREAST-CANCER; TUMOR-GROWTH; SERUM LEVELS; INTERLEUKIN-10; CELLS; VACCINE; PROGRESSION; CARCINOMA AB Production of cytokines (CKs) in the tumor micro-environment may modulate tumor-host interactions. However, preclinical models often provide conflicting data and there is no established role for CKs as modulators of the natural or treatment-related behavior of tumors. Serial sampling by fine-needle aspirates (FNAs) of identical metastases from patients affected with metastatic melanoma and undergoing IL-2-based vaccination allowed prospective measurement of IL-10, TGF-beta1, TGF-beta2 and IFN-gamma transcriptional levels assessed by quantitative real-time PCR, Thus, it was possible to prospectively document the expression of markers relevant to a given treatment and follow at the same time the clinical outcome of the lesions left in place. Eight of 27 metastatic lesions completely regressed in response to the treatment and I demonstrated >50% shrinkage, These regressions occurred after the follow-up FNA had been obtained. IL-10 transcript was differentially expressed in pre-treatment FNA of responding lesions (t-test p(2) = 0.002). During treatment, INF-gamma transcript levels significantly increased in regressing compared to non-regressing lesions (t-test P-2 = 0.03), These data suggest that the pre-treatment CK profile of the tumor micro-environment may determine clinical responsiveness to immune therapy. Furthermore, temporal changes in CK expression during treatment might describe the biological characteristics of an effective immune response. Published 2001 Wiley-Liss, Inc. C1 NCI, Dept Transfus Med, Ctr Clin, NIH, Bethesda, MD 20892 USA. NCI, Surg Branch, Ctr Clin, NIH, Bethesda, MD 20892 USA. RP Marincola, FM (reprint author), NCI, Dept Transfus Med, Ctr Clin, NIH, Bldg 10,Room 1C711,10 Ctr Dr MSC 1502, Bethesda, MD 20892 USA. NR 30 TC 54 Z9 57 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 15 PY 2001 VL 93 IS 2 BP 236 EP 242 DI 10.1002/ijc.1328 PG 7 WC Oncology SC Oncology GA 442RR UT WOS:000169299200013 PM 11410872 ER PT J AU Cella, D Davis, K Breitbart, W Curt, G AF Cella, D Davis, K Breitbart, W Curt, G CA Fatigue Coalition TI Cancer-related fatigue: Prevalence of proposed diagnostic criteria in a United States sample of cancer survivors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID FUNCTIONAL ASSESSMENT; HODGKINS-DISEASE; CHEMOTHERAPY; THERAPY; GRANISETRON; ONDANSETRON; PERCEPTIONS; PATIENT; QUALITY; ANEMIA AB Purpose: To evaluate the proposed cancer-related fatigue (CRF) diagnostic criteria in a sample of cancer survivors, More accurate prevalence estimates of CRF may result in improved diagnosis and management of one of the most common symptoms associated with cancer and its treatment. Methods: Three hundred seventy-nine individuals who had been treated with chemotherapy, either alone or in combination with radiation therapy, were surveyed. Patients were asked background questions about their current condition, their medical history, and the frequency of fatigue during their chemotherapy, Additionally, patients who reported experiencing fatigue at least a few days each month during treatment were asked a series of questions about the impact of fatigue on their daily functioning. Results: One hundred forty-one (37%) individuals reported at least 2 weeks of fatigue in the previous month, Of the respondents who had received their last treatment more than 5 years ago, 33% still reported at least a 2-week period of fatigue in the month before the interview. Evaluation of the proposed criteria revealed that 17% of respondents met at least two criteria for CRF. Conclusion: The prevalence of diagnosable CRF in the individuals in this sample, most of whom had completed treatment more than 1 year ago, was 17%-lower than expected based on previous reports that have used less-strict criteria. In a sizable number of people, CRF persists well beyond active treatment and should be a focus of intervention, Although they will require replication in other samples and clinical validation, these formal diagnostic criteria can be a step toward common language and a better understanding of the severity range and persistence of CRF, (C) 2001 by American Society of Clinical Oncology. C1 Northwestern Univ, Evanston, IL USA. Evanston NW Healthcare, Evanston, IL USA. NCI, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Cella, D (reprint author), Ctr Outcomes Res & Educ, 1033 Univ Pl,Ste 100, Evanston, IL 60201 USA. NR 37 TC 282 Z9 286 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2001 VL 19 IS 14 BP 3385 EP 3391 PG 7 WC Oncology SC Oncology GA 452DB UT WOS:000169840900011 PM 11454886 ER PT J AU Li, Q Li, T Wu, JG AF Li, Q Li, T Wu, JG TI Electrical conductivity of water/sodium bis(2-ethylhexyl) sulfosuccinate/n-heptane and water/sodium bis(2-ethylhexyl) phosphate/n-heptane systems: The influences of water content, bis(2-ethylhexyl) phosphoric acid, and temperature SO JOURNAL OF COLLOID AND INTERFACE SCIENCE LA English DT Article DE mixed reverse micelles; conductivity; AOT; NaDEHP; HDEHP ID IN-OIL MICROEMULSIONS; CHARGE FLUCTUATION MODEL; REVERSE MICELLES; AEROSOL OT; N-HEPTANE; INVERTED MICELLES; FT-IR; BEHAVIOR; BENZENE; CRYSTALLITES AB Conductance behaviors of reverse micelles/microemulsions have been investigated by means of electrical conductometry, with emphasis on the influences of water content, bis(2-ethylhexyl) phosphoric acid (HDEHP) content, and temperature. Two systems were prepared and studied, i.e., sodium bis(2-ethylhexyl) sulfosuccinate (AOT) in n-heptane (H2O/AOT/n-heptane) and sodium bis(2-ethylhexyl) phosphate (NaDEHP) in n-heptane (H2O/NaDEHP/n-heptane). The conductance behaviors of AOT + HDEHP and NaDEHP + HDEHP systems are dependent upon water content (W-0, expressed as the molar ratio of solubilized water and surfactant(s)), HDEHP content, and temperature. With an increase of water content, the conductivity-We curves of the AOT + HDEHP system show maximum conductivity and no percolation conductance, different from that of the AOT system. The conductivity of the NaDEHP + HDEHP system varies with the NaDEHP to HDEHP ratio. For the systems with the NaDEHP to HDEHP ratios of 80:20 and 70:30, both maximum conductivity and percolation phenomenon can be observed, while for the system with the NaDEHP to HDEHP ratio of 90: 10, neither maximum conductance nor percolation conductance occurs. With varying temperature, markedly different conductance behaviors were observed in AOT + HDEHP and NaDEHP + HDEHP systems. Percolation conductance occurs in the AOT + HDEHP system and the onset temperature for percolation conductance decreases with increasing water content and/or HDEHP content. In the H2O/(NaDEHP, HDEHP)ln-heptane system, however, the conductivity decreases markedly with increasing temperature until a minimum, followed by a slow recovery of the conductivity. These phenomena could be attributed to the different aggregation states of the surfactants and the different transition mechanisms of charge carriers in respective systems at different water contents, HDEHP contents, and temperatures. (C) 2001 Academic Press. C1 Peking Univ, Coll Chem & Mol Engn, Beijing 100871, Peoples R China. RP Li, Q (reprint author), NIH, Bldg 10,Rm 20D08,10 Ctr Dr, Bethesda, MD 20892 USA. NR 35 TC 38 Z9 40 U1 0 U2 6 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0021-9797 J9 J COLLOID INTERF SCI JI J. Colloid Interface Sci. PD JUL 15 PY 2001 VL 239 IS 2 BP 522 EP 527 DI 10.1006/jcis.2001.7613 PG 6 WC Chemistry, Physical SC Chemistry GA 452AT UT WOS:000169835500028 ER PT J AU Brown, MJ Hallam, JA Liu, Y Yamada, KM Shaw, S AF Brown, MJ Hallam, JA Liu, Y Yamada, KM Shaw, S TI Cutting edge: Integration of human T lymphocyte cytoskeleton by the cytolinker plectin SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERMEDIATE FILAMENT-BINDING; CULTURED-CELLS; LAMIN-B; POLARIZATION; PROTEINS; ASSOCIATION; ADHESION; VIMENTIN; IDENTIFICATION; LOCALIZATION AB Chemokine-induced polarization of lymphocytes involves the rapid collapse of vimentin intermediate filaments (IFs) into an aggregate within the uropod. Little is known about the interactions of lymphocyte vimentin with other cytoskeletal elements. We demonstrate that human peripheral blood T lymphocytes express plectin, an IEF-binding, cytoskeletal crosslinking protein. Plectin associates with a complex of structural proteins including vimentin, actin, fodrin, moesin, and lamin B in resting peripheral blood T lymphocytes. During chemokine-induced polarization, plectin redistributes to the uropod associated with vimentin and fodrin; their spatial distribution indicates that this vimentin-plectin-fodrin complex provides a continuous linkage from the nucleus (lamin B) to the cortical cytoskeleton. Overexpression of the plectin IF-binding domain in the T cell line Jurkat induces the perinuclear aggregation of vimentin IFs. Plectin is therefore likely to serve as an important organizer of the lymphocyte cytoskeleton and may regulate changes of lymphocyte cytoarchitecture during polarization and extravasation. C1 NCI, Human Immunol Sect, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Brown, MJ (reprint author), NCI, Human Immunol Sect, Expt Immunol Branch, NIH, Bldg 10,Rm 4B36,10 Ctr Dr,MSC 1360, Bethesda, MD 20892 USA. OI Yamada, Kenneth/0000-0003-1512-6805 NR 33 TC 33 Z9 34 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 2001 VL 167 IS 2 BP 641 EP 645 PG 5 WC Immunology SC Immunology GA 471VL UT WOS:000170949300006 PM 11441066 ER PT J AU Chung, DH Belyakov, IM Derby, MA Wang, J Boyd, LF Berzofsky, JA Margulies, DH AF Chung, DH Belyakov, IM Derby, MA Wang, J Boyd, LF Berzofsky, JA Margulies, DH TI Competitive inhibition in vivo and skewing of the T cell repertoire of antigen-specific CTL priming by an anti-peptide-MHC monoclonal antibody SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SURFACE-PLASMON RESONANCE; CLASS-I MOLECULES; MULTIPLE-SCLEROSIS; RESTRICTED SPECIFICITY; TOLERANCE INDUCTION; BASIC-PROTEIN; HIV-1 GP160; LONG-TERM; MICE AB We have recently described a mAb, KP15, directed against the MHC-I/peptide molecular complex consisting of H-2D(d) and a decamer peptide corresponding to residues 311-320 of the HIV IIIB envelope glycoprotein gp160. When administered at the time of primary immunization with a vaccinia virus vector encoding gp160, the mAb blocks the subsequent appearance of CDS' CTL with specificity for the immunodominant Ag, P18-I10 presented by H-2D(d). This inhibition is specific for this particular peptide Ag; another H-2D(d)-restricted gp160 encoded epitope from a different HIV strain is not affected, and an H-2L(d)-restricted epitope encoded by the viral vector is also not affected. Using functional assays and specific immunofluorescent staining with multivalent, labeled H-2D(d)/P18I10 complexes (tetramers), we have enumerated the effects of blocking of priming on the subsequent appearance, avidity, and TCR V beta usage of Ag-specific CTL. Ab blocking skews the proportion of high avidity cells emerging from immunization. Surprisingly, V beta7-bearing Ag-specific TCR are predominantly inhibited, while TCR of several other families studied are not affected. The ability of a specific MHC/peptide mAb to inhibit and divert the CD8(+) T cell response holds implications for vaccine design and approaches to modulate the immune response in autoimmunity. C1 Natl Inst Allergy & Infect Dis, Immunol Lab, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Margulies, DH (reprint author), Natl Inst Allergy & Infect Dis, Immunol Lab, NIH, Bldg 10,Rm 11N311,10 Ctr Dr, Bethesda, MD 20892 USA. RI Chung, Doo Hyun/J-2791-2012; Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 NR 63 TC 7 Z9 7 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 2001 VL 167 IS 2 BP 699 EP 707 PG 9 WC Immunology SC Immunology GA 471VL UT WOS:000170949300013 PM 11441073 ER PT J AU Robbins, WA Witt, KL Haseman, JK Dunson, DB Troiani, L Cohen, MS Hamilton, CD Perreault, SD Libbus, B Beyler, SA Raburn, DJ Tedder, ST Shelby, MD Bishop, JB AF Robbins, WA Witt, KL Haseman, JK Dunson, DB Troiani, L Cohen, MS Hamilton, CD Perreault, SD Libbus, B Beyler, SA Raburn, DJ Tedder, ST Shelby, MD Bishop, JB TI Antiretroviral therapy effects on genetic and morphologic end points in lymphocytes and sperm of men with human immunodeficiency virus infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IN-SITU HYBRIDIZATION; CHROMATID EXCHANGE FREQUENCIES; PERIPHERAL-BLOOD LYMPHOCYTES; TYPE-1 SEROPOSITIVE MEN; HUMAN-POPULATION SAMPLE; TANDEM DNA PROBES; 1CEN-1Q12 REGION; HIV-INFECTION; 3'-AZIDO-2',3'-DIDEOXYTHYMIDINE AZT; CHROMOSOMAL ABERRATION AB Many human immunodeficiency virus (HIV)-infected persons receive prolonged treatment with DNA-reactive antiretroviral drugs. A prospective study was conducted of 26 HIV-infected men who provided samples before treatment and at multiple times after beginning treatment, to investigate effects of antiretrovirals on lymphocyte and sperm chromosomes and semen quality. Several antiretroviral regimens, all including a nucleoside component, were used. Lymphocyte metaphase analysis and sperm fluorescence in situ hybridization were used for cytogenetic studies. Semen analyses included conventional parameters (volume, concentration, viability, motility, and morphology). No significant effects on cytogenetic parameters, semen volume, or sperm concentration were detected. However, there were significant improvements in sperm motility for men with study entry CD4 cell counts > 200 cells/mm(3), sperm morphology for men with entry CD4 cell counts less than or equal to 200 cells/mm(3), and the percentage of viable sperm in both groups. These findings suggest that nucleoside-containing antiretrovirals administered via recommended protocols do not induce chromosomal changes in lymphocytes or sperm but may produce improvements in semen quality. C1 NIEHS, Toxicol Lab, Res Triangle Pk, NC 27709 USA. ILS, Informat Sci Div, Res Triangle Pk, NC USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. US EPA, Reprod Toxicol Div, Res Triangle Pk, NC 27711 USA. Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA. Univ N Carolina, Sch Med, Dept Obstet & Gynecol, Chapel Hill, NC USA. Univ N Carolina, Sch Med, Dept Genet Res, Chapel Hill, NC USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA. RP Bishop, JB (reprint author), NIEHS, Toxicol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. FU NIEHS NIH HHS [N01-ES-35356, N01-ES-35357, N01-ES-65401]; PHS HHS [DM RO1, 273-97-C-0058, 273-98-C-0072] NR 53 TC 29 Z9 31 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUL 15 PY 2001 VL 184 IS 2 BP 127 EP 135 DI 10.1086/322002 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 447DM UT WOS:000169554500002 PM 11424008 ER PT J AU Chougnet, C Jankelevich, S Fowke, K Liewehr, D Steinberg, SM Mueller, BU Pizzo, PA Yarchoan, R Shearer, GM AF Chougnet, C Jankelevich, S Fowke, K Liewehr, D Steinberg, SM Mueller, BU Pizzo, PA Yarchoan, R Shearer, GM TI Long-term protease inhibitor-containing therapy results in limited improvement in T cell function but not restoration of interleukin-12 production in pediatric patients with AIDS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNODEFICIENCY-VIRUS INFECTION; ANTIRETROVIRAL THERAPY; HIV DISEASE; CHILDREN; RESPONSES; RECONSTITUTION AB This study investigated whether immune restoration occurred in 26 human immunodeficiency virus (HIV) type 1-infected children treated first with indinavir for 16 weeks and then with combination antiretroviral therapy for >2 years. Compared with baseline, a significant, although modest, decrease in virus loads (maximum median, -0.86 log(10)) and increase in the number of CD4(+) lymphocytes, especially naive cells, were observed at several time points after 2 years. A maximum of 7% of treated children achieved undetectable viremia. There was a marked increase in the proliferative response and skin reactivity to recall antigens. However, responses to an HIV antigen remained depressed, and the production of interleukin-12 remained unchanged and abnormally low. The magnitude of virus suppression did not correlate with these measures of functional immune reconstitution. These findings suggest that long-term nonsuppressive antiretroviral therapy can induce limited improvement in immune function in pediatric AIDS patients and that the effect of suppressive treatments should be investigated. C1 NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. NIH, Div Clin Sci, Biostat & Data Management Sect, Bethesda, MD 20892 USA. RP Shearer, GM (reprint author), NCI, Expt Immunol Branch, Bldg 10,Rm 4B36,10 Ctr Dr,MSC 1906, Bethesda, MD 20892 USA. OI Fowke, Keith/0000-0001-8227-6649 NR 15 TC 15 Z9 15 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUL 15 PY 2001 VL 184 IS 2 BP 201 EP 205 DI 10.1086/322006 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 447DM UT WOS:000169554500013 PM 11424019 ER PT J AU Dumont, RA Lins, U Filoteo, AG Penniston, JT Kachar, B Gillespie, PG AF Dumont, RA Lins, U Filoteo, AG Penniston, JT Kachar, B Gillespie, PG TI Plasma membrane Ca2+-ATPase isoform 2a is the PMCA of hair bundles SO JOURNAL OF NEUROSCIENCE LA English DT Article DE hair cells; stereocilia; cochlea; calcium; calcium pump; isozymes ID CA2+ PUMP; MECHANOELECTRICAL-TRANSDUCTION; CALCIUM-PUMP; INNER-EAR; MONOCLONAL-ANTIBODIES; BULLFROGS SACCULUS; CELL STEREOCILIA; GERBIL COCHLEA; TIP LINKS; ATPASE AB Mechanoelectrical transduction channels of hair cells allow for the entry of appreciable amounts of Ca2+, which regulates adaptation and triggers the mechanical activity of hair bundles. Most Ca2+ that enters transduction channels is extruded by the plasma membrane Ca2+-ATPase (PMCA), a Ca2+ pump that is highly concentrated in hair bundles and may be essential for normal hair cell function. Because PMCA isozymes and splice forms are regulated differentially and have distinct biochemical properties, we determined the identity of hair bundle PMCA in frog and rat hair cells. By screening a bullfrog saccular cDNA library, we identified abundant PMCA1b and PMCA2a clones as well as rare PMCA2b and PMCA2c clones. Using immunocytochemistry and immunoprecipitation experiments, we showed in bullfrog sacculus that PMCA1b is the major isozyme of hair cell and supporting cell basolateral membranes and that PMCA2a is the only PMCA present in hair bundles. This complete segregation of PMCA1 and PMCA2 isozymes holds for rat auditory and vestibular hair cells; PMCA2a is the only PMCA isoform in hair bundles of outer hair cells and vestibular hair cells and is the predominant PMCA of hair bundles of inner hair cells. Our data suggest that hair cells control plasma membrane Ca2+-pumping activity by targeting specific PMCA isozymes to distinct subcellular locations. Because PMCA2a is the only Ca2+ pump present at appreciable levels in hair bundles, the biochemical properties of this pump must account fully for the physiological features of transmembrane Ca2+ pumping in bundles. C1 Oregon Hlth Sci Univ, Oregon Hearing Res Ctr, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Vollum Inst, Portland, OR 97201 USA. Johns Hopkins Univ, Dept Physiol, Baltimore, MD 21205 USA. Natl Inst Deafness & Other Commun Disorders, Sect Struct Cell Biol, NIH, Bethesda, MD 20892 USA. Mayo Clin & Mayo Fdn, Dept Biochem & Mol Biol, Rochester, MN 55905 USA. RP Gillespie, PG (reprint author), Oregon Hlth Sci Univ, Oregon Hearing Res Ctr, L335A,3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. RI Lins, Ulysses/N-7282-2015; OI Lins, Ulysses/0000-0002-1786-1144; Barr-Gillespie, Peter/0000-0002-9787-5860 FU NIDCD NIH HHS [DC00979, DC02368, DC04200, DC04571]; NIGMS NIH HHS [GM28835] NR 53 TC 137 Z9 145 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL 15 PY 2001 VL 21 IS 14 BP 5066 EP 5078 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 449NR UT WOS:000169692800016 PM 11438582 ER PT J AU Miyakawa, T Yamada, M Duttaroy, A Wess, J AF Miyakawa, T Yamada, M Duttaroy, A Wess, J TI Hyperactivity and intact hippocampus-dependent learning in mice lacking the M-1 muscarinic acetylcholine receptor SO JOURNAL OF NEUROSCIENCE LA English DT Article DE acetylcholine; muscarinic receptor; M-1 receptor; hyperactivity; learning; gene targeting; knock-out; behavioral phenotyping ID SUBTYPE-SPECIFIC ANTIBODIES; MORRIS WATER TASK; ANIMAL-MODEL; CHOLINERGIC INNERVATION; ALZHEIMERS-DISEASE; LOCOMOTOR-ACTIVITY; MAZE PERFORMANCE; MESSENGER-RNAS; KNOCKOUT MICE; BASAL GANGLIA AB Members of the muscarinic acetylcholine receptor family are thought to play key roles in the regulation of a large number of important functions of the CNS. However, the precise roles of the individual muscarinic receptor subtypes in modulating these processes are not well understood at present, primarily because of the lack of ligands with sufficient receptor subtype selectivity. To investigate the behavioral significance of the M-1 muscarinic receptor (M1R), which is abundantly expressed in the forebrain, we subjected M-1 receptor-deficient mice (M1R-/- mice) to a battery of behavioral tests. M1R-/- mice showed no significant impairments in neurological reflexes, motor coordination, pain sensitivity, and prepulse inhibition. Strikingly, however, M1R-/- mice consistently exhibited a pronounced increase in locomotor activity in various tests, including open field, elevated plus maze, and light/dark transition tests. Moreover, M1R-/- mice showed reduced immobilization in the Porsolt forced swim lest and reduced levels of freezing after inescapable footshocks, suggesting that M1R-/- mice are hyperactive under stressful conditions as well. An increased number of social contacts was observed in a social interaction test. Surprisingly, M1R-/- mice displayed no significant cognitive impairments in the Morris water maze and in contextual fear conditioning. M1R-/- mice showed slight performance deficits in auditory-cued fear conditioning and in an eight-arm radial maze, most likely because of the hyperactivity phenotype displayed by the M1R-/- mice. Our results indicate that M-1 muscarinic receptors play an important role in the regulation of locomotor activity but appear to be less critical for cognitive processes, as generally assumed. C1 Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37205 USA. Vanderbilt Univ, Med Ctr, Ctr Mol Neurosci, Nashville, TN 37205 USA. NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA. RP MIT, Ctr Learning & Memory, Bldg E17-342,77 Massachusetts Ave, Cambridge, MA 02139 USA. EM miyakawa@mit.edu RI Miyakawa, Tsuyoshi/A-7741-2008 OI Miyakawa, Tsuyoshi/0000-0003-0137-8200 NR 65 TC 237 Z9 242 U1 0 U2 7 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL 15 PY 2001 VL 21 IS 14 BP 5239 EP 5250 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 449NR UT WOS:000169692800033 PM 11438599 ER PT J AU Chen, Y Rathbone, MP Hertz, L AF Chen, Y Rathbone, MP Hertz, L TI Guanosine-induced increase in free cytosolic calcium concentration in mouse astrocytes in primary cultures: Does it act on an A3 adenosine receptor? SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE adenosine; astrocytes; A3 receptor; free cytosolic calcium concentration; guanosine; inosine ID MAST-CELL DEGRANULATION; PRIMARY RAT ASTROCYTES; CYCLIC-AMP; A(3) RECEPTORS; HIPPOCAMPAL ASTROCYTES; INTRACELLULAR CALCIUM; GLIAL-CELLS; ACTIVATION; ACCUMULATION; BRAIN AB Purinergic receptors play an important role in the regulation of free cytosolic calcium concentration ([Ca2+](i)) in astrocytes, in the present study, 10 muM adenosine caused an increase in [Ca2+](i) in 85% of the cultures studied, i,e., primary cultures of mouse astrocytes, differentiated by culturing in the presence of dibutyryl cyclic AMP. Antagonist sensitivity and rapid desensitization suggested that it did so by acting on A3 receptors, Another biologically important purine, guanosine, also caused an increase in astrocytic [Ca2+](i) (at concentrations of 0.1-100 muM). Although this response did not show the same rapid desensitization as the response to adenosine, it may also have been exerted on an A3 receptor, It supports this idea that inosine also caused an increase in [Ca2+](i), because inosine is known to activate A3 receptors in mast cells and structurally is even more closely related to guanosine than is adenosine, (C) 2001 Wiley-Liss, Inc. C1 Univ Saskatchewan, Dept Pharmacol, Saskatoon, SK, Canada. McMaster Univ, Dept Med, Hamilton, ON, Canada. RP Chen, Y (reprint author), NICHD, LCMN, NIH, Bldg 49,Room 5A78,49 Convent Dr,MSC 4495, Bethesda, MD 20892 USA. NR 47 TC 7 Z9 9 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD JUL 15 PY 2001 VL 65 IS 2 BP 184 EP 189 DI 10.1002/jnr.1141 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 449XX UT WOS:000169713400010 PM 11438987 ER PT J AU Cutler, RG Mattson, MP AF Cutler, RG Mattson, MP TI Sphingomyelin and ceramide as regulators of development and lifespan SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE aging; cancer; cardiovascular disease; oxidative stress; antioxidant; evolution; sphingolipids; tumor necrosis factor ID TUMOR-NECROSIS-FACTOR; PROTECTS HIPPOCAMPAL-NEURONS; NIEMANN-PICK-DISEASE; NF-KAPPA-B; DIETARY RESTRICTION; INDUCED APOPTOSIS; FACTOR-ALPHA; ACID SPHINGOMYELINASE; SERINE PALMITOYLTRANSFERASE; NEUTRAL SPHINGOMYELINASE AB Sphingomyelin (SM) is a prominent phospholipid component of cell membranes that has evolved diverse functions in cells beyond its role in membrane structural organization. Cleavage of SM by acid or neutral sphingomyelinase results in the liberation of ceramide, an intracellular messenger that regulates the activities of an array of kinases, phosphatases and transcription factors. Signals that activate sphingomyelinases range from growth factors and cytokines. to neurotransmitters, hormones and reactive oxygen species. Studies of experimental cell culture and animal models, and of patients with inherited defects in sphingomyelin metabolism suggest important roles for SM-ceramide signaling in the regulation of cell proliferation, differentiation and survival. At low concentrations SM and ceramide can stimulate cell proliferation and survival, whereas higher levels can induce cell dysfunction or death. Analyses of development and aging suggest a major role for SM metabolism in regulating development rate and lifespan. Several factors that alter the metabolism of sphingolipids, including oxidative and metabolic stress, also increase risk and progression of age-related diseases. In addition, recent findings have linked alterations in SM metabolism to the pathogenesis of several age-related diseases including cancers and neurodegenerative disorders. The emerging data suggest the possibility that dietary and pharmacological manipulations of SM metabolism might prove effective in extending lifespan and treating various age-related diseases. (C) 2001 Published by Elsevier Science Ireland Ltd. C1 NIA, Neurosci Lab, Ctr Gerontol Res, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Ctr Gerontol Res, 4F02,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 79 TC 89 Z9 93 U1 1 U2 5 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD JUL 15 PY 2001 VL 122 IS 9 BP 895 EP 908 DI 10.1016/S0047-6374(01)00246-9 PG 14 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 444HA UT WOS:000169393000003 PM 11348657 ER PT J AU Pedersen, WA Wan, RQ Mattson, MP AF Pedersen, WA Wan, RQ Mattson, MP TI Impact of aging on stress-responsive neuroendocrine systems SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Review DE hypothalamic-pituitary-adrenal axis; Alzheimer's disease; neuroendocrine stress responses ID CORTICOTROPIN-RELEASING-FACTOR; PITUITARY-ADRENAL AXIS; RECEPTOR-BINDING CAPACITY; FOCAL CEREBRAL-ISCHEMIA; AGE-RELATED ALTERATIONS; MESSENGER-RNA LEVELS; BROWN-NORWAY RAT; ALZHEIMERS-DISEASE; DIETARY RESTRICTION; FACTOR CRF AB Throughout life organisms are challenged with various physiological and psychological stressors, and the ability to handle these stressors can have profound effects on the overall health of the organism. In mammals, the effects of stressors on the aging process and age-related diseases are complex, involving the nervous, endocrine and immune systems. Certain types of mild stress, such as caloric restriction, may extend lifespan and reduce the risk of diseases, whereas some types of psychosocial stress are clearly detrimental. We now have a basic understanding of the brain regions involved in stress responses, their neuroanatomical connections with neuroendocrine pathways, and the neuropeptides and hor mones involved in controlling responses of different organ systems to stress. Not surprisingly, brain regions involved in learning and memory and emotion play prominent roles in stress responses, and monoaminergic and glutamatergic synapses play particularly important roles in transducing stressful sensory inputs into neuroendocrine responses. Among the neuropeptides involved in stress responses. corticotropin-releasing hormone appears to be a pivotal regulator of fear and anxiety responses. This neuropeptide is responsible for activation of the hypothalamic-pituitary-adrenal (HPA) axis, which is critical for mobilizing energy reserves and immune responses, and improper regulation of the HPA axis mediates many of the adverse effects of chronic physical and psychosocial stress. C1 NIA, Neurosci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Pedersen, WA (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 99 TC 60 Z9 63 U1 1 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD JUL 15 PY 2001 VL 122 IS 9 BP 963 EP 983 DI 10.1016/S0047-6374(01)00250-0 PG 21 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 444HA UT WOS:000169393000007 PM 11348661 ER PT J AU Schaffer, AA Aravind, L Madden, TL Shavirin, S Spouge, JL Wolf, YI Koonin, EV Altschul, SF AF Schaffer, AA Aravind, L Madden, TL Shavirin, S Spouge, JL Wolf, YI Koonin, EV Altschul, SF TI Improving the accuracy of PSI-BLAST protein database searches with composition-based statistics and other refinements SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ACID SUBSTITUTION MATRICES; AFFINE GAP COSTS; SEQUENCE ALIGNMENT; PROFILE SEARCHES; LOCAL SEQUENCE; INFORMATION; WEIGHTS; SIMILARITIES; ALGORITHM; DOMAIN AB PSI-BLAST is an iterative program to search a database for proteins with distant similarity to a query sequence. We investigated over a dozen modifications to the methods used in PSI-BLAST, with the goal of improving accuracy in finding true positive matches. To evaluate performance we used a set of 103 queries for which the true positives in yeast had been annotated by human experts, and a popular measure of retrieval accuracy (ROC) that can be normalized to take on values between 0 (worst) and 1 (best). The modifications we consider novel improve the ROC score from 0.758 +/- 0.005 to 0.895 +/- 0.003. This does not include the benefits from four modifications we included in the 'baseline' version, even though they were not implemented in PSI-BLAST version 2.0. The improvement in accuracy was confirmed on a small second test set. This test involved analyzing three protein families with curated lists of true positives from the non-redundant protein database. The modification that accounts for the majority of the improvement is the use, for each database sequence, of a position-specific scoring system tuned to that sequence's amino acid composition. The use of composition-based statistics is particularly beneficial for large-scale automated applications of PSI-BLAST. C1 NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Schaffer, AA (reprint author), NIH, Natl Ctr Biotechnol Informat, 8600 Rockville Pike, Bethesda, MD 20894 USA. RI Schaffer, Alejandro/F-2902-2012 NR 60 TC 817 Z9 851 U1 3 U2 28 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL 15 PY 2001 VL 29 IS 14 BP 2994 EP 3005 DI 10.1093/nar/29.14.2994 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 456WG UT WOS:000170105300009 PM 11452024 ER PT J AU Longnecker, MP Klebanoff, MA Zhou, HB Brock, JW AF Longnecker, MP Klebanoff, MA Zhou, HB Brock, JW TI Association between maternal serum concentration of the DDT metabolite DDE and preterm and small-for-gestational-age babies at birth SO LANCET LA English DT Article ID POLYCHLORINATED-BIPHENYLS PCBS; HUMAN-MILK; ORGANOCHLORINE PESTICIDES; RESIDUE LEVELS; PREMATURE; P,P'-DDE; DELIVERY; MALARIA; BLOOD; WOMEN AB Background DDT (1,1,1-trichloro-2.2-bis(p-chlorophenyl) ethane) is highly effective against most malaria-transmitting mosquitoes and is being widely used in malaria-endemic areas. The metabolite, DDE (1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene), has been linked to preterm birth in small studies, but these findings are inconclusive. Our aim was to investigate the association between DDE exposure and preterm birth. Methods Our study was based on the US Collaborative Perinatal Project (CPP). From this study we selected a subset of more than 44 000 eligible children born between 1959 and 1966 and measured the DDE concentration in their mothers' serum samples stored during pregnancy. Complete data were available for 2380 children, of whom 361 were born preterm and 221 were small-for-gestational age. Findings The median maternal DDE concentration was 25 mug/L (range 3-178)-several fold higher than current US concentrations. The adjusted odds ratios (OR) of preterm birth increased steadily with increasing concentrations of serum DDE (ORs=1, 1.5, 1.6, 2.5, 3.1; trend p<0.0001). Adjusted odds of small-for-gestational-age also increased, but less consistently (ORs=1, 1.9, 1.7, 1.6, 2.6; trend p=0.04). After excluding preterm births, the association of DDE with small-for-gestational-age remained. Interpretation The findings strongly suggest that DDT use increases preterm births, which is a major contributor to infant mortality. If this association is causal, it should be included in any assessment of the costs and benefits of vector control with DDT. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. NICHHD, Div Epidemiol Stat & Prevent Res, Rockville, MD USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. RP Longnecker, MP (reprint author), NIEHS, Epidemiol Branch, POB 12233 MD A3-05, Res Triangle Pk, NC 27709 USA. OI Longnecker, Matthew/0000-0001-6073-5322 NR 38 TC 262 Z9 270 U1 7 U2 25 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JUL 14 PY 2001 VL 358 IS 9276 BP 110 EP 114 DI 10.1016/S0140-6736(01)05329-6 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 452BR UT WOS:000169837700011 PM 11463412 ER PT J AU Hohenstein, AC Roche, PA AF Hohenstein, AC Roche, PA TI SNAP-29 is a promiscuous syntaxin-binding SNARE SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE SNARE; SNAP-29; SNAP-23; protein transport ID INSULIN-INDUCED TRANSLOCATION; TRANSPORT VESICLES; MEMBRANE-FUSION; CELL-SURFACE; COMPLEX; EXOCYTOSIS; FAMILY; HOMOLOG; GLUT4 AB SNARE proteins are key regulators of membrane fusion and are proposed to dictate the specificity with which particular vesicles fuse with particular target organelles. On intracellular organelles that serve as targets for transport vesicles, organelle-specific syntaxins form heterodimers with either SNAP-23 or its recently described homolog SNAP-29. We have performed a variety of in vitro and in vivo binding assays in an attempt to determine whether SNAP-23 and SNAP-29 differ in their ability to form binary SNARE complexes with different intracellular syntaxins. While SNAP-23 preferentially binds to plasma membrane-localized syntaxins, SNAP-29 binds Ito both plasma membrane and intracellular syntaxins equally well. Furthermore, binding to SNAP-29 augments the ability of syntaxin to bind to vesicle-associated SNAREs and the presence of vesicle SNAREs dramatically increases SNAP-29 binding to syntaxin. These data suggest that SNAP-23 preferentially regulates plasma membrane-vesicle fusion events while SNAP-29 plays a role in the maintenance of various intracellular protein trafficking pathways. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Roche, PA (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Room 4B36, Bethesda, MD 20892 USA. NR 23 TC 39 Z9 39 U1 0 U2 5 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 13 PY 2001 VL 285 IS 2 BP 167 EP 171 DI 10.1006/bbrc.2001.5141 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 455HF UT WOS:000170020900002 PM 11444821 ER PT J AU Kastanos, EK Zajac-Kaye, M Dennis, PA Allegra, CJ AF Kastanos, EK Zajac-Kaye, M Dennis, PA Allegra, CJ TI Downregulation of p21/WAF1 expression by thymidylate synthase SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE thymidylate synthase induction; p21 downregulation; p53 ID COLON-CANCER-CELLS; IN-VIVO; RIBONUCLEOPROTEIN COMPLEX; P53; RNA; PROTEIN; GAMMA; IDENTIFICATION; 5-FLUOROURACIL; TRANSLATION AB We developed a cell system where expression of thymidylate synthase (TS), an enzyme essential for DNA synthesis, can be modulated by a Zn2+-inducible promoter in MCF-7 cells, We found that overexpression of TS resulted in downregulation of p21 protein and mRNA levels. Statistical analysis demonstrated a significant downregulation of p21, but not a statistically significant decrease in p53 protein levels following TS induction. Since p21 is known to be transcriptionally activated by p53, these results suggest that TS downregulation of p21 may be occurring through a p53 independent mechanism in this in vitro cell system. In addition, cell cycle analysis demonstrated that down regulation of p21 by TS resulted in a decreased G(1)/S ratio in MCF-7 cells. C1 NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, 31 Ctr Dr MSC 2440,Bldg 31,Room 3A-44, Bethesda, MD 20892 USA. EM allegrac@exchange.nih.gov NR 25 TC 13 Z9 14 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 13 PY 2001 VL 285 IS 2 BP 195 EP 200 DI 10.1006/bbrc.2001.5145 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 455HF UT WOS:000170020900006 PM 11444825 ER PT J AU Allers, T Lichten, M AF Allers, T Lichten, M TI Differential timing and control of noncrossover and crossover recombination during meiosis SO CELL LA English DT Article ID MEIOTIC GENE CONVERSION; DOUBLE-STRAND BREAKS; YEAST SACCHAROMYCES-CEREVISIAE; MISMATCH REPAIR; INITIATION SITE; CROSSING-OVER; HOLLIDAY JUNCTIONS; PACHYTENE ARREST; HETERODUPLEX DNA; BRANCH MIGRATION AB Unitary models of meiotic recombination postulate that a central intermediate containing Holliday junctions is resolved to generate either noncrossover or crossover recombinants, both of which contain heteroduplex DNA. Contrary to this expectation, we find that during meiosis in Saccharomyces cerevisiae, noncrossover heteroduplex products are formed at the same time as Holliday junction intermediates. Crossovers appear later, when these intermediates are resolved. Furthermore, noncrossover and crossover recombination are regulated differently. ndt80 mutants arrest in meiosis with unresolved Holliday junction intermediates and very few crossovers, while noncrossover heteroduplex products are formed at normal levels and with normal timing. These results suggest that crossovers are formed by resolution of Holliday junction intermediates, while most noncrossover recombinants arise by a different, earlier pathway. C1 NCI, Biochem Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Lichten, M (reprint author), NCI, Biochem Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RI Allers, Thorsten/G-5503-2010; Lichten, Michael/C-5795-2013 OI Allers, Thorsten/0000-0002-7308-3332; Lichten, Michael/0000-0001-9707-2956 NR 58 TC 402 Z9 411 U1 2 U2 26 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JUL 13 PY 2001 VL 106 IS 1 BP 47 EP 57 DI 10.1016/S0092-8674(01)00416-0 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 452QM UT WOS:000169870300008 PM 11461701 ER PT J AU Aprelikova, O Pace, AJ Fang, B Koller, BH Liu, ET AF Aprelikova, O Pace, AJ Fang, B Koller, BH Liu, ET TI BRCA1 is a selective co-activator of 14-3-3 sigma gene transcription in mouse embryonic stem cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-DAMAGE RESPONSE; EXPRESSION; APOPTOSIS; REPAIR; PHOSPHORYLATION; ASSOCIATION; FREQUENCY; PROTEIN; LEADS; P53 AB BRCA1 gene is a tumor suppressor for breast and ovarian cancers with the putative role in DNA repair and transcription. To characterize the role of BRCA1 in transcriptional regulation, we analyzed gene expression profiles of mouse embryonic stem cells deficient in BRCA1 using microarray technology. We found that loss of BRCA1 correlated with decreased expression of several groups of genes including stress response genes, cytoskeleton genes, and genes involved in protein synthesis and degradation. Previous study showed that BRCA1 is a transcriptional co-activator of p53 protein; however the majority of p53 target genes remained at the same expression levels in BRCA1 knockout cells as in the wild type cells, The only p53 target gene downregulated with the loss of BRCA1 was 14-3-3 sigma, a major G(2)/M checkpoint control gene. Similar to cells with decreased 14-3-3 sigma activity, BRCA1-deficient cells were unable to sustain G(2)/M growth arrest after exposure to ionizing radiation. We find that BRCA1 induction of 14-3-3 sigma requires the presence of wild type p53 and can be regulated by a minimal p53 response element. C1 NCI, Div Clin Sci, Sect Mol Signaling & Oncogenesis, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Curriculum Genet & Mol Biol, Chapel Hill, NC 27599 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. RP Liu, ET (reprint author), ATC Bldg,Rm 121,8717 Grovemont Cr, Gaithersburg, MD 20878 USA. RI Liu, Edison/C-4141-2008 FU NCI NIH HHS [CA82423] NR 30 TC 84 Z9 87 U1 1 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 13 PY 2001 VL 276 IS 28 BP 25647 EP 25650 DI 10.1074/jbc.C100265200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 451VP UT WOS:000169823300003 PM 11384963 ER PT J AU West, KL Ito, Y Birger, Y Postnikov, Y Shirakawa, H Bustin, M AF West, KL Ito, Y Birger, Y Postnikov, Y Shirakawa, H Bustin, M TI HMGN3a and HMGN3b, two protein isoforms with a tissue-specific expression pattern, expand the cellular repertoire of nucleosome-binding proteins SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MOBILITY-GROUP PROTEINS; GROUP CHROMOSOMAL-PROTEINS; HUMAN CDNA SEQUENCE; MULTIGENE FAMILY; FUNCTIONAL GENE; HISTONE H1; NF-Y; CHROMATIN; HMG-14; TRANSCRIPTION AB HMGN1 (HMG-14) and HMGN2 (HMG-17) are nuclear proteins that bind specifically to nucleosomes reduce the compactness of the chromatin fiber, and enhance transcription from chromatin templates. Here we report that many vertebrates contain an additional type of HMGN protein named HMGN3 (Trip 7), The human HMGN3 gene is located on chromosome 6 and spans 32 kilobase pairs, which is nearly 10-fold longer than the closely related HMGN2 gene. However, the intron/exon boundaries of the HMGN3 gene are identical to those of HMGN1 and HMGN2. Unique within the HMGN family, the HMGN3 transcript undergoes alternative splicing and generates two different variants, HMGN3a and HMGN3b. The shorter variant, HMGN3b, arises from an additional splice site that truncates exon V and causes a frameshift. The resulting HMGN3b protein lacks the majority of the C-terminal chromatin-unfolding domain. Both splice variants are found in many vertebrates from frogs to man and are expressed in many tissues. The pattern of tissue-specific expression differs considerably from those of HMGN1 and HMGN2 at both the mRNA and the protein level. Our results expand the multiplicity of the HMGN protein family and raise the possibility that these nucleosome-binding proteins function as co-activators in tissue-specific gene expression. C1 NCI, Div Basic Sci, Prot Sect,Lab Metab, NIH, Bethesda, MD 20892 USA. RP West, KL (reprint author), NCI, Div Basic Sci, Prot Sect,Lab Metab, NIH, Bldg 37,Rm 3C12, Bethesda, MD 20892 USA. RI Shirakawa, Hitoshi/D-1406-2009; Bustin, Michael/G-6155-2015 NR 55 TC 31 Z9 36 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 13 PY 2001 VL 276 IS 28 BP 25959 EP 25969 DI 10.1074/jbc.M101692200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 451VP UT WOS:000169823300044 PM 11356838 ER PT J AU Millman, JS Qi, HY Vulcu, F Bernstein, HD Andrews, DW AF Millman, JS Qi, HY Vulcu, F Bernstein, HD Andrews, DW TI FtsY binds to the Escherichia coli inner membrane via interactions with phosphatidylethanolamine and membrane proteins SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNAL-RECOGNITION PARTICLE; SEQUENCE RECOGNITION; ACIDIC PHOSPHOLIPIDS; TARGETING PATHWAYS; NONBILAYER LIPIDS; PLASMA-MEMBRANE; ALPHA-SUBUNIT; BETA-SUBUNIT; NG DOMAIN; RECEPTOR AB Targeting of many polytopic proteins to the inner membrane of prokaryotes occurs via an essential signal recognition particle-like pathway. FtsY, the Escherichia coli homolog of the eukaryotic signal recognition particle receptor alpha -subunit, binds to membranes via its amino-terminal AN domain. We demonstrate that FtsY assembles on membranes via interactions with phosphatidylethanolamine and with a trypsin-sensitive component. Both interactions are mediated by the AN domain of FtsY, In the absence of phosphatidylethanolamine, the trypsin-sensitive component is sufficient for binding and function of FtsY in the targeting of membrane proteins. We propose a two-step mechanism for the assembly of FtsY on the membrane similar to that of SecA on the E, coli inner membrane. C1 McMaster Univ, Dept Biochem, Hamilton, ON L8N 3Z5, Canada. NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. RP Andrews, DW (reprint author), McMaster Univ, Dept Biochem, 1200 Main St W, Hamilton, ON L8N 3Z5, Canada. OI Millman, Jonathan/0000-0002-1766-2348 NR 40 TC 44 Z9 45 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 13 PY 2001 VL 276 IS 28 BP 25982 EP 25989 DI 10.1074/jbc.M011331200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 451VP UT WOS:000169823300047 PM 11353766 ER PT J AU Kim, SJ Rahbar, R Hegde, RS AF Kim, SJ Rahbar, R Hegde, RS TI Combinatorial control of prion protein biogenesis by the signal sequence and transmembrane domain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ENDOPLASMIC-RETICULUM MEMBRANE; TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES; HUMAN P-GLYCOPROTEIN; CHARGED RESIDUES; HYDROPHOBIC DOMAIN; TERMINAL DOMAIN; ANCHOR PROTEINS; STOP-TRANSFER; ER MEMBRANE; ORIENTATION AB The prion protein (PrP) is synthesized in three topologic forms at the endoplasmic reticulum, (PrP)-Pr-sec is fully translocated into the endoplasmic reticulum lumen, whereas (NPrP)-Pr-tm and (PrP)-Pr-Ctm are single-spanning membrane proteins of opposite orientation. Increased generation of (PrP)-Pr-Ctm in either transgenic mice or humans is associated with the development of neurodegenerative disease, To study the mechanisms by which PrP can achieve three topologic outcomes, we analyzed the translocation of proteins containing mutations introduced into either the N-terminal signal sequence or potential transmembrane domain (TMD) of PrP, Although mutations in either domain were found to affect PrP topogenesis, they did so in qualitatively different ways. In addition to its traditional role in mediating protein targeting, the signal was found to play a surprising role in determining orientation of the PrP N terminus. By contrast, the TMD was found to influence membrane integration. Analysis of various signal and TMD double mutants demonstrated that the topologic consequence of TMD action was directly dependent on the previous, signal-mediated step. Together, these results reveal that PrP topogenesis is controlled at two discrete steps during its translocation and provide a framework for understanding how these steps act coordinately to determine the final topology achieved by PrP. C1 NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. RP Hegde, RS (reprint author), NCI, Cellular Oncol Lab, NIH, Bldg 36,Rm 1D32,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 48 TC 74 Z9 80 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 13 PY 2001 VL 276 IS 28 BP 26132 EP 26140 DI 10.1074/jbc.M101638200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 451VP UT WOS:000169823300067 PM 11359769 ER PT J AU Sachdev, P Jiang, YX Li, WQ Miki, T Maruta, H Nur-e-Kamal, MSA Wang, LH AF Sachdev, P Jiang, YX Li, WQ Miki, T Maruta, H Nur-e-Kamal, MSA Wang, LH TI Differential requirement for Rho family GTPases in an oncogenic insulin-like growth factor-I receptor-induced cell transformation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATED PROTEIN-KINASES; FOCAL ADHESION KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; V-SRC; CYTOSKELETAL REORGANIZATION; GUANOSINE TRIPHOSPHATASES; PHOSPHOINOSITIDE 3-KINASE; TYROSINE PHOSPHORYLATION; RAS TRANSFORMATION; CYCLE PROGRESSION AB Insulin-like growth factor I receptor (IGFR) plays an important role in cell growth and transformation. We dissected the downstream signaling pathways of an oncogenic variant of IGFR, Gag-IGFR, called NM1, Loss of function mutants of NM1, Phe-1136 and dS2, that retain kinase activity but are attenuated in their transforming ability were used to identify signaling pathways that are important for transformation of NIH 3T3 cells. MAPK, phospholipase C gamma, and Stat3 were activated to the same extent by NM1 and its two mutants, suggesting that activation of these pathways, individually or in combination, was not sufficient for NM1-induced cell transformation. The mutant dS2 has decreased IRS-1 phosphorylation levels and IRS-l-associated phosphatidylinositol 3 ' -kinase activity, suggesting that this impairment may be in part responsible for the defectiveness of dS2, We show that Rho family members, RhoA, Rad, and Cdc42 are activated by NM1, and this activation, particularly RhoA and Cdc42, is attenuated in both mutants of NM1, Dominant negative mutants of Rho, Rac, and Cdc42 inhibited NM1-induced cell transformation, as measured by focus and colony forming ability. Dominant negative Rho most potently inhibited the focus forming activity, whereas Cdc42 was most effective in inhibiting the colony forming ability of NM1-expressing cells. Conversely, constitutively activated (ca) Rho is more effective than ca Rac or ca Cdc42 in rescuing the focus forming ability of the mutants. By contrast, ca Cdc42 is most effective in rescuing the colony forming ability of both mutants. C1 CUNY Mt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USA. Brockton W Roxbury Vet Affairs Med Ctr, Dept Med, Bronx, NY 10468 USA. Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Washington, DC 20007 USA. NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Ludwig Inst Canc Res, Melbourne, Vic 3050, Australia. Univ Med & Dent New Jersey, RW Johnson Med Sch, Dept Pharmacol, Piscataway, NJ 08854 USA. RP Wang, LH (reprint author), CUNY Mt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USA. FU NCI NIH HHS [CA55054] NR 69 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 13 PY 2001 VL 276 IS 28 BP 26461 EP 26471 DI 10.1074/jbc.M010995200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 451VP UT WOS:000169823300108 PM 11346642 ER PT J AU Reffey, SB Wurthner, JU Parks, WT Roberts, AB Duckett, CS AF Reffey, SB Wurthner, JU Parks, WT Roberts, AB Duckett, CS TI X-linked inhibitor of apoptosis protein functions as a cofactor in transforming growth factor-beta signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; NECROSIS-FACTOR RECEPTOR; PROGRAMMED CELL-DEATH; TGF-BETA; CYTOCHROME-C; TRANSCRIPTIONAL REGULATION; BACULOVIRUS IAP; SMAD4 COOPERATE; GENE-EXPRESSION; KINASE RECEPTOR AB X-linked inhibitor of apoptosis protein (XIAP) is a potent suppressor of apoptotic cell death, which functions by directly inhibiting caspases, the principal effecters of apoptosis. Here we report that XIAP can also function as a cofactor in the regulation of gene expression by transforming growth factor-beta (TGF-beta), XIAP, but not the related proteins c-IAP1 or c-IAP2, associated with several members of the type I class of the TGF-beta receptor superfamily and potentiated TGF-beta -induced signaling, Although XIAP-mediated activation of c-Jun N-terminal kinase and nuclear factor kappaB was found to require the TGF-beta signaling intermediate Smad4, the ability of XIAP to suppress apoptosis was found to be Smad4-independent, These data implicate a role for XIAP in TGF-beta -mediated signaling that is distinct from its anti-apoptotic functions. C1 NCI, Metab Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Lab Cell Regulat & Carcinogenesis, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Duckett, CS (reprint author), NCI, Metab Branch, Canc Res Ctr, NIH, 10 Ctr Dr,Room 6B-05, Bethesda, MD 20892 USA. NR 70 TC 108 Z9 110 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 13 PY 2001 VL 276 IS 28 BP 26542 EP 26549 DI 10.1074/jbc.M100331200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 451VP UT WOS:000169823300118 ER PT J AU Chipuk, JE Bhat, M Hsing, AY Ma, JJ Danielpour, D AF Chipuk, JE Bhat, M Hsing, AY Ma, JJ Danielpour, D TI Bcl-xL, blocks transforming growth factor-beta 1-induced apoptosis by inhibiting cytochrome c release and not by directly antagonizing Apaf-1-dependent caspase activation in prostate epithelial cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA SIGNAL-TRANSDUCTION; RAT VENTRAL PROSTATE; HUMAN HEPATOMA-CELLS; TGF-BETA; IMMUNOHISTOCHEMICAL ANALYSIS; ANIMAL DEVELOPMENT; CANCER CELLS; BCL-X(L); DEATH; EXPRESSION AB The mechanism by which transforming growth factor-pi (TGF-beta1) induces apoptosis of prostate epithelial cells was studied in the NRP-154 rat prostate epithelial cell line. TGF-beta1 down-regulates expression of Bcl-xL and poly(ADP-ribosyl)polymerase (PARP), promotes cytochrome c release, up-regulates expression of latent caspase-3, and activates caspases 3 and 9, We tested the role of Bcl-xL in this cascade by stably overexpressing Bcl-xL to prevent loss by TGF-beta1, Clones overexpressing Bcl-xL are resistant to TGF-beta1 with respect to induction of apoptosis, cytochrome c release, activation of caspases 9 and 3, and cleavage of PARP; yet they remain sensitive to TGF-beta1 by cell cycle arrest, induction of both fibronectin and latent caspase-3 expression, and loss of PARP expression, We show that Bcl-xL associates with Apaf-1 in NRP-154 cells; but this association does not inhibit the activation of caspases 9 and 3 by cytochrome c, Together, our data suggest that TGF-beta1 induces apoptosis through loss of Bcl-xL, leading to cytochrome c release and the subsequent activation of caspases 9 and 3, Moreover, our data demonstrate that the antiapoptotic effect of Bcl-xL occurs by inhibition of mitochondrial cytochrome c release and not through antagonizing Apaf-1-dependent processing of caspases 9 and 3. C1 Case Western Reserve Univ, Ireland Canc Ctr, Dept Pharmacol, Res Labs,Univ Hosp Cleveland, Cleveland, OH 44106 USA. Case Western Reserve Univ, Ireland Canc Ctr, Dept Physiol & Biophys, Res Labs,Univ Hosp Cleveland, Cleveland, OH 44106 USA. NCI, Lab Cell Regualt & Carcinogensis, NIH, Bethesda, MD 20892 USA. RP Danielpour, D (reprint author), Case Western Reserve Univ, Ireland Canc Ctr, Dept Pharmacol, Res Labs, Samuel Gerber Bldg,Suite 200,Lab 3,11001 Cedar Rd, Cleveland, OH 44106 USA. OI Chipuk, Jerry Edward/0000-0002-1337-842X FU NCI NIH HHS [1R01-CA30369-01, P30CA43703] NR 89 TC 74 Z9 78 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 13 PY 2001 VL 276 IS 28 BP 26614 EP 26621 DI 10.1074/jbc.M100913200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 451VP UT WOS:000169823300126 PM 11320089 ER PT J AU Vashee, S Simancek, P Challberg, MD Kelly, TJ AF Vashee, S Simancek, P Challberg, MD Kelly, TJ TI Assembly of the human origin recognition complex SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-REPLICATION; FISSION YEAST; S-PHASE; SCHIZOSACCHAROMYCES-POMBE; CHROMOSOME-REPLICATION; DROSOPHILA HOMOLOG; ORC1 HOMOLOG; IDENTIFICATION; PROTEINS; XENOPUS AB The six-subunit origin recognition complex (ORC) was originally identified in the yeast Saccharomyces cerevisiae, Yeast ORC binds specifically to origins of replication and serves as a platform for the assembly of additional initiation factors, such as Cdc6 and the Mcm proteins. Human homologues of all six ORC subunits have been identified by sequence similarity to their yeast counterparts, but little is known about the biochemical characteristics of human ORC (HsORC), We have extracted HsORC from HeLa cell chromatin and probed its subunit composition using specific antibodies. The endogenous HsORC, identified in these experiments, contained homologues of Orc1-Orc5 but lacked a putative homologue of Orc6, By expressing HsORC subunits in insect cells using the baculovirus system, we were able to identify a complex containing all six subunits, To explore the subunit-subunit interactions that are required for the assembly of HsORC, we carried out extensive co-immunoprecipitation experiments with recombinant ORC subunits expressed in different combinations. These studies revealed the following binary interactions: HsOrc2-HsOrc3, HsOrc2-HsOrc4, HsOrc3-HsOrc4, HsOrc2-HsOrc6, and HsOrc3-HsOrc6. HsOrc5 did not form stable binary complexes with any other HsORC subunit but interacted with sub-complexes containing any two of subunits HsOrc2, HsOrc3, or HsOrc4, Complex formation by HsOrc1 required the presence of HsOrc2, HsOrc3, HsOrc4, and HsOrc5 subunits, These results suggest that the subunits HsOrc2, HsOrc3, and HsOrc4 form a core upon which the ordered assembly of HsOrc5 and HsOrc1 takes place. The characterization of HsORC should facilitate the identification of human origins of DNA replication. C1 Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Kelly, TJ (reprint author), Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, 725 N Wolfe St, Baltimore, MD 21205 USA. FU NCI NIH HHS [CA40414]; NIGMS NIH HHS [GM19675] NR 45 TC 107 Z9 109 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 13 PY 2001 VL 276 IS 28 BP 26666 EP 26673 DI 10.1074/jbc.M102493200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 451VP UT WOS:000169823300132 PM 11323433 ER PT J AU Dupont, J Fernandez, AM Glackin, CA Helman, L LeRoith, D AF Dupont, J Fernandez, AM Glackin, CA Helman, L LeRoith, D TI Insulin-like growth factor 1 (IGF-1)-induced Twist expression is involved in the anti-apoptotic effects of the IGF-1 receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FACTOR-I RECEPTOR; TYROSINE KINASE-ACTIVITY; BHLH PROTEIN TWIST; SIGNAL TRANSDUCTION; PHOSPHATIDYLINOSITOL 3'-KINASE; INHIBITS APOPTOSIS; CELL-DEATH; ANNEXIN-V; ACTIVATION; DIFFERENTIATION AB In this study we investigated the molecular mechanisms whereby insulin-like growth factor 1 (IGF-1) induced Twist gene expression and the role of Twist in the anti-apoptotic actions of the IGF-1 receptor. In NIH-3T3 fibroblasts overexpressing the human IGF-1 receptor (NWTb3), treatment with IGF-1 (10(-8) M) for 1 and 4 h increased the level of Twist mRNA as well as protein by 3-fold. In contrast, insulin at physiological concentrations did not stimulate Twist expression in NIH-3T3 fibroblasts overexpressing the human insulin receptor. The IGF-1 effect was specific for the IGF-1 receptor since, in cells overexpressing a dominant negative IGF-1 receptor, IGF-1 failed to increase Twist expression. Preincubation with the ERK1/2 inhibitor U0126 or expression of a dominant negative MEK-1 abolished the effect of IGF-1 on Twist mRNA expression in NWTb3 cells, suggesting that Twist induction by IGF-1 occurs via the mitogen-activated protein kinase signaling pathway. In vivo, IGF-1 injection increased the mRNA level of Twist in mouse skeletal muscle, the major site of Twist expression. Finally, using an antisense strategy, we demonstrated that a reduction of 40% in Twist expression decreased significantly the ability of IGF-1 to rescue NWTb3 cells from etoposide-induced apoptosis, Taken together, these results define Twist as an important factor involved in the anti-apoptotic actions of the IGF-1 receptor. C1 NIDDK, Clin Endocrinol Branch, Sect Mol & Cell Physiol, NIH, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. Beckman Res Inst, Dept Mol Med, Duarte, CA 91010 USA. RP LeRoith, D (reprint author), NIDDK, Clin Endocrinol Branch, Sect Mol & Cell Physiol, NIH, Rm 8D12,Bldg 10, Bethesda, MD 20892 USA. NR 56 TC 77 Z9 82 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 13 PY 2001 VL 276 IS 28 BP 26699 EP 26707 DI 10.1074/jbc.M102664200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 451VP UT WOS:000169823300137 PM 11323435 ER PT J AU Degenhardt, A Schwarz, M Winterhalter, P Ito, Y AF Degenhardt, A Schwarz, M Winterhalter, P Ito, Y TI Evaluation of different tubing geometries for high-speed counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE counter-current chromatography; column geometry; partition efficiency; efficiency; instrumentation; anthocyanins ID ROTATING COIL; FLOW-RATE; SEPARATION AB Different tubing geometries were evaluated for use in high-speed counter-current chromatography. Standard round tubing was compared to rectangular and twisted rectangular tubing. The number of theoretical plates for a standard anthocyanin mixture from black currant was determined for each experiment. The results of twisted rectangular tubing were superior to a standard setup. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Tech Univ Braunschweig, Inst Food Technol, DE-38106 Braunschweig, Germany. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Winterhalter, P (reprint author), Tech Univ Braunschweig, Inst Food Technol, Schleinitzstr 20, DE-38106 Braunschweig, Germany. NR 9 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD JUL 13 PY 2001 VL 922 IS 1-2 BP 355 EP 358 DI 10.1016/S0021-9673(01)00908-6 PG 4 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 454LY UT WOS:000169975100035 PM 11486882 ER PT J AU Shinomiya, K Kabasawa, Y Toida, T Imanari, T Ito, Y AF Shinomiya, K Kabasawa, Y Toida, T Imanari, T Ito, Y TI Separation of chondroitin sulfate and hyaluronic acid fragments by centrifugal precipitation chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE centrifugal precipitation chromatography; chondroitin sulfate; hyaluronic acid; glycosaminoglycans; carbohydrates ID AMMONIUM-SULFATE AB Centrifugal precipitation chromatography (CPC) was applied for the first time to the separation of fragments of chondroitin sulfate (ChS) and hyaluronic acid (HA). The separation was performed using a gradient elution system between ethanol and water since solubility of these biopolymers highly depends on the concentration of ethanol in aqueous solution. ChS and HA were each eluted into several peaks through a flow-through UV detector at 275 nm, despite they have almost no absorbance at this wavelength in an aqueous solution. The separation was also confirmed by redissolving the dried fraction in water and measuring the absorbance at 210 nm. These results suggest that the CPC system can detect small precipitates of these biopolymers by light scattering at 275 nm. The separated fragments of biopolymers are not easily characterized because no suitable analytical method is available for identification of these compounds. However, the overall results demonstrate that CPC may be a useful separation of biopolymers such as glycosaminoglycans which quantitatively produce precipitates in an organic solvent mixture. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Nihon Univ, Coll Pharm, Funabashi, Chiba 2748555, Japan. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. Chiba Univ, Fac Pharmaceut Sci, Inage Ku, Chiba 2638522, Japan. RP Shinomiya, K (reprint author), Nihon Univ, Coll Pharm, Div Analyt Chem, 7-1 Narashinodai 7 Chome, Funabashi, Chiba 274, Japan. NR 9 TC 7 Z9 7 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD JUL 13 PY 2001 VL 922 IS 1-2 BP 365 EP 369 DI 10.1016/S0021-9673(01)00959-1 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 454LY UT WOS:000169975100037 PM 11486884 ER PT J AU Herbert, B Kim, IH Kirk, KL AF Herbert, B Kim, IH Kirk, KL TI Synthesis of 2-fluoro- and 6-fluoro-(2S,3R)-(3,4-dihydroxyphenyl) serine as potential in vivo precursors of fluorinated norepinephrines SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID SULFUR EXTRUSION; CONVERSION; THIOCARBONYL; THIOAMIDES; ANALOGS AB The title compounds were prepared by the aldol condensation of 3,4-dibenzyloxy-2-fluorobenzaldehyde and 4,5-dibenzyloxy-2-fluorobenzaldehyde with the oxazolidinone 2, a chiral glycine equivalent. Removal of the chiral auxiliary and blocking groups produced the target amino acids 2-fluoro- and 6-fluoro-(2S,3R)-(3,4-dihydroxyphenyl)serine (1b and 1c) in > 98% ee. C1 NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Kirk, KL (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NR 19 TC 18 Z9 18 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD JUL 13 PY 2001 VL 66 IS 14 BP 4892 EP 4897 DI 10.1021/jo010327y PG 6 WC Chemistry, Organic SC Chemistry GA 451DH UT WOS:000169785500025 PM 11442422 ER PT J AU da Costa, APC Ma, XM Ingram, CD Lightman, SL Aguilera, G AF da Costa, APC Ma, XM Ingram, CD Lightman, SL Aguilera, G TI Hypothalamic and amygdaloid corticotropin-releasing hormone (CRH) and CRH receptor-1 mRNA expression in the stress-hyporesponsive late pregnant and early lactating rat SO MOLECULAR BRAIN RESEARCH LA English DT Article DE hypothalamic-pituitary-adrenal axis; medial preoptic area; central nucleus amygdala; medial nucleus amygdala; hypothalamic paraventricular nucleus ID MESSENGER-RNA EXPRESSION; MEDIAL PREOPTIC AREA; PITUITARY-ADRENAL AXIS; CENTRAL NERVOUS-SYSTEM; EARLY GENE-EXPRESSION; PARAVENTRICULAR NUCLEUS; MATERNAL-BEHAVIOR; C-FOS; DIFFERENTIAL REGULATION; GLUTAMATE-DECARBOXYLASE AB This study investigated the expression of corticotropin releasing hormone (CRH) and its receptor CRHR-1, and arginine vasopressin (AVP) mRNAs during the stress hyporesponsive periods of late pregnancy and lactation (day-3) and in virgin stress-responsive females. In situ hybridization histochemistry showed that basal CRH mRNA in the paraventricular nucleus (PVN) decreased in pregnant and increased in lactating rats (compared with virgin controls), whereas it increased after restraint stress only in virgin rats. Basal PVN CRHR-1 mRNA increased markedly in all groups but reached lower levels in pregnant rats. Basal AVP mRNA in the parvocellular PVN was higher in lactating rats, and in contrast to CRH mRNA, it increased after stress in all groups. In medial preoptic area (MPOA) CRH mRNA levels were higher in lactating females compared with virgin and pregnant rats, and unexpectedly they decreased markedly after stress only in virgin rats. CRH mRNA levels in the central and medial nuclei of the amygdala were higher in lactating rats than in virgin or pregnant ones, and stress had no effect in either group. These data suggest that these stress hyporesponsive periods: (1)do not depend on basal CRH mRNA expression in the PVN; (2) appear to have intact stress-activated afferent pathways to the PVN, as shown by preservation of CRHR-1 and AVP responses to stress, but the information may be differently processed; (3) are associated with an alteration in a CRH mediated pathway from the MPOA. (C) 2001 Published by Elsevier Science B.V. C1 NICHD, Sect Endocrine Physiol, NIH, Bethesda, MD 20892 USA. Univ Bristol, Bristol Royal Infirm, Univ Res Ctr Neuroendocrinol, Bristol BS2 8HW, Avon, England. RP da Costa, APC (reprint author), Babraham Inst, Dept Neurobiol, Cognit & Dev Neurosci Lab, Cambridge CB2 4AT, England. RI Ingram, Colin/C-1661-2009; chen, xuanlan/H-4158-2011 OI Ingram, Colin/0000-0001-6434-3350; NR 61 TC 53 Z9 55 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 JUL 13 PY 2001 VL 91 IS 1-2 BP 119 EP 130 DI 10.1016/S0169-328X(01)00137-1 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 455ZA UT WOS:000170056600013 PM 11457499 ER PT J AU Jayanthi, S Lewis, BD Cadet, JL AF Jayanthi, S Lewis, BD Cadet, JL TI Fas-induced apoptosis of glioma cells is associated with down-regulation of the hSCO1 protein, a subunit of complex IV SO MOLECULAR BRAIN RESEARCH LA English DT Article DE neuroglioma; anti-Fas antibody; apoptosis; hSCO1 gene; cytochrome-c oxidase; differential display ID CYTOCHROME-C-OXIDASE; MITOCHONDRIAL ELECTRON-TRANSPORT; TUMOR-NECROSIS-FACTOR; YEAST SCO1 PROTEIN; MEDIATED APOPTOSIS; OXIDATIVE STRESS; DEATH DOMAIN; ACTIVATION; CHAIN; FADD AB ApoI/Fas belongs to the tumor necrosis factor receptor (TNFR) superfamily and mediates cell death in various cell types. Earlier studies from this laboratory have shown that Fas-mediated cell death of glioma cells occur, in part, through the production of reactive oxygen species (ROS). To further dissect the molecular mechanisms that are involved in Fas-induced cell death, we compared gene expression between Fas-treated and saline-treated human neuroglioma H4 cells by using the technique of mRNA differential display. This approach led to the identification of hSCO1, a component of the inner mitochondrial membrane, which is required for the correct assembly, and catalytic function of cytochrome-c oxidase, as a Fas down-regulated gene. The decrease in hSCO1 mRNA expression was time-dependent, becoming most prominent after 4 h of Fas-treatment. Morphological changes observed by confocal microscopy revealed that after 3 h of Fas-treatment, the cells undergo membrane blebbing and early formation of apoptotic bodies. These observations are discussed in terms of their support for an important role of mitochondrial events in Fas-induced apoptosis. (C) 2001 Elsevier Science B.V. All rights reserved. C1 NIDA, IRP, Mol Neuropsychiat Sect, NIH, Baltimore, MD 21224 USA. RP Cadet, JL (reprint author), NIDA, IRP, Mol Neuropsychiat Sect, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 45 TC 5 Z9 5 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 JUL 13 PY 2001 VL 91 IS 1-2 BP 131 EP 136 DI 10.1016/S0169-328X(01)00138-3 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 455ZA UT WOS:000170056600014 ER PT J AU Imam, SZ Itzhak, Y Cadet, JL Islam, F Slikker, W Ali, SF AF Imam, SZ Itzhak, Y Cadet, JL Islam, F Slikker, W Ali, SF TI Methamphetamine-induced alteration in striatal p53 and bcl-2 expressions in mice SO MOLECULAR BRAIN RESEARCH LA English DT Article DE methamphetamine; gene expression; peroxynitrite; transgenic mouse ID DNA-DAMAGING AGENTS; DOPAMINERGIC NEUROTOXICITY; TRANSGENIC MICE; IN-VITRO; INDUCTION; PROTECTS; ARREST; VIVO AB Methamphetamine (METH)-induced alterations in the expression of p53 and bcl-2 protein were studied in the striatum of wild type, neuronal nitric oxide synthase knockout (nNOS -/-) and copper zinc superoxide dismutase overexpressed (SOD-Tg) mice. METH treatment up-regulated p53 and down-regulated bcl-2 expression in the striatum of wild type mice. No significant alterations were observed in the expression of these proteins in the nNOS -/- or SOD-Tg mice. These data suggest that METH might cause its neurotoxic effects via the production of free radicals and secondary perturbations in the expression of genes known to be involved in apoptosis and cell death machinery. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. Univ Miami, Sch Med, Dept Psychiat & Behav Sci, Miami, FL USA. Natl Inst Drug Abuse, Mol Neuropsychiat Sect, Intramural Res Program, Baltimore, MD USA. Hamdard Univ, Dept Med Elementol & Toxicol, Neurotoxicol Lab, New Delhi, India. RP Ali, SF (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, 3900 NCTR Rd,HFT-132, Jefferson, AR 72079 USA. NR 24 TC 13 Z9 13 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 JUL 13 PY 2001 VL 91 IS 1-2 BP 174 EP 178 DI 10.1016/S0169-328X(01)00139-5 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 455ZA UT WOS:000170056600021 ER PT J AU Schwartzberg, PL AF Schwartzberg, PL TI Immunology - Tampering with the immune system SO SCIENCE LA English DT Editorial Material ID RECEPTOR TYROSINE KINASE; FAMILY C1 NHGRI, NIH, Bethesda, MD 20892 USA. RP Schwartzberg, PL (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. NR 8 TC 5 Z9 5 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUL 13 PY 2001 VL 293 IS 5528 BP 228 EP 229 DI 10.1126/science.1063291 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 452TK UT WOS:000169875200036 PM 11452106 ER PT J AU Germain, RN AF Germain, RN TI The art of the probable: System control in the adaptive immune system SO SCIENCE LA English DT Review ID CD4(+) T-CELLS; IN-VIVO; LYMPHOCYTE-RESPONSES; DENDRITIC CELLS; GENE-EXPRESSION; SELF-TOLERANCE; MEMORY CELLS; ANTIGEN; CYTOKINES; SIGNAL AB The immune system provides very effective hose defense against infectious agents. Although many details are known about the cells and molecules involved, a broader "systems engineering" view of this complex system is just beginning to emerge. Here the argument is put forward that stochastic events, potent amplification mechanisms, feedback controls, and heterogeneity arising from spatially dispersed cell interactions give rise to many of the gross properties of the immune system. A better appreciation of these underlying features will not only add to our basic understanding of how immunity develops or goes awry, but also illuminate new directions far manipulating the system in prophylactic and therapeutic settings. C1 NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Germain, RN (reprint author), NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bldg 10,Room 11N311,10 Ctr Dr MSC-1892, Bethesda, MD 20892 USA. NR 59 TC 122 Z9 124 U1 2 U2 11 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUL 13 PY 2001 VL 293 IS 5528 BP 240 EP 245 DI 10.1126/science.1062946 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 452TK UT WOS:000169875200042 PM 11452112 ER PT J AU Dupuis, S Dargemont, C Fieschi, C Thomassin, N Rosenzweig, S Harris, J Holland, SM Schreiber, RD Casanova, JL AF Dupuis, S Dargemont, C Fieschi, C Thomassin, N Rosenzweig, S Harris, J Holland, SM Schreiber, RD Casanova, JL TI Impairment od mycobacterial but not viral immunity by a germline human STAT1 mutation SO SCIENCE LA English DT Article ID INTERFERON-GAMMA-RECEPTOR; CALMETTE-GUERIN INFECTION; TARGETED DISRUPTION; DEFICIENCY; SUSCEPTIBILITY; MICE; GENE; DEFENSE; CHILD; CHAIN AB Interferons (IFN) alpha/beta and gamma induce the formation of two transcriptional activators: gamma-activating factor (CAF) and interferon-stimulated gamma factor 3 (ISGF3). We report a natural heterozygous germline STAT1 mutation associated with susceptibility to mycobacterial but not viral disease. This mutation causes a loss of CAF and ISGF3 activation but is dominant for one cellular phenotype and recessive for the other. It impairs the nuclear accumulation of GAF but not of ISGF3 in heterozygous cells stimulated by IFNs. Thus, the antimycobacterial, but not the antiviral, effects of human IFNs are principally mediated by GAF. C1 Univ Paris 05, Fac Med Necker Enfants Malad, INSERM,UMR550, Lab Genet Humaine Malad Infect, F-75015 Paris, France. Hop Necker Enfants Malad, INSERM, U429, F-75015 Paris, France. Univ Paris 06, CNRS, Inst Jacques Monod, F-75005 Paris, France. Univ Paris 07, CNRS, UMR 7592, F-75005 Paris, France. Ctr Hosp Gen, F-58000 Nevers, France. NIAID, Host Def Lab, Bethesda, MD 20892 USA. Univ San Francisco, Dept Pediat, San Francisco, CA 94117 USA. Washington Univ, Dept Pathol, St Louis, MO 63110 USA. Hop Necker Enfants Malad, Unite Hematol Immunol Pediat, F-75015 Paris, France. RP Casanova, JL (reprint author), Univ Paris 05, Fac Med Necker Enfants Malad, INSERM,UMR550, Lab Genet Humaine Malad Infect, F-75015 Paris, France. RI Schreiber, Robert/A-1276-2013 OI Schreiber, Robert/0000-0001-6311-0432 NR 24 TC 267 Z9 273 U1 1 U2 7 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUL 13 PY 2001 VL 293 IS 5528 BP 300 EP 303 DI 10.1126/science.1061154 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 452TK UT WOS:000169875200059 PM 11452125 ER PT J AU Hsieh, P AF Hsieh, P TI Molecular mechanisms of DNA mismatch repair SO MUTATION RESEARCH-DNA REPAIR LA English DT Review DE MutS proteins; mismatch repair; hereditary non-polyposis; colorectal cancer; X-ray crystallography ID CELL NUCLEAR ANTIGEN; CEREVISIAE MSH2-MSH6 COMPLEX; NEGATIVE MUTATOR MUTATIONS; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; HETERODUPLEX DNA; ATPASE ACTIVITY; HMUTS-ALPHA; POLYMERASE-DELTA; DISTINCT ROLES AB DNA mismatch repair (MMR) safeguards the integrity of the genome. In its role in postreplicative repair, this repair pathway corrects base-base and insertion/deletion (I/D) mismatches that have escaped the proofreading function of replicative polymerases. In its absence, cells assume a mutator phenotype in which the rate of spontaneous mutation is greatly elevated. The discovery that defects in mismatch repair segregate with certain cancer predisposition syndromes highlights its essential role in mutation avoidance. Recently, three-dimensional structures of MutS, a key repair protein that recognizes mismatches, have been determined by X-ray crystallography. This article provides an overview of the structural features of MutS proteins and discusses how the structural data together with biochemical and genetic studies reveal new insights into the molecular mechanisms of mismatch repair. Published by Elsevier Science B.V. C1 NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. RP Hsieh, P (reprint author), NIDDKD, Genet & Biochem Branch, NIH, Bldg 10 Rm 9D06,10 Ctr Dr MSC 1810, Bethesda, MD 20892 USA. NR 114 TC 131 Z9 135 U1 1 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8777 J9 MUTAT RES-DNA REPAIR JI Mutat. Res.-DNA Repair PD JUL 12 PY 2001 VL 486 IS 2 BP 71 EP 87 DI 10.1016/S0921-8777(01)00088-X PG 17 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 451AZ UT WOS:000169780100002 PM 11425513 ER PT J AU Grimm, JW Hope, BT Wise, RA Shaham, Y AF Grimm, JW Hope, BT Wise, RA Shaham, Y TI Neuroadaptation - Incubation of cocaine craving after withdrawal SO NATURE LA English DT Article ID RELAPSE; SENSITIZATION; ABSTINENCE; ADDICTION; STRESS C1 NIDA, Behav Neurosci Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Grimm, JW (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Wise, Roy/A-6465-2012; Hope, Bruce/A-9223-2010; shaham, yavin/G-1306-2014 OI Hope, Bruce/0000-0001-5804-7061; FU Intramural NIH HHS [Z01 DA000434-08] NR 13 TC 453 Z9 461 U1 1 U2 25 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUL 12 PY 2001 VL 412 IS 6843 BP 141 EP 142 DI 10.1038/35084134 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 451AJ UT WOS:000169778700038 PM 11449260 ER PT J AU Roux, AVD Merkin, SS Arnett, D Chambless, L Massing, M Nieto, FJ Sorlie, P Szklo, M Tyroler, HA Watson, RL AF Roux, AVD Merkin, SS Arnett, D Chambless, L Massing, M Nieto, FJ Sorlie, P Szklo, M Tyroler, HA Watson, RL TI Neighborhood of residence and incidence of coronary heart disease. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ALAMEDA-COUNTY; CARDIOVASCULAR-DISEASE; ATHEROSCLEROSIS RISK; SOCIOECONOMIC-STATUS; MULTILEVEL ANALYSIS; PHYSICAL-ACTIVITY; UNITED-STATES; SOCIAL-CLASS; HEALTH; MORTALITY AB Background: Where a person lives is not usually thought of as an independent predictor of his or her health, although physical and social features of places of residence may affect health and health-related behavior. Methods: Using data from the Atherosclerosis Risk in Communities Study, we examined the relation between characteristics of neighborhoods and the incidence of coronary heart disease. Participants were 45 to 64 years of age at base line and were sampled from four study sites in the United States: Forsyth County, North Carolina; Jackson, Mississippi; the northwestern suburbs of Minneapolis; and Washington County, Maryland. As proxies for neighborhoods, we used block groups containing an average of 1000 people, as defined by the U.S. Census. We constructed a summary score for the socioeconomic environment of each neighborhood that included information about wealth and income, education, and occupation. Results: During a median of 9.1 years of follow-up, 615 coronary events occurred in 13,009 participants. Residents of disadvantaged neighborhoods (those with lower summary scores) had a higher risk of disease than residents of advantaged neighborhoods, even after we controlled for personal income, education, and occupation. Hazard ratios for coronary heart disease among low-income persons living in the most disadvantaged neighborhoods, as compared with high-income persons in the most advantaged neighborhoods, were 3.1 among whites (95 percent confidence interval, 2.1 to 4.8) and 2.5 among blacks (95 percent confidence interval, 1.4 to 4.5). These associations remained unchanged after adjustment for established risk factors for coronary heart disease. Conclusions: Even after controlling for personal income, education, and occupation, we found that living in a disadvantaged neighborhood is associated with an increased incidence of coronary heart disease. (N Engl J Med 2001;345:99-106.) Copyright (C) 2001 Massachusetts Medical Society. C1 Columbia Univ, Columbia Coll Phys & Surg, Div Gen Med, New York, NY USA. Columbia Univ, Joseph T Mailman Sch Publ Hlth, Div Epidemiol, New York, NY USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. Univ N Carolina, Collaborat Studies Coordinating Ctr, Chapel Hill, NC USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Univ Mississippi, Med Ctr, Dept Prevent Med, Jackson, MS 39216 USA. RP Roux, AVD (reprint author), Columbia Presbyterian Med Ctr, Div Gen Med, 622 W 168th St,PH9 E,Rm 105, New York, NY 10032 USA. NR 44 TC 425 Z9 435 U1 4 U2 24 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 12 PY 2001 VL 345 IS 2 BP 99 EP 106 DI 10.1056/NEJM200107123450205 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 451AH UT WOS:000169776900005 ER PT J AU Sergueev, K Yu, DG Austin, S Court, D AF Sergueev, K Yu, DG Austin, S Court, D TI Cell toxicity caused by products of the p(L) operon of bacteriophage lambda SO GENE LA English DT Article DE kil; gam; cell division; flow cytometry ID ESCHERICHIA-COLI; PHAGE-LAMBDA; GENE; PROTEIN AB Induction of a lambda prophage causes the death of the host cell even in the absence of phage replication and lytic functions due to expression of functions from the lambdap(L) operon. We genetically modified the lambda prophage to determine which lambdap(L) operon functions were involved in cell killing. Viability assays and How cytometry were used to monitor cell death and filamentation. The kil gene was shown to cause cell death and filamentation as described previously. Another killing activity was mapped within the PL operon to the gam gene. Inspection of the DNA sequence showed that there are two possible translation start points for both kil and gain. In both cases, the shorter of the two possible products could cause cell killing. The shorter products were also sufficient for the known filamentation and recombination activities of the respective Kil and Gam functions. The expression level of the p(L) operon is down-regulated by Cro repressor. In the absence of Cro, higher P-L expression levels allow either Kil or Gam to be lethal or growth inhibitory, whereas at lowered expression in Cro-repressed conditions, only Kil is lethal. The filamentation function of Kil and recombination activity of Gam are unaffected at Cro-repressed levels of expression. Published by Elsevier Science B.V. C1 NCI, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. RP Court, D (reprint author), NCI, Gene Regulat & Chromosome Biol Lab, Bldg 539,Rm 243, Frederick, MD 21702 USA. NR 15 TC 27 Z9 28 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JUL 11 PY 2001 VL 272 IS 1-2 BP 227 EP 235 DI 10.1016/S0378-1119(01)00535-2 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 467WR UT WOS:000170727200026 PM 11470529 ER PT J AU Hermankova, M Ray, SC Ruff, C Powell-Davis, M Ingersoll, R D'Aquila, RT Quinn, TC Siliciano, RF Persaud, D AF Hermankova, M Ray, SC Ruff, C Powell-Davis, M Ingersoll, R D'Aquila, RT Quinn, TC Siliciano, RF Persaud, D TI HIV-1 drug resistance profiles in children and adults with viral load of < 50 copies/mL receiving combination therapy SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; ACTIVE ANTIRETROVIRAL THERAPY; REVERSE-TRANSCRIPTASE; LATENT RESERVOIR; GENOTYPIC RESISTANCE; PROTEASE INHIBITOR; CONFERS RESISTANCE; INFECTED PATIENTS; PLASMA VIREMIA; IN-VIVO AB Context The continued release of human immunodeficiency virus type 1 (HIV-1) into plasma at very low levels during highly active antiretroviral therapy (HAART) can be detected using specialized techniques, but the nature and significance of this low-level viremia, especially as related to acquisition of drug resistance mutations, are unclear. Objective To determine genetic resistance profiles of low-level plasma HIV-1 in patients with prolonged viral suppression (<50 copies/mL of plasma HIV-1 RNA) while receiving HAART. Design and Setting Cross-sectional study conducted at a US academic hospital from November 1999 to February 2001 using a novel method for amplification of low levels of viral genomes in plasma. Patients Eighteen HIV-1-infected patients (7 children and 11 adults), enrolled in a longitudinal study of HIV-1 reservoirs, who had suppression of viral replication while receiving protease inhibitor-containing combination therapy. Two patients (1 adult and 1 child) with less optimal suppression of viral replication were included to assess virus predominating when plasma HIV-1 RNA levels are low but detectable (<1000 copies/mL). Follow-up analyses were conducted in 3 patients. Main Outcome Measure Detection of drug resistance mutations in clones amplified from low-level plasma virus. Results Viral sequences were amplified from 8 of the 18 patients with simultaneous plasma HIV-1 measurements of less than 50 copies/mL and from 2 patients with 231 and 50 copies/mL. Clones from 3 treatment-naive patients with less than 50 copies/mL of plasma HIV-1 RNA showed continued release, for as long as 42 months, of wild-type drug-sensitive virus. The 7 patients with prior nonsuppressive therapy, with viral loads below 50 copies/mL and during "blips" to 231 and 64 copies/mL, had only resistance mutations consistent with pre-HAART therapy (although reverse transcriptase inhibitor mutations may have continued to occur), New HAART-related mutations were seen in a control patient with prior viral load levels of about 400 to 1000 copies/mL. For phylogenetic analysis, sequences were available for both resting CD4(+) T cells and plasma HIV for 7 of 10 patients and showed patient-specific clustering of sequences and a close relationship between virus in the plasma and the latent reservoir. Conclusions Based on the samples that could be amplified, low-level viremia in children and adults receiving HAART with prolonged suppression of viremia to less than 50 copies/mL of HIV-1 RNA may result primarily from archival, pre-HAART virus, reflecting earlier treatment conditions, and does not appear to require development of new, HAART-selected mutations reflecting partial resistance to therapy. Low-level viremia below 50 copies/mL may represent less of a concern regarding impending drug failure of current HAART regimens, However, the archival drug-resistant virus may be relevant regarding future treatment strategies. C1 Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Inst Genet, Baltimore, MD USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Persaud, D (reprint author), Johns Hopkins Univ, Sch Med, Dept Pediat, 600 N Wolfe St,256 Pk Bldg, Baltimore, MD 21287 USA. RI Quinn, Thomas/A-2494-2010; Ray, Stuart/B-7527-2008 OI Ray, Stuart/0000-0002-1051-7260 FU NIAID NIH HHS [AI29193, AI43222]; NICHD NIH HHS [P30HD27799] NR 47 TC 162 Z9 166 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 11 PY 2001 VL 286 IS 2 BP 196 EP 207 DI 10.1001/jama.286.2.196 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 451JJ UT WOS:000169798700025 PM 11448283 ER PT J AU Qin, SF Chock, PB AF Qin, SF Chock, PB TI Bruton's tyrosine kinase is essential for hydrogen peroxide-induced calcium signaling SO BIOCHEMISTRY LA English DT Article ID CELL ANTIGEN RECEPTOR; X-LINKED AGAMMAGLOBULINEMIA; TEC FAMILY KINASES; B-CELLS; MEMBRANE ASSOCIATION; PROTEIN-KINASE; BTK FUNCTION; SH2 DOMAIN; T-CELLS; ACTIVATION AB Using Btk-deficient DT40 cells and the transfectants expressing wild type Btk or Btk mutants in either kinase (Arg(525) to Gln), Src homology 2 (SH2, Arg(307) to Ala), or pleckstrin homology (PH Arg(28) to Cys) domains, we investigated the roles and structure-function relationships of Btk in hydrogen peroxide-induced calcium mobilization. Our genetic evidence showed that Btk deficiency resulted in a significant reduction in hydrogen peroxide-induced calcium response. This impaired calcium signaling is correlated with the complete elimination of IP3 production and the significantly reduced tyrosine phosphorylation of PLC gamma2 in Btk-deficient DT40 cells, All of these defects were fully restored by the expression of wildtype Btk in Btk-deficient DT40 cells. The data from the point mutation study revealed that a defect at any one of the three functional domains would prevent a full recovery of Btk-mediated hydrogen peroxide-induced intracellular calcium mobilization. However, mutation at either the SH2 or PH domain did not affect the hydrogen peroxide-induced activation of Btk. Mutation at the SH2 domain abrogates both IP3 generation and calcium release, while the mutant with the nonfunctional PH domain can partially activate PLC gamma2 and catalyze IP3 production bur fails to produce significant calcium mobilization. Thus, these observations suggest that Btk-dependent tyrosine phosphorylation of PLC gamma2 is required but not sufficient for hydrogen peroxide-induced calcium mobilization. Furthermore, hydrogen peroxide stimulates a Syk-, but not Btk-, dependent tyrosine phosphorylation of B cell linker protein BLNK, The overall results, together with those reported earlier [Qin et al. (2000) Proc, Natl. Acad. Sci, U.S.A, 97, 7118], are consistent with the notion that functional SH2 and PH domains are required for Btk to form a complex with PLC gamma2 through BLNK in order to position the Btk, PLC gamma2, and phosphatidylinositol 4,5-bisphosphate in close proximity for efficient activation of PLC gamma2 and to maximize its catalytic efficiency for IP3 production. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Chock, PB (reprint author), NHLBI, Biochem Lab, NIH, Bldg 50,Room 2134,50 South Dr,MSC-8012, Bethesda, MD 20892 USA. OI Qin, Suofu/0000-0002-3323-8846 NR 55 TC 12 Z9 12 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUL 10 PY 2001 VL 40 IS 27 BP 8085 EP 8091 DI 10.1021/bi0100788 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 451ZV UT WOS:000169833400015 PM 11434777 ER PT J AU Padayatty, SJ Levine, M AF Padayatty, SJ Levine, M TI Exploring the actions of vitamin C - authors response SO CANADIAN MEDICAL ASSOCIATION JOURNAL LA English DT Letter C1 NIDDKD, Mol & Clin Nutr Sect, NIH, Bethesda, MD 20892 USA. RP Padayatty, SJ (reprint author), NIDDKD, Mol & Clin Nutr Sect, NIH, Bethesda, MD 20892 USA. RI Padayatty, Sebastian/A-8581-2012 OI Padayatty, Sebastian/0000-0001-8758-3170 NR 5 TC 0 Z9 0 U1 0 U2 0 PU CANADIAN MEDICAL ASSOCIATION PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 3Y6, CANADA SN 0820-3946 J9 CAN MED ASSOC J JI Can. Med. Assoc. J. PD JUL 10 PY 2001 VL 165 IS 1 BP 14 EP 14 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 450CY UT WOS:000169725000006 ER PT J AU Oshima, Y Puri, RK AF Oshima, Y Puri, RK TI Suppression of an IL-13 autocrine growth loop in a human Hodgkin/Reed-Sternberg tumor cell line by a novel IL-13 antagonist SO CELLULAR IMMUNOLOGY LA English DT Article DE interleukin-13 (IL-13); IL-13 antagonist; IL-13 cytotoxin; Hodgkin lymphoma; Hodgkin cells; Reed-Sternberg cells; Hodgkin/Reed-Sternberg tumor cells; autocrine; paracrine ID HUMAN GLIOMA-CELLS; PSEUDOMONAS EXOTOXIN; CHIMERIC PROTEIN; CARCINOMA-CELLS; INTERLEUKIN-13 RECEPTORS; SARCOMA-CELLS; CHAIN; BINDING; LYMPHOMA; DISEASE AB IL-13 has been proposed to be an autocrine growth factor for Hodgkin/Reed-Sternberg tumor cells (H/RS cells). Since we have recently identified and produced a novel IL-13 antagonist (IL-13E13K) that can suppress the biological activity of IL-13, here we examined whether IL-13E13K can inhibit growth of Hodgkin lymphoma (HL)-derived cell lines. IL-13E13K not only inhibited the growth of an unstimulated H/RS cell line (L1236) but also cells that were stimulated by exogenous IL-13 in a dose-dependent manner. Several HL-derived cell lines expressed IL-13 message and protein and message for various chains of IL-13R. FURS cell lines expressed mRNA for the IL-13R alpha1, IL-4R alpha, and IL-2R gamma chains. However, none of these cell lines expressed the IL-13R alpha2 chain. An H/R,S cell line (L1236) internalized the ligand-receptor complex after binding to a fusion protein composed of IL-13 and a mutated form of Pseudomonas exotoxin A (IL-13PE38QQR, or IL-13 cytotoxin), as IL-13 cytotoxin was specifically cytotoxic to H/RS cells an vitro. These results indicate that IL-13E13K and IL-13 cytotoxin can effectively suppress growth of a L1236 MRS cell line. Therefore, additional studies should be performed to determine the expression of IL-13 and IL-13R in primary clinical samples of Hodgkin's lymphoma and both agents should be further tested in vitro and an vivo as possible therapeutic agents for HL. C1 US FDA, Ctr Biol Evaluat & Res, Lab Molec Tumor Biol, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Molec Tumor Biol, Div Cellular & Gene Therapies, 29 Lincoln Dr,NIH Bldg 29B,Room 2NN10, Bethesda, MD 20892 USA. NR 29 TC 17 Z9 18 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD JUL 10 PY 2001 VL 211 IS 1 BP 37 EP 42 DI 10.1006/cimm.2001.1828 PG 6 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 479NY UT WOS:000171411500005 PM 11585386 ER PT J AU Feng, DL Lindpaintner, K Larson, MG O'Donnell, CJ Lipinska, I Sutherland, PA Mittleman, M Muller, JE D'Agostino, RB Levy, D Tofler, GH AF Feng, DL Lindpaintner, K Larson, MG O'Donnell, CJ Lipinska, I Sutherland, PA Mittleman, M Muller, JE D'Agostino, RB Levy, D Tofler, GH TI Platelet glycoprotein IIIa Pl(A) polymorphism, fibrinogen, and platelet aggregability - The Framingham heart study SO CIRCULATION LA English DT Article DE platelets; genetics; glycoproteins; fibrinogen ID CORONARY-ARTERY DISEASE; MYOCARDIAL-INFARCTION; RISK; ASSOCIATION; THROMBOSIS; RECEPTOR; BINDING; GPIIIA; AGGREGATION; STROKE AB Background-Recent data suggest that the Pl(A2) allele of the platelet glycoprotein IIIa receptor may be a genetic risk factor fur cardiovascular disease. We previously reported that the Pl(A2) allele was associated with increased platelet aggregability, as indicated by lower epinephrine threshold concentrations. Paradoxically, however, it has been reported that Pl(A2)-positive platelets have reduced fibrinogen binding. Because fibrinogen mediates platelet aggregability, we hypothesized that plasma fibrinogen levels may interact with PP genotype in modulating platelet aggregability, Methods and Results-Glycoprotein ma PIA genotype, fibrinogen level, and platelet aggregability were ascertained in 1340 subjects enrolled into the Framingham Offspring Study. Platelet aggregability was evaluated by the Barn method. Higher fibrinogen levels were associated with increased epinephrine-induced aggregation (P=0.002) and a trend for ADP-induced aggregation (P=0.07). The fibrinogen effect was genotype specific, however, in that the increase in platelet aggregability with higher fibrinogen was present for the pl(A1/A1) genotype (P=0.0005 and P=0.03 for epinephrine- and ADP-induced aggregation respectively) but not for the Pl(A2)-positive genotype (P >0.90). Conclusion-Higher fibrinogen levels were associated with increased platelet aggregability, However, the association between fibrinogen and platelet aggregability was genotype specific. This interaction may be responsible for the conflicting findings regarding PIA genotype and platelet aggregability. Further study of this gene-environment interaction may provide insight into cardiovascular disease risk. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Inst Prevent Cardiovasc Dis, Boston, MA 02215 USA. Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Boston Univ, Dept Math, Stat & Consulting Unit, Boston, MA 02215 USA. NHLBI, Framingham Heart Study, NIH, Framingham, MA USA. Royal N Shore Hosp, Sydney, NSW, Australia. RP Feng, DL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, 55th Fruit St,Bulfinch 106, Boston, MA 02114 USA. FU NHLBI NIH HHS [K04-HL-03138-01, R01-HL48157] NR 33 TC 44 Z9 47 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL 10 PY 2001 VL 104 IS 2 BP 140 EP 144 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 453BJ UT WOS:000169896600015 PM 11447076 ER PT J AU Latham, VM Yu, EHS Tullio, AN Adelstein, RS Singer, RH AF Latham, VM Yu, EHS Tullio, AN Adelstein, RS Singer, RH TI A Rho-dependent signaling pathway operating through myosin localizes beta-actin mRNA in fibroblasts SO CURRENT BIOLOGY LA English DT Article ID MESSENGER-RNA LOCALIZATION; HEAVY-CHAIN ISOFORMS; PROTEIN-KINASE-C; FOCAL ADHESIONS; BINDING PROTEIN; SMOOTH-MUSCLE; CULTURED-CELLS; STRESS FIBERS; PHOSPHORYLATION; TRANSDUCTION AB Background: The sorting of mRNA is a determinant of cell asymmetry. The cellular signals that direct specific RNA sequences to a particular cellular compartment are unknown. In fibroblasts, beta -actin mRNA has been shown to be localized toward the leading edge, where it plays a role in cell motility and asymmetry. Results: We demonstrate that a signaling pathway initiated by extracellular receptors, acting through Rho GTPase and Rho-kinase regulates this spatial aspect of gene expression in fibroblasts by localizing beta -actin mRNA via actomyosin interactions Consistent with the role of Rha as an activator of myosin, we found that inhibition of myosin ATPase, myosin light chain kinase (MLCK), and the knockout of myosin II-B in mouse embryonic fibroblasts all inhibited beta -actin mRNA from localizing in response to growth factors. Conclusions: We therefore conclude that the sorting of beta -actin mRNA in fibroblasts requires a Rho mediated pathway operating through a myosin Il-B-dependent step and postulate that polarized actin bundles direct the mRNA to the leading edge of the cell. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Anat & Struct Biol, Bronx, NY 10461 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Singer, RH (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Anat & Struct Biol, 1300 Morris Pk Ave, Bronx, NY 10461 USA. FU NIAMS NIH HHS [AR41480] NR 34 TC 57 Z9 60 U1 1 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JUL 10 PY 2001 VL 11 IS 13 BP 1010 EP 1016 DI 10.1016/S0960-9822(01)00291-3 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 451RC UT WOS:000169814200016 PM 11470405 ER PT J AU Frattali, CM Liow, K Craig, GH Korenman, LM Makhlouf, F Sato, S Biesecker, LG Theodore, WH AF Frattali, CM Liow, K Craig, GH Korenman, LM Makhlouf, F Sato, S Biesecker, LG Theodore, WH TI Cognitive deficits in children with gelastic seizures and hypothalamic hamartoma SO NEUROLOGY LA English DT Article ID PRECOCIOUS PUBERTY; EPILEPSY; TOPIRAMATE; EEG AB Objective: To characterize the cognitive deficits in children with gelastic seizures and hypothalamic hamartoma and investigate the relationship of seizure severity to cognitive abilities. Methods: Eight children with gelastic seizures and hypothalamic hamartoma completed a neuropsychological battery of standardized and age-normed tests, including the Woodcock-Johnson Psyche-Educational Battery-Revised: Tests of Cognitive Ability, Peabody Picture Vocabulary Test-III, and initial-letter word fluency measure. Results: All children displayed cognitive deficits, ranging from mild to severe. Gelastic/complex partial seizure severity was correlated with broad cognitive ability standard scores (r = -0.79; r(2) = 0.63; (F[1,6] = 10.28; p = 0.018]. Frequency of gelastic/complex partial seizures was also correlated with broad cognitive ability standard scores (r = -0.72; r(2) = 0.52; F[1,6] = 6.44; p = 0.044). Significant intracognitive standard score differences were found, with relative weaknesses in long-term retrieval (mean = 64.1; SD = 13.3) and processing speed (mean = 67.7; SD = 21.6) and a relative strength in visual processing (mean = 97.6; SD = 12.8). Performance in visual processing differed from performance in long-term retrieval (p = 0.009) and processing speed (p = 0.029). Conclusion: These findings are consistent with cognitive functions and affective/emotional states associated with conduction pathways of the hypothalamus involving cortical association areas and amygdala and hippocampal formation. These abnormalities can account for the prominent deficit found in integrating information in the processing of memories. C1 NIH, Speech Language Pathol Sect, Dept Rehabil Med, WG Magnuson Clin Ctr, Bethesda, MD 20892 USA. NINDS, Epilepsy Res Branch, Bethesda, MD 20892 USA. NHGRI, Ctr Informat & Technol, NIH, Bethesda, MD 20892 USA. NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. RP Frattali, CM (reprint author), NIH, Speech Language Pathol Sect, Dept Rehabil Med, WG Magnuson Clin Ctr, 10 Ctr Dr,MSC 1604,Bldg 10,Rm 6S 235, Bethesda, MD 20892 USA. NR 21 TC 51 Z9 52 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL 10 PY 2001 VL 57 IS 1 BP 43 EP 46 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 449TD UT WOS:000169702500009 PM 11445626 ER PT J AU Gaillard, WD Pugliese, M Grandin, CB Braniecki, SH Kondapaneni, P Hunter, K Xu, B Petrella, JR Balsamo, L Basso, G AF Gaillard, WD Pugliese, M Grandin, CB Braniecki, SH Kondapaneni, P Hunter, K Xu, B Petrella, JR Balsamo, L Basso, G TI Cortical localization of reading in normal children - An fMRI language study SO NEUROLOGY LA English DT Article ID FUNCTIONAL MRI; PREFRONTAL CORTEX; BRAIN; DOMINANCE; COMPREHENSION; ACTIVATION; RETRIEVAL; TASK; PET; HEMISPHERE AB Background: fMRI provides a noninvasive means of identifying the location and organization of neural networks that underlie cognitive functions. Objective: To identify, using fMRI, brain regions involved in processing written text in children. Methods: The authors studied nine normal right-handed native English-speaking children, aged 10.2 years (range 7.9 to 13.3 years), with two paradigms: reading Aesop's Fables and "Read Response Naming" treading a description of an object that was then silently named). Data were acquired using blood oxygen level-dependent fMRI. Group data were analyzed with statistical parametric mapping; individual data sets were analyzed with a region-of-interest approach from individual study t maps. The number of activated pixels was determined in brain regions and an asymmetry index (AI = [L - R]/[L + R]) calculated for each region. Results: The authors found strong activation in the left, middle temporal gyrus and left midfrontal gyrus and variable activation in left inferior frontal gyrus for both reading tasks in the group analysis (z > 5.5 to 9.1). All subjects had strong left-sided lateralization for both tasks in middle/superior temporal gyrus, inferior frontal gyrus, and middle frontal gyrus (AI = 0.76 to 1.0 for t = 4). Reading Fables activated twice as many pixels in temporal cortex as the Read Response Naming task; activation in dorsolateral prefrontal cortex was similar for both tasks. Small homologous right middle temporal region activation was seen with reading a fable. Conclusions: The neural networks that process reading appear to be lateralized and localized by middle to late childhood. Reading text paradigms may prove useful for identifying frontal and temporal language-processing areas and for determining language dominance in children experiencing epilepsy or undergoing tumor surgery. C1 Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. Univ Louvain, St Luc Univ Hosp, Dept Radiol, Louvain, Belgium. NINDS, Lab Radiol Res & Dev, NIH, Bethesda, MD 20892 USA. NINDS, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. NINDS, Epilepsy Res Branch, NIH, Bethesda, MD 20892 USA. RP Gaillard, WD (reprint author), Childrens Natl Med Ctr, Dept Neurol, 111 Michigan Ave NW, Washington, DC 20010 USA. RI Basso, Gianpaolo/A-9208-2012 OI Basso, Gianpaolo/0000-0002-6245-9402 FU NINDS NIH HHS [KO8-NS1663] NR 44 TC 75 Z9 76 U1 3 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL 10 PY 2001 VL 57 IS 1 BP 47 EP 54 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 449TD UT WOS:000169702500010 PM 11445627 ER PT J AU Bastian, LA Lipkus, IM Kuchibhatla, MN Weng, HH Halabi, S Ryan, PD Skinner, CS Rimer, BK AF Bastian, LA Lipkus, IM Kuchibhatla, MN Weng, HH Halabi, S Ryan, PD Skinner, CS Rimer, BK TI Women's interest in chemoprevention for breast cancer SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of Veterans Affairs Health Services Research and Development CY FEB 23, 2000 CL WASHINGTON, D.C. ID POSTMENOPAUSAL WOMEN; TAMOXIFEN TREATMENT; RANDOMIZED TRIAL; RISK; PERCEPTIONS; PREVENTION; THERAPY AB Background: Chemoprevention is the use of pharmacologic or natural agents to inhibit the development of cancer. Tamoxifen citrate is the only approved chemopreventive agent for breast cancer. We sought to determine whether women are interested in taking a drug to prevent breast cancer and to assess the relationship between objective and subjective breast cancer risk and interest in chemoprevention. Methods: We conducted telephone interviews (November 3, 1997, to May 6, 1998) among a community sample of women aged 40 to 45 and 50 to 55 years enrolled in a randomized controlled trial to evaluate the efficacy of a tailored mammography decision aid. Objective breast cancer risk was measured using the 5-year Gall score. Subjective breast cancer risk was measured using perceptions of absolute risk, perceptions of comparative risk, and worry about getting breast cancer. At 12-month follow-up (November 2, 1998, to July 20, 1999), we measured interest in taking a drug to prevent breast cancer. Results: Among the 1273 women surveyed, 23% were interested in taking a drug to prevent breast cancer; 8% were potentially eligible for tamoxifen therapy (5-year Gall score greater than or equal to1.66%). Eligibility for chemoprevention, based on the 5-year Call score, was not associated with interest in taking a drug to prevent breast cancer. Women who were worried about breast cancer were 3 times more likely to be interested in taking a drug to prevent breast cancer than those who were not worried. Conclusion: Women's interest in chemoprevention might arise more from worries about getting breast cancer than from their objective risk factors. C1 Duke Univ, Med Ctr, Dept Internal Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Family & Community Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Durham Vet Affairs Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC 27705 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Bastian, LA (reprint author), Durham Vet Affairs Med Ctr, Ctr Hlth Serv Res Primary Care, 508 Fulton St 152, Durham, NC 27705 USA. FU NCI NIH HHS [CA72099] NR 27 TC 35 Z9 35 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUL 9 PY 2001 VL 161 IS 13 BP 1639 EP 1644 DI 10.1001/archinte.161.13.1639 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 447QX UT WOS:000169584900008 PM 11434796 ER PT J AU Newman, AH Zou, MF Ferrer, JV Javitch, JA AF Newman, AH Zou, MF Ferrer, JV Javitch, JA TI [H-3]MFZ 2-12: A novel radioligand for the dopamine transporter SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID ADDICTIVE DRUGS; RAT-BRAIN; COCAINE; SITES; BINDING; ANALOGS AB In an effort to develop a tritiated dopamine transporter radioligand with higher affinity than the widely used [H-3]WIN 35,428, we have synthesized [H-3]3 beta -carbomethoxy-3 beta-(3 ' .4 ' -dichloroph ([H-3]MFZ 2 12). Unlabeled MFZ 2-12 and the N-demethylated intermediate (MFZ 2-13) inhibited dopamine uptake by the human dopamine transporter with IC50's of 1.1 and 1.4 nM, respectively. The N-nor-intermediate (MFZ 2-13) was treated with CT,I resulting in [H-3]MFZ 2-12, S.A. = 80 Ci/mmol). [H-3]MFZ 2-12 reversibly bound with a KD of 2.8 nM to human dopamine transporter expressed heterologously in EM4 cells. Published by Elsevier Science Ltd. C1 Natl Inst Drug Abuse, Med Chem Sect, Intramural Res Program, Baltimore, MD 21224 USA. Columbia Univ, Ctr Mol Recognit, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, Dept Pharmacol, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. RP Newman, AH (reprint author), Natl Inst Drug Abuse, Med Chem Sect, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. FU NIDA NIH HHS [DA11495]; NIMH NIH HHS [MH57324] NR 12 TC 8 Z9 8 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD JUL 9 PY 2001 VL 11 IS 13 BP 1659 EP 1661 DI 10.1016/S0960-894X(01)00271-2 PG 3 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 446ZC UT WOS:000169543200010 PM 11425531 ER PT J AU Muller, WG Walker, D Hager, GL McNally, JG AF Muller, WG Walker, D Hager, GL McNally, JG TI Large-scale chromatin decondensation and recondensation regulated by transcription from a natural promoter SO JOURNAL OF CELL BIOLOGY LA English DT Article DE higher order chromatin structure; transcription; glucocorticoid receptor ID MAMMARY-TUMOR VIRUS; RNA-POLYMERASE-II; GLUCOCORTICOID RECEPTOR; LIVING CELLS; CHIRONOMUS-TENTANS; MMTV PROMOTER; BINDING PROTEIN; IN-VIVO; ELONGATION; GENE AB We have examined the relationship between transcription and chromatin structure using a tandem array of the mouse mammary tumor virus (MMTV) promoter driving a ras reporter. The array was visualized as a distinctive fluorescent structure in live cells stably transformed with a green fluorescent protein (GFP)-tagged glucocorticoid receptor (GR), which localizes to the repeated MMTV elements after steroid hormone treatment. Also found at the array by immunofluorescence were two different steroid receptor coactivators (SRC1 and CBP) with acetyltransferase activity, a chromatin remodeler (BRG1), and two transcription factors (NFI and AP-2). Within 3 h after hormone addition, arrays visualized by GFP-GR or DNA fluorescent in situ hybridization (FISH) decondensed to varying degrees, in the most pronounced cases from a similar to0.5-mum spot to form a fiber 1-10 mum long. Arrays later recondensed by 3-8 h of hormone treatment. The degree of decondensation was proportional to the amount of transcript produced by the array as detected by RNA FISH. Decondensation was blocked by two different drugs that inhibit polymerase II, 5,6-dichloro-1-beta -D-ribofuranosylbenzimidazole (DRB) and alpha -amanitin. These observations demonstrate a role for polymerase in producing and maintaining decondensed chromatin. They also support fiber-packing models of higher order structure and suggest that transcription from a natural promoter may occur at much higher DNA-packing densities than reported previously. C1 NCI, Lab Receptor Biol & gene Express, NIH, Bethesda, MD 20892 USA. RP McNally, JG (reprint author), NCI, Lab Receptor Biol & gene Express, NIH, Bldg 41,Rm B-602,41 Lib Dr,MSC 5055, Bethesda, MD 20892 USA. NR 56 TC 122 Z9 123 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUL 9 PY 2001 VL 154 IS 1 BP 33 EP 48 DI 10.1083/jcb.200011069 PG 16 WC Cell Biology SC Cell Biology GA 452FB UT WOS:000169845900010 PM 11448988 ER PT J AU Daigle, N Beaudouin, J Hartnell, L Imreh, G Hallberg, E Lippincott-Schwartz, J Ellenberg, J AF Daigle, N Beaudouin, J Hartnell, L Imreh, G Hallberg, E Lippincott-Schwartz, J Ellenberg, J TI Nuclear pore complexes form immobile networks and have a very low turnover in live mammalian cells SO JOURNAL OF CELL BIOLOGY LA English DT Article DE nuclear pore complex; nuclear envelope; confocal microscopy; FRAP; live cell imaging ID CYTOPLASMIC ANNULATE LAMELLAE; INTEGRAL MEMBRANE-PROTEIN; GREEN FLUORESCENT PROTEIN; LIVING CELLS; FUNCTIONAL-ORGANIZATION; ELECTRON-MICROSCOPY; MUSCULAR-DYSTROPHY; NUCLEOPORIN NUP153; IN-VIVO; ENVELOPE AB The nuclear pore complex (NPC) and its relationship to the nuclear envelope (NE) was characterized in living cells using POM121-green fluorescent protein (GFP) and GFP-Nup153, and GFP-lamin B1. No independent movement of single pore complexes was found within the plane of the NE in interphase. Only large arrays of NPCs moved slowly and synchronously during global changes in nuclear shape, strongly suggesting mechanical connections which form an NPC network. The nuclear lamina exhibited identical movements. NPC turnover measured by fluorescence recovery after photobleaching of POM121 was less than once per cell cycle. Nup153 association with NPCs was dynamic and turnover of this nucleoporin was three orders of magnitude faster. Overexpression of both nucleoporins induced the formation of annulate lamellae (AL) in the endoplasmic reticulum (ER). Turnover of AL pore complexes was much higher than in the NE (once every 2.5 min). During mitosis, POM121 and Nup153 were completely dispersed and mobile in the ER (POM121) or cytosol (Nup153) in metaphase, and rapidly redistributed to an immobilized pool around chromatin in late anaphase. Assembly and immobilization of both nucleoporins occurred before detectable recruitment of lamin B1, which is thus unlikely to mediate initiation of NPC assembly at the end of mitosis. C1 European Mol Biol Lab, Gene Express Program, D-69117 Heidelberg, Germany. European Mol Biol Lab, Cell Biol Biophys Program, D-69117 Heidelberg, Germany. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Sodertorns Hogskola Univ, S-14104 Huddinge, Sweden. RP Ellenberg, J (reprint author), European Mol Biol Lab, Gene Express Program, Meyerhofstr 1, D-69117 Heidelberg, Germany. RI Ellenberg, Jan/I-4688-2014 OI Ellenberg, Jan/0000-0001-5909-701X NR 62 TC 249 Z9 254 U1 0 U2 11 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUL 9 PY 2001 VL 154 IS 1 BP 71 EP 84 DI 10.1083/jcb.200101089 PG 14 WC Cell Biology SC Cell Biology GA 452FB UT WOS:000169845900013 PM 11448991 ER PT J AU Caplan, S Hartnell, LM Aguilar, RC Naslavsky, N Bonifacino, JS AF Caplan, S Hartnell, LM Aguilar, RC Naslavsky, N Bonifacino, JS TI Human Vam6p promotes lysosome clustering and fusion in vivo SO JOURNAL OF CELL BIOLOGY LA English DT Article DE lysosome biogenesis; vacuolar protein sorting; vesicle tethering; vesicle docking; lysosome fusion ID HOMOTYPIC VACUOLE FUSION; LATE ENDOSOME-LYSOSOME; CIS-SNARE COMPLEX; PROTEIN COMPLEX; DOCKING; MACROPHAGES; BIOGENESIS; TRAFFICKING; SYNTAXIN-7; ORGANELLE AB Regulated fusion of mammalian lysosomes is critical to their ability to acquire both internalized and biosynthetic materials. Here, we report the identification of a novel human protein, hVam6p, that promotes lysosome clustering and fusion in vivo. Although hVam6p exhibits homology to the Saccharomyces cerevisiae vacuolar protein sorting gene product Vam6p/Vps39p, the presence of a citron homology (CNH) domain at the NH2 terminus is unique to the human protein. Overexpression of hVam6p results in massive clustering and fusion of lysosomes and late endosomes into large (2-3 mum) juxtanuclear structures. This effect is reminiscent of that caused by expression of a constitutively activated Rab7. However, hVam6p exerts its effect even in the presence of a dominant-negative Rab7, suggesting that it functions either downstream of, or in parallel to, Rab7. Data from gradient fractionation, two-hybrid, and coimmunoprecipitation analyses suggest that hVam6p is a homooligomer and that its self-assembly is mediated by a clathrin heavy chain repeat domain in the middle of the protein. Both the CNH and clathrin heavy chain repeat domains are required for induction of lysosome clustering and fusion. This study implicates hVam6p as a mammalian tethering/docking factor characterized with intrinsic ability to promote lysosome fusion in vivo. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Bonifacino, JS (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bldg 18T Room 101, Bethesda, MD 20892 USA. OI Bonifacino, Juan S./0000-0002-5673-6370 NR 41 TC 100 Z9 102 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUL 9 PY 2001 VL 154 IS 1 BP 109 EP 121 DI 10.1083/jcb.200102142 PG 13 WC Cell Biology SC Cell Biology GA 452FB UT WOS:000169845900016 PM 11448994 ER PT J AU Cameron, HA McKay, RDG AF Cameron, HA McKay, RDG TI Adult neurogenesis produces a large pool of new granule cells in the dentate gyrus SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE bromodeoxyuridine; thymidine; cell cycle; mitosis; hippocampus; neurons ID CENTRAL-NERVOUS-SYSTEM; BRAIN-BARRIER PERMEABILITY; UNSCHEDULED DNA-SYNTHESIS; NMDA RECEPTOR ACTIVATION; MOUSE-BRAIN; BLOOD-BRAIN; HIPPOCAMPAL NEUROGENESIS; NUCLEOSIDE TRANSPORT; TRANSIENT INCREASE; ADRENAL-STEROIDS AB Knowing the rate of addition of new granule cells to the adult dentate gyrus is critical to understanding the function of adult neurogenesis. Despite the large number of studies of neurogenesis in the adult dentate gyrus, basic questions about the magnitude of this phenomenon have never been addressed. The S-phase marker bromodeoxyuridine (BrdU) has been extensively used in recent studies of adult neurogenesis, but it has been carefully tested only in the embryonic brain. Here, we show that a high dose of BrdU (300 mg/kg) is a specific, quantitative, and nontoxic marker of dividing cells in the adult rat dentate gyrus, whereas lower doses label only a fraction of the S-phase cells. By using this high dose of BrdU along with a second S-phase marker, [H-3]thymidine, we found that young adult rats have 9,400 dividing cells proliferating with a cell cycle time of 25 hours, which would generate 9,000 new cells each day, or more than 250,000 per month. Within 5-12 days of BrdU injection, a substantial pool of immature granule neurons, 50% of all BrdU-labeled cells in the dentate gyrus, could be identified with neuron-specific antibodies TuJ1 and TUC-4. This number of new granule neurons generated each month is 6% of the total size of the granule cell population and 30-60% of the size of the afferent and efferent populations (West et al. [1991] Anat Rec 231:482-497; Mulders et al. [1997] J Comp Neurol 385:83-94). The large number of the adult-generated granule cells supports the idea that these new neurons play an important role in hippocampal function. Published 2001 Wiley-Liss, Inc.(dagger). C1 NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Cameron, HA (reprint author), NINDS, Mol Biol Lab, NIH, Bldg 36-3C12 MSC 4092, Bethesda, MD 20892 USA. RI Cameron, Heather/E-6221-2011 OI Cameron, Heather/0000-0002-3245-5777 NR 69 TC 1026 Z9 1089 U1 8 U2 47 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JUL 9 PY 2001 VL 435 IS 4 BP 406 EP 417 DI 10.1002/cne.1040 PG 12 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 443AM UT WOS:000169317200003 PM 11406822 ER PT J AU Wang, XW Hussain, SP Huo, T Wu, CG Forgues, M Hofseth, LJ Brechot, C Harris, CC AF Wang, XW Hussain, SP Huo, T Wu, CG Forgues, M Hofseth, LJ Brechot, C Harris, CC TI Molecular pathogenesis of human hepatocellular carcinoma SO TOXICOLOGY LA English DT Meeting Abstract C1 NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. Necker Inst, Paris, France. NR 0 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 0300-483X J9 TOXICOLOGY JI Toxicology PD JUL 8 PY 2001 VL 164 IS 1-3 SU S BP 5 EP 5 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 452ZA UT WOS:000169888500011 ER PT J AU Negishi, M AF Negishi, M TI The role of CAR in the regulation of CYP gene expression by phenobarbital SO TOXICOLOGY LA English DT Meeting Abstract C1 NIEHS, Pharmacogenet Sect, LRDT, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD JUL 8 PY 2001 VL 164 IS 1-3 SU S BP 15 EP 15 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 452ZA UT WOS:000169888500043 ER PT J AU Cannon, R Tennant, RW AF Cannon, R Tennant, RW TI Transgenic mouse models - an alternative approach to carcinogenicity testing SO TOXICOLOGY LA English DT Meeting Abstract C1 NIEHS, Lab Environm Carcinogen & Mutagen, Res Triangle Pk, NC USA. NR 0 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 0300-483X J9 TOXICOLOGY JI Toxicology PD JUL 8 PY 2001 VL 164 IS 1-3 SU S BP 19 EP 19 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 452ZA UT WOS:000169888500055 ER PT J AU Gonzalez, FJ AF Gonzalez, FJ TI Transgenic models in xenobiotic metabolism and toxicity SO TOXICOLOGY LA English DT Meeting Abstract C1 NIH, NCI, Lab Metab, Bethesda, MD USA. NR 0 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 0300-483X J9 TOXICOLOGY JI Toxicology PD JUL 8 PY 2001 VL 164 IS 1-3 SU S BP 19 EP 19 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 452ZA UT WOS:000169888500054 ER PT J AU Schonwalder, C AF Schonwalder, C TI Toxicology and epidemiology must join forces to understand the effects of environmental agents on human health SO TOXICOLOGY LA English DT Meeting Abstract C1 US Natl Inst Hlth, Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. NR 0 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 0300-483X J9 TOXICOLOGY JI Toxicology PD JUL 8 PY 2001 VL 164 IS 1-3 SU S BP 29 EP 29 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 452ZA UT WOS:000169888500084 ER PT J AU Weed, DL AF Weed, DL TI Environmental epidemiology: basics and proof of cause-effect SO TOXICOLOGY LA English DT Meeting Abstract C1 NCI, Div Canc Prevent, Bethesda, MD USA. NR 0 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 0300-483X J9 TOXICOLOGY JI Toxicology PD JUL 8 PY 2001 VL 164 IS 1-3 SU S BP 29 EP 29 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 452ZA UT WOS:000169888500085 ER PT J AU Paules, RS AF Paules, RS TI Genomic interrogation of mechanisms underlying cellular responses to toxicants SO TOXICOLOGY LA English DT Meeting Abstract C1 NIEHS, Toxicol Gene Express Studies, Microarray Ctr, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD JUL 8 PY 2001 VL 164 IS 1-3 SU S BP 39 EP 39 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 452ZA UT WOS:000169888500115 ER PT J AU Wexler, P AF Wexler, P TI Internet Web resources in toxicology SO TOXICOLOGY LA English DT Meeting Abstract C1 Natl Lib Med, Toxicol & Environm Hlth Informat Program, Bethesda, MD USA. NR 0 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 0300-483X J9 TOXICOLOGY JI Toxicology PD JUL 8 PY 2001 VL 164 IS 1-3 SU S BP 40 EP 40 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 452ZA UT WOS:000169888500120 ER PT J AU Jameson, CW Lunn, RM Jeter, SP AF Jameson, CW Lunn, RM Jeter, SP TI The report on carcinogens (RoC): review and recommendations of the nominations for the 10th edition SO TOXICOLOGY LA English DT Meeting Abstract C1 NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. NR 0 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 0300-483X J9 TOXICOLOGY JI Toxicology PD JUL 8 PY 2001 VL 164 IS 1-3 SU S BP 54 EP 54 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 452ZA UT WOS:000169888500163 ER PT J AU Goshorn, JC Thoman, M Phillips, SP AF Goshorn, JC Thoman, M Phillips, SP TI Reinvention of toxnet's hazardous substance database for the web SO TOXICOLOGY LA English DT Meeting Abstract C1 Natl Lib Med, NIH, DHHS, Bethesda, MD USA. Broadlawns Med Ctr, Des Moines, IA USA. NR 0 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 0300-483X J9 TOXICOLOGY JI Toxicology PD JUL 8 PY 2001 VL 164 IS 1-3 SU S BP 56 EP 56 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 452ZA UT WOS:000169888500172 ER PT J AU Tchounwou, PB Ishaque, AB Shen, E AF Tchounwou, PB Ishaque, AB Shen, E TI Cytotoxicity and stress gene induction in human liver carcinoma cells (HepG2) exposed to lead nitrate SO TOXICOLOGY LA English DT Meeting Abstract C1 Jackson State Univ, Mol Toxicol Res Lab, NIH Ctr Environm Hlth, Sch Sci & Technol, Jackson, MS USA. Xenometrix Inc, Client Res Lab, Boulder, CO USA. NR 0 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 0300-483X J9 TOXICOLOGY JI Toxicology PD JUL 8 PY 2001 VL 164 IS 1-3 SU S BP 65 EP 65 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 452ZA UT WOS:000169888500202 ER PT J AU Willems, BAT Davis, BJ Portier, CJ AF Willems, BAT Davis, BJ Portier, CJ TI Physiologically based modeling of the rat estrus cycle and human menstrual cycle including a link to breast cancer incidence rates SO TOXICOLOGY LA English DT Meeting Abstract C1 Lab Computat Biol & Risk Anal, Res Triangle Pk, NC USA. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD JUL 8 PY 2001 VL 164 IS 1-3 SU S BP 127 EP 127 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 452ZA UT WOS:000169888500404 ER PT J AU Nukaya, M Takahashi, Y Gonzalez, FJ Kamataki, T AF Nukaya, M Takahashi, Y Gonzalez, FJ Kamataki, T TI Aryl hydrocarbon receptor (AhR) target genes involved in the toxicity caused by aromatic hydrocarbons in mice SO TOXICOLOGY LA English DT Meeting Abstract C1 Hokkaido Univ, Sch Pharmaceut Sci, Lab Drug Metab, Sapporo, Hokkaido, Japan. Natl Canc Inst, Lab Metab, Bethesda, MD USA. NR 0 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 0300-483X J9 TOXICOLOGY JI Toxicology PD JUL 8 PY 2001 VL 164 IS 1-3 SU S BP 155 EP 155 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 452ZA UT WOS:000169888500493 ER PT J AU Goedert, JI Fung, MM Felton, S Battjes, RJ Engels, EA AF Goedert, JI Fung, MM Felton, S Battjes, RJ Engels, EA TI Cause-specific mortality associated with HIV and HTLV-II infections among injecting drug users in the USA SO AIDS LA English DT Article DE HIV infection; HTLV-II infection; injecting drug use; mortality; overdose; tuberculosis; pneumonia; cancer ID VIRUS TYPE-II; HAIRY-CELL LEUKEMIA; NON-AIDS MORTALITY; T-CELL; BLOOD-DONORS; KAYAPO INDIANS; UNITED-STATES; FOLLOW-UP; BRAZIL; COINFECTION AB Background: Human T-lymphotropic virus type II (HTLV-II) is widespread among injecting drug users (IDU) and may contribute to the risk of leukemia/lymphoma, neurodegenerative disease, and perhaps pneumonia, especially with HIV co-infection. Methods: In 1987-1991, 6570 IDU were tested for HIV and HTLV-II antibodies. In 1998, they were matched to the National Death Index. Numbers of observed deaths of each cause were compared by standardized mortality ratios with the numbers expected, using sex-, race-, age-, and year-specific rates in the general population. Relative risk (RR) associated with each virus, compared to uninfected drug users, was estimated by Poisson modeling. Results: There were 1351 deaths, including 683 (15%) of 4604 participants who enrolled seronegative for both viruses; 328 (47%) of 701 who had HIV but not HTLV-II infection; 220 (21%) of 1033 who had HTLV-II but not HIV infection; and 120 (52%) of 232 who were infected by both viruses. Compared to the general population, mortality for participants with neither virus was increased 4.3-fold [95% confidence interval (CI), 4.0-4.7] and was significantly elevated for virtually every cause of death. With HIV, mortality from medical causes, but not external causes, was increased 3.7-fold (95% CI, 3.3-4.2), particularly with AIDS and related conditions. With HTLV-II, all-cause mortality was reduced (RR, 0.8; 95% CI, 0.7-0.9), with no statistically significant reduction or elevation for any specific cause. A non-significant excess of tuberculosis deaths (RR 4.6; 95% CI, 0.8-25.2) was noted with HTLV-II, but there was no excess mortality from leukemia/lymphoma, other malignancies, or neurodegenerative disease. Conclusions: Without HIV or HTLV-II, IDU had profoundly increased mortality from medical and external causes. HIV was specifically associated with death due to AIDS and related conditions. HTLV-II infection was not significantly associated with mortality from any cause, suggesting that it is not a significant human pathogen, even when present with HIV infection. (C) 2001 Lippincott Williams & Wilkins. C1 NCI, Viral Epidemiol Branch, Rockville, MD USA. Res Triangle Inst, Washington, DC USA. Friends Res Inst, Baltimore, MD USA. NIDA, Rockville, MD USA. RP Goedert, JI (reprint author), 6120 Execut Blvd,Suite 8012, Rockville, MD 20852 USA. FU NCI NIH HHS [N02-CP-01004, N02-CP-91027]; PHS HHS [271-90-4000] NR 34 TC 33 Z9 34 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JUL 6 PY 2001 VL 15 IS 10 BP 1295 EP 1302 DI 10.1097/00002030-200107060-00012 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 448XP UT WOS:000169655500011 PM 11426075 ER PT J AU Biggar, RJ Broadhead, R Janes, M Kumwenda, N Taha, TET Cassol, S AF Biggar, RJ Broadhead, R Janes, M Kumwenda, N Taha, TET Cassol, S TI Viral levels in newborn African infants undergoing primary HIV-1 infection SO AIDS LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; DISEASE PROGRESSION; LYMPHOCYTE COUNT; CHILDREN; LOAD; RNA; ASSOCIATION; MORTALITY; DYNAMICS AB We examined weekly changes in viral levels in seven untreated infants infected with HIV at birth. Viral levels spiked immediately but reverted quickly to plateau levels typical of infant HIV infection within 2 weeks of first detected viraemia. We speculated that the depletion of naive, susceptible cells is responsible for the rapid decrease in spike levels and that the rapid replacement of lymphocytes in infants causes the high plateau viral levels (10(5) copies/ml) to be sustained. C1 NCI, Viral Epidemiol Branch, Bethesda, MD 20892 USA. Univ Malawi, Dept Paediat, Blantyre, Malawi. Univ Ottawa, Ottawa, ON, Canada. Johns Hopkins Univ Univ Malawi Project, Blantyre, Malawi. Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. RP Biggar, RJ (reprint author), NCI, Viral Epidemiol Branch, Bethesda, MD 20892 USA. NR 14 TC 16 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JUL 6 PY 2001 VL 15 IS 10 BP 1311 EP 1313 DI 10.1097/00002030-200107060-00015 PG 3 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 448XP UT WOS:000169655500014 PM 11426078 ER PT J AU Zhou, XM Jiang, GS Zhao, AP Bondeva, T Hirszel, P Balla, T AF Zhou, XM Jiang, GS Zhao, AP Bondeva, T Hirszel, P Balla, T TI Inhibition of Na,K-ATPase activates P13 kinase and inhibits apoptosis in LLC-PK1 cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE ouabain; potassium; Na,K-ATPase; PI3 kinase; akt; LLC-PK1 cells; actinomycin D; apoptosis ID NA+,K+-ATPASE ALPHA-SUBUNIT; CEREBELLAR GRANULE CELLS; VASCULAR SMOOTH-MUSCLE; CARDIAC MYOCYTES; OUABAIN; SURVIVAL; PATHWAYS; PROLIFERATION; ENDOCYTOSIS; MECHANISMS AB In the present study we used LLC-PK1 cells, a porcine renal proximal tubular cell line, to investigate whether PI3 kinase activation was involved in the anti-apoptotic effect of ouabain, a specific inhibitor of Na,K-ATPase, Apoptosis was induced by actinomycin D (Act D, 5 muM) and assessed by appearance of hypodiploid nuclei and DNA fragmentation. Ouabain attenuated Act D-induced apoptotic response in a dose-dependent manner. Incubation in a low K+ medium (0.1 mM) which is another way to decrease Na,K-ATPase activity also had anti-apoptotic effect. Both ouabain and low K+ medium increased the PI3 kinase activity in p85 immunoprecipitates, Ouabain, as well as incubation in the low K+ medium, also increased the phosphorylation of Akt, Inhibition of PI3 kinase by either wortmannin or LY294002 reversed the cytoprotective effect of ouabain, These data together indicate that inhibition of Na,K-ATPase activates PI3 kinase in LLC-PK1 cells which could then exert the cytoprotective effect. C1 Uniformed Serv Univ Hlth Sci, Dept Med, Div Nephrol, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Dept Anat Cell Biol & Physiol, Bethesda, MD 20814 USA. NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Zhou, XM (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med, Div Nephrol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. NR 32 TC 47 Z9 48 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 6 PY 2001 VL 285 IS 1 BP 46 EP 51 DI 10.1006/bbrc.2001.5126 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 451ZU UT WOS:000169833300008 PM 11437370 ER PT J AU Ozvegy, C Litman, T Szakacs, G Nagy, Z Bates, S Varadi, A Sarkadi, B AF Ozvegy, C Litman, T Szakacs, G Nagy, Z Bates, S Varadi, A Sarkadi, B TI Functional characterization of the human multidrug transporter, ABCG2, expressed in insect cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE multidrug resistance; ABC half-transporter; ABCG2; MXR; BCRP; Sf9 cells; drug-stimulated ATPase activity ID HUMAN P-GLYCOPROTEIN; STIMULATED ATPASE ACTIVITY; CANCER RESISTANCE PROTEIN; CARCINOMA CELLS; MITOXANTRONE; OVEREXPRESSION; GENE; ACCUMULATION; MOLECULES; MUTANTS AB ABCG2 (also called MXR (3), BCRP (4), or ABCP (5)) is a recently-identified ABC half-transporter, which causes multidrug resistance in cancer. Here we report that the expression of the ABCG2 protein in Sf9 insect cells resulted in a high-capacity, vanadate-sensitive ATPase activity in isolated membrane preparations. ABCG2 was expressed underglycosylated, and its ATPase activity was stimulated by daunorubicin, doxorubicin, mitoxantrone, prazosin and rhodamine 123, compounds known to be transported by this protein. ABCG2-ATPase was inhibited by low concentrations of Na-orthovanadate, N-ethylmaleimide and cyclosporin A Verapamil had no effect, while Fumitremorgin C, reversing ABCG2-dependent cancer drug resistance, strongly inhibited this ATPase activity. The functional expression of ABCG2 in this heterologous system indicates that no additional partner protein is required for the activity of this multidrug transporter, probably working as a homodimer, We suggest that the Sf9 cell membrane ATPase system is an efficient tool for examining the interactions of ABCG2 with pharmacological agents. (C) 2001 Academic Press. C1 Hungarian Acad Sci, Natl Inst Haematol & Immunol, Membrane Res Grp, H-1113 Budapest, Hungary. Hungarian Acad Sci, Biol Res Ctr, Inst Enzymol, H-1113 Budapest, Hungary. Herlev Univ Hosp, Lab Oncol, DK-2730 Herlev, Denmark. SOLVO Biotechnol Co, Res Grp, H-6722 Szeged, Hungary. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. RP Sarkadi, B (reprint author), Hungarian Acad Sci, Natl Inst Haematol & Immunol, Membrane Res Grp, Daroczi Ut 24, H-1113 Budapest, Hungary. RI Szakacs, Gergely/A-2580-2009; Varadi, Andras/A-2055-2012; Sarkadi, Balazs/I-5024-2013 OI Szakacs, Gergely/0000-0002-9311-7827; NR 32 TC 214 Z9 216 U1 1 U2 12 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 6 PY 2001 VL 285 IS 1 BP 111 EP 117 DI 10.1006/bbrc.2001.5130 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 451ZU UT WOS:000169833300018 PM 11437380 ER PT J AU Zeyda, T Diehl, N Paylor, R Brennan, MB Hochgeschwender, U AF Zeyda, T Diehl, N Paylor, R Brennan, MB Hochgeschwender, U TI Impairment in motor learning of somatostatin null mutant mice SO BRAIN RESEARCH LA English DT Article DE targeted disruption; mouse mutant; motor learning; cerebellum; development; growth hormone ID CEREBELLAR GRANULE CELLS; GROWTH-HORMONE; DEVELOPMENTAL EXPRESSION; NEURITE OUTGROWTH; STARTLE RESPONSE; MOUSE-BRAIN; RAT; GENE; NEUROPEPTIDE; CYSTEAMINE AB Somatostatin was first identified as a hypothalamic factor which inhibits the release of growth hormone from the anterior pituitary (somatotropin release inhibitory factor, SRIF). Both SRIF and its receptors were subsequently found widely distributed within and outside the nervous system. in the adult as well as in the developing organism. Reflecting this wide distribution. somatostatin has: been implicated regulating a diverse array of biological processes. These include body growth, homeostasis, sensory perception. autonomous functions, rate of intestinal absorption, behavior, including cognition and memory, and developmental processes. We produced null mutant mice lacking somatostatin through targeted mutagenesis. The mutant mice are healthy, fertile, and superficially indistinguishable from their heterozygous and wildtype littermates. A 'first round' phenotype screen revealed that mice lacking somatostatin have elevated plasma growth hormone levels, despite normal body size, and have elevated basal plasma corticosterone levels. In order to uncover subtle and unexpected differences, we carried out a systematic behavioral phenotype screen which identified a significant impairment in motor learning revealed when increased demands were made on motor coordination. Motor coordination and motor learning require an intact cerebellum. While somatostatin is virtually absent from the adult cerebellum, the ligand and its receptor(s) are transiently expressed at high levels in the developing cerebellum This result suggests the functional significance of transient expression of SRIF and its receptors in the development of the cerebellum. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Oklahoma Med Res Fdn, Dev Biol Program, Oklahoma City, OK 73104 USA. NIMH, Mol Genet Unit, Clin Neurosci Branch, Bethesda, MD 20892 USA. NIMH, Sect Behav Neuropharmacol, Expt Therapeut Branch, Bethesda, MD 20892 USA. Eleanor Roosevelt Inst Canc Res, Denver, CO 80206 USA. RP Hochgeschwender, U (reprint author), Oklahoma Med Res Fdn, Dev Biol Program, 825 NE 13th St,MS 49, Oklahoma City, OK 73104 USA. NR 47 TC 67 Z9 68 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 6 PY 2001 VL 906 IS 1-2 BP 107 EP 114 DI 10.1016/S0006-8993(01)02563-X PG 8 WC Neurosciences SC Neurosciences & Neurology GA 452RZ UT WOS:000169873700012 PM 11430867 ER PT J AU Wagner, JA Jarai, Z Batkai, S Kunos, G AF Wagner, JA Jarai, Z Batkai, S Kunos, G TI Hemodynamic effects of cannabinoids: coronary and cerebral vasodilation mediated by cannabinoid CB1 receptors SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE anandamide; cannabinoid CB1 receptor; HU-210; R-methanandamide; microsphere ID SENSORY NERVES MEDIATE; MESENTERIC VASODILATION; VANILLOID RECEPTORS; INDUCED HYPOTENSION; BLOOD-FLOW; ANANDAMIDE; RAT; ENDOTHELIUM; INHIBITION; ARTERIES AB Activation of peripheral cannabinoid CB1 receptors elicits hypotension. Using the radioactive microsphere technique, we examined the effects of cannabinoids on systemic hemodynamics in anesthetized rats. The potent cannabinoid CB1 receptor agonist HU-210 ({-}-11-OH-Delta (9) tetrahydrocannabinol dimethylheptyl, 10 mug/kg i.v.) reduced mean blood pressure by 57 +/- 5 mm Hg by decreasing cardiac index from 37 +/- 1 to 23 +/- 2 ml/min/100 g (P < 0.05) without significantly affecting systemic vascular resistance index. HU-210 elicited a similar decrease in blood pressure following ganglionic blockade and vasopressin infusion. The endogenous cannabinoid anandamide (arachidonyl ethanolamide, 4 mg/kg i.v.) decreased blood pressure by 40 +/- 7 mm Hg by reducing systemic vascular resistance index from 3.3 +/- 0.1 to 2.3 +/- 0.1 mm ng min/ml/100 g (P < 0.05), leaving cardiac index and stroke volume index unchanged. HU-210, anandamide, and its metabolically stable analog, R-methanandamide, lowered vascular resistance primarily in the coronaries and the brain. These vasodilator effects remained unchanged when autoregulation was prevented by maintaining blood pressure through volume replacement, but were prevented by pretreatment with the cannabinoid CB1 receptor antagonist SR141716A (N-{piperidin-1-yl}-5-{4-chlorophenyl}-1-(3,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide HCl; 3 mg/kg i.v.). Only anandamide and R-methanandamide were vasodilators in the mesentery. We conclude that cannabinoids elicit profound coronary and cerebral vasodilation in vivo by direct activation of vascular cannabinoid CB1 receptors, rather than via autoregulation, a decrease in sympathetic tone or, in the case of anandamide, the action of a non-cannabinoid metabolite. Differences between the hemodynamic profile of various cannabinoids may reflect quantitative differences in cannabinoid CB1 receptor expression in different tissues and/or the involvement of as-yet-unidentified receptors. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Med Coll Virginia, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. RP Kunos, G (reprint author), NIAAA, NIH, 12420 Parklawn Dr,MSC-8115, Bethesda, MD 20892 USA. RI Batkai, Sandor/G-3889-2010; Batkai, Sandor/H-7983-2014 FU NHLBI NIH HHS [R01-HL49938, R01-HL59257] NR 43 TC 118 Z9 123 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 6 PY 2001 VL 423 IS 2-3 BP 203 EP 210 DI 10.1016/S0014-2999(01)01112-8 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 454CZ UT WOS:000169956000016 PM 11448486 ER PT J AU Song, LN Huse, B Rusconi, S Simons, SS AF Song, LN Huse, B Rusconi, S Simons, SS TI Transactivation specificity of glucocorticoid versus progesterone receptors - Role of functionally different interactions of transcription factors with amino- and carboxyl-terminal receptor domains SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID THYROID-HORMONE RECEPTOR; TUMOR VIRUS PROMOTER; PARTIAL AGONIST ACTIVITY; HUMAN ESTROGEN-RECEPTOR; BREAST-CANCER CELLS; NUCLEAR RECEPTOR; ANDROGEN RECEPTOR; GENE-EXPRESSION; DNA-BINDING; STEROID-RECEPTORS AB A major unanswered question of glucocorticoid and progesterone action is how different whole cell responses arise when both of the cognate receptors can bind to, and activate, the same hormone response elements. We have documented previously that the EC,, of agonist complexes, and the partial agonist activity of antagonist complexes, of both glucocorticoid receptors (GRs) and progesterone receptors (PRs) are modulated by increased amounts of homologous receptor and of coregulators. We now ask whether these components can differentially alter GR and PR transcriptional properties. To remove possible cell-specific differences, we have examined both receptors in the common environment of a line of mouse mammary adenocarcinoma (1470.2) cells, In order to segregate the responses that might be due to unequal nucleosome reorganization by the two receptors from those reflecting interactions with other components, we chose a transiently transfected reporter containing a simple glucocorticoid response element (i.e. GREtkLUC), No significant differences are found with elevated levels of either receptor. However, major, qualitative differences are seen with the corepressors SMRT and NCoR, which afford opposite responses with GR and PR. Studies with chimeric GR/PR receptors indicate that no one segment of PR or G;R is responsible for these properties and that the composite response likely involves interactions with both the amino and carboxyl termini of receptors, Collectively, the data suggest that GR and PR induction of responsive genes in a given cell can be differentially controlled, in part, by unequal interactions of multiple receptor domains with assorted nuclear cofactors. C1 NIDDK, Steroid Hormones Sect, LMCB, NIH, Bethesda, MD 20892 USA. Univ Fribourg, CH-1700 Fribourg, Switzerland. RP Simons, SS (reprint author), NIDDK, Steroid Hormones Sect, LMCB, NIH, Bldg 8,Rm B2A-07, Bethesda, MD 20892 USA. RI Rusconi, Stefano/H-9263-2012 NR 89 TC 39 Z9 39 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 6 PY 2001 VL 276 IS 27 BP 24806 EP 24816 DI 10.1074/jbc.M102610200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 451KF UT WOS:000169800700053 PM 11333273 ER PT J AU Zhang, F Romano, PR Nagamura-Inoue, T Tian, B Devert, TE Mathews, MB Ozato, K Hinnebusch, AG AF Zhang, F Romano, PR Nagamura-Inoue, T Tian, B Devert, TE Mathews, MB Ozato, K Hinnebusch, AG TI Binding of double-stranded RNA to protein kinase PKR is required for dimerization and promotes critical autophosphorylation events in the activation loop SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID N-TERMINAL DOMAIN; IN-VIVO; INITIATION FACTOR-2-ALPHA; SACCHAROMYCES-CEREVISIAE; PHOSPHORYLATION SITES; TRANSLATIONAL CONTROL; CATALYTIC SUBUNIT; INTERFERON ACTION; MOLECULAR-BASIS; MAP KINASE AB Protein kinase PKR is activated by double-stranded RNA (dsRNA) and phosphorylates translation initiation factor 2 alpha to inhibit protein synthesis in virus-infected mammalian cells. PKR contains two dsRNA binding motifs (DRBMs I and II) required for activation by dsRNA, There is strong evidence that PKR activation requires dimerization, but the role of dsRNA in dimer formation is controversial. By making alanine substitutions predicted to remove increasing numbers of side chain contacts between the DRBMs and dsRNA we found that dimerization of full-length PKR in yeast was impaired by the minimal combinations of mutations required to impair dsRNA binding in vitro. Mutation of Ala-67 to Glu in DRBM-I, reported to abolish dimerization without affecting dsRNA binding, destroyed both activities in our assays. By contrast, deletion of a second dimerization region that overlaps the kinase domain had no effect on PKR dimerization in yeast, Human PKR contains at least 15 autophosphorylation sites, but only Thr-446 and Thr-451 in the activation loop were found here to be critical for kinase activity in yeast. Using an antibody specific for phosphorylated Thr-451, we showed that Thr-451 phosphorylation is stimulated by dsRNA binding, Our results provide strong evidence that dsRNA binding is required for dimerization of full-length PKR molecules in vivo, leading to autophosphorylation in the activation loop and stimulation of the eIF2 alpha kinase function of PKR. C1 NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Biochem & Mol Biol, Newark, NJ 07103 USA. Thomas Jefferson Univ, Jefferson Ctr Biomed Res, Doylestown, PA 18901 USA. RP Hinnebusch, AG (reprint author), NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. OI Tian, Bin/0000-0001-8903-8256 FU NIAID NIH HHS [R01-AI34552] NR 56 TC 114 Z9 119 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 6 PY 2001 VL 276 IS 27 BP 24946 EP 24958 DI 10.1074/jbc.M102108200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 451KF UT WOS:000169800700069 PM 11337501 ER PT J AU Vaidyanathan, VV Puri, N Roche, PA AF Vaidyanathan, VV Puri, N Roche, PA TI The last exon of SNAP-23 regulates granule exocytosis from mast cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INSULIN-INDUCED TRANSLOCATION; SNARE COMPLEX; MEMBRANE-FUSION; CLOSTRIDIAL NEUROTOXINS; T-SNARE; SYNTAXIN; INHIBITION; PROTEINS; BINDING; RELEASE AB SNAP-25 and its ubiquitous homolog SNAP-23 are members of the SNARE family of proteins that regulate membrane fusion during exocytosis, Although SNAP-23 has been shown to participate in a variety of intracellular transport processes, the structural domains of SNAP-23 that are required for its interaction with other SNAREs have not been determined. By employing deletion mutagenesis we found that deletion of the aminoterminal 18 amino acids of SNAP-23 (encoded in the first exon) dramatically inhibited binding of SNAP-23 to both the target SNARE syntaxin and the vesicle SNARE vesicle-associated membrane protein(VAMP). By contrast, deletion of the carboxyl-terminal 23 amino acids (encoded in the last exon) of SNAP-23 does not affect SNAP-23 binding to syntaxin but profoundly inhibits its binding to VAMP. To determine the functional relevance of the modular structure of SNAP-23, we overexpressed SNAP-23 in cells possessing the capacity to undergo regulated exocytosis. Expression of human SNAP-23 in a rat mast cell line significantly enhanced exocytosis, and this effect was not observed in transfectants expressing the carboxyl-terminal VAMP-binding mutant of SNAP-23. Despite considerable amino acid identity, we found that human SNAP-23 bound to SNAREs more efficiently than did rat SNAP-23, These data demonstrate that the introduction of a "better" SNARE binder into secretory cells augments exocytosis and defines the carboxyl terminus of SNAP-23 as an essential regulator of exocytosis in mast cells. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Roche, PA (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Rm 4B36, Bethesda, MD 20892 USA. NR 33 TC 36 Z9 36 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 6 PY 2001 VL 276 IS 27 BP 25101 EP 25106 DI 10.1074/jbc.M103536200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 451KF UT WOS:000169800700090 PM 11350976 ER PT J AU Kawakami, K Takeshita, F Puri, RK AF Kawakami, K Takeshita, F Puri, RK TI Identification of distinct roles for a dileucine and a tyrosine internalization motif in the interleukin (IL)-13 binding component IL-13 receptor alpha 2 chain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNAL TRANSDUCER GP130; CARCINOMA CELL-LINES; DI-LEUCINE MOTIF; CYTOPLASMIC DOMAIN; TRANSFERRIN RECEPTOR; PSEUDOMONAS EXOTOXIN; IL-13R-ALPHA-1 CHAIN; JANUS KINASE; GAMMA-CHAIN; IN-VITRO AB Interleukin (IL)-13 receptor alpha2 (IL-13R alpha2) chain is an essential binding component for IL-13-mediated ligand binding. Recently, we have demonstrated that this receptor chain also plays an important role in the internalization of IL-13. To study the mechanism of IL-13 internalization, we generated mutated IL-13R alpha2 chains that targeted trileucine residues (Leu(335), Leu(336), and Leu(337)) in the transmembrane domain and a tyrosine motif (Tyr(343)) in the intracellular domain and transfected these cDNAs in COS-7 cells. Cells that expressed a C-terminally truncated IL-13R alpha2 chain (Delta 335) did not bind IL-13, suggesting that the trileucine region modulates IL-13 binding. Truncation of IL-13R alpha2 chain with a mutation in the trileucine region resulted in significantly decreased internalization compared with wild type IL-13R alpha2 chain transfected cells. COS-7 cells transfected with tyrosine motif mutants exhibited a similar internalization level compared with wild type IL-13R alpha2 chain transfected cells; however, dissociation of cell surface IL-13 was faster compared with wild type IL-13R alpha2 transfectants. These results were further confirmed by determining the cytotoxicity of a chimeric protein composed of IL-13 and a mutated form of Pseudomonas exotoxin (IL13-PE38QQR) to cells that expressed IL-13R alpha2 chain mutants. We further demonstrate that the IL-13R alpha2 chain is not ubiquitinated and that internalization of IL-13R alpha2 did not depend on ubiquitination, Together, our findings suggest that the dileucine motif in the trileucine region and tyrosine motif participate in IL-13R alpha2 internalization in distinct manners. C1 US FDA, NIH, Lab Mol Tumor Biol,Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Retroviral Immunol Sect, Div Viral Prod, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, NIH, Lab Mol Tumor Biol,Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bldg 29B,Rm 2NN10,29 Lincoln Dr,MSC 4555, Bethesda, MD 20892 USA. NR 51 TC 37 Z9 38 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 6 PY 2001 VL 276 IS 27 BP 25114 EP 25120 DI 10.1074/jbc.M100936200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 451KF UT WOS:000169800700092 PM 11352909 ER PT J AU Tomita, K Saijo, K Yamasaki, S Iida, T Nakatsu, F Arase, H Ohno, H Shirasawa, T Kuriyama, T O'Shea, JJ Saito, T AF Tomita, K Saijo, K Yamasaki, S Iida, T Nakatsu, F Arase, H Ohno, H Shirasawa, T Kuriyama, T O'Shea, JJ Saito, T TI Cytokine-independent Jak3 activation upon T cell receptor (TCR) stimulation through direct association of Jak3 and the TCR complex SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MICE LACKING JAK3; SIGNAL-TRANSDUCTION; ANTIGEN RECEPTOR; GAMMA-CHAIN; IL-2 RECEPTOR; LYMPHOID DEVELOPMENT; INTERFERON-ALPHA; GENETIC-EVIDENCE; CD3 COMPLEX; INTERLEUKIN-2 AB Jak3 is responsible for growth signals by various cytokines such as interleukin (IL)-2, IL-4, and IL-7 through association with the common gamma chain (gammac) in lymphocytes. We found that T cells from Jak3-deficient mice exhibit impairment of not only cytokine signaling but also early activation signals and that Jak3 is phosphorylated upon T cell receptor (TCR) stimulation. TCR-mediated phosphorylation of Jak3 is independent of IL-2 receptor/gammac but is dependent on Lck and ZAP-70. Jak3 was found to be assembled with the TCR complex, particularly through direct association with CD3 zeta via its JH4 region, which is a different region from that for gammac association. These results suggest that Jak3 plays a role not only in cell growth but also in T cell activation and represents cross-talk of a signaling molecule between TCR and growth signals. C1 Chiba Univ, Grad Sch Med, Dept Mol Genet, Chuo Ku, Chiba 2608790, Japan. Tokyo Metropolitan Inst Gerontol, Dept Neurophysiol, Itabashi Ku, Tokyo 1730015, Japan. Chiba Univ, Sch Med, Inst Pulm Canc Res, Dept Internal Med,Chuo Ku, Chiba 2608790, Japan. NIAMS, Lymphocyte Cell Biol Sect, NIH, Bethesda, MD 20892 USA. RP Saito, T (reprint author), Chiba Univ, Grad Sch Med, Dept Mol Genet, Chuo Ku, 1-8-1 Inohana, Chiba 2608790, Japan. RI Arase, Hisashi/C-8442-2009; Saito, Takashi/C-9684-2009; Ohno, Hiroshi/L-7899-2014 OI Arase, Hisashi/0000-0002-1153-3166; Saito, Takashi/0000-0001-9495-3547; Ohno, Hiroshi/0000-0001-8776-9661 NR 42 TC 24 Z9 24 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 6 PY 2001 VL 276 IS 27 BP 25378 EP 25385 DI 10.1074/jbc.M011363200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 451KF UT WOS:000169800700126 PM 11349123 ER PT J AU Qu, W Bradbury, JA Tsao, CC Maronpot, R Harry, GJ Parker, CE Davis, LS Breyer, MD Waalkes, MP Falck, JR Chen, JY Rosenberg, RL Zeldin, DC AF Qu, W Bradbury, JA Tsao, CC Maronpot, R Harry, GJ Parker, CE Davis, LS Breyer, MD Waalkes, MP Falck, JR Chen, JY Rosenberg, RL Zeldin, DC TI Cytochrome P450CYP2J9, a new mouse arachidonic acid omega-1 hydroxylase predominantly expressed in brain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IN-SITU HYBRIDIZATION; ARTERIAL SMOOTH-MUSCLE; RAT-BRAIN; EPOXYEICOSATRIENOIC ACIDS; MOLECULAR-CLONING; CDNA CLONING; 5,6-EPOXYEICOSATRIENOIC ACID; MONOOXYGENASE ACTIVITIES; MULTIPLE FORMS; MESSENGER-RNA AB A cDNA encoding a new cytochrome P450 was isolated from a mouse brain library. Sequence analysis reveals that this 1,958-base pair cDNA encodes a 57-58-kDa 502-amino acid polypeptide that is 70-91% identical to CYP2J subfamily P450s and is designated CYP2J9. Recombinant CYP2J9 was co-expressed with NADPH-cytochrome P450 oxidoreductase (CYPOR) in Sf9 cells using a baculovirus system. Microsomes of CYP2J9/CYPOR-transfected cells metabolize arachidonic acid to 19-hydroxyeicosatetraenoic acid (HETE) thus CYP2J9 is enzymologically distinct from other P450s. Northern analysis reveals that CYP2J9 transcripts are present at high levels in mouse brain. Mouse brain microsomes biosynthesize 19-HETE. RNA polymerase chain reaction analysis demonstrates that CYP2J9 mRNAs are widely distributed in brain and most abundant in the cerebellum. Immunoblotting using an antibody raised against human CYP2J2 that cross-reacts with CYP2J9 detects a 56-kDa protein band that is expressed in cerebellum and other brain segments and is regulated during postnatal development. In situ hybridization of mouse brain sections with a CYP2J9-specific riboprobe and immunohistochemical staining with the anti-human CYP2J2 IgG reveals abundant CYP2J9 mRNA and protein in cerebellar Purkinje cells. Importantly, 19-HETE inhibits the activity of recombinant P/Q-type Ca2+ channels that are known to be expressed preferentially in cerebellar Purkinje cells and are involved in triggering neurotransmitter release. Based on these data, we conclude that CYP2J9 is a developmentally regulated P450 that is abundant in brain, localized to cerebellar Purkinje cells, and active in the biosynthesis of 19-HETE, an eicosanoid that inhibits activity of P/Q-type Ca2+ channels. We postulate that CYP2J9 arachidonic acid products play important functional roles in the brain. C1 NIEHS, Pulm Pathobiol Lab, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. Vanderbilt Univ, Dept Med, Nashville, TN 37232 USA. NIEHS, Inorgan Carcinogensis Sect, NCI, NIH, Res Triangle Pk, NC 27709 USA. Univ Texas, SW Med Ctr, Dept Biochem, Dallas, TX 75235 USA. Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA. RP NIEHS, Pulm Pathobiol Lab, Div Intramural Res, NIH, Bldg 101,Rm D236,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM zeldin@niehs.nih.gov FU NHLBI NIH HHS [HL49449]; NIDDK NIH HHS [P01-DK38226]; NIGMS NIH HHS [GM-31278] NR 77 TC 58 Z9 60 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 6 PY 2001 VL 276 IS 27 BP 25467 EP 25479 DI 10.1074/jbc.M100545200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 451KF UT WOS:000169800700137 PM 11328810 ER PT J AU Lavrik, OI Prasad, R Sobol, RW Horton, JK Ackermann, EJ Wilson, SH AF Lavrik, OI Prasad, R Sobol, RW Horton, JK Ackermann, EJ Wilson, SH TI Photoaffinity labeling of mouse fibroblast enzymes by a base excision repair intermediate - Evidence for the role of poly(ADP-ribose) polymerase-1 in DNA repair SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MOLECULAR NICK-SENSOR; REVERSE-TRANSCRIPTASE; INDUCED CYTOTOXICITY; MAMMALIAN-CELLS; BOVINE TESTIS; SITE REPAIR; BETA; PROTEIN; DAMAGE; STEP AB To examine the interaction of mammalian base excision repair (BER) enzymes with DNA intermediates formed during BER, we used a novel photoaffinity labeling probe and mouse embryonic fibroblast cellular extracts. The probe was formed in situ, using an end-labeled oligonucleotide containing a synthetic abasic site; this site was incised by apurinic/apyrimidinic endonuclease creating a nick with 3 ' -hydroxyl and 5 ' -reduced sugar phosphate groups at the margins, and then a dNMP carrying a photoreactive adduct was added to the 3 ' -hydroxyl group. With near-UV light (312 nm) exposure of the extract/probe mixture, six proteins were strongly labeled. Four of these include poly(ADP-ribose) polymerase-1 (PARP-1) and the BER participants flap endonuclease-1, DNA polymerase beta, and apurinic/apyrimidinic endonuclease, The amount of the probe cross-linked to PARP-1 was greater than that cross-linked to the other proteins. The specificity of PARP-1 labeling was examined using various competitor oligonucleotides and DNA probes with alternate structures. PARP-1 labeling was stronger with a DNA representing a BER intermediate than with a nick in double-stranded DNA, These results indicate that proteins interacting preferentially with a photoreactive BER intermediate can be selected from the crude cellular extract. C1 NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. Russian Acad Sci, Siberian Div, Novosibirsk Bioorgan Chem Inst, Novosibirsk 630090, Russia. Pacific NW Natl Lab, Richland, WA 99352 USA. RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, NIH, 111 TW Alexandra Dr, Res Triangle Pk, NC 27709 USA. RI Lavrik, Olga /G-4641-2013; Sobol, Robert/E-4125-2013 OI Sobol, Robert/0000-0001-7385-3563 NR 52 TC 127 Z9 137 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 6 PY 2001 VL 276 IS 27 BP 25541 EP 25548 DI 10.1074/jbc.M102125200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 451KF UT WOS:000169800700145 PM 11340072 ER PT J AU Du, QZ Cheng, H Ito, Y AF Du, QZ Cheng, H Ito, Y TI Separation of radioactive metabolites in cultured tea cells fed with [C-14]phenylalanine using high-speed counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE counter-current chromatography; tea; catechins; polyphenols AB Separation of radioactive metabolites in cultured tea cells fed with [C-14]phenylalanine was conducted using high-speed counter-current chromatography. Among seven components obtained our studies focused two metabolites, i.e. (-)-epicatechin and D,L-catechin. The specific radioactivity of (-)-epicatechin was 212.01 KBq/mg, amounting to 8.5% of the total radioactivity of ethyl acetate extract while that of D,L-catechin was 1.0006 MBq/mg or 5.4% of the total. (C) 2001 Elsevier Science B.V. All rights reserved. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. Hangzhou Univ Commerce, Inst Food & Biol Engn, Hangzhou 310035, Peoples R China. Chinese Acad Agr Sci, Tea Res Inst, Hangzhou 31008, Peoples R China. RP Ito, Y (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 10,Rm 7N322,10 Ctr Dr MSC 1676, Bethesda, MD 20892 USA. NR 7 TC 7 Z9 7 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD JUL 6 PY 2001 VL 921 IS 2 BP 331 EP 334 DI 10.1016/S0021-9673(01)00862-7 PG 4 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 448VT UT WOS:000169651200023 PM 11471817 ER PT J AU Sausville, EA AF Sausville, EA TI Scientific summation and future goals SO JOURNAL OF CONTROLLED RELEASE LA English DT Editorial Material C1 NCI, DCTD, Dev Therapeut Program, NIH, Rockville, MD 20852 USA. RP Sausville, EA (reprint author), NCI, DCTD, Dev Therapeut Program, NIH, 6130 Execut Blvd,Suite 8000, Rockville, MD 20852 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-3659 J9 J CONTROL RELEASE JI J. Control. Release PD JUL 6 PY 2001 VL 74 IS 1-3 BP 1 EP 6 DI 10.1016/S0168-3659(01)00305-4 PG 6 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 465RK UT WOS:000170603600002 PM 11489478 ER PT J AU Banerjee, RK van Osdol, WW Bungay, PM Sung, C Dedrick, RL AF Banerjee, RK van Osdol, WW Bungay, PM Sung, C Dedrick, RL TI Finite element model of antibody penetration in a prevascular tumor nodule embedded in normal tissue SO JOURNAL OF CONTROLLED RELEASE LA English DT Article; Proceedings Paper CT International Symposium on Tumor Targeted Delivery Systems CY SEP 25-27, 2000 CL BETHESDA, MARYLAND SP NCI, Controlled Release Soc DE monoclonal antibody; diffusion; pharmacokinetics; tumor antigen; finite element method ID PROTOCOLS; BINDING; BIOTIN AB We have developed a pharmacokinetic model for monoclonal antibodies (mAb) to aid in investigating protocols for targeting small primary tumors or sites of metastatic disease. The model describes the uptake of systemically-administered antibody by a prevascular spherical tumor nodule embedded in normal tissue. The model incorporates plasma kinetics, transcapillary transport, interstitial diffusion, binding reactions, and lymphatic clearance. Antigen internalization can easily be incorporated. Simulations obtained from a three-dimensional finite element analysis are used to assess errors in predictions from earlier models in which the influence of the normal tissue was collapsed into a boundary condition at the tumor surface. The model employing a Dirichlet boundary condition substantially overpredicted the mean total tumor mAb concentration at all times. Although the model with a concentration-dependent flux (composite) boundary condition underpredicted mAb concentration, the discrepancy with finite element results is only notable at early times. Sensitivity analyses were performed on mAb dose and on the coefficients for mAb diffusion in the tissue regions, since reported antibody diffusivity values have varied over 30-fold. The results of the study suggest that rnAb diffusivity and mAb binding site density in tumors should have major influences on optimizing doses and scheduling of mAb administration in tumor targeting protocols. (C) 2001 Elsevier Science B.V. All rights reserved. C1 ALZA Corp, Mt View, CA 94043 USA. Human Genome Sci Inc, Rockville, MD 20850 USA. Off Res Serv, Div Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA. RP Bungay, PM (reprint author), DBEPS, NIH, Bldg 13-3N17 MSC 5766, Bethesda, MD 20892 USA. NR 9 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-3659 J9 J CONTROL RELEASE JI J. Control. Release PD JUL 6 PY 2001 VL 74 IS 1-3 BP 193 EP 202 DI 10.1016/S0168-3659(01)00317-0 PG 10 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 465RK UT WOS:000170603600019 PM 11489495 ER PT J AU Kasuya, Y Lu, ZR Kopeckova, P Minko, T Tabibi, SE Kopecek, J AF Kasuya, Y Lu, ZR Kopeckova, P Minko, T Tabibi, SE Kopecek, J TI Synthesis and characterization of HPMA copolymer-aminopropylgeldanamycin conjugates SO JOURNAL OF CONTROLLED RELEASE LA English DT Article; Proceedings Paper CT International Symposium on Tumor Targeted Delivery Systems CY SEP 25-27, 2000 CL BETHESDA, MARYLAND SP NCI, Controlled Release Soc DE geldanamycin; HPMA copolymer; ovarian carcinoma; heat shock protein; drug delivery system ID N-(2-HYDROXYPROPYL)METHACRYLAMIDE CO-POLYMERS; OVARIAN-CARCINOMA CELLS; BOUND ADRIAMYCIN; ANTITUMOR AGENT; IN-VITRO; GELDANAMYCIN; ANSAMYCINS; ANTIBODY; COMPLEX; TUMOR AB Geldanamycin (GDM) is a benzoquinone ansamycin antibiotic with anticancer activity. The use of drug delivery systems based on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers containing lysosomally degradable oligopeptide (GFLG) spacers results in an increased therapeutic efficacy of anticancer drugs. The objective of this study was to synthesize HPMA copolymer-GDM conjugates with anticancer activity and reduced toxic side-effect of the compound. 17-(3-Aminopropylamino)-17-demethoxygeldanamycin (AP-GDM) was synthesized and converted into a polymerizable GDM derivative, N-methacryloylglycylphenytalanylglycyl-17-(3-aminopropylamino)-17-demethoxygeldanamycin [MA-GFLG-(AP-GDM)]. The structures of AP-GDM and MA-GFLG-(AP-GDM) were validated by mass spectroscopy, elemental analysis, and two-dimensional nuclear magnetic resonance. MA-GFLG-(AP-GDM) was copolymerized with HPMA and N-methacryloyglycylglycine p-nitrophenylester by radical precipitation polymerization, Water-soluble HPMA copolymer-AP-GDM conjugates (M-c = 16 kDa) were obtained. Monoclonal antibody OV-TL16. which recognizes the OA-3 antigen expressed on the OVCAR-3 human ovarian carcinoma cell line, was optionally attached to the HPMA copolymer-AP-GDM conjugate. Cytotoxicity of polymer-bound AP-GDM (both targeted and non-targeted) was determined using OVCAR-3 and another human ovarian carcinoma cell line, A2780, The HPMA copolymer-AP-GDM conjugate was cytotoxic toward A2780 cells. Attachment of OV-TL16 antibody enhanced cytotoxicity of the conjugate toward OVCAR-3 cells. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Univ Utah, Dept Pharmaceut & Pharmaceut Chem, CCCD, Salt Lake City, UT 84112 USA. Univ Utah, Dept Bioengn, Salt Lake City, UT 84112 USA. NCI, Pharmaceut Resources Branch, NIH, Bethesda, MD 20892 USA. RP Kopecek, J (reprint author), Univ Utah, Dept Pharmaceut & Pharmaceut Chem, CCCD, 30 S 2000 E Room 301, Salt Lake City, UT 84112 USA. FU NCI NIH HHS [CA51578] NR 41 TC 39 Z9 42 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-3659 J9 J CONTROL RELEASE JI J. Control. Release PD JUL 6 PY 2001 VL 74 IS 1-3 BP 203 EP 211 DI 10.1016/S0168-3659(01)00318-2 PG 9 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 465RK UT WOS:000170603600020 PM 11489496 ER PT J AU Plewnia, C Bartels, M Cohen, L Gerloff, C AF Plewnia, C Bartels, M Cohen, L Gerloff, C TI Noradrenergic modulation of human cortex excitability by the presynaptic alpha(2)-antagonist yohimbine SO NEUROSCIENCE LETTERS LA English DT Article DE transcranial magnetic stimulation; motor cortex; yohimbine; motor system excitability; norepinephrine; intracortical facilitation; intracortical inhibition ID HUMAN MOTOR CORTEX; BRAIN INJURY; RECOVERY; AMPHETAMINE; PHARMACOTHERAPY; PLASTICITY; INHIBITION; ABLATION; THERAPY; STROKE AB The objective of this study was to determine if yohimbine, a central norepinephrine enhancing drug, increases corticomotoneuronal excitability in intact humans. Transcranial magnetic, stimulation was used to assess excitability of the motor system reflected in the parameters motor threshold, recruitment curve, intracortical inhibition and intracortical facilitation before and after oral administration of 20 and 40 mg yohimbine. Oral intake of 40 but not 20 mg yohimbine increased slope and plateau of the recruitment curve and intracortical facilitation. Motor threshold and intracortical inhibition remained unchanged. The data show that pharmacological enhancement of central norepinephrine in humans is effective to increase the cortico-motoneuronal excitability. Since cortical excitability is closely linked to neuroplasticity, this observation might be of possible relevance for strategies to enhance rehabilitative processes after cortical lesions by pairing noradrenergic drugs with motor training. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Tubingen, Cort Physiol Res Grp, Dept Neurol, D-72076 Tubingen, Germany. Univ Tubingen, Neurophysiol Sect, Dept Psychiat, D-72076 Tubingen, Germany. NINDS, Human Cort Physiol Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Gerloff, C (reprint author), Univ Tubingen, Cort Physiol Res Grp, Dept Neurol, Hoppe Seyler Str 3, D-72076 Tubingen, Germany. RI Plewnia, Christian/D-1652-2015 NR 18 TC 35 Z9 35 U1 0 U2 3 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 6 PY 2001 VL 307 IS 1 BP 41 EP 44 DI 10.1016/S0304-3940(01)01921-8 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 448FD UT WOS:000169615500011 PM 11516570 ER PT J AU Boguna, M Kullman, L Bezrukov, SM Berezhkovskii, AM Weiss, GH AF Boguna, M Kullman, L Bezrukov, SM Berezhkovskii, AM Weiss, GH TI Rate constants from uncorrelated single-molecule data SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID RESIDENCE TIME DENSITIES; NON-MARKOVIAN SYSTEMS AB We describe a method for estimating rate constants of a two-state Markov system from data obtained by a single-molecule (SM) type of experiment corrupted by white noise. The method is effective even when the characteristic (or resolution) time of the measurement is much longer than a characteristic time of the two-state system, and the data are uncorrelated. We apply our suggested method to data from an SM:experiment on the transport of sugar molecules through cell membrane channels. The method is quite accurate in analyzing this set of data. We also demonstrate that in some cases the method can be used to check whether the system is Markovian or not. C1 NICHD, Ctr Informat Technol, NIH, Bethesda, MD 20892 USA. NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. St Petersburg Nucl Phys Inst, Gatchina 188350, Russia. Karpov Inst Phys Chem, Moscow 103064, Russia. RP Weiss, GH (reprint author), NICHD, Ctr Informat Technol, NIH, Bethesda, MD 20892 USA. RI Boguna, Marian/B-7795-2011 OI Boguna, Marian/0000-0001-7833-3487 NR 14 TC 3 Z9 3 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1089-5647 J9 J PHYS CHEM B JI J. Phys. Chem. B PD JUL 5 PY 2001 VL 105 IS 26 BP 6246 EP 6250 DI 10.1021/jp0106451 PG 5 WC Chemistry, Physical SC Chemistry GA 449YB UT WOS:000169713800026 ER PT J AU Shen, XH Knutson, JR AF Shen, XH Knutson, JR TI Subpicosecond fluorescence spectra of tryptophan in water SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID TIME-RESOLVED FLUORESCENCE; STATE PROTON-TRANSFER; EXCITED-STATE; INDOLE-DERIVATIVES; SOLVENT RELAXATION; DYE MOLECULES; SOLVATION; DYNAMICS; PROTEINS; PHOTOIONIZATION AB A femtosecond ultraviolet fluorescence spectrophotofluorometer has been exploited for the study of tryptophan and analogues. Using a time resolution better than 300 fs, time-resolved emission spectra have been constructed for TRP in water. They reveal an initial spectrum shifted 4900 cm(-1) from the putative 0-0 band at 295 nm, along with a picosecond relaxation to a spectrum 412 cm(-1) lower and 322 cm(-1) wider. The time constant of this "solvent relaxation" of tryptophan in water was similar to1.2 ps, as expected for forced diffusive reorientation of nearby solvent molecules upon excitation. Emission anisotropy measurements on the same time scale, obtained at a wide range of excitation and emission wavelengths, yielded "r(0)" (apparent initial anisotropies) compatible with classical measurements in glassy: solvents and single-exponential anisotropy decay. This implies that any state conversion must occur well within the impulse response of our instrument; eg., tau (IC) < 300 fs. Even upon "red edge" (301 nm) excitation, the initial anisotropy of tryptophan was still well below the theoretical. limit, 0.4. Either L-1(b) overlap of L-1(a) persists there, or the orientation of the emission transition dipole is not strictly parallel with that of L-1(a) absorption. C1 NHLBI, Opt Spect Sect, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Knutson, JR (reprint author), NHLBI, Opt Spect Sect, Biophys Chem Lab, NIH, Bldg 10,Rm 5D10, Bethesda, MD 20892 USA. NR 44 TC 81 Z9 81 U1 4 U2 18 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1089-5647 J9 J PHYS CHEM B JI J. Phys. Chem. B PD JUL 5 PY 2001 VL 105 IS 26 BP 6260 EP 6265 DI 10.1021/jp010384v PG 6 WC Chemistry, Physical SC Chemistry GA 449YB UT WOS:000169713800028 ER PT J AU Hovey, RC Davey, HW Vonderhaar, BK Mackenzie, DDS McFadden, TB AF Hovey, RC Davey, HW Vonderhaar, BK Mackenzie, DDS McFadden, TB TI Paracrine action of keratinocyte growth factor (KGF) during ruminant mammogenesis SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE keratinocyte growth factor; mammary; epithelial-stromal; ovarian hormones; fat pad ID MAMMARY EPITHELIAL-CELLS; FACTOR GENE-EXPRESSION; FAT PAD; GLAND DEVELOPMENT; IN-VIVO; MORPHOGENESIS; RECEPTOR; DIFFERENTIATION; RNA; INDUCTION AB Keratinocyte growth factor (KGF) is a stroma-derived mitogen mediating epithelial-stromal interactions. We investigated the role of KGF during epithelial-stromal interactions accompanying ruminant marnmogenesis. Target-specificity of KGF was demonstrated in that KGF-stimulated proliferation of bovine mammary epithelial, but not ovine mammary stromal cells. Consistent with a paracrine function, 4.6, 2.4, 1.5 and 0.9 kb mRNA transcripts were expressed by bovine stromal, but not epithelial cells. Within the ovine mammary gland, 2.4 and 1.5 kb KGF mRNAs were expressed in the fat pad while only the 2.4 kb transcript was transcribed in parenchyma. The abundance of KGF mRNA was greater in the extra-parenchymal fat pad than in the contralateral epithelium-free fat pad prior to puberty, and was less in parenchyma than in the intact or epithelium-free fat pads. Ovariectomy tended to increase KGF transcription while estrogen reduced expression. Of several tissues, mammary parenchyma expressed a 2.4 kb mRNA while adipose tissues expressed a 1.5 kb transcript. These results demonstrate local and systemic regulation of KGF transcription and support a paracrine role for KGF during ruminant mammogenesis. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20814 USA. Massey Univ, Dept Anim Sci, Palmerston North, New Zealand. AgRes, Ruakura Res Ctr, Hamilton, New Zealand. RP Hovey, RC (reprint author), NCI, Tumor Immunol & Biol Lab, NIH, Room 5B47,Bldg 10,10 Ctr Dr, Bethesda, MD 20814 USA. NR 50 TC 7 Z9 8 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD JUL 5 PY 2001 VL 181 IS 1-2 BP 47 EP 56 DI 10.1016/S0303-7207(01)00537-8 PG 10 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 466HK UT WOS:000170640000005 PM 11476940 ER PT J AU Khattar, SK Yunus, AS Collins, PL Samal, SK AF Khattar, SK Yunus, AS Collins, PL Samal, SK TI Deletion and substitution analysis defines regions and residues within the phosphoprotein of bovine respiratory syncytial virus that affect transcription, RNA replication, and interaction with the nucleoprotein SO VIROLOGY LA English DT Article ID VESICULAR STOMATITIS-VIRUS; P-PROTEIN; NUCLEOCAPSID PROTEIN; GENOME REPLICATION; TERMINAL DOMAIN; MAMMALIAN-CELLS; CALCIUM-BINDING; 2-HYBRID SYSTEM; MESSENGER-RNAS; NP PROTEIN AB The phosphoprotein (P) of bovine respiratory syncytial virus (BRSV) is a multifunctional protein that plays a central role in transcription and replication of the viral genomic RNA. To investigate the domains and specific residues involved in different activities of the P protein, we generated a total of 22 deletion and 17 point mutants of the P protein. These mutants were characterized using an intracellular BRSV-CAT minigenome replication system for the ability to (1) direct minigenome transcription, (2) direct minigenome replication, and (3) form complexes with nucleocapsid protein (N) and large polymerase protein (L). These studies revealed that all the regions of P protein except amino acids 41-80 are essential for minigenome transcription and replication. Interestingly, amino acids 41-60 appeared to contain sequences that negatively regulate transcription and replication. Analysis of the N- or C-terminal ends indicated that deletion of up to 3 amino acids from the N- or C-terminus completely ablated the replication, while leaving substantial residual transcription. Single amino acid substitutions within the N-terminal 4 or C-terminal 13 amino acids showed that substitution at position 2, 4, 234, 236, 238, 240, or 241 was highly inhibitory to both transcription and replication, whereas substitution at position 3 was highly inhibitory to replication while leaving substantial residual transcription. Substitution of serine residues at the C-terminus indicated that loss of phosphorylation sites did not appear to have any effect on transcription and replication. Coimmunoprecipitation of P-N and P-L complexes with P-specific antiserum revealed that substitution mutations at the N- or C;terminus did not affect binding to N and L proteins, except that substitution mutation at C-terminus position 234, 236, 238, 240, or 241 affected binding to N protein by 10-fold. (C) 2001 Academic Press. C1 Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA. NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. RP Samal, SK (reprint author), Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA. NR 45 TC 13 Z9 13 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JUL 5 PY 2001 VL 285 IS 2 BP 253 EP 269 DI 10.1006/viro.2001.0960 PG 17 WC Virology SC Virology GA 451ZE UT WOS:000169832000009 PM 11437660 ER PT J AU Golinelli, MP Hughes, SH AF Golinelli, MP Hughes, SH TI Self-priming of retroviral minus-strand strong-stop DNAs SO VIROLOGY LA English DT Article DE self-priming; reverse transcriptase; nucleocapsid protein ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 NUCLEOCAPSID PROTEIN; REVERSE-TRANSCRIPTASE; SECONDARY STRUCTURE; MOLECULAR-CLONING; ESCHERICHIA-COLI; TRANS-ACTIVATOR; RNA; HIV-1; SPECIFICITY AB After minus-strand strong-stop DNA (-sssDNA) is synthesized, the RNA template is degraded by the RNase H activity of the reverse transcriptase (RT), generating a single-stranded DNA. The 3 ' end of -sssDNA from HIV-1 can form a hairpin; this hairpin will self-prime in vitro. We previously used a model substrate, -R ssDNA, which corresponds to the 3 ' end of the -sssDNA of HIV-1, to show that the self-priming of this model substrate could be prevented by annealing a 17-nt-long DNA oligonucleotide to the 3 ' end of -R ssDNA in the presence of HIV-1 nucleocapsid (NC) protein. Similar model substrates were prepared for HIV-2 and HTLV-l;the R regions of these two viruses are longer and form more complex structures than the R region of the HIV-1 genome. However, the size of the R region and the complexity of the secondary structures they can form do not affect self-priming or its prevention. The efficiency of the self-priming is related to the relative stabilities of the conformations of -R ssDNA that can and cannot induce self-priming. For the three viruses (HIV-1, HIV-2, and HTLV-1), the size of the DNA oligonucleotide needed to block self-priming in the presence of NC is similar to the expected size of the piece of RNA left after degradation of the RNA template during reverse transcription. We also found that when the 3 ' end of -R ssDNA is annealed to a complementary DNA oligonucleotide, it is a good substrate for efficient nonspecific strand transfer to other single-stranded DNA molecules. C1 NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. RP Hughes, SH (reprint author), NCI, HIV Drug Resistance Program, POB B,Bldg 539,Room 130A, Frederick, MD 21702 USA. RI Golinelli, Marie-Pierre/K-4287-2013 OI Golinelli, Marie-Pierre/0000-0002-6738-8631 NR 37 TC 20 Z9 22 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JUL 5 PY 2001 VL 285 IS 2 BP 278 EP 290 DI 10.1006/viro.2001.0970 PG 13 WC Virology SC Virology GA 451ZE UT WOS:000169832000011 PM 11437662 ER PT J AU Swain, SM AF Swain, SM TI Tamoxifen and contralateral breast cancer: the other side SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID ESTROGEN-RECEPTOR; RANDOMIZED TRIAL; THERAPY; TUMORS C1 NCI, Med Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Swain, SM (reprint author), NIH, 10 Ctr Dr,Bldg 10,Rm 12N226,MSC 1906, Bethesda, MD 20892 USA. NR 15 TC 8 Z9 8 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUL 4 PY 2001 VL 93 IS 13 BP 963 EP 965 DI 10.1093/jnci/93.13.963 PG 3 WC Oncology SC Oncology GA 447TK UT WOS:000169588400001 PM 11438553 ER PT J AU Kleinman, HK Liau, G AF Kleinman, HK Liau, G TI Gene therapy for antiangiogenesis SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID ANGIOGENESIS; ENDOSTATIN; GROWTH; CANCER C1 Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. Genet Therapy Inc, Gaithersburg, MD USA. RP Kleinman, HK (reprint author), NIH, Bldg 30,Rm 407, Bethesda, MD 20902 USA. NR 21 TC 16 Z9 16 U1 0 U2 3 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUL 4 PY 2001 VL 93 IS 13 BP 965 EP 967 DI 10.1093/jnci/93.13.965 PG 3 WC Oncology SC Oncology GA 447TK UT WOS:000169588400002 PM 11438554 ER PT J AU Eifel, P Axelson, JA Costa, J Crowley, J Curran, WJ Deshler, A Fulton, S Hendricks, CB Kemeny, M Kornblith, AB Louis, TA Markman, M Mayer, R Roter, D AF Eifel, P Axelson, JA Costa, J Crowley, J Curran, WJ Deshler, A Fulton, S Hendricks, CB Kemeny, M Kornblith, AB Louis, TA Markman, M Mayer, R Roter, D CA Natl Inst Hlth Consensus Dev Panel TI National Institutes of Health Consensus Development Conference statement: Adjuvant therapy for breast cancer, November 1-3, 2000 SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HIGH-DOSE CHEMOTHERAPY; COOPERATIVE-ONCOLOGY-GROUP; RANDOMIZED TRIAL; PREMENOPAUSAL WOMEN; PROGNOSTIC FACTORS; STAGE-II; DOXORUBICIN-CYCLOPHOSPHAMIDE; PREOPERATIVE CHEMOTHERAPY; TAMOXIFEN THERAPY; CELL SUPPORT AB Our goal was to provide health-care providers, patients, and the general public with an assessment of currently available data regarding the use of adjuvant therapy for breast cancer. Participants: The participants included a non-Federal, non-advocate, 14-member panel representing the fields of oncology, radiology, surgery, pathology, statistics, public health, and health policy as well as patient representatives. In addition, 30 experts in medical oncology, radiation oncology, biostatistics, epidemiology, surgical oncology, and clinical trials presented data to the panel and to a conference audience of 1000. Evidence: The literature was searched with the use of MEDLINE(R) for January 1995 through July 2000, and an extensive bibliography of 2230 references was provided to the panel. Experts prepared abstracts for their conference presentations with relevant citations from the literature. Evidence from randomized clinical trials and evidence from prospective studies were given precedence over clinical anecdotal experience. Consensus Process: The panel, answering predefined questions, developed its conclusions based on the evidence presented in open forum and the scientific literature. The panel composed a draft statement, which 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. The draft statement was made available on the World Wide Web immediately after its release at the conference and was updated with the panel's final revisions. The statement is available at http://consensus.nih.gov. Conclusions. The panel concludes that decisions regarding adjuvant hormonal therapy should be based on the presence of hormone receptor protein in tumor tissues. Adjuvant hormonal therapy should be offered only to women whose tumors express hormone receptor protein. Because adjuvant polychemotherapy improves survival, it should be recommended to the majority of women with localized breast cancer regardless of lymph node, menopausal, or hormone receptor status. The inclusion of anthracyclines in adjuvant chemotherapy regimens produces a small but statistically significant improvement in survival over non-anthracycline-containing regimens. Available data are currently inconclusive regarding the use of taxanes in adjuvant treatment of lymph node-positive breast cancer. The use of adjuvant dose-intensive chemotherapy regimens in high-risk breast cancer and of taxanes in lymph node-negative breast cancer should be restricted to randomized trials. Ongoing studies evaluating these treatment strategies should be supported to determine if such strategies have a role in adjuvant treatment. Studies to date have included few patients older than 70 years. There is a critical need for trials to evaluate the role of adjuvant chemotherapy in these women. There is evidence that women with a high risk of locoregional tumor recurrence after mastectomy benefit from postoperative radiotherapy. This high-risk group includes women with four or more positive lymph nodes or an advanced primary cancer. Currently, the role of postmastectomy radiotherapy for patients with one to three positive lymph nodes remains uncertain and should be tested in a randomized controlled trial. Individual patients differ in the importance they place on the risks and benefits of adjuvant treatments. Quality of life needs to be evaluated in selected randomized clinical trials to examine the impact of the major acute and long-term side effects of adjuvant treatments, particularly premature menopause, weight gain, mild memory loss, and fatigue. Methods to support shared decision-making between patients and their physicians have been successful in trials; they need to be tailored for diverse populations and should be tested for broader dissemination. C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Hematol & Oncol Associates, Jackson, MI USA. Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. Yale Univ, Sch Med, Yale Canc Ctr, New Haven, CT USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Thomas Jefferson Univ Hosp, Dept Radiat Oncol, Philadelphia, PA 19107 USA. Inst Res & Educ Hlth Syst Minnesota, Metro Minnesota Community Clin Oncol Program, St Louis Pk, MN USA. Superior Court Judge Off, Charlotte, NC USA. Suburban Specialty Care Phys PC, Bethesda, MD USA. SUNY Stony Brook, Univ Hosp & Med Ctr, Div Surg Oncol, Stony Brook, NY 11794 USA. Beth Israel Med Ctr, Dept Pain Med & Palliat Care, New York, NY 10003 USA. Beth Israel Med Ctr, Ctr Canc, New York, NY 10003 USA. RAND Corp, Arlington, VA USA. Cleveland Clin Fdn, Dept Hematol & Med Oncol, Lee & Jerome Burkons Res Chair Oncol, Cleveland, OH 44195 USA. Cleveland Clin, Taussig Canc Ctr, Cleveland, OH 44106 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD USA. RP Eifel, P (reprint author), Care of Bowersox JA, NIH, Off Med Applicat Res, Bldg 31,Rm 1B03, Bethesda, MD 20892 USA. RI Roter, Debra/N-8830-2014 NR 88 TC 504 Z9 515 U1 5 U2 25 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUL 4 PY 2001 VL 93 IS 13 BP 979 EP 989 PG 11 WC Oncology SC Oncology GA 447TK UT WOS:000169588400008 PM 11438563 ER PT J AU Gupta, A Nines, R Rodrigo, KA Aziz, RA Carlton, PS Gray, DL Steele, VE Morse, MA Stoner, GD AF Gupta, A Nines, R Rodrigo, KA Aziz, RA Carlton, PS Gray, DL Steele, VE Morse, MA Stoner, GD TI Effects of dietary N-(4-hydroxyphenyl)retinamide on N-nitrosomethylbenzylamine metabolism and esophageal tumorigenesis in the Fischer 344 rat SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ORNITHINE DECARBOXYLASE ACTIVITY; RETINYL ACETATE; MAMMARY CARCINOGENESIS; TUMOR PROMOTION; A/J MICE; CANCER; CHEMOPREVENTION; INHIBITION; ACID; NITROSOBENZYLMETHYLAMINE AB Background: 9-cis-Retinoic acid (9-cis-RA) and N-(4-hydroxyphenyl)retinamide (4-HPR) are effective chemopreventive. agents against epithelial tumors in the oral cavity, breast,and prostate. We tested the inhibitory activity of these retinoids against N-nitrosomethylbenzylamine (NMBA)-induced tumorigenesis in the rat esophagus, Methods: Male Fischer 344 rats were randomly assigned to receive diets either lacking or containing 9-cis-RA or 4-HPR for 1 week before tumor initiation with NMBA and then for the duration of the study. NMBA metabolism, O-6-methylguanine adduct formation, and cytochrome P450 messenger RNA (mRNA) expression in the esophagi of the rats were studied to investigate the mechanisms by which dietary 4-HPR affects tumorigenesis. All statistical tests were two-sided. Results: Dietary 4-HPR resulted in a dose-dependent and statistically significant enhancement (P < .05) of tumorigenesis in response to NMBA, In two different tumor bioassays, the mean tumor multiplicity for rats fed the highest concentration of dietary 4-HPR (0.8 g/kg diet) was increased by 5.9 tumors (95% confidence interval [CI] = 1.7 to 10.1 tumors) and 6.7 tumors (95% CI = 5.6 to 7.8 tumors) compared with the mean tumor multiplicity for rats that received the control diet lacking 4-HPR. Animals fed diets containing 9-cis-RA displayed no statistically significant increase in tumorigenesis, Compared with animals fed a diet lacking 4-HPR; animals fed 4-HPR had increased NMBA metabolism in esophageal explant cultures and had higher levels of O-6-methylguanine DNA adducts and CYP2A3 mRNA in their esophagi. Conclusions: Dietary 4-HPR enhances tumorigenesis in response to NMBA in the rat esophagus by increasing tumor initiation events. Dietary 4-HPR may exert paradoxical effects at some sites, such as the aerodigestive tract, by modulating the bioactivation of carcinogens in target tissues. C1 Ohio State Univ, Sch Publ Hlth, Div Environm Hlth Sci, Columbus, OH 43210 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. NCI, Div Canc Prevent & Control, Bethesda, MD 20892 USA. RP Stoner, GD (reprint author), Ohio State Univ, Sch Publ Hlth, James Canc Hosp & Solove Res Inst, Div Environm Hlth Sci, 300 W 10th Ave, Columbus, OH 43210 USA. FU NCI NIH HHS [P01CA46535, P30CA16058-22] NR 57 TC 8 Z9 9 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUL 4 PY 2001 VL 93 IS 13 BP 990 EP 998 DI 10.1093/jnci/93.13.990 PG 9 WC Oncology SC Oncology GA 447TK UT WOS:000169588400009 PM 11438564 ER PT J AU Feldman, AL Alexander, HR Hewitt, SM Lorang, D Thiruvathukal, CE Turner, EM Libutti, SK AF Feldman, AL Alexander, HR Hewitt, SM Lorang, D Thiruvathukal, CE Turner, EM Libutti, SK TI Effect of retroviral endostatin gene transfer on subcutaneous and intraperitoneal growth of murine tumors SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ANGIOGENESIS INHIBITOR TNP-470; PLASMIDS ENCODING ANGIOSTATIN; NUDE-MICE; BREAST-CANCER; TRANSGENE EXPRESSION; MALIGNANT ASCITES; LIVER METASTASES; HIGH-LEVEL; THERAPY; ADENOVIRUS AB Background: Inhibiting tumor angiogenesisis a promising new strategy for treating cancer. Difficulties with the stability,: manufacture, and long-term administration of recombinant antiangiogenic proteins have prompted investigators to use gene therapy to generate these proteins in vivo. We investigated whether transfer of the gene encoding the angiogenesis inhibitor endostatin into the murine liver cell line NMuLi could inhibit tumor growth in vivo. Methods: NMuLi cells were transduced with retroviral vectors containing the murine endostatin gene, The presence and function of endostatin in transduced cell supernatants were confirmed by competitive enzyme immunoassay and endothelial cell proliferation assays. Nude mice were given a subcutaneous or intraperitoneal injection with NMuLi cells, control transduced cells (NEF-null), or endostatin-transduced clones (NEF-Endo1 to 4) and were monitored for tumor growth. All statistical tests were two-sided. Results: Supernatants from the clone secreting the lowest amount of endostatin (NEF-Endo4,: 28 ng/mL) inhibited endothelial cell proliferation by 6% (95% confidence interval [CI] = 0% to 12%), and those from the clone secreting the highest amount (NEF-Endo1, 223 ng/mL) inhibited endothelial cell proliferation by 20% (95% CI = 13% to 27%). Increased levels of endostatin were detected in tumor lysates, but not serum, of mice given a subcutaneous injection of: NEF-Endo1 cells. After 63 days, mice given a subcutaneous injection of parental NMuLi or NEF-null cells had tumor volumes of 2400 mm(3) (95% CI = 1478 mm(3) to 3300 mm(3)) and 2700 mm(3) (95% CI = 2241 mm(3) to 3144 mm(3)),:respectively, compared with mean tumor volumes of less than 30 mm(3) in mice given an injection of NEF-Endo clones, a statistically significant difference (P < .001), After 123 days, all 16 mice given an intraperitoneal injection of parental NMuLi or NEF-null cells had died, compared with only three (9%) of 32 mice given an injection of NEF-Endo clones. Conclusions: Retroviral endostatin gene transfer leads to secretion of functional endostatin that is sufficiently active to inhibit tumor growth. Further studies of retroviral endostatin gene transfer for the treatment of cancer are warranted. C1 NCI, Surg Metab Sect, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Libutti, SK (reprint author), NIH, Bldg 10,Rm 3C428, Bethesda, MD 20892 USA. RI Feldman, Andrew/D-5028-2012; OI Hewitt, Stephen/0000-0001-8283-1788 NR 35 TC 43 Z9 50 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUL 4 PY 2001 VL 93 IS 13 BP 1014 EP 1020 DI 10.1093/jnci/93.13.1014 PG 7 WC Oncology SC Oncology GA 447TK UT WOS:000169588400012 PM 11438567 ER PT J AU Ronckers, CM Land, CE Verduijn, PG Hayes, RB Stovall, M van Leeuwen, FE AF Ronckers, CM Land, CE Verduijn, PG Hayes, RB Stovall, M van Leeuwen, FE TI Cancer mortality after nasopharyngeal radium irradiation in the Netherlands: a cohort study SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID IONIZING-RADIATION; SKIN HEMANGIOMA; POOLED ANALYSIS; UNITED-STATES; FOLLOW-UP; RADIOTHERAPY; CHILDHOOD; EXPOSURE; TUMORS; SUBMARINERS C1 Netherlands Canc Inst, Dept Epidemiol, NL-1066 CX Amsterdam, Netherlands. Reinaert Klin, Dept Ear Nose & Throat Med, Maastricht, Netherlands. NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. RP Ronckers, CM (reprint author), Netherlands Canc Inst, Dept Epidemiol, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands. FU NCI NIH HHS [N01CP330013] NR 42 TC 10 Z9 11 U1 1 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUL 4 PY 2001 VL 93 IS 13 BP 1021 EP 1027 DI 10.1093/jnci/93.13.1021 PG 7 WC Oncology SC Oncology GA 447TK UT WOS:000169588400013 PM 11438568 ER PT J AU Murphy, EL Collier, AC Kalish, LA Assmann, SF Para, MF Flanigan, TP Kumar, PN Mintz, L Wallach, FR Nemo, GJ AF Murphy, EL Collier, AC Kalish, LA Assmann, SF Para, MF Flanigan, TP Kumar, PN Mintz, L Wallach, FR Nemo, GJ CA Viral Activation Transfusion Study TI Highly active antiretroviral therapy decreases mortality and morbidity in patients with advanced HIV disease SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS INFECTION; PNEUMOCYSTIS-CARINII PNEUMONIA; CYTOMEGALOVIRUS RETINITIS; COMBINATION THERAPY; PROTEASE INHIBITORS; DECLINING MORBIDITY; INCREASING SURVIVAL; AIDS PATIENTS; IMPACT; RISK AB Background: Mortality and morbidity related to AIDS have decreased among HIV-infected patients taking highly active antiretroviral therapy (HAART), but previous studies may have been confounded by other changes in treatment. Objective: To assess the benefit of HAART in patients with advanced AIDS and anemia. Design: Prospective, multicenter cohort study. Setting: The Viral Activation Transfusion Study (VATS), with enrollment from August 1995 through July 1998 and follow-up through June 1999. Patients: 528 HIV-infected patients with cytomegalovirus (CMV) seropositivity or disease who were receiving a first red blood cell transfusion for anemia. Measurements: In a person-year analysis of follow-up before and after initiation of HAART, Poisson regression was used to calculate crude rate ratios and rate ratios adjusted for CD4 count, HIV RNA level, calendar period, time on study, sex, ethnicity, and injection drug use. Results: At baseline, patients had a median CD4(+) lymphocyte count of 0.015 x 10(9) cell/L, median plasma HIV RNA level of 4.8 log(10) copies/mL, and median hemoglobin concentration of 73 g/L. Use of HAART increased from 1% of active patients in January 1996 to 79% of active patients in January 1999. The crude death rate was 0.24 event/person-year among patients taking HAART and 0.88 event/person-year among those not taking HAART (rate ratio, 0.26; adjusted rate ratio, 0.38; P < 0.001 for both comparisons). Rates of non-CMV disease were 0.15 event/ person-year after HAART and 0.45 event/person-year before HAART (crude rate ratio, 0.34 [P < 0.001]; adjusted rate ratio, 0.66 [P < 0.05]). Rates of CMV disease were 0.10 event/person-year after HAART and 0.25 before HAART (crude rate ratio, 0.42 [P < 0.01]; adjusted rate ratio, 1.01 [P > 0.2]). Results were similar in patients with baseline CD4(+) lymphocyte counts less than 0.010 x 10(9) cells/L. Conclusions: The data support an independent reduction in mortality and opportunistic events attributable to HAART, even in patients with very advanced HIV disease. However, patients with CMV infection or disease may not have a reduction in new CMV events due to HAART. C1 Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. Univ Washington, Seattle, WA 98104 USA. New England Res Inst, Watertown, MA 02172 USA. Ohio State Univ, Columbus, OH 43210 USA. Brown Univ, Sch Med, Miriam Hosp, Providence, RI 02906 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Mt Sinai Med Ctr, New York, NY 10029 USA. NHLBI, Bethesda, MD 20892 USA. RP Murphy, EL (reprint author), Univ Calif San Francisco, Dept Lab Med, Box 0884, San Francisco, CA 94143 USA. FU NHLBI NIH HHS [N01-HB-57121] NR 35 TC 340 Z9 363 U1 3 U2 10 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUL 3 PY 2001 VL 135 IS 1 BP 17 EP 26 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 449JC UT WOS:000169680500003 PM 11434728 ER PT J AU Sinz, A Wang, K AF Sinz, A Wang, K TI Mapping protein interfaces with a fluorogenic cross-linker and mass spectrometry: Application to nebulin-calmodulin complexes SO BIOCHEMISTRY LA English DT Article ID SKELETAL-MUSCLE; ACTIN-FILAMENTS; CALCIUM-BINDING; THIN-FILAMENTS; FRAGMENTS; LINKING; IDENTIFICATION; SPECTROSCOPY; ARCHITECTURE; RESOLUTION AB Nebulin is a giant multifunctional protein that is thought to serve as both a length-regulating protein ruler and calcium/CaM-mediated regulatory protein on the thin filaments of the skeletal muscle sarcomere. To define molecular interfaces between nebulin and CaM, we thiolated lysines of CaM and ND66, a four-module cloned fragment from the C-terminus of nebulin, with 2-iminothiolane and crosslinked the complex with dibromobimane, which alkylates thiol pairs within similar to6 Angstrom of each other to form a fluorescent adduct, Such a two-stage cross-linking generated mainly 1:1 complexes of ND66 and CaM, with a limited extent of intramolecular cross-linking. In-gel chymotryptic digestion of the dibromobimane-cross-linked complexes yielded peptides that were first screened by HPLC with fluorescence detection and then scored for cross-linking with mass spectrometry. Several inter- and intramolecular sites were identified and confirmed further by ESI-MS/MS experiments, defining molecular interfaces and patterns of protein folding. In particular, five intermolecular cross-linking products of sequences within the region of amino acids 83-99 (YKENMGKGTPLPVTPEM) in ND66 and several sequences of CaM indicate that the nebulin-CaM interface is close to, and may overlap with, the nebulin-actin interface. This proximity suggests a potential competition between CaM and actin for this nebulin interface, Intramolecular cross-linking of amino acids 13-16 (KEAF) and 13-18 (KEAFSL) with amino acids 145-148 (MTAK) and 146-148 (TAK) in CaM suggests the interaction of two lobes across the central helix. The crosslinking of amino acids 1-6 (MKTPEM) with amino acids 114-129 (YKENVGKATATPVTPE) and 115-129 (KENVGKATATPVTPE) in ND66 hints at an association of noncontiguous nebulin modules in solution. C1 NIAMSD, Phys Biol Lab, NIH, Bethesda, MD 20892 USA. RP Wang, K (reprint author), NIAMSD, Phys Biol Lab, NIH, Bldg 6,Rm 401, Bethesda, MD 20892 USA. NR 38 TC 46 Z9 48 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUL 3 PY 2001 VL 40 IS 26 BP 7903 EP 7913 DI 10.1021/bi010259+ PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 448CR UT WOS:000169610100018 PM 11425319 ER PT J AU Lavigne, MC Malech, HL Holland, SM Leto, TL AF Lavigne, MC Malech, HL Holland, SM Leto, TL TI Genetic demonstration of p47phox-dependent superoxide anion production in murine vascular smooth muscle cells SO CIRCULATION LA English DT Article DE muscle, smooth; NADPH oxidase; p47phox; transduction; superoxide ID CHRONIC GRANULOMATOUS-DISEASE; NADPH OXIDASE; ANGIOTENSIN-II; SIGNAL-TRANSDUCTION; ENDOTHELIAL-CELLS; NAD(P)H OXIDASE; EXPRESSION; ATHEROSCLEROSIS; HYPERTENSION; SYSTEM AB Background-Previous investigations provide evidence that an enzyme related to the phagocyte NADPH oxidase produces superoxide in the blood vessel wall. These data, however, are confounded by observations that both NADPH and NADH serve as substrates for superoxide production in vascular cells. To clarify this issue, we compared the superoxide-generating capabilities of vascular smooth muscle cells (VSMCs) derived from wild-type (p47phox(+/+); phagocyte oxidase) mice with those from mice that lack p47phox (p47phox(-/-); "knockout"), an essential component of the phagocyte NADPH oxidase, Methods nod Results-VSMCs were derived from aortic explants harvested from p47phox(+/+) or p47phox(-/-) mice. VSMCs from p47phox(+/+) but not those from p47phox(-/-) mice produced superoxide after stimulation by phorbol myristate acetate. Consistent with this, p47phox was detected only in p47phox(+/+) VSMCs. p47phox-transduced p47phox(-/-) but not enhanced green fluorescent protein-transduced p47phox(-/-) VSMCs generated significant levels of superoxide after stimulation by angiotensin II or platelet-derived growth factor-BE (PDGF-BB). Enhanced expression of recombinant p47phox in p47phox-transduced p47phox(-/-) cells correlated with superoxide production in these cells. Conclusions-These data provide direct functional proof that an oxidase requiring the p47phox component mediates superoxide release from VSMCs in the blood vessel wall in response to angiotensin II or PDGF-BB. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Leto, TL (reprint author), NIAID, Host Def Lab, NIH, Bldg 10,Room 11N106,10 Ctr Dr, Bethesda, MD 20892 USA. NR 35 TC 106 Z9 108 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL 3 PY 2001 VL 104 IS 1 BP 79 EP 84 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 449VE UT WOS:000169707200018 PM 11435342 ER PT J AU Diaz-Cabiale, Z Hurd, Y Guidolin, D Finnman, UB Zoli, M Agnati, LF Vanderhaeghen, JJ Fuxe, K Ferre, S AF Diaz-Cabiale, Z Hurd, Y Guidolin, D Finnman, UB Zoli, M Agnati, LF Vanderhaeghen, JJ Fuxe, K Ferre, S TI Adenosine A2A agonist CGS 21680 decreases the affinity of dopamine D2 receptors for dopamine in human striatum SO NEUROREPORT LA English DT Article DE A2A receptor; adenosine; D2 receptor; dopamine; human; striatum ID BASAL GANGLIA; CELLS; STIMULATION; BINDING; BRAIN AB Adenosine A2A receptors (A2AR) and dopamine D2 receptors (D2R) are highly concentrated in the striatum, where they are co-localized and exert reciprocal antagonistic interactions. It has been suggested that the A2R/D2R interactions might provide a therapeutic approach for basal ganglia disorders, such as Parkinson's disease, and schizophrenia. In the present work evidence is presented for the existence of an A2AR/D2R interaction in human brain by using quantitative autoradiography. The areas analyzed were the dorsal caudate nucleus and putamen. Parallel studies were performed in rat striatal sections. The A2AR agonist CGS 21680 was found to significantly increase IC50 values of competitive inhibition curves of the D2R/D3R antagonist [I-125]iodosulpiride vs dopamine both in rat striatal and human striatal brain sections. NeuroReport 12:1831-1834 (C) 2001 Lippincott Williams & Wilkins. C1 NIDA, Behav Neurosci Branch, NIH, Intramural Res Program, Baltimore, MD 21224 USA. Karolinska Inst, Dept Neurosci, Stockholm, Sweden. Karolinska Hosp, Dept Clin Neurosci, S-10401 Stockholm, Sweden. Univ Modena & Reggio Emilia, Dept Biomed Sci, Physiol Sect, Modena, Italy. Free Univ Brussels, Fac Med, Neurophysiol Lab, Brussels, Belgium. RP Ferre, S (reprint author), NIDA, Behav Neurosci Branch, NIH, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Ferre, Sergi/K-6115-2014; Zoli, Michele/C-8899-2016; OI Ferre, Sergi/0000-0002-1747-1779; Zoli, Michele/0000-0002-8034-2849; Diaz-Cabiale, Zaida/0000-0002-1582-2088; Fuxe, Kjell/0000-0001-8491-4288; Guidolin, Diego/0000-0003-2133-3552; Diaz Cabiale, Maria Zaida/0000-0003-4613-9430 NR 16 TC 49 Z9 49 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JUL 3 PY 2001 VL 12 IS 9 BP 1831 EP 1834 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 446HZ UT WOS:000169509000009 PM 11435907 ER PT J AU Malkova, L Bachevalier, J Mishkin, M Saunders, RC AF Malkova, L Bachevalier, J Mishkin, M Saunders, RC TI Neurotoxic lesions of perirhinal cortex impair visual recognition memory in rhesus monkeys SO NEUROREPORT LA English DT Article DE ibotenic acid; medial temporal lobe; rhinal cortex ID HIPPOCAMPUS; AMYGDALA; REMOVAL; BRAIN AB Recent excitotoxic lesion studies in monkeys have shown that the recognition memory deficits originally attributed to amygdalo-hippocampal damage were due in whole or in part to the accompanying damage to surrounding tissue, including fibers of passage. Here we show that the same conclusion does not apply to the visual recognition impairment produced by aspiration lesions of perirhinal cortex inasmuch as equally severe impairment was found after excitotoxic lesions of this cortex. The finding demonstrates that damage limited to perirhinal neurons is sufficient to impair visual memory and that damage to fibers of passage neither caused nor exacerbated the effect described initially. NeuroReport 12:1913-1917 (C) 2001 Lippincott Williams & Wilkins. C1 Georgetown Univ, Med Ctr, Dept Pharmacol, Washington, DC 20007 USA. Univ Texas, Med Ctr, Dept Neurobiol & Anat, Houston, TX 77001 USA. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Malkova, L (reprint author), Georgetown Univ, Med Ctr, Dept Pharmacol, W217 TRB 3950 Reservoir Rd NW, Washington, DC 20007 USA. FU NIA NIH HHS [AG14580] NR 17 TC 57 Z9 58 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JUL 3 PY 2001 VL 12 IS 9 BP 1913 EP 1917 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 446HZ UT WOS:000169509000024 PM 11435922 ER PT J AU Zhang, L Rubinow, DR Xaing, GQ Li, BS Chang, YH Maric, D Barker, JL Ma, W AF Zhang, L Rubinow, DR Xaing, GQ Li, BS Chang, YH Maric, D Barker, JL Ma, W TI Estrogen protects against beta-amyloid-induced neurotoxicity in rat hippocampal neurons by activation of Akt SO NEUROREPORT LA English DT Article DE Akt; Alzheimer's disease; amyloid; estrogen; hippocampus; neuronal survival; neuroprotection ID CULTURED CORTICAL-NEURONS; PHOSPHATIDYLINOSITOL 3-KINASE; ALZHEIMERS-DISEASE; APOPTOSIS; NEUROPROTECTION; PROLIFERATION; EXPRESSION; PRECURSOR; PATHWAY; KINASE AB The cellular mechanisms underlying the neuroprotective effects of estrogen are only beginning to be elucidated. Here we examined the role of protein kinase B (Akt) activation in 17 beta -estradiol (E2) inhibition of beta -amyloid peptide (31-35) (A beta (31-35))induced neurotoxicity in cultured rat hippocampal neurons. A beta (31-35) (25-30 betaM) significantly decreased the total number of microtubule associated protein-2 positive cells (MAP2(+)). This decrease was significantly reversed by pre-treatment with 100 nM E2. Further, 100 nM E2 alone significantly increased the total number of protein kinase B and microtubule associated protein-2 positive cells compared with controls. Such E2-induced increases were inhibited by LY294002 (20 muM), a specific P13-K inhibitor, as well as by tamoxifen, an estrogen receptor antagonist/selective estrogen receptor modulator. These results indicate that the neuroprotective effects of E2 may be mediated at least in part via estrogen receptor-mediated protein kinase B activation. NeuroReport 12:1919-1923 (C) 2001 Lippinicott Williams & Wilkins. C1 NIMH, Behav Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. USN, Res Lab, Ctr Biomol Sci & Engn, Washington, DC 20375 USA. RP Rubinow, DR (reprint author), NIMH, Behav Endocrinol Branch, NIH, Bldg 10,Room 3N238, Bethesda, MD 20892 USA. NR 20 TC 93 Z9 97 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JUL 3 PY 2001 VL 12 IS 9 BP 1919 EP 1923 DI 10.1097/00001756-200107030-00030 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 446HZ UT WOS:000169509000025 PM 11435923 ER PT J AU Nguyen, JB Sanchez-Pernaute, R Cunningham, J Bankiewicz, KS AF Nguyen, JB Sanchez-Pernaute, R Cunningham, J Bankiewicz, KS TI Convection-enhanced delivery of AAV-2 combined with heparin increases TK gene transfer in the rat brain SO NEUROREPORT LA English DT Article DE AAV-2; convection enhanced delivery; gene transfer; heparan sulfate receptors; heparin ID ADENOASSOCIATED VIRUS VECTORS; GLYCOPROTEIN-C; SULFATE; MEMBRANE; BINDING; VIRIONS; TYPE-1; VIVO AB Adeno-associated virus type2 (AAV-2) binds to heparan-sulfate proteoglycans on the cell surface. In vivo, attachment of viral particles to cells adjacent to the injection tract limits the distribution of AAV-2 when infused into the CNS parenchyma and heparin co-infusion might decrease the binding of AAV-2 particles to cells in the vicinity of the infusion tract. We have previously shown that heparin co-infusion combined with convection enhanced delivery enhances distribution of the GDNF family trophic factors (heparin-binding proteins) in the rat brain. In this work we show that heparin co-infusion significantly increases the volume of distribution of AAV-2 as demonstrated by immunoreactivity to the transgene product 6 days after infusion into the rat striatum. NeuroReport 12:1961-1964 (C) 2001 Lippincott Williams & Wilkins. C1 NINDS, Mol Therapeut Sect, NIH, Bethesda, MD 20892 USA. Avigen Inc, Alameda, CA USA. RP Bankiewicz, KS (reprint author), Univ Calif San Francisco, Dept Neurosurg, Mission Ctr Bldg,Room 230,1855 Folsom St, San Francisco, CA 94103 USA. NR 20 TC 90 Z9 93 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JUL 3 PY 2001 VL 12 IS 9 BP 1961 EP 1964 DI 10.1097/00001756-200107030-00037 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 446HZ UT WOS:000169509000032 PM 11435930 ER PT J AU Hodes, R AF Hodes, R TI Molecular targeting of cancer: Telomeres as targets SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID HUMAN-CELLS LEADS; REVERSE-TRANSCRIPTASE; MOUSE; RNA; INHIBITION; EXPRESSION; IMMUNITY C1 NIH, Bethesda, MD 20892 USA. RP Hodes, R (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 20 TC 36 Z9 40 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 3 PY 2001 VL 98 IS 14 BP 7649 EP 7651 DI 10.1073/pnas.151267698 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 450LK UT WOS:000169744200001 PM 11438716 ER PT J AU O'Brien, SJ AF O'Brien, SJ TI Cell culture forensics SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID CROSS-CONTAMINATION; HUMAN DNA; FINGERPRINTS C1 NCI, Lab Genom Divers, Frederick, MD 21702 USA. RP O'Brien, SJ (reprint author), NCI, Lab Genom Divers, Frederick, MD 21702 USA. NR 21 TC 20 Z9 22 U1 1 U2 3 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 3 PY 2001 VL 98 IS 14 BP 7656 EP 7658 DI 10.1073/pnas.141237598 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 450LK UT WOS:000169744200004 PM 11438719 ER PT J AU Rutkowski, DT Lingappa, VR Hegde, RS AF Rutkowski, DT Lingappa, VR Hegde, RS TI Substrate-specific regulation of the ribosome-translocon junction by N-terminal signal sequences SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ENDOPLASMIC-RETICULUM MEMBRANE; NASCENT SECRETORY PROTEINS; RECOGNITION PARTICLE; PRION PROTEIN; ER MEMBRANE; ENVIRONMENT; POLYPEPTIDE; INTEGRATION; RECEPTOR; PEPTIDES AB Amino-terminal signal sequences target nascent secretory and membrane proteins to the endoplasmic reticulum for translocation. Subsequent interactions between the signal sequence and components of the translocation machinery at the endoplasmic reticulum are thought to be important for the productive engagement of the translocon by the ribosome-nascent chain complex. However, it is not clear whether all signal sequences carry out these posttargeting steps identically, or if there are differences in the interactions directed by one signal sequence versus another. In this study, we find substantial differences in the ability of signal sequences from different substrates to mediate closure of the ribosome-translocon junction early in translocation. We also show that these differences in some cases necessitate functional coordination between the signal sequence and mature domain for faithful translocation. Accordingly, the translocation of some proteins is sensitive to replacement of their signal sequences. In a particularly dramatic example, the topology of the prion protein was found to depend highly on the choice of signal sequence used to direct its translocation. Taken together, our results reveal an unanticipated degree of substrate-specific functionality encoded in N-terminal signal sequences. C1 Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. NIH, Cellular Oncol Lab, Bethesda, MD 20892 USA. RP Lingappa, VR (reprint author), Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA. NR 36 TC 48 Z9 49 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 3 PY 2001 VL 98 IS 14 BP 7823 EP 7828 DI 10.1073/pnas.141125098 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 450LK UT WOS:000169744200034 PM 11416167 ER PT J AU Kudoh, T Dawid, IB AF Kudoh, T Dawid, IB TI Role of the iroquois3 homeobox gene in organizer formation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ONE-EYED PINHEAD; BETA-CATENIN; MESODERM INDUCTION; ENDODERM FORMATION; XENOPUS HOMOLOG; EMBRYONIC AXIS; HEAD INDUCTION; DROSOPHILA EYE; ZEBRAFISH; ENCODES AB In zebrafish, the organizer is thought to consist of two regions, the yolk syncytial layer (YSL) and the shield. The dorsal YSL appears to send signals that affect formation of the shield in the overlying mesendoderm. We show here that a domain of dorsal deep cells located between the YSL and the shield is marked by expression of the iro3 gene. As gastrulation proceeds, the iro3 positive domain involutes and migrates to the animal pole. Iro3 expression is regulated by Nodal and bone morphogenic protein antagonists. Overexpression of iro3 induced ectopic expression of shield-specific genes. This effect was mimicked by an Iro3-Engrailed transcriptional repressor domain fusion, whereas an Iro3-VP16 activator domain fusion behaved as a dominant negative or antimorphic form. These results suggest that Iro3 acts as a transcriptional repressor and further implicate the iro3 gene in regulating organizer formation. We propose that the iro3-expressing dorsal deep cells represent a distinct organizer domain that receives signals from the YSL and in turn sends signals to the forming shield, thereby influencing its expansion and differentiation. C1 NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Dawid, IB (reprint author), NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. EM idawid@nih.gov NR 46 TC 41 Z9 41 U1 1 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 3 PY 2001 VL 98 IS 14 BP 7852 EP 7857 DI 10.1073/pnas.141224098 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 450LK UT WOS:000169744200039 PM 11438735 ER PT J AU Grogan, DW Carver, GT Drake, JW AF Grogan, DW Carver, GT Drake, JW TI Genetic fidelity under harsh conditions: Analysis of spontaneous mutation in the thermoacidophilic archaeon Sulfolobus acidocaldarius SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID AQUATICUS DNA-POLYMERASE; REPLICATION FIDELITY; BIOCHEMICAL BASIS; REACTION PH; ENVIRONMENTS; PROTEINS; RATES AB Microbes whose genomes are encoded by DNA and for which adequate information is available display similar genomic mutation rates (average 0.0034 mutations per chromosome replication, range 0.0025 to 0,0046). However, this value currently is based on only a few well characterized microbes reproducing within a narrow range of environmental conditions. In particular, no genomic mutation rate has been determined either for a microbe whose natural growth conditions may extensively damage DNA or for any member of the archaea, a prokaryotic lineage deeply diverged from both bacteria and eukaryotes. Both of these conditions are met by the extreme thermoacidophile Sulfolobus acidocaldarius. We determined the genomic mutation rate for this species when growing at pH 3.5 and 75 degreesC based on the rate of forward mutation at the pyrE gene and the nucleotide changes identified in 101 independent mutants. The observed value of about 0.0018 extends the range of DNA-based microbes with rates close to the standard rate simultaneously to an archaeon and to an extremophile whose cytoplasmic pH and normal growth temperature greatly accelerate the spontaneous decomposition of DNA, The mutations include base pair substitutions (BPSs) and additions and deletions of various sizes, but the S, acidocaldarius spectrum differs from those of other DNA-based organisms in being relatively poor in BPSs. The paucity of BPSs cannot yet be explained by known properties of DNA replication or repair enzymes of Sulfolobus spp, It suggests, however, that molecular evolution per genome replication may proceed more slowly in S. acidocaldarius than in other DNA-based organisms examined to date. C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. Univ Cincinnati, Dept Biol Sci, Cincinnati, OH 45221 USA. RP Drake, JW (reprint author), NIEHS, Mol Genet Lab, POB 12233, Res Triangle Pk, NC 27709 USA. NR 31 TC 97 Z9 103 U1 0 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 3 PY 2001 VL 98 IS 14 BP 7928 EP 7933 DI 10.1073/pnas.141113098 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 450LK UT WOS:000169744200053 PM 11427720 ER PT J AU Baldassarre, G Fedele, M Battista, S Vecchione, A Klein-Szanto, AJP Santoro, M Waldmann, TA Azimi, N Croce, CM Fusco, A AF Baldassarre, G Fedele, M Battista, S Vecchione, A Klein-Szanto, AJP Santoro, M Waldmann, TA Azimi, N Croce, CM Fusco, A TI Onset of natural killer cell lymphomas in transgenic mice carrying a truncated HMGI-C gene by the chronic stimulation of the IL-2 and IL-15 pathway SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID IN-VIVO; POTENTIAL ROLE; MESSENGER-RNA; BONE-MARROW; INTERLEUKIN-15; RECEPTOR; PROTEIN; EXPRESSION; CYTOKINE; PROLIFERATION AB Rearrangements of the high mobility group protein I-C (HMGI-C) gene, consisting in the loss of the carboxyl-terminal tail, have been frequently detected in benign human tumors of mesenchymal origin. We have previously demonstrated that transgenic (TG) mice carrying a truncated HMGI-C construct (HMCI-C/T) exhibit a giant phenotype together with a predominantly abdominal/pelvic lipomatosis. Here, we report that HMGI-C/T TG mice develop natural killer (NK)-T/NK cell lymphomas starting from 12 months of age. We found an increased expression of IL-2 and IL-15 proteins and their receptors in these lymphomas, and we demonstrate that HMGI-C/T protein positively regulates their expression in vitro. Therefore, the HRGI-C/T-mediated chronic stimulation of the IL2/IL-15 pathway could be responsible for the onset of NK-T/NK cell lymphomas in HMCI-C/T TG mice. C1 Univ Naples Federico II, Dipartimento Biol & Patol Cellulare & Mol, Fac Med & Chirurg, Ctr Endocrinol Oncol Sperimentale,CNR, I-80131 Naples, Italy. Jefferson Med Coll, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Univ Catanzaro, Fac Med & Chirurgia Catanzaro, Dipartimento Med Sperimentale & Clin, I-88100 Catanzaro, Italy. RP Fusco, A (reprint author), Univ Naples Federico II, Dipartimento Biol & Patol Cellulare & Mol, Fac Med & Chirurg, Ctr Endocrinol Oncol Sperimentale,CNR, Via Pansini 5, I-80131 Naples, Italy. RI Klein-Szanto, Andres/E-6218-2010; Fedele, Monica/C-1417-2015; Baldassarre, Gustavo/K-1350-2016; OI Baldassarre, Gustavo/0000-0002-9750-8825; Fusco, Alfredo/0000-0003-3332-5197 FU NCI NIH HHS [P01CA76259, P01 CA076259, P30 CA056036, P30CA56036] NR 40 TC 69 Z9 69 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 3 PY 2001 VL 98 IS 14 BP 7970 EP 7975 DI 10.1073/pnas.141224998 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 450LK UT WOS:000169744200060 PM 11427729 ER PT J AU Khanna-Gupta, A Zibello, T Sun, H Lekstrom-Himes, J Berliner, N AF Khanna-Gupta, A Zibello, T Sun, H Lekstrom-Himes, J Berliner, N TI C/EBP epsilon mediates myeloid differentiation and is regulated by the CCAAT displacement protein (CDP/cut) SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LACTOFERRIN GENE PROMOTER; SENSORY ORGAN IDENTITY; HOMEODOMAIN PROTEIN; GRANULE DEFICIENCY; DNA-BINDING; TRANSCRIPTION FACTORS; CUT HOMEODOMAIN; MESSENGER-RNA; EXPRESSION; LEUKEMIA AB Neutrophils from CCAAT enhancer binding protein epsilon (C/ EBP epsilon) knockout mice have morphological and biochemical features similar to those observed in patients with an extremely rare congenital disorder called neutrophil-specific secondary granule deficiency (SGD), SCD is characterized by frequent bacterial infections attributed, in part, to the lack of neutrophil secondary granule proteins (SCP). A mutation that results in loss of functional C/EBP epsilon activity has recently been described in an SGD patient, and has been postulated to be the cause of the disease in this patient. We have previously demonstrated that overexpression of CCAAT displacement protein (CDP/cut), a highly conserved transcriptional repressor of developmentally regulated genes, suppresses expression of SGP genes in 32Dcl3 cells. This phenotype resembles that observed in both C/EBP epsilon-/- mice and in SGD patients. Based on these observations we investigated potential interactions between C/EBP epsilon and CDP/cut during neutrophil maturation, In this study, we demonstrate that inducible expression of C/EBP epsilon in 32Dcl3/tet cells results in granulocytic differentiation. Furthermore, Northern blot analysis of G-CSF-induced CDP/cut overexpressing 32Dc13 cells revealed absence of C/EBP epsilon mRNA, We therefore hypothesize that C/EBP epsilon positively regulates SCP gene expression, and that C/EBPe is itself negatively regulated by CDP/cut during neutrophil maturation. We further demonstrate that the C/EBP epsilon promoter is regulated by CDP/cut during myeloid differentiation. C1 Yale Univ, Sch Med, Sect Hematol WWW 428, New Haven, CT 06510 USA. NIAID, Bethesda, MD 20892 USA. RP Berliner, N (reprint author), Yale Univ, Sch Med, Sect Hematol WWW 428, 333 Cedar St, New Haven, CT 06510 USA. FU NHLBI NIH HHS [P01 HL063357, P01-HL63357]; NIDDK NIH HHS [R01-DK53471] NR 47 TC 41 Z9 43 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 3 PY 2001 VL 98 IS 14 BP 8000 EP 8005 DI 10.1073/pnas.141229598 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 450LK UT WOS:000169744200065 PM 11438745 ER PT J AU Hendrix, MJC Seftor, EA Meltzer, PS Gardner, LMG Hess, AR Kirschmann, DA Schatteman, GC Seftor, REB AF Hendrix, MJC Seftor, EA Meltzer, PS Gardner, LMG Hess, AR Kirschmann, DA Schatteman, GC Seftor, REB TI Expression and functional significance of VE-cadherin in aggressive human melanoma cells: Role in vasculogenic mimicry SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID VASCULAR-ENDOTHELIAL-CADHERIN; BLOOD-VESSEL FORMATION; CANCER METASTASIS; ANGIOGENESIS; GENE; MORPHOGENESIS; MECHANISMS; PHENOTYPE; CONTACTS; IMPAIRS AB We recently have introduced the term vasculogenic mimicry to describe the unique ability of aggressive melanoma tumor cells to form tubular structures and patterned networks in three-dimensional culture, which "mimics" embryonic vasculogenic networks formed by differentiating endothelial cells. In the current study, we address the biological significance of several endothelial-associated molecules (revealed by microarray analysis) with respect to expression and function in highly aggressive and poorly aggressive human cutaneous melanoma cell lines (established from the same patient). In a comparative analysis, CD31 was not expressed by any of the melanoma cell lines, whereas TIE-1 (tyrosine kinase with 1g and epidermal growth factor homology domains-1) was strongly expressed in the highly aggressive tumor cells with a low level of expression in one of the poorly aggressive cell lines. Vascular endothelial (VE)-cadherin was exclusively expressed by highly aggressive melanoma cells and was undetectable in the poorly aggressive tumor cells, suggesting the possibility of a vasculogenic switch. Down-regulation of VE-cadherin expression in the aggressive melanoma cells abrogated their ability to form vasculogenic networks and directly tested the hypothesis that VE-cadherin is critical in melanoma vasculogenic mimicry. These results highlight the plasticity of aggressive melanoma cells and call into question their possible genetic reversion to an embryonic phenotype, This finding could pose a significant clinical challenge in targeting tumor cells that may masquerade as circulating endothelial cells or other embryonic-like stem cells. C1 Univ Iowa, Dept Anat & Cell Biol, Iowa City, IA 52242 USA. Univ Iowa, Holden Comprehens Canc Ctr, Iowa City, IA 52242 USA. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Hendrix, MJC (reprint author), Univ Iowa, Dept Anat & Cell Biol, 51 Newton Rd,1-100 BSB, Iowa City, IA 52242 USA. FU NCI NIH HHS [R37 CA059702, CA59702, CA80318, CA83137, R01 CA059702]; NIDDK NIH HHS [DK55965, R01 DK055965] NR 36 TC 251 Z9 277 U1 2 U2 13 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 3 PY 2001 VL 98 IS 14 BP 8018 EP 8023 DI 10.1073/pnas.131209798 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 450LK UT WOS:000169744200068 PM 11416160 ER PT J AU Ganguly, S Gastel, JA Weller, JL Schwartz, C Jaffe, H Namboodiri, MAA Coon, SL Hickman, AB Rollag, M Obsil, T Beauverger, P Ferry, G Boutin, JA Klein, DC AF Ganguly, S Gastel, JA Weller, JL Schwartz, C Jaffe, H Namboodiri, MAA Coon, SL Hickman, AB Rollag, M Obsil, T Beauverger, P Ferry, G Boutin, JA Klein, DC TI Role of a pineal cAMP-operated arylalkylamine N-acetyltransferase/14-3-3-binding switch in melatonin synthesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SEROTONIN N-ACETYLTRANSFERASE; STRUCTURAL-ANALYSIS; 14-3-3-PROTEINS; RHYTHM; SPECIFICITY; PROTEOLYSIS; METABOLISM; PROTEINS; COMPLEX; BINDING AB The daily rhythm in melatonin levels is controlled by cAMP through actions on the penultimate enzyme in melatonin synthesis, arylalkylamine IV-acetyltransferase (AANAT; serotonin IV-acetyltransferase, EC 2.3.1.87). Results presented here describe a regulatory/binding sequence in AANAT that encodes a cAMP-operated binding switch through which cAMP-regulated protein kinase-catalyzed phosphorylation [RRHTLPAN --> RRHpTLPAN] promotes formation of a complex with 14-3-3 proteins. Formation of this AANAT/14-3-3 complex enhances melatonin production by shielding AANAT from dephosphorylation and/or proteolysis and by decreasing the K-m for 5-hydroxytryptamine (serotonin). Similar switches could play a role in cAMP signal transduction in other biological systems. C1 NICHHD, Dev Neurobiol Lab, Sect Neuroendocrinol, NIH, Bethesda, MD 20892 USA. NINDS, Prot Sequencing Facil, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Circadian Res Ctr, Bethesda, MD 20814 USA. NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Inst Rech Servier, F-78290 Croissy Sur Seine, France. RP Klein, DC (reprint author), NICHHD, Dev Neurobiol Lab, Sect Neuroendocrinol, NIH, Bethesda, MD 20892 USA. RI Obsil, Tomas/B-7142-2012 OI Obsil, Tomas/0000-0003-4602-1272 FU NINDS NIH HHS [R01 NS039387, R01 NS39387] NR 24 TC 128 Z9 145 U1 2 U2 7 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 3 PY 2001 VL 98 IS 14 BP 8083 EP 8088 DI 10.1073/pnas.141118798 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 450LK UT WOS:000169744200079 PM 11427721 ER PT J AU Duzel, E Vargha-Khadem, F Heinze, HJ Mishkin, M AF Duzel, E Vargha-Khadem, F Heinze, HJ Mishkin, M TI Brain activity evidence for recognition without recollection after early hippocampal damage SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE hippocampus; episodic memory; event-related potentials; amnesia ID CONSCIOUS RECOLLECTION; PROCESS DISSOCIATION; DECLARATIVE MEMORY; EPISODIC MEMORY; SEMANTIC MEMORY; RETRIEVAL; AMNESIA; POTENTIALS; REPETITION; AWARENESS AB Amnesic patients with early and seemingly isolated hippocampal injury show relatively normal recognition memory scores, The cognitive profile of these patients raises the possibility that this recognition performance is maintained mainly by stimulus familiarity in the absence of recollection of contextual information. Here we report electrophysiological data on the status of recognition memory in one of the patients, Jon, Jon's recognition of studied words lacks the event-related potential (ERP) index of recollection, viz., an increase in the late positive component (500-700 ms), under conditions that elicit it reliably in normal subjects. On the other hand, a decrease of the ERP amplitude between 300 and 500 ms, also reliably found in normal subjects, is well preserved. This so-called N400 effect has been linked to stimulus familiarity in previous ERP studies of recognition memory. In Jon, this link is supported by the finding that his recognized and unrecognized studied words evoked topographically distinct ERP effects in the N400 time window. These data suggest that recollection is more dependent on the hippocampal formation than is familiarity, consistent with the view that the hippocampal formation plays a special role in episodic: memory, for which recollection is so critical. C1 Otto Von Guericke Univ, Dept Neurol 2, D-39120 Magdeburg, Germany. UCL, Inst Child Hlth, Dev Cognit Neurosci Unit, London WC1N 2AP, England. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Duzel, E (reprint author), Otto Von Guericke Univ, Dept Neurol 2, D-39120 Magdeburg, Germany. EM emrah.duezel@medizin.unimagdeburg.de RI Vargha-Khadem, Faraneh/C-2558-2008; Duzel, Emrah/A-1794-2010 NR 38 TC 170 Z9 173 U1 0 U2 3 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 3 PY 2001 VL 98 IS 14 BP 8101 EP 8106 DI 10.1073/pnas.131205798 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 450LK UT WOS:000169744200082 PM 11438748 ER PT J AU Longenecker, KL Lewis, ME Chikumi, H Gutkind, JS Derewenda, ZS AF Longenecker, KL Lewis, ME Chikumi, H Gutkind, JS Derewenda, ZS TI Structure of the RGS-like domain from PDZ-RhoGEF: Linking heterotrimeric G protein-coupled signaling to Rho GTPases SO STRUCTURE LA English DT Article DE RhoGEF; RGS proteins; GPCR signalling; G alpha(12/13); KIAA0380; GTRAP48 ID NUCLEOTIDE EXCHANGE FACTOR; CELL-SHAPE CHANGES; CRYSTAL-STRUCTURE; G-ALPHA; FAMILY PROTEINS; SMOOTH-MUSCLE; P115 RHOGEF; DB1 FAMILY; BINDING; IDENTIFICATION AB Background: The multidomain PDZ-RhoGEF is,one of many known guanine nucleotide exchange factors that upregulate Rho GTPases. PDZ-RhoGEF and related family members play a critical role in a molecular signaling pathway from heterotrimeric G protein-coupled receptors to Rho proteins. A similar to 200 residue RGS-like (RGSL) domain in PDZ-RhoGEF and its homologs is responsible for the direct association with G alpha (12/13) proteins. To better understand structure-function relationships, we initiated crystallographic studies of the RGSL domain from human PDZ-RhoGEF. Results: A recombinant construct of the RGSL domain was expressed in Escherichia coli and purified, but it did not crystallize. Alternative constructs were designed based on a novel strategy of targeting lysine and glutamic acid residues for mutagenesis to alanine. A triple-point mutant functionally identical to the wild-type protein was crystallized, and its structure was determined by the MAD method using Se-methionine (Se-Met) incorporation. A molecular model of the RGSL domain was refined at 2.2 Angstrom resolution, revealing an all-helical tertiary fold with the mutations located at intermolecular lattice contacts. Conclusions: The first nine helices adopt a fold similar to that observed for RGS proteins, although the sequence identity with other such known structures is below 20%. The last three helices are an integral extension of the RGS fold, packing tightly against helices 3 and 4 with multiple hydrophobic interactions. Comparison with RGS proteins suggests features that are likely relevant for interaction with G proteins. Finally, we conclude that the strategy used to produce crystals was beneficial and might be applicable to other proteins resistant to crystallization. C1 Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. RP Derewenda, ZS (reprint author), Univ Virginia, Dept Mol Physiol & Biol Phys, POB 800736, Charlottesville, VA 22908 USA. RI Gutkind, J. Silvio/A-1053-2009 FU NHLBI NIH HHS [HL48807] NR 54 TC 60 Z9 62 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0969-2126 J9 STRUCTURE JI Structure PD JUL 3 PY 2001 VL 9 IS 7 BP 559 EP 569 DI 10.1016/S0969-2126(01)00620-7 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 450VX UT WOS:000169766500002 PM 11470431 ER PT J AU Li, J Gao, XL Ortega, JQ Nazif, T Joss, L Bogyo, M Steven, AC Rechsteiner, M AF Li, J Gao, XL Ortega, JQ Nazif, T Joss, L Bogyo, M Steven, AC Rechsteiner, M TI Lysine 188 substitutions convert the pattern of proteasome activation by REG gamma to that of REGs alpha and beta SO EMBO JOURNAL LA English DT Article DE affinity labeling; chimera; enzyme specificity; mutagenesis ID 20S PROTEASOME; THERMOPLASMA-ACIDOPHILUM; PROTEIN ACTIVATOR; 11S REGULATOR; PA28; SUBUNITS; PURIFICATION; BINDING; ANTIGEN; SITE AB 11S REGs (PA28s) are multimeric rings that bind proteasomes and stimulate peptide hydrolysis. Whereas REG alpha activates proteasomal hydrolysis of peptides with hydrophobic, acidic or basic residues in the P1 position, REG gamma only activates cleavage after basic residues. We have isolated REG gamma mutants capable of activating the hydrolysis of fluorogenic peptides diagnostic for all three active proteasome beta subunits, The most robust REG gamma specificity mutants involve substitution of Glu or Asp for Lys188. REG gamma (K188E/D) variants are virtually identical to REG alpha in proteasome activation but assemble into less stable heptamers/hexamers. Based on the REG alpha crystal structure, Lys188 of REG gamma faces the aqueous channel through the heptamer, raising the possibility that REG channels function as substrate-selective gates. However, covalent modification of proteasome chymotrypsinlike subunits by I-125-YL3-VS demonstrates that REG gamma (K188E)'s activation of all three proteasome active sites is not due to relaxed gating, We propose that decreased stability of REG gamma (K188E) heptamers allows them to change conformation upon proteasome binding, thus relieving inhibition of the CT and PGPH sites normally imposed by the wild-type REG gamma molecule. C1 Univ Utah, Sch Med, Dept Biochem, Salt Lake City, UT 84132 USA. NIAMS, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA. RP Rechsteiner, M (reprint author), Univ Utah, Sch Med, Dept Biochem, Salt Lake City, UT 84132 USA. FU NIGMS NIH HHS [GM60334] NR 40 TC 37 Z9 40 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD JUL 2 PY 2001 VL 20 IS 13 BP 3359 EP 3369 DI 10.1093/emboj/20.13.3359 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 451LN UT WOS:000169803700009 PM 11432824 ER PT J AU Eden, S Constancia, M Hashimshony, T Dean, W Goldstein, B Johnson, AC Keshet, I Reik, W Cedar, H AF Eden, S Constancia, M Hashimshony, T Dean, W Goldstein, B Johnson, AC Keshet, I Reik, W Cedar, H TI An upstream repressor element plays a role in Igf2 imprinting SO EMBO JOURNAL LA English DT Article DE GCF; imprinting; methylation ID GROWTH-FACTOR-II; DNA METHYLATION; DEVELOPMENTAL CONTROL; HISTONE DEACETYLASE; CHROMATIN STRUCTURE; MOLECULAR-CLONING; SILENCER ELEMENT; ACTIVE CHROMATIN; BINDING FACTOR; MOUSE IGF2 AB The imprinted Igf2 gene is associated with a small upstream region that is differentially methylated on the active paternal allele, We have identified a repressor element within this sequence and shown that repression is probably mediated through a transacting factor, GCF2, DNA methylation of this site abrogates both protein binding and repressor activity. Targeting experiments demonstrate that this element plays a role in the repression of the maternal Igf2 gene in vivo. C1 Hadassah Univ Hosp, Dept Cellular Biochem, IL-91120 Jerusalem, Israel. Babraham Inst, Inst Grassland & Anim Prod, Cambridge CB2 4AT, England. NCI, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Cedar, H (reprint author), Hadassah Univ Hosp, Dept Cellular Biochem, Ein Kerem, IL-91120 Jerusalem, Israel. RI Reik, Wolf/I-6794-2012; Constancia, Miguel/F-6654-2013; OI Reik, Wolf/0000-0003-0216-9881 NR 38 TC 69 Z9 71 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD JUL 2 PY 2001 VL 20 IS 13 BP 3518 EP 3525 DI 10.1093/emboj/20.13.3518 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 451LN UT WOS:000169803700023 PM 11432838 ER PT J AU Kosofsky, BE Hyman, SE AF Kosofsky, BE Hyman, SE TI No time for complacency: The fetal brain on drugs SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Editorial Material ID CHRONIC COCAINE EXPOSURE; VISUAL-CORTEX; RHESUS-MONKEY; NEURONS; MICE; INNERVATION; DEFICIENT; SEROTONIN; LACKING C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Lab Mol & Dev Neurosci, Charlestown, MA 02129 USA. NIMH, NIH, Bethesda, MD 20892 USA. RP Kosofsky, BE (reprint author), Harvard Univ, Sch Med, Lab Mol & Dev Neurosci, MGH E,149 13th St, Charlestown, MA 02129 USA. NR 29 TC 13 Z9 13 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JUL 2 PY 2001 VL 435 IS 3 BP 259 EP 262 DI 10.1002/cne.1027 PG 4 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 438EY UT WOS:000169041700001 PM 11406809 ER PT J AU Foletta, VC Nishiyama, K Rayborn, ME Shadrach, KG Young, WS Hollyfield, JG AF Foletta, VC Nishiyama, K Rayborn, ME Shadrach, KG Young, WS Hollyfield, JG TI SPACRCAN in the developing retina and pineal gland of the rat: Spatial and temporal pattern of gene expression and protein synthesis SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE retina; pineal gland; development; interphotoreceptor matrix; SPACRCAN ID FIBROBLAST GROWTH-FACTOR; RD-MUTANT MICE; INTERPHOTORECEPTOR MATRIX; BINDING PROTEIN; IMMUNOCYTOCHEMICAL LOCALIZATION; ALBINO-RAT; PIGMENT-EPITHELIUM; ROD CELLS; PHOTORECEPTORS; ADHESIVENESS AB SPACRCAN is a hyaluronan-binding proteoglycan that is present in the pineal gland and interphotoreceptor matrix of the retina. Here, we evaluate the pattern of SPACRCAN gene expression and protein appearance during retinal and pineal gland development in the rat. In situ hybridization histochemistry with SPACRCAN riboprobes indicates that hybridization signals are first evident in the retina over developing photoreceptor cells at embryonic day 16 (E16) and in the pineal gland at E21. Immunocytochemistry using a SPACRCAN antibody shows localization of SPACRCAN protein in the developing interphotoreceptor matrix by Postnatal day 5 (P5) and in the pineal gland by P6. These studies suggest that SPACRCAN mRNA expression may occur substantially earlier than the time when SPACRCAN protein is detectable in both the retina and the pineal gland. The period of retinal histogenesis when SPACRCAN is detected first is coincident with the time photoreceptors begin to extend from the outer retinal surface, suggesting that SPACRCAN may participate in the maturation and maintenance of the light-sensitive photoreceptor outer segment, (C) 2001 Wiley-Liss, Inc. C1 Cleveland Clin Fdn, Cole Eye Inst, Cleveland, OH 44195 USA. NIMH, NIH, Bethesda, MD 20892 USA. RP Hollyfield, JG (reprint author), Cleveland Clin Fdn, Cole Eye Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA. RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 FU NEI NIH HHS [EY 02362] NR 35 TC 7 Z9 8 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JUL 2 PY 2001 VL 435 IS 3 BP 354 EP 363 DI 10.1002/cne.1035 PG 10 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 438EY UT WOS:000169041700009 PM 11406817 ER PT J AU Jiang, ZG Piggee, C Heyes, MP Murphy, C Quearry, B Bauer, M Zheng, J Gendelman, HE Markey, SP AF Jiang, ZG Piggee, C Heyes, MP Murphy, C Quearry, B Bauer, M Zheng, J Gendelman, HE Markey, SP TI Glutamate is a mediator of neurotoxicity in secretions of activated HIV-1-infected macrophages SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE dementia; mononuclear phagocyte; neurodegeneration; NMDA; lipopolysaccharide ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS DEMENTIA COMPLEX; HIV-ASSOCIATED DEMENTIA; EXCITATORY AMINO-ACIDS; MONONUCLEAR PHAGOCYTES; CEREBROSPINAL-FLUID; QUINOLINIC ACID; COAT PROTEIN; HIV-1-ASSOCIATED DEMENTIA; EXTRACELLULAR GLUTAMATE AB We sought to identify neurotoxin(s) secreted by HIV-1-infected mononuclear phagocytes that could contribute to the pathophysiology of HIV-1-associated dementia (HAD). Neurotoxic factors were characterized in batches of conditioned media (CM) from human monocyte-derived macrophages (MDM) infected with HIV-1(ADA) and/or activated with lipopolysaccharide (LPS). All of the neurotoxicity was: present in the < 3000-Da fraction; blocked by 5 M MK801; and not trypsin sensitive or extractable into polar organic solvents. Glutamate measured in CM accounted for all neurotoxic effects observed from HIV/LPS CM in astrocyte-poor neuronal cultures and may contribute to the pathophysiology of HIV-1-associated dementia. (C) 2001 Elsevier Science B.V. All rights reserved. C1 NIMH, Lab Neurotoxicol, NIH, Bethesda, MD 20892 USA. Univ Nebraska, Med Ctr, Ctr Neurovirol & Neurodegenerat Disorders, Omaha, NE 68198 USA. Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA. RP Markey, SP (reprint author), NIMH, Lab Neurotoxicol, NIH, 10 Ctr Dr,Room 3D42, Bethesda, MD 20892 USA. FU NIMH NIH HHS [1Z01-MH00279]; NINDS NIH HHS [2 R01 NS34239-04A1] NR 69 TC 93 Z9 96 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD JUL 2 PY 2001 VL 117 IS 1-2 BP 97 EP 107 DI 10.1016/S0165-5728(01)00315-0 PG 11 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 457ZD UT WOS:000170168100011 PM 11431009 ER PT J AU Carvan, MJ Sonntag, DM Cmar, CB Cook, RS Curran, MA Miller, GL AF Carvan, MJ Sonntag, DM Cmar, CB Cook, RS Curran, MA Miller, GL TI Oxidative stress in zebrafish cells: potential utility of transgenic zebrafish as a deployable sentinel for site hazard ranking SO SCIENCE OF THE TOTAL ENVIRONMENT LA English DT Article; Proceedings Paper CT Conference on Toxicology and Risk Assessment Approaches for the 21st Century CY APR 10-13, 2000 CL KINGS ISL, OHIO SP Tri Serv USAF, USA, USN Toxicol, Natl Ctr Environm Assessment, US EPA, ATSDR, Div Toxicol, Natl Inst Occupat Safety & Hlth, Natl Res Council, Natl Acad Sci DE zebrafish; oxidative stress; electrophile response element; sentinel animal ID GENE-EXPRESSION; RESPONSIVE ELEMENTS; REACTIVE OXYGEN; LIVING MAMMALS; SUBUNIT GENE; INDUCTION; FISH; CULTURES; ENZYMES; DIOXIN AB In order to quickly assess potential environmental hazards of forwardly deployed military bases, we have focussed our efforts on biochemical and molecular changes in vertebrate cells following exposure to aqueous soil extracts. To this end, we are designing a series of deployable transgenic fish. Fish exhibit many of the same general defenses against toxic chemicals as do mammals, including enzyme induction, and the generation of oxidative stress. In response to many foreign compounds that generate oxidative stress, the transcription of certain protective genes is induced via specific DNA motifs called electrophile response elements (EPREs). We have made a plasmid construct containing a single murine EPRE fused to a minimal promoter and the cDNA encoding firefly luciferase (EPRE LUG). In this paper, we have shown that the treatment of zebrafish cell line ZEM2S with a variety of chemicals known to induce EPRE-dependent transcription in cultured mammalian cells, results in dose-dependent induction of the transiently-transfected EPRE-LUC reporter construct. Compounds tested include aromatic hydrocarbons, heavy metals, and organophosphates. We observed similar dose-dependent responses when we treated ZEM2S and human cells in vitro with identical aqueous extracts of soil from hazardous waste sites. This suggests that the mechanism by which these compounds activate transcription is well conserved between mammals and zebrafish, and that transgenic zebrafish lines containing EPRE-driven reporter constructs might be useful as sentinels for the early detection of oxidative stress-inducing chemicals. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Univ Wisconsin, Great Lakes Water Inst, Milwaukee, WI 53204 USA. Univ Wisconsin, NIEHS, Marine & Freshwater Biomed Sci Ctr, Milwaukee, WI 53204 USA. USAF, Res Lab, Human Effectiveness Directorate, Operat Toxicol Branch,HEST, Wright Patterson AFB, OH 45433 USA. Univ Cincinnati, Med Ctr, Dept Environm Hlth, Cincinnati, OH 45267 USA. RP Carvan, MJ (reprint author), Univ Wisconsin, Great Lakes Water Inst, 600 E Greenfield Ave, Milwaukee, WI 53204 USA. FU NIEHS NIH HHS [P30 ES04184, R01 ES07058, P30 ES06096] NR 30 TC 32 Z9 39 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0048-9697 J9 SCI TOTAL ENVIRON JI Sci. Total Environ. PD JUL 2 PY 2001 VL 274 IS 1-3 BP 183 EP 196 DI 10.1016/S0048-9697(01)00742-2 PG 14 WC Environmental Sciences SC Environmental Sciences & Ecology GA 450EH UT WOS:000169728200017 PM 11453295 ER PT J AU Chang, LC Otero-Quintero, S Nicholas, GM Bewley, CA AF Chang, LC Otero-Quintero, S Nicholas, GM Bewley, CA TI Phyllolactones A-E: new bishomoscalarane sesterterpenes from the marine sponge Phyllospongia lamellosa SO TETRAHEDRON LA English DT Article DE marine metabolites; terpenes; biologically active metabolites ID SCALARANE-TYPE BISHOMOSESTERTERPENES; FOLIASCENS; ASSAY AB Five new bishomoscalarane sesterterpenes, phyllolactones A-E (1-5), have been isolated from the marine sponge Phyllospongia lamellosa. The structures were elucidated by 1D and 2D H-1 and C-13 NMR, unambiguous assignments of overlapping H-1 and C-13 resonances were made by analysis of an HSQC-TOCSY spectrum, and relative stereochemistry established by analysis of coupling constants and ROESY and NOESY spectra. A summary of previously reported carbolactone-containing bishomoscalarane structures and the range of C-13 chemical shifts arising from the various oxy substituents at C-3, C-12, C-16, C-20 and C-24 is included. Phyllolactones A-E modestly inhibit HIV-1 envelope-mediated fusion in vitro with IC(50)s of similar to2 muM, and show negligible cytotoxicity toward the cell lines used in the fusion assay (BS-C-1 and NIH 3T3). Published by Elsevier Science Ltd. C1 NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Bewley, CA (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NR 24 TC 14 Z9 16 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4020 J9 TETRAHEDRON JI Tetrahedron PD JUL 2 PY 2001 VL 57 IS 27 BP 5731 EP 5738 PG 8 WC Chemistry, Organic SC Chemistry GA 446XU UT WOS:000169540100004 ER PT J AU Rashid, MA Gustafson, KR Cartner, LK Pannell, LK Boyd, MR AF Rashid, MA Gustafson, KR Cartner, LK Pannell, LK Boyd, MR TI New nitrogenous constituents from the South African marine ascidian Pseudodistoma sp. SO TETRAHEDRON LA English DT Article DE beta-carboline; ascidian; pseudodistamine; Pseudodistoma ID MOSHER METHOD; ABSOLUTE-CONFIGURATIONS; PIPERIDINE ALKALOIDS; NMR APPLICATION; BETA-CARBOLINE; KANOKO AB Cytotoxicity-guided fractionation of an extract of the South African marine ascidian Pseudodistoma sp. provided pseudodistamine (1), a new bis alkyl amine, two new aliphatic amines 2 and 3, and a new P-carboline alkaloid 4. The structures of compounds 1-4 were elucidated by spectroscopic methods and by comparison with spectral data from structurally related compounds. The absolute stereochemistry of 1 was assigned by Mosher's ester analyses, while the stereochemistry of 2 and 3 was established by degradation and derivatization studies. Compound 2 demonstrated cytotoxic activity against four different human tumor cell lines, with an IC50 of approximately 6.0 mug/mL. Published by Elsevier Science Ltd. C1 NCI, Mol Target Drug Dev Program, Canc Res Ctr, Frederick, MD 21702 USA. NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA. SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. RP Boyd, MR (reprint author), NCI, Mol Target Drug Dev Program, Canc Res Ctr, Bldg 1052,Room 121, Frederick, MD 21702 USA. NR 27 TC 13 Z9 14 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4020 J9 TETRAHEDRON JI Tetrahedron PD JUL 2 PY 2001 VL 57 IS 27 BP 5751 EP 5755 DI 10.1016/S0040-4020(01)00518-X PG 5 WC Chemistry, Organic SC Chemistry GA 446XU UT WOS:000169540100006 ER PT J AU Dauter, Z Adamiak, DA AF Dauter, Z Adamiak, DA TI Anomalous signal of phosphorus used for phasing DNA oligomer: importance of data redundancy SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID ATOMIC-RESOLUTION; CRYSTAL-STRUCTURE; MACROMOLECULAR CRYSTALLOGRAPHY; ANGSTROM RESOLUTION; MOLECULAR-STRUCTURE; HELICAL DNA; SCATTERING; PROTEIN; REFINEMENT; DISPERSION AB The crystal structure of a left-handed Z-DNA hexamer duplex d(CGCGCG)(2) has been solved based on the anomalous diffraction signal of inherent P atoms using data collected at the single wavelength of 1.54 Angstrom. The anomalous signal of about 2% of the total diffracted intensity, constant for all nucleic acids, may be generally useful for solving crystal structures of DNA and RNA oligomers. The multiplicity of intensity measurements is shown to crucially affect the data quality and the ability to solve the phase problem. The anisotropic model refined to an R factor of 8.9% at 0.95 Angstrom resolution. C1 NCI, Synchrotron Radiat Res Sect, Macromol Crystallog Lab, Upton, NY 11973 USA. Brookhaven Natl Lab, NSLS, Upton, NY 11973 USA. Polish Acad Sci, Inst Bioorgan Chem, PL-617 Poznan, Poland. RP Dauter, Z (reprint author), NCI, Synchrotron Radiat Res Sect, Macromol Crystallog Lab, Bldg 725A-X9, Upton, NY 11973 USA. EM dauter@bnl.gov NR 39 TC 81 Z9 81 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD JUL PY 2001 VL 57 BP 990 EP 995 DI 10.1107/S0907444901006382 PN 7 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 446VK UT WOS:000169534700008 PM 11418767 ER PT J AU Nagem, RAP Dauter, Z Polikarpov, I AF Nagem, RAP Dauter, Z Polikarpov, I TI Protein crystal structure solution by fast incorporation of negatively and positively charged anomalous scatterers SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID PHASE REFINEMENT; DIFFRACTION AB The preparation of derivatives by the traditional methods of soaking is one of the most time-consuming steps in protein crystal structure solution by X-ray diffraction techniques. The `quick cryosoaking' procedure for derivatization with halides (monovalent anions) offers the possibility of significantly speeding up this process [Dauter et al. (2000), Acta Cryst. D56, 232-237]. In the present work, an extension of this technique is proposed and the use of two different classes of compounds (monovalent and polyvalent cations) that can be successfully utilized in the quick cryosoaking procedure for the derivatization and phasing of protein crystals is described. This approach has been tested on hen egg-white lysozyme and has been successfully used to solve the structure of a novel trypsin inhibitor. The possibility of using cations in the fast cryosoaking procedure gives additional flexibility in the process of derivatization and increases the chances of success in phase determination. This method can be applied to high-throughput crystallographic projects. C1 Lab Nacl Luz Sincrotron, BR-13084971 Campinas, SP, Brazil. UNICAMP, Dept Fis, BR-13084971 Campinas, SP, Brazil. NCI, Synchrotron Radiat Res Sect, Upton, NY 11973 USA. Brookhaven Natl Lab, Upton, NY 11973 USA. RP Polikarpov, I (reprint author), Lab Nacl Luz Sincrotron, Caixa Postal 6192, BR-13084971 Campinas, SP, Brazil. RI Nagem, Ronaldo/K-3995-2012; Polikarpov, Igor/D-2575-2012; OI Nagem, Ronaldo/0000-0001-7219-1625 NR 25 TC 59 Z9 61 U1 0 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD JUL PY 2001 VL 57 BP 996 EP 1002 DI 10.1107/S0907444901007260 PN 7 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 446VK UT WOS:000169534700009 PM 11418768 ER PT J AU Ji, XH Blaszczyk, J Chen, X AF Ji, XH Blaszczyk, J Chen, X TI The absorption edge of protein-bound mercury and a double-edge strategy for HgMAD data acquisition SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID CRYSTAL-STRUCTURE; DIFFRACTION DATA; SELENOMETHIONYL PROTEINS; 3-DIMENSIONAL STRUCTURE; PHASE DETERMINATION; ESCHERICHIA-COLI; MAD; LYSOZYME AB The L-III absorption edge of protein-bound mercury (Hg) has been experimentally determined using X-ray data collection from a crystal. This absorption edge is 12 291 eV, 4 eV higher than the theoretical value of elemental Hg. Considering the possible shift of the Hg absorption edge with the chemical environment in different protein crystals, a double-edge strategy for multiwavelength anomalous diffraction (MAD) data collection has been developed. The approach provides a convenient way to optimize the dispersive signal between a remote wavelength and two edge wavelengths separated from each other by 4 eV. The dispersive signals derived from both edges are used, along with anomalous signals, in MAD phasing and phase refinement. This approach has been used in the crystal structure determination of three proteins containing one Hg atom per 186-196 amino-acid residues at 2.0, 2.6 and 2.7 Angstrom resolution. A set of four wavelengths is recommended for HgMAD data acquisition: 1.0087 Angstrom (12 291 eV, edge1), 1.0084 Angstrom (12 295 eV, edge2), 1.0064 Angstrom (12 320 eV, peak) and 0.9918 Angstrom (12 500 eV, remote). Although it is no longer necessary to determine the L-III absorption edge of protein-bound Hg experimentally, an initial fluorescence scan on the crystal for data collection is still necessary to verify the existence of Hg in the crystal. C1 NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. RP Ji, XH (reprint author), NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. RI Ji, Xinhua/C-9664-2012 OI Ji, Xinhua/0000-0001-6942-1514 NR 26 TC 5 Z9 5 U1 0 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD JUL PY 2001 VL 57 BP 1003 EP 1007 DI 10.1107/S0907444901006370 PN 7 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 446VK UT WOS:000169534700010 PM 11418769 ER PT J AU Fricchione, G Daly, R Rogers, MP Stefano, GB AF Fricchione, G Daly, R Rogers, MP Stefano, GB TI Neuroimmunologic influences in neuropsychiatric and psychophysiologic disorders SO ACTA PHARMACOLOGICA SINICA LA English DT Review DE psychoneuroimmunology; psychiatry; psychophysiology; stress; neuroimmunomodulation; cytokines ID CHRONIC FATIGUE SYNDROME; MAJOR DEPRESSIVE DISORDER; PITUITARY-ADRENAL AXIS; IMMUNE-SYSTEM; INVERTEBRATE IMMUNOCYTES; LYMPHOCYTE FUNCTION; DISEASE-ACTIVITY; VIRUS-INFECTION; NITRIC-OXIDE; STRESS AB Top down central nervous system (CNS) influences on the immune system and bottom up immune system influences on the CNS take part in a complex feedforward and feedback loop which may be responsible for initiating events and perpetuating circumstances in the course of neuropsychiatric as well as immune system diseases. In this paper the authors examine the neuroendocrine-neuroimmune stress response system, the concept of autoimmunoregulation, and recent studies of immune and pharmacological dysregulation in neuropsychiatric and psychosomatic illnesses. The authors review the recent English-language literature on these subjects. Support for the hypothesis that macrophages play an important role in neurodevelopment and in the pathophysiology of various neuropsychiatric conditions is found. The interplay between neurologic and immune systems may help to uncover the pathophysiologies of certain neuropsychiatric systems. This may provide new strategies for pharmacologic anti-inflammatory treatments. The monocyte/macrophage, which crosses the blood-brain barrier is an essential candidate cell in the study of psychoneuroimmunology. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. NIMH, Psychoneuroendocrinol Branch, Bethesda, MD 20892 USA. SUNY Coll Old Westbury, Inst Neurosurg, Old Westbury, NY 11568 USA. RP Fricchione, G (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. FU NIDA NIH HHS [NIDA 47392] NR 88 TC 8 Z9 8 U1 2 U2 3 PU ACTA PHARMACOLOGICA SINICA PI SHANGHAI PA 294 TAI-YUAN ROAD, SHANGHAI 200031, PEOPLES R CHINA SN 0253-9756 J9 ACTA PHARMACOL SIN JI Acta Pharmacol. Sin. PD JUL PY 2001 VL 22 IS 7 BP 577 EP 587 PG 11 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 454AJ UT WOS:000169950000001 PM 11749820 ER PT J AU Heishman, SJ Singleton, EG Liguori, A AF Heishman, SJ Singleton, EG Liguori, A TI Marijuana Craving Questionnaire: development and initial validation of a self-report instrument SO ADDICTION LA English DT Article ID SEEKING TREATMENT; SMOKING URGES; DRUG URGES; COCAINE; ADDICTION; ALCOHOL; WITHDRAWAL; TOBACCO; DEPENDENCE; ACTIVATION AB Aims. To develop and validate a multi-dimensional questionnaire on marijuana craving. Design and measurements. Current marijuana smokers (n = 217) not seeking treatment completed a 47-item Marijuana Craving Questionnaire (MCQ) and forms assessing demographics, drug use history, marijuana quit attempts and current mood. Findings. Exploratory and confirmatory factor analyses indicated that a four-factor solution best described the item structure. Factor subscales derived from the 17 items with significant loadings had respectable internal consistencies and were stable across settings and subgroups. The subscales exhibited low to moderate, positive intercorrelations and were significantly correlated with marijuana use history and a wide range of single-item measures of craving. Conclusions. Findings suggested that four specific constructs characterize craving for marijuana: (1) compulsivity, an inability to control marijuana use; (2) emotionality, use of marijuana in anticipation of relief from withdrawal or negative mood; (3) expectancy, anticipation of positive outcomes from smoking marijuana; and (4) purposefulness, intention and planning to use marijuana for positive outcomes. These data indicate that the MCQ is a valid and reliable instrument for assessing marijuana craving in individuals not seeking drug abuse treatment and that marijuana craving can be measured in the absence of withdrawal. C1 NIDA, Clin Pharmacol & Therapeut Branch, Intramural Res Program, Baltimore, MD 21224 USA. Univ Baltimore, Baltimore, MD 21201 USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. RP Heishman, SJ (reprint author), NIDA, Clin Pharmacol & Therapeut Branch, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Singleton, Edward G./0000-0003-3442-877X FU NIDA NIH HHS [R03-DA10997] NR 45 TC 83 Z9 86 U1 4 U2 10 PU CARFAX PUBLISHING PI BASINGSTOKE PA RANKINE RD, BASINGSTOKE RG24 8PR, HANTS, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD JUL PY 2001 VL 96 IS 7 BP 1023 EP 1034 DI 10.1046/j.1360-0443.2001.967102312.x PG 12 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 448YK UT WOS:000169657400012 PM 11440613 ER PT J AU Miele, GM Carpenter, KM Cockerham, MS Trautman, KD Blaine, J Hasin, DS AF Miele, GM Carpenter, KM Cockerham, MS Trautman, KD Blaine, J Hasin, DS TI Substance Dependence Severity Scale - Reliability and validity for ICD-10 substance use disorders SO ADDICTIVE BEHAVIORS LA English DT Article DE ICD-10 diagnoses; drug dependence; substance use; SDSS; dependence severity ID DSM-IV ALCOHOL; DIAGNOSIS; SDSS AB The Substance Dependence Severity Scale (SDSS) is a semistructured interview that assesses the severity of the DSM-IV diagnoses of dependence and abuse and the ICD-10 diagnoses of substance dependence and harmful use across a wide range of substances. Previous research has demonstrated that the SDSS' DSM-IV dependence scales are reliable and valid indicators of diagnostic severity. However, the ICD-10 scales have not been psychometrically tested. This study investigated the test-retest reliability, internal consistency, diagnostic concordance, and concurrent validity of the SDSS' ICD-10 dependence and harmful use scales in 180 (112 male and 68 female) treated substance users. Test-retest reliabilities for the ICD-10 dependence scales ranged from good to excellent for alcohol, cocaine, heroin, and cannabis, Test-retest reliabilities for the SDSS' ICD-10 harmful use scales were in the good range for alcohol, cocaine, and heroin and the poor to fair range for cannabis. Internal consistency, diagnostic concordance, sind concurrent validity results were comparable to the test-retest findings. These results support the use of the SDSS for assessing the severity of the ICD-10 dependence and harmful use diagnoses. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. New York State Psychiat Inst, New York, NY 10032 USA. NIDA, Bethesda, MD 20892 USA. Columbia Univ, Joseph L Mailman Sch Publ Hlth, New York, NY USA. RP Carpenter, KM (reprint author), 60 Haven Ave,4D, New York, NY 10032 USA. FU NIAAA NIH HHS [AA00161, R01 AA08159]; NIDA NIH HHS [N44DA-6-6501] NR 28 TC 14 Z9 14 U1 3 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD JUL-AUG PY 2001 VL 26 IS 4 BP 603 EP 612 DI 10.1016/S0306-4603(00)00137-4 PG 10 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 444UE UT WOS:000169417800009 PM 11456080 ER PT J AU Bakke, B Stewart, P Ulvestad, B Eduard, W AF Bakke, B Stewart, P Ulvestad, B Eduard, W TI Dust and gas exposure in tunnel construction work SO AIHAJ LA English DT Article DE alpha-quartz; epidemiology; exposure assessment; nitrogen dioxide; oil mist; tunnel ID DIESEL EXHAUST; INDUSTRY; DISEASE; HEALTH; ASTHMA; AIRWAYS; RISKS; FUEL AB Personal exposures to dust and gases were measured among 189 underground construction workers who were divided into seven occupational groups performing similar tasks in similar working conditions: drill and blast crew; shaft-drilling crew; tunnel-boring machine crew; shotcreting operators; support workers; concrete workers; and electricians. Outdoor tunnel workers were included as a low-exposed reference group. The highest geometric mean (GM) exposures to total dust (6-7 mg/m(3)) and respirable dust (2-3 mg/m(3)) were found for the shotcreters, shaft drillers, and tunnel-boring machine workers. Shaft drillers and tunnel-boring machine workers also had the highest GM exposures to respirable a-quartz (0.3-0.4 mg/m(3)), which exceeded the Norwegian occupational exposure limit (OEL) of 0.1 mg/m(3). Shaft drillers had the highest exposure to oil mists (GM=1.4 mg/m(3)), which was generated mainly from pneumatic drilling. For other groups, exposure to oil mist from diesel exhaust and spraying of oil onto concrete forms resulted in exposures of 0.1-0.5 mg/m(3). Exposure to nitrogen dioxide was similar across all groups (GM=0.4-0.9 ppm), except for shaft drillers and tunnel-boring machine workers, who had lower exposures. High short-term exposures (> 10 ppm), however, occurred when workers were passing through the blasting cloud. C1 Natl Inst Occupat Hlth, N-0033 Oslo, Norway. NCI, Rockville, MD 20852 USA. Selmer ASA, N-0107 Oslo, Norway. RP Bakke, B (reprint author), Natl Inst Occupat Hlth, POB 8149 Dep, N-0033 Oslo, Norway. NR 34 TC 18 Z9 21 U1 1 U2 12 PU AMER INDUSTRIAL HYGIENE ASSOC PI FAIRFAX PA 2700 PROSPERITY AVE #250, FAIRFAX, VA 22031-4307 USA SN 1529-8663 J9 AIHAJ JI AIHAJ PD JUL-AUG PY 2001 VL 62 IS 4 BP 457 EP 465 DI 10.1202/0002-8894(2001)062<0457:DAGEIT>2.0.CO;2 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 466YH UT WOS:000170673400007 PM 11549139 ER PT J AU Sillanaukee, P Strid, N Jousilahti, P Vartiainen, E Poikolainen, K Nikkari, S Allen, JP Alho, H AF Sillanaukee, P Strid, N Jousilahti, P Vartiainen, E Poikolainen, K Nikkari, S Allen, JP Alho, H TI Association of self-reported diseases and health care use with commonly used laboratory markers for alcohol consumption SO ALCOHOL AND ALCOHOLISM LA English DT Article ID GAMMA-GLUTAMYL-TRANSFERASE; CARBOHYDRATE-DEFICIENT TRANSFERRIN; CORONARY-HEART-DISEASE; ALL-CAUSE MORTALITY; RHEUMATOID-ARTHRITIS; DIABETES-MELLITUS; BLOOD-PRESSURE; LIVER-DISEASE; SERUM; TRANSPEPTIDASE AB The relationships of carbohydrate-deficient transferrin (CDT), gamma-glutamyltransferase (GGT) and their mathematical combination (gamma -CDT) with self-reported diseases were evaluated in a large cross-sectional risk factor survey. Significant gender effects were observed in associations of the markers with several medical conditions as well as with general health care utilization. In men, CDT was associated with rheumatoid arthritis. In both genders, GGT was positively associated with hypertension and diabetes. gamma -CDT was positively associated with hypertension in males and with asthma in females. This general population study demonstrates that these markers, although most commonly used to assess alcohol misuse, might also serve as health risk indicators. C1 FIT Biotech OYj Plc, Tampere 33520, Finland. NS Associates, Vattholma, Sweden. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. Tampere Sch Publ Hlth, Tampere, Finland. Natl Publ Hlth Inst, Dept Mental Hlth & Alcohol Res, Helsinki, Finland. Jarvenpaa Addict Hosp, Helsinki, Finland. Univ Tampere, Sch Med, Dept Biochem Med, FIN-33101 Tampere, Finland. NIAAA, Rockville, MD 20852 USA. Natl Publ Hlth Inst, Alcohol Res Ctr, Helsinki, Finland. Univ Helsinki, Alcohol Dis Res Unit, FIN-00014 Helsinki, Finland. RP Sillanaukee, P (reprint author), FIT Biotech OYj Plc, Lenkkeilijankatu 10, Tampere 33520, Finland. NR 68 TC 16 Z9 16 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0735-0414 J9 ALCOHOL ALCOHOLISM JI Alcohol Alcohol. PD JUL-AUG PY 2001 VL 36 IS 4 BP 339 EP 345 DI 10.1093/alcalc/36.4.339 PG 7 WC Substance Abuse SC Substance Abuse GA 456YW UT WOS:000170111200012 PM 11468136 ER PT J AU Ahnert, L Lamb, ME AF Ahnert, L Lamb, ME TI The East German child care system: Associations with caretaking and caretaking beliefs, and children's early attachment and adjustment SO AMERICAN BEHAVIORAL SCIENTIST LA English DT Article ID FORMER GDR; ORGANIZATION; RESPONSES; QUALITY; INFANTS; MOTHER AB This article describes the origins of the child care system in East Germany Exploring the changes that followed German reunification and democracy, the authors specifically focus on the political interactions between the East and West and the unique child cure situation in the reunified city of Berlin. Drawing on studies conducted before and after reunification, the authors examine the early care practices and caretaking beliefs in Eastern and Western families and in public child cure. reviewing research on children's early attachment and adjustment. Two questions are particularly important: (a) whether patterns of early care in socialist East Germany adversely affected development and (b) whether the process of sociopolitical change itself introduced levels of stress that affected child rearing and child adjustment Data from numerous studies suggest that the sociopolitical changes contributed to behavior problems and insecure attachments when parents had difficulty adapting suggesting that preoccupation with their own problems. rather than the political system itself was responsible for adverse effects on children. C1 Interdisciplinary Ctr Appl Res Socializat, D-13125 Berlin, Germany. NICHHD, Bethesda, MD 20892 USA. RP Ahnert, L (reprint author), Interdisciplinary Ctr Appl Res Socializat, Tichauer Str 46, D-13125 Berlin, Germany. NR 68 TC 10 Z9 10 U1 1 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0002-7642 J9 AM BEHAV SCI JI Am. Behav. Sci. PD JUL PY 2001 VL 44 IS 11 BP 1843 EP 1863 DI 10.1177/00027640121958186 PG 21 WC Psychology, Clinical; Social Sciences, Interdisciplinary SC Psychology; Social Sciences - Other Topics GA 442PU UT WOS:000169294800004 ER PT J AU Ziegler, RG AF Ziegler, RG TI The future of phytochemical databases SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Editorial Material ID DIETARY-INTAKE; CAROTENOIDS; VEGETABLES C1 NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Ziegler, RG (reprint author), NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Execut Plaza S 8098, Bethesda, MD 20892 USA. NR 13 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUL PY 2001 VL 74 IS 1 BP 4 EP 5 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 445BF UT WOS:000169437700003 PM 11451712 ER PT J AU Obarzanek, E Sacks, FM Vollmer, RM Bray, GA Miller, ER Lin, PH Karanja, NM Most-Windhauser, MM Moore, TJ Swain, JF Bales, CW Proschan, MA AF Obarzanek, E Sacks, FM Vollmer, RM Bray, GA Miller, ER Lin, PH Karanja, NM Most-Windhauser, MM Moore, TJ Swain, JF Bales, CW Proschan, MA CA DASH Res Grp TI Effects on blood lipids of a blood pressure-lowering diet: the Dietary Approaches to Stop Hypertension (DASH) Trial SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE diet; plasma total cholesterol; LDL cholesterol; HDL cholesterol; triacyglycerol; feeding study; Dietary Approaches to Stop Hypertension Trial; DASH ID AMERICAN-HEART-ASSOCIATION; DENSITY LIPOPROTEIN CHOLESTEROL; HEALTH-CARE PROFESSIONALS; RISK-FACTOR; FATTY-ACIDS; CARDIOVASCULAR RISK; CLINICAL-TRIAL; SERUM-LIPIDS; METAANALYSIS; CARBOHYDRATE AB Background: Effects of diet on blood lipids are best known in white men, and effects of type of carbohydrate on triacylglycerol concentrations are not well defined. Objective: Our goal was to determine the effects of diet on plasma lipids, focusing on subgroups by sex, race, and baseline lipid concentrations. Design: This was a randomized controlled outpatient feeding trial conducted in 4 field centers. The subjects were 436 participants of the Dietary Approaches to Stop Hypertension (DASH) Trial [mean age: 44.6 +/-; 60% African American; baseline total cholesterol: less than or equal to6.7 mmol/L (less than or equal to 260 mg/dL)]. The intervention consisted of 8 wk of a control diet, a diet increased in fruit and vegetables, or a diet increased in fruit, vegetables, and low-fat dairy products and reduced in saturated fat, total fat, and cholesterol (DASH diet), during which time subjects remained weight stable. The main outcome measures were fasting total cholesterol, LDL cholesterol, HDL cholesterol, and triacylglycerol. Results: Relative to the control diet, the DASH diet resulted in lower total (-0.35 mmol/L, or -13.7 mg/dL), LDL(-0.28 mmol/L, or -10.7 mg/dL), and HDL- (-0.09 mmol/L, or -3.7 mg/dL) cholesterol concentrations (all P < 0.0001), without significant effects on triacylglycerol. The net reductions in total and LDL cholesterol in men were greater than those in women by 0.27 mmol/L, or 10.3 mg/dL (P = 0.052), and by 0.29 mmol/L, or 11.2 mg/dL (P < 0.02), respectively. Changes in lipids did not differ significantly by race or baseline lipid concentrations, except for HDL, which decreased more in participants with higher baseline HDL-cholesterol concentrations than in those with lower baseline HDL-cholesterol concentrations. The fruit and vegetable diet produced few significant lipid changes. Conclusions: The DASH diet is likely to reduce coronary heart disease risk. The possible opposing effect on coronary heart disease risk of HDL reduction needs further study. C1 NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrine Hypertens, Boston, MA 02115 USA. Kaiser Permanente, Ctr Hlth Res, Portland, OR USA. Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. Johns Hopkins Univ, Welch Ctr Prevent, Baltimore, MD USA. Duke Univ, Sch Med, Sarah W Stedman Ctr Nutr Studies, Durham, NC USA. Merck & Co Inc, Boston, MA USA. Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Durham, NC 27705 USA. RP Obarzanek, E (reprint author), NHLBI, Div Epidemiol & Clin Applicat, NIH, 6701 Rockledge Dr,Room 8136,MSC 7936, Bethesda, MD 20892 USA. FU NCRR NIH HHS [RR00722, RR02635]; NHLBI NIH HHS [U10-HL50981, U01-HL50968, U01-HL50972, U10-HL50977, U10-HL50982] NR 50 TC 228 Z9 237 U1 4 U2 21 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUL PY 2001 VL 74 IS 1 BP 80 EP 89 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 445BF UT WOS:000169437700012 PM 11451721 ER PT J AU Lindsay, RS Hanson, RL Knowler, WC AF Lindsay, RS Hanson, RL Knowler, WC TI Tracking of body mass index from childhood to adolescence: a 6-y follow-up study in China SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Letter C1 NIDDKD, Phoenix, AZ 85014 USA. RP Lindsay, RS (reprint author), NIDDKD, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 1 TC 4 Z9 4 U1 0 U2 3 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUL PY 2001 VL 74 IS 1 BP 149 EP 149 PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 445BF UT WOS:000169437700022 PM 11451731 ER PT J AU Ahmed, ZM Riazuddin, S Bernstein, SL Ahmed, Z Khan, S Griffith, AJ Morell, RJ Friedman, TB Riazuddin, S Wilcox, ER AF Ahmed, ZM Riazuddin, S Bernstein, SL Ahmed, Z Khan, S Griffith, AJ Morell, RJ Friedman, TB Riazuddin, S Wilcox, ER TI Mutations of the protocadherin gene PCDH15 cause Usher syndrome type 1F SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID MYOSIN-VIIA GENE; SYNDROME TYPE-I; SYNDROME TYPE 1D; HEARING-LOSS; GENOMIC DNA; CADHERIN SUPERFAMILY; RECESSIVE DEAFNESS; WALTZER; CDH23; MAPS AB Human chromosome 10q21-22 harbors USH1F in a region of conserved synteny to mouse chromosome 10. This region of mouse chromosome 10 contains Pcdh15, encoding a protocadherin gene that is mutated in ames waltzer and causes deafness and vestibular dysfunction. Here we report two mutations of protocadherin 15 (PCDH15) found in two families segregating Usher syndrome type 1F. A Northern blot probed with the PCDH15 cytoplasmic domain showed expression in the retina, consistent with its pathogenetic role in the retinitis pigmentosa associated with USH1F. C1 Natl Inst Deafness & Other Commun Disorders, Genet Mol Lab, NIH, Rockville, MD 20850 USA. Natl Inst Deafness & Other Commun Disorders, Neurootol Branch, NIH, Rockville, MD 20850 USA. Univ Maryland, Sch Med, Dept Ophthalmol, Baltimore, MD 21201 USA. Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore, Pakistan. RP Wilcox, ER (reprint author), Natl Inst Deafness & Other Commun Disorders, Genet Mol Lab, NIH, 5 Res Court,2A-19, Rockville, MD 20850 USA. EM wilcoxe@nidcd.nih.gov OI Morell, Robert/0000-0003-1537-7356 FU NIDCD NIH HHS [Z01 DC00035, T32 DC000035] NR 52 TC 240 Z9 245 U1 1 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUL PY 2001 VL 69 IS 1 BP 25 EP 34 DI 10.1086/321277 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 456XM UT WOS:000170108100003 PM 11398101 ER PT J AU Blair, A Zheng, T Linos, A Stewart, PA Zhang, YW Cantor, KP AF Blair, A Zheng, T Linos, A Stewart, PA Zhang, YW Cantor, KP TI Occupation and leukemia: A population-based case-control study in Iowa and Minnesota SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE leukemia; industry; occupation; nursing; health care work; solvents; agriculture; janitors; metal industries; myelodysplasia ID CANCER MORTALITY; RISK-FACTORS; CONSTRUCTION-INDUSTRY; ELECTRICAL WORKERS; UNITED-STATES; EXPOSURE; MEN; WOMEN; EMPLOYMENT; RADIATION AB Background Studies have suggested that risk of leukemia may be associated with occupational or industrial exposures and risk may vary by the histological type of the disease. Methods A population-based case-control study was conducted in Iowa and Minnesota to evaluate the association between various occupations, industries, and occupational exposures and leukemia risk. A total of 513 cases and 1,087 controls was included in the study. A lifetime occupational history and other risk factor information were collected through in-person interviews, and a job-exposure matrix was used to assess possible risks associated with specific exposures. Results A significantly increased risk of leukemia was observed among agricultural service industries and among nursing and healthcare workers. Janitors, cleaners, and light truck drivers also experienced increased risk. Those employed in plumbing, heating and air conditioning industries, and sales of nondurable goods (such as paints and varnishes) had an increased risk. Printers, painters, and workers in the food and metal industries had a nonsignificantly increased risk of leukemia. Analyses by specific exposures and histology of leukemia showed that risk of leukemia associated with occupational or industrial exposures may vary by histological type of the disease. Conclusions An increased risk of leukemia among workers employed in agricultural industries, nursing and healthcare workers, and in a few occupations with possible exposure to solvents is consistent with earlier studies. Associations of risk with occupations not observed previously deserve further assessment. Published 2001 Wiley-Liss, Inc.(dagger). C1 NCI, Occupat Epidemiol Branch, Bethesda, MD 20892 USA. Yale Univ, Sch Publ Hlth, Div Environm Sci, New Haven, CT USA. Univ Athens, Dept Epidemiol, GR-15771 Athens, Greece. RP Blair, A (reprint author), NCI, Occupat Epidemiol Branch, 6120 Execut Blvd,EPS 8118,MSC 7240, Bethesda, MD 20892 USA. NR 54 TC 33 Z9 35 U1 1 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD JUL PY 2001 VL 40 IS 1 BP 3 EP 14 DI 10.1002/ajim.1066 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 448YL UT WOS:000169657500002 PM 11439392 ER PT J AU Zhang, J Yancey, MK Klebanoff, MA Schwarz, J Schweitzer, D AF Zhang, J Yancey, MK Klebanoff, MA Schwarz, J Schweitzer, D TI Does epidural analgesia prolong labor and increase risk of cesarean delivery? A natural experiment SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE epidural analgesia; labor; delivery; cesarean delivery; forceps; vacuum; oxytocin ID RANDOMIZED TRIAL; RATES; MEPERIDINE; DYSTOCIA; MODE AB OBJECTIVE: More than 50% of pregnant women in the United States are using epidural analgesia for labor pain. However, whether epidural analgesia prolongs labor and increases the risk of cesarean delivery remains controversial. STUDY DESIGN: We examined this question in a community-based, tertiary military medical center where the rate of continuous epidural analgesia in labor increased from 1% to 84% in a 1-year period while other conditions remained unchanged-a natural experiment. We systematically selected 507 and 581 singleton, nulliparous, term pregnancies with spontaneous onset of labor and vertex presentation from the respective times before and after the times that epidural analgesia was available on request during labor. We compared duration of labor, rate of cesarean delivery, instrumental delivery, and oxytocin use between these two groups. RESULTS: Despite a rapid and dramatic increase in epidural analgesia during labor (from 1% to 84% in 1 year), rates of cesarean delivery overall and for dystocia remained the same (for overall cesarean delivery: adjusted relative risk, 0.8; 95% confidence interval, 0.6-1.2; for dystocia: adjusted relative risk, 1.0; 95% confidence interval, 0.7-1.6). Overall instrumental delivery did not increase (adjusted relative risk, 1.0; 95% confidence interval, 0.8-1.4), nor did the duration of the first stage and the active phase of labor (multivariate analysis; P > .1). However, the second stage of labor was significantly longer by about 25 minutes (P < .001). CONCLUSION: Epidural analgesia during labor does not increase the risk of cesarean delivery, nor does it necessarily increase oxytocin use or instrumental delivery caused by dystocia. The duration of the active phase of labor appears unchanged, but the second stage of labor is likely prolonged. C1 NICHHD, Epidemiol Branch, NIH, Bethesda, MD 20892 USA. Tripler Army Med Ctr, Dept Obstet & Gynecol, Honolulu, HI 96859 USA. RP Zhang, J (reprint author), NICHHD, Epidemiol Branch, NIH, NIH Bldg 6100,Room 7B03, Bethesda, MD 20892 USA. NR 21 TC 45 Z9 56 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JUL PY 2001 VL 185 IS 1 BP 128 EP 134 DI 10.1067/mob.2001.113874 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 458WP UT WOS:000170218700024 PM 11483916 ER PT J AU Fuhrer, MJ AF Fuhrer, MJ TI Assistive technology outcomes research - Challenges met and yet unmet SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE research outcomes assistive technology ID PROGRAM AB This article highlights the special requirements, achievements, and yet unmet challenges of assessing the outcomes of assistive technology services. The current status of this research is considered from the standpoint of developmental stages that seem to characterize many areas of outcomes research. Those stages include exhortation, sober appraisal, infrastructure building, and "getting on with it." The status of measuring assistive technology outcomes is described, and efforts to develop new measures are critically reviewed. Three as yet unmet challenges are discussed that are faced alike by assistive technology outcomes research and by rehabilitation outcomes research in general. They are as follows: (1) operationalizing a multiple-stakeholder approach to outcomes research; (2) formulating adequate treatment theories; and (3) creating shared databases. C1 NIH, Washington, DC USA. RP Fuhrer, MJ (reprint author), 13 Kings Valley Court, Damascus, MD 20872 USA. NR 28 TC 47 Z9 47 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD JUL PY 2001 VL 80 IS 7 BP 528 EP 535 DI 10.1097/00002060-200107000-00013 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 442ZC UT WOS:000169314000009 PM 11421522 ER PT J AU Chen, GP Carroll, S Racay, P Dick, J Pette, D Traub, I Vrbova, G Eggli, P Celio, M Schwaller, B AF Chen, GP Carroll, S Racay, P Dick, J Pette, D Traub, I Vrbova, G Eggli, P Celio, M Schwaller, B TI Deficiency in parvalbumin increases fatigue resistance in fast-twitch muscle and upregulates mitochondria SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE muscle fatigue; calcium-binding protein; EF hand; compensation ID CONTRACTION-RELAXATION CYCLE; LOW-FREQUENCY STIMULATION; SKELETAL-MUSCLE; CALCIUM TRANSIENTS; GENE-EXPRESSION; SINGLE FIBERS; SLOW; RAT; BINDING; CELLS AB The soluble Ca(2+)-binding protein parvalbumin (PV) is expressed at high levels in fast-twitch muscles of mice. Deficiency of PV in knockout mice (PV -/-) slows down the speed of twitch relaxation, while maximum force generated during tetanic contraction is unaltered. We observed that PV-deficient fast-twitch muscles were significantly more resistant to fatigue than were the wild type. Thus components involved in Ca(2+) homeostasis during the contraction-relaxation cycle were analyzed. No upregulation of another cytosolic Ca(2+)-binding protein was found. Mitochondria are thought to play a physiological role during muscle relaxation and were thus analyzed. The fractional volume of mitochondria in the fast-twitch muscle extensor digitorum longus (EDL) was almost doubled in PV -/- mice, and this was reflected in an increase of cytochrome c oxidase. A faster removal of intracellular Ca(2+) concentration ([Ca(2+)](i)) 200-700 ms after fast-twitch muscle stimulation observed in PV -/- muscles supports the role for mitochondria in late [Ca(2+)](i) removal. The present results also show a significant increase of the density of capillaries in EDL muscles of PV -/- mice. Thus alterations in the dynamics of Ca(2+) transients detected in fast-twitch muscles of PV -/- mice might be linked to the increase in mitochondria volume and capillary density, which contribute to the greater fatigue resistance of these muscles. C1 Univ Fribourg, Inst Histol & Gen Embryol, Program Neurosci, CH-1705 Fribourg, Switzerland. Univ Bern, Inst Anat, CH-3012 Bern, Switzerland. NIH, Bethesda, MD 20814 USA. UCL, Dept Anat, London WC1E 6BT, England. Univ Constance, Fac Biol, D-78457 Constance, Germany. RP Schwaller, B (reprint author), Univ Fribourg, Inst Histol & Gen Embryol, Program Neurosci, CH-1705 Fribourg, Switzerland. EM beat.schwaller@unifr.ch RI Celio, Marco/O-5193-2014 NR 38 TC 37 Z9 37 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD JUL PY 2001 VL 281 IS 1 BP C114 EP C122 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 444DQ UT WOS:000169384100014 PM 11401833 ER PT J AU Fedorova, OV Anderson, DE Lakatta, EG Bagrov, AY AF Fedorova, OV Anderson, DE Lakatta, EG Bagrov, AY TI Interaction of NaCl and behavioral stress on endogenous sodium pump ligands in rats SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE hypertension; salt sensitivity; social stress; endogenous Na-K-ATPase inhibitors; cardiovascular remodeling ID OUABAIN-LIKE COMPOUND; DIGITALIS-LIKE-FACTOR; MARINOBUFAGENIN-LIKE; ESSENTIAL-HYPERTENSION; PLASMA; IMMUNOREACTIVITY; INHIBITORS; SUBSTANCE; VOLUME; HYPOVENTILATION AB Our study investigated the hypothesis that the combination of a high NaCl diet and social isolation stress would increase systolic blood pressure (SBP) and endogenous sodium pump ligands (SPL), ouabainlike compound (OLC), and marinobufagenin (MBG). Excretion of MBG and OLC, SBP, and organ weights were studied in four groups (n = 8) of male Fisher 344 x Norwegian brown rats: controls, socially isolated (Iso), 4% NaCl diet (Salt), and the combination of Salt and Iso (Iso+Salt). In Salt, MBG excretion increased by 78% (P< 0.01), whereas SBP and OLC remained unchanged. In Iso, SBP and MBG did not change, but OLC peaked on day 1. In the Iso+Salt, SBP increased by 9 mmHg, MBG excretion increased (42.0 +/- 7.6 vs. 10.0 +/- 1.5 pmol/24 h, P< 0.01), whereas OLC peaked at day 1 (25.0 +/- 2.5 vs. 10.0 +/- 2.0 pmol/24 h, P< 0.01) and remained elevated. Heart and kidney weights were increased in Salt and Iso+Salt. Aortic weights were increased in Iso and Iso+Salt. Thus a high NaCl intake stimulates MBG excretion, whereas isolation stress stimulates OLC. The combination of Salt and Iso is accompanied by marked stimulation of both SPL. C1 NIA, Cardiovasc Sci Lab, Intramural Res Program, Gerontol Res Ctr,NIH, Baltimore, MD 21224 USA. RP Fedorova, OV (reprint author), NIA, Cardiovasc Sci Lab, Intramural Res Program, Gerontol Res Ctr,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 50 TC 22 Z9 22 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD JUL PY 2001 VL 281 IS 1 BP R352 EP R358 PG 7 WC Physiology SC Physiology GA 444DP UT WOS:000169384000041 PM 11404312 ER PT J AU Bradford, AD Terris, JM Ecelbarger, CA Klein, JD Sands, JM Chou, CL Knepper, MA AF Bradford, AD Terris, JM Ecelbarger, CA Klein, JD Sands, JM Chou, CL Knepper, MA TI 97-and 117-kDa forms of collecting duct urea transporter UT-A1 are due to different states of glycosylation SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE kidney; urea; vasopressin ID LONG-TERM REGULATION; RAT-KIDNEY; VASOPRESSIN; AQUAPORIN-2; EXPRESSION; MEMBRANE; CHANNEL; PERMEABILITY; PROTEINS; SYSTEM AB UT-A1 is an extremely hydrophobic 929-amino acid integral membrane protein, expressed in the renal inner medullary collecting duct, with a central role in the urinary concentrating mechanism. Previous immunoblotting studies in rats have revealed that UT-A1 is present in kidney in 97- and 117-kDa monomeric forms and that the relative abundance of the two forms is altered by vasopressin treatment and other treatments that altered urinary inner medullary urea concentration. The present studies were carried out using protein chemistry techniques to determine the origin of the two forms. Peptide-directed polyclonal antibodies targeted to five sites along the polypeptide sequence from the NH(2) to the COOH terminus labeled both forms, thus failing to demonstrate a significant deletion in the primary amino acid chain. The 97- and 117-kDa monomeric forms were both reduced to 88 kDa by deglycosylation with N-glycosidase F, indicating that a single polypeptide chain is glycosylated to two different extents. Studies using nonionic detergents for membrane solubilization or using homobifunctional cross-linkers demonstrated that UT-A1 exists as a 206-kDa protein complex in native kidney membranes. The mobility of this complex was also increased by deglycosylation. Both the 97- and 117-kDa proteins, as well as the 206-kDa complex, were immunoprecipitated with UT-A1 antibodies. We conclude that UT-A1 is a glycoprotein and that the two monomeric forms (97 and 117 kDa) in inner medullary collecting duct are the consequence of different states of glycosylation. C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Physiol, Bethesda, MD 20814 USA. Emory Univ, Dept Med, Div Renal, Atlanta, GA 30322 USA. RP Knepper, MA (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bldg 10,Rm 6N260,10 Ctr Dr,MSC 1603, Bethesda, MD 20892 USA. EM knep@helix.nih.gov FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999]; NCRR NIH HHS [RRO1-DK41707]; NHLBI NIH HHS [Z01-HL-01282-KE]; NIDDK NIH HHS [R01 DK041707, PP01-DK-50268] NR 30 TC 64 Z9 66 U1 1 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JUL PY 2001 VL 281 IS 1 BP F133 EP F143 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 446FJ UT WOS:000169502000014 PM 11399654 ER PT J AU Li, CL Wang, WD Kwon, TH Isikay, L Wen, JG Marples, D Djurhuus, JC Stockwell, A Knepper, MA Nielsen, S Froklaer, J AF Li, CL Wang, WD Kwon, TH Isikay, L Wen, JG Marples, D Djurhuus, JC Stockwell, A Knepper, MA Nielsen, S Froklaer, J TI Downregulation of AQP1,-2, and-3 after ureteral obstruction is associated with a long-term urine-concentrating defect SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE collecting duct; nephrogenic diabetes insipidus; obstructive nephropathy; polyuria; proximal tubule; aquaporin-1; aquaporin-2; aquaporin-3 ID WATER CHANNEL EXPRESSION; INDUCED DOWN-REGULATION; KIDNEY COLLECTING DUCT; AQUAPORIN-1 NULL MICE; RAT-KIDNEY; POSTOBSTRUCTIVE DIURESIS; PLASMA-MEMBRANE; PERMEABILITY; PATHOPHYSIOLOGY; HEMODYNAMICS AB Previously, we demonstrated that 24 h of bilateral ureteral obstruction (BUO) and short-term release of BUO was associated with a decrease in the expression of aquaporin-2 (AQP2), polyuria, and a reduced urinary concentrating capacity (10). The purposes of the present study were to examine whether BUO and the long-term release of BUO (BUO-R) for 3, 14, and 30 days were associated with changes in the expression of renal AQP1, AQP2, and AQP3 and whether such changes were associated with parallel changes in urinary output and urinary concentrating capacity. Rats (n = 4-7 in each group) were kept in metabolic cages for measurements of urinary output. Kidneys were removed to determine the expression levels of AQP1, AQP2, and AQP3 by semiquantitative immunoblotting. AQP2 was downregulated after 24 h of BUO (42 +/- 3%). Downregulation of AQP2 persisted 3 (43 +/- 14%; P < 0.01) and 15 days after BUO-R (48 +/- 11%; P < 0.01) but was normalized 90 days after BUO-R. AQP3 showed a similar pattern. Moreover, AQP1 was downregulated in response to BUO (65 +/- 7%) and remained downregulated 3 days after BUO-R (41 +/- 5%), 14 days after BUO-R (57 +/- 8%), and 30 days after BUO-R (59 +/- 5%). BUO-R resulted in a significant polyuria that gradually decreased, although it remained significant at day 30. Urinary concentrating capacity remained significantly impaired when determined 3, 14, and 30 days after BUO-R in response to a 24-h period of thirst (1,712 +/- 270 vs. 2,880 +/- 91 mosmol/kgH(2)O at day 30, P < 0.05). In conclusion, the expression of AQP1, AQP2, and AQP3 were long-term downregulated after BUO-R, suggesting that dysregulation of aquaporins located at the proximal tubule, thin descending limb of the loop of Henle, and the collecting duct may contribute to the long-term polyuria and impairment of urinary concentrating capacity associated with obstructive nephropathy. C1 Univ Aarhus, Inst Expt Clin Res, DK-8200 Aarhus N, Denmark. Aarhus Univ, Hosp Skejby, Dept Clin Physiol, DK-8200 Aarhus N, Denmark. Aarhus Univ, Inst Astron, Dept Cell Biol, DK-8000 Aarhus C, Denmark. Univ Leeds, Sch Biomed Sci, Leeds LS2 9NQ, W Yorkshire, England. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Froklaer, J (reprint author), Aarhus Univ, Hosp Skejby, Inst Expt Clin Res, DK-8200 Aarhus, Denmark. EM JF@IEKF.AU.DK RI wen, jianguo/P-3185-2014 OI wen, jianguo/0000-0003-0952-118X FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999] NR 43 TC 62 Z9 68 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JUL PY 2001 VL 281 IS 1 BP F163 EP F171 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 446FJ UT WOS:000169502000017 PM 11399657 ER PT J AU Rosenberg, PS AF Rosenberg, PS TI HIV in the late 1990s: What we don't know may hurt us SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; UNITED-STATES; INFECTION; PREVALENCE; EPIDEMIC C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. RP Rosenberg, PS (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8020, Rockville, MD 20852 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUL PY 2001 VL 91 IS 7 BP 1016 EP 1017 DI 10.2105/AJPH.91.7.1016 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 461BR UT WOS:000170345500003 PM 11441722 ER PT J AU Helfand, WH Lazarus, J Theerman, P AF Helfand, WH Lazarus, J Theerman, P TI "You can help defeat cancer": A multi-cultural society confronts a disease SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article C1 Natl Lib Med, Hist Med Div, Bethesda, MD 20894 USA. RP Theerman, P (reprint author), Natl Lib Med, Hist Med Div, 8600 Rockville Pike, Bethesda, MD 20894 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUL PY 2001 VL 91 IS 7 BP 1018 EP 1018 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 461BR UT WOS:000170345500004 ER PT J AU Kumar, S Lawlor, C Jaffe, ES AF Kumar, S Lawlor, C Jaffe, ES TI Hepatosplenic T-cell lymphoma of alpha beta lineage SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Letter C1 Childrens Natl Med Ctr, Dept Pathol, Washington, DC USA. Childrens Natl Med Ctr, Dept Hematol Oncol, Washington, DC USA. NCI, Hematopathol Sect, NIH, Bethesda, MD USA. RP Kumar, S (reprint author), Childrens Natl Med Ctr, Dept Pathol, Washington, DC USA. NR 3 TC 9 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JUL PY 2001 VL 25 IS 7 BP 970 EP 971 DI 10.1097/00000478-200107000-00020 PG 2 WC Pathology; Surgery SC Pathology; Surgery GA 448XE UT WOS:000169654600020 PM 11420473 ER PT J AU Batty, DS Swanson, SJ Kirk, AD Ko, CW Agodoa, LY Abbott, KC AF Batty, DS Swanson, SJ Kirk, AD Ko, CW Agodoa, LY Abbott, KC TI Hepatitis C virus seropositivity at the time of renal transplantation in the United States: Associated factors and patient survival SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE African-American; diabetes; dialysis; donor; hepatitis C; hospitalization; kidney; liver; male; mortality; repeat transplant ID KIDNEY ALLOGRAFT RECIPIENTS; DIALYSIS PATIENTS; CIRRHOTIC GLOMERULONEPHRITIS; HEMODIALYSIS-PATIENTS; INTERFERON-ALPHA; INFECTION; DISEASE; IMPACT; PREVALENCE; ANTIBODIES AB National statistics for patient characteristics and survival of renal transplant recipients positive for hepatitis C virus (HCV+) at the time of renal transplant are presented. A historical cohort analysis of 33479 renal transplant recipients in the United States Renal Data System from I July, 1994 to 30 June, 1997 has been carried out. The medical evidence form was also used for additional variables, but because of fewer available values, this was analyzed in a separate model. Outcomes were patient characteristics and survival associated with HCV+. Of 28692 recipients with valid HCV serologies, 1624 were HCV+ at transplant (5.7% prevalence). In logistic regression analysis, HCV+ was associated with African-American race, male gender, cadaveric donor type, increased duration of pre-transplant dialysis, previous transplant, donor HCV+, recipient (but not donor) age, serum albumin, alcohol use, and increased all-cause hospitalizations. Diabetes and IgA nephropathy were less associated with HCV+. Total all-cause, unadjusted mortality was 13.1% in HCV+ vs. 8.5% in HCV- patients (p <0.01 by log rank test). In Cox regression, mortality was higher for HCV+ (adjusted hazard ratio = 1.23, 95% confidence interval = 1.01-1.49, p = 0.04). HCV+ recipients were more likely to be African-American, male, older, and to have received repeat transplants and donor HCV+ transplants. HCV+ recipients also had substantially longer waiting times for transplant. In contrast to recent studies, diabetes did not have an Increased association with HCV+, perhaps due to limitations of the database. HCV+ recipients had increased mortality and hospitalization rates compared with other transplant recipients. C1 Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Walter Reed Army Med Ctr, Organ transplantat Serv, Bethesda, MD USA. NIH, Bethesda, MD 20892 USA. NIDCD, Epidemiol Stat & Data Syst Branch, NIH, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD 20892 USA. RP Abbott, KC (reprint author), Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. RI Kirk, Allan/B-6905-2012; OI Abbott, Kevin/0000-0003-2111-7112 NR 29 TC 71 Z9 71 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUL PY 2001 VL 1 IS 2 BP 179 EP 184 PG 6 WC Surgery; Transplantation SC Surgery; Transplantation GA 514XP UT WOS:000173466600012 PM 12099367 ER PT J AU Koenig, JL Wang, SQ Bhargava, R AF Koenig, JL Wang, SQ Bhargava, R TI FTIR images SO ANALYTICAL CHEMISTRY LA English DT Article ID PLANE ARRAY DETECTION; TRANSFORM INFRARED MICROSCOPY; IMAGING MICROSCOPY; POLYMERIC SYSTEMS; LIQUID-CRYSTALS; REAL-TIME; SPECTROMETER; DIFFUSION C1 Case Western Reserve Univ, Dept Macromol Sci, Cleveland, OH 44106 USA. Univ Akron, Akron, OH 44325 USA. NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Koenig, JL (reprint author), Case Western Reserve Univ, Dept Macromol Sci, Kent Hale Smith Bldg,Rm 212,10900 Euclid Ave, Cleveland, OH 44106 USA. NR 27 TC 33 Z9 33 U1 1 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD JUL 1 PY 2001 VL 73 IS 13 BP 360A EP 369A DI 10.1021/ac012471p PG 10 WC Chemistry, Analytical SC Chemistry GA 448ZP UT WOS:000169660100007 PM 11467585 ER PT J AU Abrantes, M Magone, MT Boyd, LF Schuck, P AF Abrantes, M Magone, MT Boyd, LF Schuck, P TI Adaptation of a surface plasmon resonance biosensor with miorofluidics for use with small sample volumes and long contact times SO ANALYTICAL CHEMISTRY LA English DT Article ID BIOMOLECULAR INTERACTION ANALYSIS; PROTEIN INTERACTIONS; BINDING-KINETICS; OPTICAL BIOSENSOR; MASS-TRANSPORT; BIACORE; ANTIBODY; CELL; RECOGNITION; TECHNOLOGY AB The efficient delivery of sample to surface-immobilized sites is a key element in biosensing, For a surface plasmon resonance (SPR) biosensor, this has been addressed by constant now through a microfluidic system with a sample injection loop (Sjloander, S,; Urbaniczky, C. Anal. Chem. 1991, 63, 2338-2345), The present study describes an alternative mode of sample delivery without constant unidirectional flow. It was implemented on a commercial Biacore X SPR biosensor equipped with a microfluidic cartridge, but with the fluidic handling performed by an externally computer-controlled syringe pump. We demonstrate that sample volumes as low as 2 muL can be reproducibly positioned to cover the sensor surfaces, manipulated in a serial fashion, efficiently mixed by applying an oscillatory now pattern, and fully recovered. Compared to the traditional continuous unidirectional now configuration, we found very similar kinetic responses at high analyte concentrations and slightly slower responses at low concentrations, most likely due to depletion of analyte from the small sample volumes due to surface binding. With the antibody-antigen systems tested, binding parameters were obtained that are generally within 10% of those from conventional experiments. In the new configuration, biosensor experiments can be conducted without the usual constraints in the surface contact time that are correlated with sample volume and mass transport rate. This can translate to improved detection limits for slow reactions and can facilitate kinetic and thermodynamic binding studies. C1 NIAID, Div Bioengn & Phys Sci, ORS, OD,Natl Eye Inst,NIH, Bethesda, MD 20892 USA. NIAID, Mol Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Schuck, P (reprint author), NIAID, Div Bioengn & Phys Sci, ORS, OD,Natl Eye Inst,NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 39 TC 46 Z9 46 U1 1 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD JUL 1 PY 2001 VL 73 IS 13 BP 2828 EP 2835 DI 10.1021/ac010042 PG 8 WC Chemistry, Analytical SC Chemistry GA 448ZP UT WOS:000169660100011 PM 11467523 ER PT J AU Michalek, JE Ketchum, NS Longnecker, MP AF Michalek, JE Ketchum, NS Longnecker, MP TI Serum dioxin and hepatic abnormalities in veterans of operation ranch hand SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE agent orange; dioxin; hepatic abnormality ID TISSUE DISTRIBUTION; LIPID-PEROXIDATION; HEALTH-STATUS; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; TCDD; EXPOSURE; RATS; EXCRETION; DIRECTION; CAUSALITY AB PURPOSE: We studied hepatic abnormalities and indices of hepatic function in relation to exposure to 2,3,7,8- tetrachlorodibenzo-p-dioxin (dioxin) in veterans of Operation Ranch Hand, the Air Force unit responsible for the aerial spraying of herbicides in Vietnam from 1962 to 1971. METHODS: The prevalence of ever having liver disease through March 1993, and level of alanine aminotransferase, aspartate aminotransferase, gamma -glutamyltransferase (GGT), lactic dehydrogenase (LDH), alkaline phosphatase, and total bilirubin were examined according to serum dioxin levels. RESULTS: We found an increased risk of "other liver disorders" among veterans with the highest dioxin levels [adjusted odds ratio (OR) = 1.6, 95% confidence interval (CI) 1.2 to 2.1], due primarily to increased transaminases or LDH (adjusted OR = 2.7, 95% CI 1.4 to 5.1) and to other nonspecific liver abnormalities (adjusted OR = 1.4, 95% CI 1.0 to 2.0). CONCLUSIONS: Whether the associations observed were causal is unclear from these data. Ann Epidemiol 2001;11:304-311. (C) 2001 Elsevier Science Inc. All rights reserved. C1 USAF, Res Lab, Brooks AFB, TX USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Michalek, JE (reprint author), AFRL HEDB, 2606 Doolittle Rd,Bldg 807, Brooks AFB, TX 78235 USA. OI Longnecker, Matthew/0000-0001-6073-5322 NR 39 TC 20 Z9 22 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD JUL PY 2001 VL 11 IS 5 BP 304 EP 311 DI 10.1016/S1047-2797(00)00218-0 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 438CQ UT WOS:000169036500005 PM 11399444 ER PT J AU McDonald, WI Compston, A Edan, G Goodkin, D Hartung, HP Lublin, FD McFarland, HF Paty, DW Polman, CH Reingold, SC Sandberg-Wollheim, M Sibley, W Thompson, AJ van den Noort, S Weinshenker, BY Wolinsky, JS AF McDonald, WI Compston, A Edan, G Goodkin, D Hartung, HP Lublin, FD McFarland, HF Paty, DW Polman, CH Reingold, SC Sandberg-Wollheim, M Sibley, W Thompson, AJ van den Noort, S Weinshenker, BY Wolinsky, JS TI Recommended diagnostic criteria for multiple sclerosis: Guidelines from the International Panel on the Diagnosis of Multiple Sclerosis SO ANNALS OF NEUROLOGY LA English DT Article ID FAST SPIN-ECHO; EVOKED-POTENTIALS; MULTIARRAY COILS; MRI; MS AB The International Panel on MS Diagnosis presents revised diagnostic criteria for multiple sclerosis (MS). The focus remains on the objective demonstration of dissemination of lesions in both time and space. Magnetic resonance imaging is integrated with clinical and other paraclinical diagnostic methods. The revised criteria facilitate the diagnosis of MS in patients with a variety of presentations, including "monosymptomatic" disease suggestive of MS, disease with a typical relapsing-remitting course, and disease with insidious progression, without clear attacks and remissions. Previously used terms such as "clinically definite" and "probable MS" are no longer recommended. The outcome of a diagnostic evaluation is either MS, "possible MS" (for those at risk for MS, but for whom diagnostic evaluation is equivocal), or "not MS." C1 Royal Coll Physicians, London NW1 4LE, England. Univ Cambridge, Cambridge, England. CHU Rennes, Rennes, France. Univ Calif San Francisco, San Francisco, CA 94143 USA. Karl Franzens Univ Graz, Graz, Austria. Mt Sinai Sch Med, New York, NY USA. Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Free Univ Amsterdam, NL-1081 HV Amsterdam, Netherlands. Natl Multiple Sclerosis Soc, New York, NY USA. Univ Lund Hosp, S-22185 Lund, Sweden. UCL, Inst Neurol, London, England. Univ Arizona, Hlth Sci Ctr, Tucson, AZ USA. Neurol Inst, London, England. Univ Calif Irvine, Irvine, CA USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Univ Texas, Hlth Sci Ctr, Houston, TX USA. RP McDonald, WI (reprint author), Royal Coll Physicians, 11 St Andrews Pl, London NW1 4LE, England. RI Thompson, Alan/C-2654-2008 OI Thompson, Alan/0000-0002-4333-8496 FU Multiple Sclerosis Society [491] NR 23 TC 4016 Z9 4173 U1 31 U2 161 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUL PY 2001 VL 50 IS 1 BP 121 EP 127 DI 10.1002/ana.1032 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 447FR UT WOS:000169561300017 PM 11456302 ER PT J AU Saif, MW Wilson, RH Harold, N Keith, B Dougherty, DS Grem, JL AF Saif, MW Wilson, RH Harold, N Keith, B Dougherty, DS Grem, JL TI Peripheral neuropathy associated with weekly oval 5-fluorouvacil, leucovorin and eniluracil SO ANTI-CANCER DRUGS LA English DT Article DE dihydropyrimidine dehydrogenase; eniluracil; fluorouracil; peripheral neuropathy ID DIHYDROPYRIMIDINE DEHYDROGENASE-DEFICIENCY; FLUORO-BETA-ALANINE; COLORECTAL-CANCER; ORAL FLUOROURACIL; PHASE-II; 5-FLUOROURACIL; NEUROTOXICITY; ENCEPHALOPATHY; ACID; METABOLITES AB 5-Fluorouracil (5-FU)-associated neurotoxicity is uncommon; symptoms may occur abruptly or more gradually during the course of chemotherapy. Peripheral neuropathy with 5-FU therapy has only rarely been reported. Two patients treated in a phase I trial of oral 5-FU, leucovorin and eniluracil, an inhibitor of dihydropyrimidine dehydrogenase (DPD), developed delayed onset symptoms of unsteady gait and reduced sensation in the legs. Magnetic resonance imaging scans of the brain and neurologic examination did not support a CNS basis for the condition, Electromyograms and nerve conduction studies revealed sensorimotor polyneuropathy. Other common etiologies of peripheral neuropathy were excluded. The neurological condition of these patients stabilized after 5-FU dose reduction and partial resolution gradually occurred when protocol therapy was stopped. Although CNS symptoms may rarely complicate 5-FU therapy, peripheral neuropathy is unexpected. Patients with DPD deficiency treated with conventional doses of 5-FU typically develop acute CNS toxicity shortly after therapy, accompanied by extremely high systemic exposure to 5-FU. Patients with normal 5-FU clearance may also experience CNS toxicity, particularly with high-dose schedules, and both parent drug and its catabolites may be contributory. Since DPD was profoundly inhibited during eniluracil therapy in these two patients, it is likely that 5-FU or its active metabolites were contributing factors to the peripheral neuropathy, [(C) 2001 Lippincott Williams & Wilkins.]. C1 Natl Naval Med Ctr, Dept Neurol, Bethesda, MD 20889 USA. NCI, Dev Therapeut Dept, Med Branch, Div Clin Sci, Bethesda, MD 20889 USA. RP Grem, JL (reprint author), Natl Naval Med Ctr, Dept Neurol, Bldg 8,Room 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA. NR 30 TC 17 Z9 20 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4973 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD JUL PY 2001 VL 12 IS 6 BP 525 EP 531 DI 10.1097/00001813-200107000-00006 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 454RZ UT WOS:000169986700006 PM 11459999 ER PT J AU Voeller, DM Parr, A Allegra, CJ AF Voeller, DM Parr, A Allegra, CJ TI Development of human anti-thymidine kinase antibodies SO ANTI-CANCER DRUGS LA English DT Article DE antibody; thymidine kinase C1 NCI, Med Branch, NIH, Bethesda, MD 20889 USA. RP Voeller, DM (reprint author), Natl Naval Med Ctr, 8901 Wisconsin Ave,Bldg 8,Room 5101, Bethesda, MD 20889 USA. NR 4 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4973 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD JUL PY 2001 VL 12 IS 6 BP 555 EP 559 DI 10.1097/00001813-200107000-00010 PG 5 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 454RZ UT WOS:000169986700010 PM 11460003 ER PT J AU Charmandari, E Lichtarowicz-Krynska, EJ Hindmarsh, PC Johnston, A Aynsley-Green, A Brook, CGD AF Charmandari, E Lichtarowicz-Krynska, EJ Hindmarsh, PC Johnston, A Aynsley-Green, A Brook, CGD TI Congenital adrenal hyperplasia: management during critical illness SO ARCHIVES OF DISEASE IN CHILDHOOD LA English DT Article DE congenital adrenal hyperplasia; critical illness; hydrocortisone; cortisol clearance ID SEPTIC SHOCK; HYDROCORTISONE AB Background-Little is known of the optimal dose and administration schedule of hydrocortisone in critically ill patients with congenital adrenal hyperplasia (CAH) caused by 21-hydroxylase deficiency. Aim-To determine plasma cortisol concentrations after intravenous administration of hydrocortisone in children with CAH and to relate these to plasma cortisol concentrations achieved by endogenous secretion in the stress of critical illness in previously healthy children. Methods-Plasma cortisol concentrations were measured in 20 patients with classical CAH (median age 11.2 years, range 6.1-16.4) following intravenous administration of hydrocortisone 15 mg/m(2); and in 60 critically ill mechanically ventilated children (median age 2.5 years, range 0.25-16.3) on admission to the paediatric intensive care unit and for 24 hours thereafter. Results-In the CAH patients, plasma cortisol reached a mean peak of 1648.3 nmol/l (SD 511.9) within 10 minutes of the intravenous bolus, and fell rapidly thereafter; levels remained greater than 450 nmol/l for 2.5 hours only. In critically iu children, mean plasma cortisol on admission to the intensive care unit was 727 nmol/l (SD 426.1). Cortisol concentrations remained raised during the first 24 hours. Conclusions-Critically ill patients with classical CAH may be best managed with a single intravenous hydrocortisone bolus followed by a constant rate infusion of hydrocortisone. C1 Great Ormond St Hosp Sick Children, London Ctr Paediat Endocrinol, London WC1N 3JH, England. UCL, Inst Child Hlth, London WC1N 3JH, England. St Batholomews & Royal London Sch Med & Dent, Dept Clin Pharmacol, London EC1M 6BQ, England. RP Charmandari, E (reprint author), NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. EM charmane@mail.nih.gov RI Hindmarsh, Peter/C-4964-2008; Charmandari, Evangelia/B-6701-2011 NR 6 TC 14 Z9 16 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-9888 J9 ARCH DIS CHILD JI Arch. Dis. Child. PD JUL PY 2001 VL 85 IS 1 BP 26 EP 28 DI 10.1136/adc.85.1.26 PG 3 WC Pediatrics SC Pediatrics GA 449QE UT WOS:000169697200010 PM 11420193 ER PT J AU Hser, YI Grella, CE Hubbard, RL Hsieh, SC Fletcher, BW Brown, BS Anglin, D AF Hser, YI Grella, CE Hubbard, RL Hsieh, SC Fletcher, BW Brown, BS Anglin, D TI An evaluation of drug treatments for adolescents in 4 US cities SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID FOLLOW-UP OUTCOMES; ABUSE TREATMENT; YOUNG ADULTHOOD; DATOS; DELINQUENCY; ANTECEDENTS; CHILDHOOD; RETENTION AB Background: Little is known about outcomes of community-based treatment programs for adolescents with drug problems. Methods: We studied 1167 adolescents (age range, 11-18 years; 368 females, 799 males) from 4 US cities (Pittsburgh, Pa; Minneapolis, Minn; Chicago, Ill; and Portland. Ore) using a naturalistic, nonexperimental evaluation design. These adolescents were consecutive admissions during the period from 1993 to 1995 at 23 community-based treatment programs in the Drug Abuse Treatment Outcome Studies for Adolescents. Included were 418 admissions to 8 residential programs, 292 admissions to 9 outpatient drug-free programs, and 457 admissions to 6 short-term inpatient programs. Results: Adolescents in treatment typically had multiple problems (eg, 58.4% of them were involved in the legal system, and 63.0% met diagnostic criteria for a mental disorder). Nevertheless, less than half (43.8%) of all patients reported weekly marijuana use in the year following treatment (dropping from 80.4% in the year before admission). Similarly, there were decreases in heavy drinking (dropping from 33.8% to 20.3%), use of other illicit drugs (dropping from 48.0% to 42.2%), and criminal involvement (dropping from 75.6% to 52.8%).;Additionally patients reported better psychological adjustment and school performance after treatment. Longer stays in treatment were positively associated with several favorable outcomes, although length of time in treatment was generally short. Conclusions: Substance abuse treatment for adolescents is effective in achieving many important behavioral and psychological improvements. Strategies specific to adolescents to improve their treatment retention and completion are needed to maximize the therapeutic benefits of drug treatment. C1 Univ Calif Los Angeles, Drug Abuse Res Ctr, Inst Neuropsychiat, Los Angeles, CA 90025 USA. Natl Dev & Res Inst Inc, Raleigh, NC USA. NIDA, Bethesda, MD 20892 USA. Univ N Carolina, Wilmington, NC 28401 USA. RP Hser, YI (reprint author), Univ Calif Los Angeles, Drug Abuse Res Ctr, Inst Neuropsychiat, 1640 S Sepulveda Blvd,Suite 200, Los Angeles, CA 90025 USA. FU NIDA NIH HHS [DA00146, K02-DA00139, U01-DA10378] NR 31 TC 182 Z9 187 U1 1 U2 15 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUL PY 2001 VL 58 IS 7 BP 689 EP 695 DI 10.1001/archpsyc.58.7.689 PG 7 WC Psychiatry SC Psychiatry GA 451KN UT WOS:000169801400010 PM 11448377 ER PT J AU Staroselskaya, IA Chaves, C Silver, B Linfante, I Edelman, RR Caplan, L Warach, S Baird, AE AF Staroselskaya, IA Chaves, C Silver, B Linfante, I Edelman, RR Caplan, L Warach, S Baird, AE TI Relationship between magnetic resonance arterial patency and perfusion-diffusion mismatch in acute ischemic stroke and its potential clinical use SO ARCHIVES OF NEUROLOGY LA English DT Article; Proceedings Paper CT 51st Annual Meeting of the American-Academy-of-Neurology CY APR 17-24, 1999 CL TORONTO, CANADA SP Amer Acad Neurol ID TISSUE-PLASMINOGEN ACTIVATOR; RANDOMIZED CONTROLLED TRIAL; MR-ANGIOGRAPHY; WEIGHTED MRI; HYPERACUTE STROKE; DWI/PWI MISMATCH; THROMBOLYSIS; EVOLUTION; PENUMBRA; STENOSIS AB Background: In patients with acute ischemic stroke the magnetic resonance (MR) perfusion-diffusion mismatch pattern (perfusion lesion at least 20% larger than the lesion on diffusion-weighted imaging) may indicate ischemically threatened but viable tissue. To our knowledge, the relationship of this MR pattern to serial changes in MR angiography (MRA) has not been reported. Objectives: To investigate the relationship between MRA changes and patterns of diffusion-weighted imaging and perfusion abnormalities and to determine if the information obtained could be used in clinical management. Methods: The MR studies of 35 patients who had undergone sequential multimodality MR imaging studies within the first 4 days of stroke were reviewed. All lesions were in the internal carotid artery territory distribution. Magnetic resonance angiographies were read by 2 observers blinded to the clinical data. Results: During the first 24 hours a perfusion-diffusion mismatch was present in 22 (92%) of the 24 patients with an MRA arterial occlusive lesion. (At this time 5 [46%] of the 11 patients with a normal MRA [P=.006] also had a mismatch.) Two to 4 days after stroke, of these 22 patients resolution of the mismatch occurred in 8 (87%) of 9 patients with recanalization on MRA compared with 5 (39%) of 13 patients without arterial recanalization (P=.03). Resolution of mismatch occurred in 3 (60%) of 5 patients with a normal MRA and a mismatch at the first time point. Conclusions: Concordance between MRA and the MR perfusion-diffusion mismatch pattern provides supportive evidence for an arterial vascular basis for this MR signature in acute stroke. Discordance between MRA lesions and mismatch may result from arterial branch occlusions undetected by MRA or from an alternate mechanism for the mismatch. The MR imaging patterns identified extend our understanding of the pathophysiology of stroke and may contribute to the improvement of stroke management in the future. C1 Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. London Hlth Sci Ctr, London, ON, Canada. RP Baird, AE (reprint author), NINDS, NIH, 36 Convent Dr,MSC 4129,Room 4A03, Bethesda, MD 20892 USA. NR 30 TC 31 Z9 31 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JUL PY 2001 VL 58 IS 7 BP 1069 EP 1074 DI 10.1001/archneur.58.7.1069 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 451WL UT WOS:000169825300004 PM 11448295 ER PT J AU Gerard, HC Wang, Z Wang, GF El-Gabalawy, H Goldbach-Mansky, R Li, Y Majeed, W Zhang, H Ngai, N Hudson, AP Schumacher, HR AF Gerard, HC Wang, Z Wang, GF El-Gabalawy, H Goldbach-Mansky, R Li, Y Majeed, W Zhang, H Ngai, N Hudson, AP Schumacher, HR TI Chromosomal DNA from a variety of bacterial species is present in synovial tissue from patients with various forms of arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID POLYMERASE-CHAIN-REACTION; CHLAMYDIA-TRACHOMATIS DNA; RIBOSOMAL-RNA; REITERS-SYNDROME; NUCLEIC-ACIDS; PNEUMONIAE; FLUID; IDENTIFICATION; PATHOGENS; ANTIGENS AB Objective. We and others have reported the presence of Chlamydia and other bacterial species in joint specimens from patients with reactive arthritis (ReA). The present study was conducted to investigate whether bacteria other than those specified by diagnostic criteria for ReA could be identified in synovial fluid (SF) or tissue from patients with various arthritides, and whether the presence of such organisms corresponds to particular clinical characteristics in any patient set or subset. Methods. DNA in synovial biopsy samples and SF obtained from 237 patients with various arthritides, including ReA, rheumatoid arthritis, and undifferentiated oligoarthritis, was assayed by polymerase chain reaction (PCR) using "panbacterial" primers; we chose only samples known to be PCR negative for Chlamydia, Borrelia, and Mycoplasma species. PCR products were cloned, and cloned amplicons from each sample were sequenced; DNA sequences were compared against all others in GenBank for identification of bacterial species involved. Results. Ten percent of patient samples were PCR positive in panbacterial screening assays. Bacterial species identified belonged to the genera Neisseria, Acinetobacter, Moraxella, Salmonella, Pseudomonas, and others. Thirty-five percent of PCR-positive patients showed the presence of DNA from more than a single bacterial species in synovium; overall, however, we could identify no clear relationship between specific single or multiple bacterial species in the synovium and any general clinical characteristics of any individual or group of patients. Conclusion. This analysis provides the first systematic attempt to relate bacterial nucleic acids in the synovium to clinical characteristics, joint findings, and outcomes. Many patients with arthritis have bacterial DNA in the joint, and, in some cases, DNA from more than a single species is present. However, except for 1 case of a control patient with staphylococcal septic arthritis, it is not clear from the present study whether the synovial presence of such organisms is related to disease pathogenesis or evolution in any or all cases. C1 Wayne State Univ, Sch Med, Dept Immunol & Microbiol, Detroit, MI 48201 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Hudson, AP (reprint author), Wayne State Univ, Sch Med, Dept Immunol & Microbiol, Gordon H Scott Hall,540 E Canfield Ave, Detroit, MI 48201 USA. FU NIAMS NIH HHS [AR-42541, AR-47186] NR 35 TC 66 Z9 68 U1 0 U2 8 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUL PY 2001 VL 44 IS 7 BP 1689 EP 1697 DI 10.1002/1529-0131(200107)44:7<1689::AID-ART293>3.0.CO;2-K PG 9 WC Rheumatology SC Rheumatology GA 498BY UT WOS:000172491000027 PM 11465721 ER PT J AU Tornwall, ME Virtamo, J Haukka, JK Albanes, D Huttunen, JK AF Tornwall, ME Virtamo, J Haukka, JK Albanes, D Huttunen, JK TI alpha-Tocopherol (vitamin E) and beta-carotene supplementation does not affect the risk for large abdominal aortic aneurysm in a controlled trial SO ATHEROSCLEROSIS LA English DT Article DE alpha-tocopherol; beta-carotene; supplementation; abdominal aortic aneurysm ID LOW-DENSITY-LIPOPROTEIN; CORONARY HEART-DISEASE; CARDIOVASCULAR-DISEASE; OXIDATIVE MODIFICATION; MYOCARDIAL-INFARCTION; E CONSUMPTION; OXIDIZED LDL; MALE SMOKERS; ANTIOXIDANT; CHOLESTEROL AB Antioxidants may retard atherogenesis and limit inflammatory processes involved in aneurysm formation. We evaluated effects of alpha -tocopherol and beta -carotene supplementation on incidence of large abdominal aortic aneurysm (AAA) in a randomised, double-blind, placebo-controlled trial. Subjects (n = 29 133) were 5069-years-old male smokers, participants: in the Finnish alpha -Tocopherol. beta -Carotene Cancer Prevention (ATBC) Study. They were randomised to receive either 50 mg/day of alpha -tocopherol, or 20 mg/day of beta -carotene, or both, or placebo in a 2 x 2 design. Incidence of AAA was: evaluated from mortality and hospital registers. During 5.8 years of follow-up, 181 men were diagnosed with either ruptured AAA (n = 77) or nonruptured large AAA treated with aneurysmectomy (n = 104). Relative risk (RR) for AAA was 0.83 (95% confidence interval [CI] 0.62 1.11) among men receiving a-tocopherol compared with those who did not, and 0.93 (95% CI 0.69-1.24) among men receiving beta -carotene compared with those who did not. A modest though nonsignificant decrease in risk for nonruptured AAA was observed among sc-tocopherol supplemented men (RR 0.71, 95% CI 0.48-1.04) compared with men not receiving alpha -tocopherol. For beta -carotene, RR for nonruptured AAA was 0.86 (95% CI 0.59 1.27) compared with men not receiving beta -carotene. Neither antioxidant affected risk for ruptured AAA. In conclusion, long-term supplementation with alpha -tocopherol or beta -carotene had no preventive effect on large AAA among male smokers. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Natl Publ Hlth Inst, ATBC Study, Dept Nutr, KTL, SF-00300 Helsinki, Finland. NCI, Bethesda, MD 20892 USA. RP Tornwall, ME (reprint author), Natl Publ Hlth Inst, ATBC Study, Dept Nutr, KTL, Mannerheimintie 166, SF-00300 Helsinki, Finland. RI Albanes, Demetrius/B-9749-2015; Haukka, Jari/G-1484-2014 OI Haukka, Jari/0000-0003-1450-6208 FU NCI NIH HHS [N01-CN-45165] NR 49 TC 25 Z9 25 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD JUL PY 2001 VL 157 IS 1 BP 167 EP 173 DI 10.1016/S0021-9150(00)00694-8 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 451NN UT WOS:000169808300020 PM 11427217 ER PT J AU Munzar, P Yasar, S Redhi, GH Justinova, Z Goldberg, SR AF Munzar, P Yasar, S Redhi, GH Justinova, Z Goldberg, SR TI High rates of midazolam self-administration in squirrel monkeys SO BEHAVIOURAL PHARMACOLOGY LA English DT Article DE midazolam; methohexital; self-administration; squirrel monkey ID RHESUS-MONKEY; FIXED-RATIO; BENZODIAZEPINES; INJECTION; BABOONS; SCHEDULES; BEHAVIOR; NICOTINE; ABUSE AB Although benzodiazepines are frequently abused by humans, they usually maintain lower rates of self-administration behavior in laboratory animals than other drugs of abuse such as psychomotor stimulants or barbiturates. In the present study, intravenous (i.v.) self-administration of the short-acting benzodiazepine midazolam was evaluated in squirrel monkeys. Monkeys (n = 3) initially self-administered the short-acting barbiturate methohexital (100 mug/kg/injection) during daily 1-hour sessions under a fixed-ratio 10, 60s time-out, schedule of i.v. drug injection. This dose of methohexital maintained high rates of responding averaging 0.9 responses per second. Midazolam was then substituted for methohexital, and midazolam dose was subsequently varied from 0.3 to 3 mug/kg/injection. Each dose of midazolam was tested for five consecutive sessions and each unit dose condition was separated by five sessions of vehicle extinction. The midazolam dose-response function was an inverted U-shaped curve, with maximal rates of self-administration responding averaging 1.01 responses/second at a dose of 1 mug/kg/injection (an average of 48 injections per 1-hour session). The rates and fixed-ratio patterns of responding maintained by self-administration of midazolam in the present study were comparable to the rates and patterns of responding maintained in squirrel monkeys by self-administration of other drugs of abuse, including cocaine, amphetamine, nicotine and tetrahydrocannabinol, under similar experimental conditions. (C) 2001 Lippincott Williams & Wilkins. C1 NIDA, Preclin Pharmacol Sect, Behav Neurosci Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Baltimore, MD USA. RP Goldberg, SR (reprint author), NIDA, Preclin Pharmacol Sect, Behav Neurosci Branch, Intramural Res Program,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Justinova, Zuzana/A-9109-2011 OI Justinova, Zuzana/0000-0001-5793-7484 NR 21 TC 12 Z9 12 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD JUL PY 2001 VL 12 IS 4 BP 257 EP 265 PG 9 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 463AK UT WOS:000170454500004 PM 11548111 ER PT J AU Kobayashi, H Kawamoto, S Saga, T Sato, N Ishimori, T Konishi, J Ono, K Togashi, K Brechbiel, MW AF Kobayashi, H Kawamoto, S Saga, T Sato, N Ishimori, T Konishi, J Ono, K Togashi, K Brechbiel, MW TI Avidin-dendrimer-(1B4M-Gd)(254): A tumor-targeting therapeutic agent for gadolinium neutron capture therapy of intraperitoneal disseminated tumor which can be monitored by MRI SO BIOCONJUGATE CHEMISTRY LA English DT Article ID MONOCLONAL-ANTIBODY; CONTRAST AGENTS; DENDRIMER; AVIDIN; BIODISTRIBUTION; ACCUMULATION; FLEXIBILITY; CLEARANCE; GROWTH; CANCER AB Peritoneal carcinomatosis is a late stage in cancer progress, for which no effective therapeutic modality exists. Targeting therapeutic agents to disseminated lesions may be a promising modality for treating peritoneal. carcinomatosis. Gadolinium (Gd-157,Gd-155) is known to generate Auger and internal conversion electrons efficiently by irradiation with a neutron beam. Auger electrons from neutron-activated Gd(III) are strongly cytotoxic, but only when Gd(III) atoms have been internalized into the cells. In the present investigation, we have developed a quickly internalizing turner-targeting system to deliver large quantities of Gd(III) atoms into tumor cells to generate the Auger emission with an external neutron beam. Simultaneously, one would be able to image its biodistribution by MRI with a shortened T1 relaxation time. Avidin-G6-(1B4M-Gd)(254) (Av-G6Gd) was synthesized from generation-6 polyamidoamine dendrimer, biotin, avidin, and 2-(p-isothiocyanatobenzyl)-6-methyl-diethylenetriaminepentaacetic acid (1B4M). The Av-G6Gd was radiolabeled with Cd(III) doped with Gd-153. All of the 1B4M's on the conjugate were fully saturated with Gd(III) atoms. An in vitro internalization study showed that Av-G6Gd accumulated and was internalized into SHIN3 cells (a human ovarian cancer) 50- and 3.5-fold greater than Gd-DTPA (Magnevist) and G6-(1B4M-Gd)(256) (GGGd). In addition, accumulation of Gd(III) in the cells was detected by the increased signal on T1-weighted MRI. A biodistribution study was performed in nude mice bearing intraperitoneally disseminated SHINS tumors. Av-G6Gd showed specific accumulation in the SHIN3 tumor (103% ID/g) 366- and 3.4-fold greater than Gd-DTPA (0.28% ID/g, p < 0.001) and G6Gd (30% ID/g, p < 0.001) 1 day after i.p. injection. Seventy-eight percent of the tumor-related radioactivity of Av-G6Gd in the SHINS tumor was located inside the cells. The SHIN3 tumor-to-normal tissue ratio was greater than 17:1 in all organs and increased up to 638:1 at 1 day after i.p. injection. In conclusion, a sufficient amount (162 ppm) of Av-G6Cd was accumulated and internalized into the SHINS cells both in vitro and in vivo to kill the cell using Gd-157/155 With external irradiation with an appropriate neutron beam while monitoring with MRI. Thus, Av-G6Gd may be a promising agent for Gd neutron capture therapy of peritoneal carcinomatosis. This reagent also has the potential to permit monitoring of its pharmacokinetic progress with MRI. C1 Kyoto Univ, Dept Nucl Med & Diagnost Imaging, Kyoto 6068507, Japan. Otsu Municipal Hosp, Dept Radiol, Otsu, Shiga 5200804, Japan. Kyoto Univ, Inst Res Reactor, Osaka 5900494, Japan. NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), Kyoto Univ, Grad Sch Med, Dept Diagnost & Intervent Imagiol, Hitachi Med Co, Kyoto 6068507, Japan. NR 32 TC 84 Z9 89 U1 2 U2 19 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JUL-AUG PY 2001 VL 12 IS 4 BP 587 EP 593 DI 10.1021/bc010002o PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 454PQ UT WOS:000169981300018 PM 11459464 ER PT J AU Kaune, WT Banks, RS Linet, MS Hatch, EE Kleinerman, RA Wacholder, S Tarone, RE Haines, C AF Kaune, WT Banks, RS Linet, MS Hatch, EE Kleinerman, RA Wacholder, S Tarone, RE Haines, C TI Static magnetic field measurements in residences in relation to resonance hypotheses of interactions between power-frequency magnetic fields and humans SO BIOELECTROMAGNETICS LA English DT Article DE DC magnetic fields; resonance mechanisms; exposure assessment; geomagnetic field; misclassification; epidemiology ID BRAIN-TISSUE INVITRO; CHILDHOOD LEUKEMIA; CALCIUM-IONS; EXPOSURE; CHILDREN; EFFLUX AB Bowman et al. used epidemiologic data to test a model in which subjects were classified as being "in-resonance" or "not-in-resonance" for 60-Hz magnetic-field exposures depending on single static magnetic-field measurements at the centers of their bedrooms. A second paper by Swanson concluded that a single static magnetic-field measurement is insufficient to meaningfully characterize a residential environment. The main objective of this study was to investigate exposure-related questions raised by these two papers in two U.S. data sets, one containing single spot measurements of static magnetic fields at two locations in homes located in eight states, and the other repeated spot measurements (seven times during the course of one year) of the static magnetic fields at the centers of bedrooms and family rooms and on the surfaces of beds in 51 single-family homes in two metropolitan areas. Using Bowman's criterion, bedrooms were first classified as being in-resonance or not-in-resonance based on the average of repeated measurements of the static magnetic field measured on the bed where the presumed important exposure actually occurred. Bedrooms were then classified a second time using single spot measurements taken at the centers of bedrooms, centers of family rooms, or on the surfaces of beds, as would be done in the typical epidemiologic study. The kappa statistics characterizing the degree of concordance between the first (on-bed averages) and second (spot measurements) methods of assessing resonance status were 0.44, 0.33, and 0.67, respectively. This level of misclassification could significantly affect the results of studies involving the determination of resonance status. (C) 2001 Wiley-Liss, Inc. C1 EM Factors, Richland, WA 99352 USA. Robert S Banks Assoicates Inc, Minneapolis, MN 55414 USA. NCI, Rockville, MD 20852 USA. WESTAT Corp, Rockville, MD 20850 USA. RP Kaune, WT (reprint author), EM Factors, 640 Jadwin Ave Ste F, Richland, WA 99352 USA. OI Kleinerman, Ruth/0000-0001-7415-2478 NR 16 TC 4 Z9 4 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0197-8462 J9 BIOELECTROMAGNETICS JI Bioelectromagnetics PD JUL PY 2001 VL 22 IS 5 BP 294 EP 305 DI 10.1002/bem.54 PG 12 WC Biology; Biophysics SC Life Sciences & Biomedicine - Other Topics; Biophysics GA 447NW UT WOS:000169580200002 PM 11424152 ER PT J AU Charney, DS Innis, RB Nestler, EJ Manji, HK AF Charney, DS Innis, RB Nestler, EJ Manji, HK TI Update: What's new in Biological Psychiatry SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material C1 NIMH, Bethesda, MD 20892 USA. Yale Univ, Sch Med, New Haven, CT USA. Univ Texas, SW Med Ctr, Dallas, TX USA. RP Charney, DS (reprint author), NIMH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUL 1 PY 2001 VL 50 IS 1 BP 1 EP 2 DI 10.1016/S0006-3223(01)01192-1 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 455HD UT WOS:000170020700001 ER PT J AU Szuba, MP O'Reardon, JP Rai, AS Snyder-Kastenberg, J Amsterdam, JD Gettes, DR Wassermann, E Evans, DL AF Szuba, MP O'Reardon, JP Rai, AS Snyder-Kastenberg, J Amsterdam, JD Gettes, DR Wassermann, E Evans, DL TI Acute mood and thyroid stimulating hormone effects of transcranial magnetic stimulation in major depression SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 54th Annual Meeting of the Society-for-Biological-Psychiatry CY MAY 13-16, 1999 CL WASHINGTON, D.C. SP Soc Biol Psychiat DE transcranial magnetic stimulation; thyroid-stimulating hormone; major depression; thyroid ID PARTIAL SLEEP-DEPRIVATION; THYROTROPIN-RELEASING-HORMONE; PREFRONTAL CORTEX; ELECTROCONVULSIVE-THERAPY; CONNECTIVITY; RESPONSES; DISORDER; TMS AB Background: Repetitive transcranial magnetic stimulation (rTMS) has recently been demonstrated to have antidepressant effects. Some wonk suggests that rTMS over prefrontal cortex administered to healthy individuals produces acute elevations of mood and serum thyroid-stimulating hormone (TSH). We sought to determine whether single rTMS sessions would produce acute mood and serum TSH elevations in subjects with major depressions. Methods: Under double-blind conditions et al 14 medication-free subjects with major depression received individual sessions of either active or sham rTMS. rTMS was administered over the left prefrontal cortex at 10 Hz et al 100% of motor threshold 20 trains over 10 min. Immediately before and after rTMS sessions, subjects' mood was rated with the Profile of Mood States (POMS) and the 6-Item Hamilton Depression Scale, and blood was drawn for later analysis of TSH. Subjects and raters were blind to treatment assignment. Results: The group receiving active stimulation manifested significantly greater improvement on the POMS subscale of Depression (p less than or equal to .0055) and a trend toward greater improvement on the modified Hamilton Rating (.05 < p .1). No hypomania was induced. The change in TSH from pre- to post-rTMS was significantly different between active and sham sessions. Conclusions: This blinded, placebo-controlled trial documents that individual rTMS sessions can acutely elevate mood and stimulate TSH release in patients experiencing major depressive episodes. Biol Psychiatry 2001;50, 22-27 (C) 2001 Society of Biological Psychiatry. C1 Univ Penn, Univ Sci Ctr, Dept Psychiat, Philadelphia, PA 19104 USA. NINDS, Bethesda, MD 20892 USA. RP Szuba, MP (reprint author), Univ Penn, Univ Sci Ctr, Dept Psychiat, 8th Floor,3600 Mkt St, Philadelphia, PA 19104 USA. FU NIA NIH HHS [K23AG00867] NR 35 TC 58 Z9 59 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUL 1 PY 2001 VL 50 IS 1 BP 22 EP 27 DI 10.1016/S0006-3223(00)01118-5 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 455HD UT WOS:000170020700005 PM 11457420 ER PT J AU Drobes, DJ Miller, EJ Hillman, CH Bradley, MM Cuthbert, BN Lang, PJ AF Drobes, DJ Miller, EJ Hillman, CH Bradley, MM Cuthbert, BN Lang, PJ TI Food deprivation and emotional reactions to food cues: implications for eating disorders SO BIOLOGICAL PSYCHOLOGY LA English DT Article DE emotion; eating disorder; anorexia; bulimia; startle ID STARTLE REFLEX; INDIVIDUAL-DIFFERENCES; ANOREXIA-NERVOSA; HEART-RATE; ATTENTION; URGES; MOTIVATION; VALIDATION; REACTIVITY; SALIVATION AB Two Studies examined emotional responding to food cues. In experiment 1, normal college students were assigned to 0, 6- or 24-h of food deprivation prior to presentations of standard emotional and food-related pictures. Food deprivation had no impact on responses elicited by standard emotional pictures. However, subjective and psychophysiological reactions to food pictures were affected significantly by deprivation. Importantly, food-deprived subjects viewing food pictures showed an enhanced startle reflex and increased heart rate. Experiment 2 replicated the food deprivation effects from experiment 1, and examined participants reporting either a habitual pattern of restrained (anorexia-like) or binge (bulimia-like) eating. Food-deprived and binge eater groups showed startle potentiation to food cues, and rated these stimuli as more pleasant, relative to restrained eaters and control subjects. The results are interpreted from the perspective that startle modulation reflects activation of defensive or appetitive motivation. Implications of the data for understanding eating disorders are considered. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Univ Florida, NIMH, Ctr Study Emot & Attent, Gainesville, FL 32610 USA. Univ Florida, Ctr Study Emot & Attent, Gainesville, FL 32611 USA. RP Drobes, DJ (reprint author), Med Univ S Carolina, Ctr Drug & Alcohol Programs, 67 President St,POB 250861, Charleston, SC 29425 USA. RI Hillman, Charles/A-4479-2009 FU NIMH NIH HHS [MH43975, P50-MH52384, MH10720, MH37757] NR 63 TC 89 Z9 90 U1 3 U2 22 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 J9 BIOL PSYCHOL JI Biol. Psychol. PD JUL-AUG PY 2001 VL 57 IS 1-3 SI SI BP 153 EP 177 DI 10.1016/S0301-0511(01)00093-X PG 25 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA 458LU UT WOS:000170196500008 PM 11454438 ER PT J AU Hild, SA Meistrich, ML Blye, RP Reel, JR AF Hild, SA Meistrich, ML Blye, RP Reel, JR TI Lupron depot prevention of antispermatogenic/antifertility activity of the indenopyridine, CDB-4022, in the rat SO BIOLOGY OF REPRODUCTION LA English DT Article DE male reproductive tract; Sertoli cells; sperm; spermatogenesis; testis ID X-IRRADIATION; HORMONAL PROTECTION; STEM SPERMATOGONIA; SPRAGUE-DAWLEY; SPERMATOGENESIS; DIFFERENTIATION; PROCARBAZINE; RECOVERY; AGONIST; TESTIS AB The goals of this study were to determine the CDB-4022 dose-response relationship for induction of acute decreases in testicular weight and germ cell depopulation in rats; establish the threshold dose of CDB-4022 required to induce infertility; and investigate whether CDB-4022-induced testicular damage could be prevented by a GnRH agonist (Lupron Depot). Reduction of testis weight and germ cell depopulation were observed 7 days after a single oral dose of 1 mg CDB-4022/kg, whereas 0.5 mg/kg had no observable effect. These effects were maximal at 12.5 or 25 mg CDB-4022/kg. After a single oral dose of either 2.5 or 5 mg/kg, CDB-4022 induced infertility in five of five treated rats by Week 5, whereas only one of five males was rendered infertile at a dose of 1 mg/kg. Proven fertile male rats (6/group) were treated with vehicle, CDB-4022 alone (2.5 mg/kg on Day 0), CDB-4022 plus Lupron Depot (on Weeks -1, 2, 5, and 8), or Lupron Depot alone. Control males demonstrated normal fertility throughout a 32-wk cohabitation period. Five of six rats were rendered transiently infertile with Lupron Depot alone, but all recovered fertility. CDB-4022 treatment resulted in infertility in all six rats, and only one of six regained fertility. Combined treatment also caused infertility in all six rats, but four of six recovered fertility (P = 0.08 compared to CDB-4022 alone). Testicular weight was decreased in the three treatment groups compared to vehicle controls; testicular weights were ranked from highest to lowest as follows: vehicle > Lupron Depot > Lupron Depot + CDB-4022 > CDB-4022. The tubule differentiation index of Lupron Depot-treated rats (96 +/- 4%) was not different from vehicle-treated rats (100%). CDB-4022 treatment decreased the number of differentiating tubules (15 +/- 8%). Lupron Depot plus CDB-4022 treatment resulted in a greater number of differentiating tubules (53 +/- 12%) than CDB-4022 alone, but this was still lower than vehicle- or Lupron Depot-treated rats. These data indicate that 2.5 mg/kg of CDB-4022 was the oral threshold dose that caused testicular damage rendering the majority of adult male rats permanently infertile within the study interval; 12.5 mg/kg of CDB-4022 induced maximal testicular damage. Suppression of gonadotropins and/or testosterone production by treatment with Lupron Depot before and af-ter CDB-4022 prevented the CDB-4022-induced irreversible testicular damage. C1 BIOQUAL Inc, Rockville, MD 20850 USA. Univ Texas, MD Anderson Canc Ctr, Dept Expt Radiat Oncol, Houston, TX 77030 USA. NICHHD, NICHD, CRHB, Rockville, MD 20852 USA. RP Hild, SA (reprint author), BIOQUAL Inc, 9600 Med Ctr Dr, Rockville, MD 20850 USA. FU NICHD NIH HHS [N01-HD-6-3259] NR 25 TC 29 Z9 30 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JUL PY 2001 VL 65 IS 1 BP 165 EP 172 PG 8 WC Reproductive Biology SC Reproductive Biology GA 446LY UT WOS:000169515800021 PM 11420236 ER PT J AU Zhang, XC Neamati, N Lee, YK Orr, A Brown, RD Whitaker, N Pommier, Y Burke, TR AF Zhang, XC Neamati, N Lee, YK Orr, A Brown, RD Whitaker, N Pommier, Y Burke, TR TI Arylisothiocyanate-containing esters of caffeic acid designed as affinity ligands for HIV-1 integrase SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID ARYL ISOTHIOCYANATES; INHIBITORS; CHROMATOGRAPHY; RECOGNITION; RECEPTORS; PROTEINS; ANALOGS; AGENTS; SITE AB Integrase is an enzyme found in human immunodeficiency virus, which is required for the viral life cycle, yet has no human cellular homologue. For this reason, HIV integrase (IN) has become an important target for the development of new AIDS therapeutics. Irreversible affinity ligands have proven to be valuable tools for studying a number of enzyme and protein systems. yet to date there have been no reports of such affinity ligands for the study of IN. As an initial approach toward irreversible ligand design directed against IN, we appended isothiocyanate functionality onto caffeic acid phenethyl ester (CAPE), a known HIV integrase inhibitor. The choice of isothiocyanate as the reactive functionality, was based on its demonstrated utility in the preparation of affinity ligands directed against a number of other protein targets. Several isomeric CAFE isothiocyanates were prepared to explore the enzyme topography for reactive nitrogen and sulfur nucleophiles vicinal to the enzyme-bound CAFE. The preparation of these CAFE isothiocyanates. required development of new synthetic methodology which employed phenyl thiocarbamates as latent isothiocyanates which could be unmasked near the end of the synthetic sequence. When it was observed that beta -mercaptoethanol (beta -ME), which is required to maintain the catalytic activity of soluble IN (a F185KC280S mutant), reacted with CAFE isothiocyanate functionality to form the corresponding hydroxyethylthiocarbamate, a variety of mutant IN were examined which did not require the presence of beta -ME for catalytic activity. Although in these latter enzymes, CAFE isothiocyanate functionality was presumed to be present and available for acylation by IN nucleophiles, they were equally effective against Cys to Ser mutants. One conclusion of these studies. is that upon binding of CAFE to the integrase, nitrogen or sulfur nucleophiles may not be properly situated in the vicinity of the phenethyl aryl ring to allow reaction with and covalent modification of reactive functionality, such as isothiocyanate groups. The fact that introduction of the isothiocyanate group onto various positions of the phenethyl ring or replacement of the phenyl ring with naphthyl rings, failed to significantly affect inhibitory potency, indicates a degree of insensitivity of this region of the molecule toward structural modification. These findings may be useful in future studies concerned with the development and use of HIV-1 integrase affinity ligands. (C) 2001 Published by Elsevier Science Ltd. C1 NCI, Med Chem Lab, Ctr Canc Res, NIH,FCRDC, Frederick, MD 21702 USA. NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NIDDD, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Neamati, N (reprint author), NCI, Med Chem Lab, Ctr Canc Res, NIH,FCRDC, 376 Boyles St,POB 13, Frederick, MD 21702 USA. RI Burke, Terrence/N-2601-2014 NR 31 TC 38 Z9 40 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JUL PY 2001 VL 9 IS 7 BP 1649 EP 1657 DI 10.1016/S0968-0896(01)00075-X PG 9 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 447NZ UT WOS:000169580500001 PM 11425564 ER PT J AU Lee, J Lee, J Szabo, T Gonzalez, AF Welter, JD Blumberg, PM AF Lee, J Lee, J Szabo, T Gonzalez, AF Welter, JD Blumberg, PM TI N-(3-acyloxy-2-benzylpropyl)-N '-dihydroxytetrahydrobenzazepine and tetrahydroisoquinoline thiourea analogues as vanilloid receptor ligands SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID ROOT GANGLION NEURONS; CAPSAICIN-RECEPTOR; AGONIST ACTIVITY; PAIN; RAT; RESINIFERATOXIN; CAPSAZEPINE; ANTAGONIST; BINDING; CHANNEL AB The vanilloid receptor represents a promising target for drug development. Building on our previous strategies which have generated potent agonists for VR1, we now describe a series of novel N-(3-acyloxy-2-benzylpropyl)-N'-dihydroxytetrahydro-benzazepine and tetrahydroisoquinoline thiourea analogues, several of which are potent VRI antagonists. We report here the rationale for the design, the synthesis, and the in vitro characterization of activity in assays for [H-3]resiniferatoxin binding and Ca-45 influx using heterologously expressed rat VRI. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Seoul Natl Univ, Coll Pharm, Med Chem Lab, Seoul 151742, South Korea. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Div Basic Sci, Bethesda, MD 20892 USA. RP Lee, J (reprint author), Seoul Natl Univ, Coll Pharm, Med Chem Lab, Shinlim Dong, Seoul 151742, South Korea. EM jeewoo@snu.ac.kr OI Lee, Jiyoun/0000-0003-3819-5889 NR 26 TC 20 Z9 22 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JUL PY 2001 VL 9 IS 7 BP 1713 EP 1720 DI 10.1016/S0968-0896(01)00068-2 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 447NZ UT WOS:000169580500009 PM 11425572 ER PT J AU Gold, B Bergeron, J Lachtermacher-Triunfol, M Dean, M AF Gold, B Bergeron, J Lachtermacher-Triunfol, M Dean, M TI Human duplex sex determination PCR SO BIOTECHNIQUES LA English DT Article ID POLYMERASE-CHAIN-REACTION; PREIMPLANTATION EMBRYOS; GENDER DETERMINATION; GENE; DNA; AMPLIFICATION; SEQUENCES; VERIFICATION; CHROMOSOME; AMELOGENIN C1 Natl Canc Inst, Lab Genomic Divers, Frederick, MD 21702 USA. RP Gold, B (reprint author), Natl Canc Inst, Lab Genomic Divers, Bldg 560,Room 11-85, Frederick, MD 21702 USA. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 26 TC 2 Z9 2 U1 1 U2 3 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD JUL PY 2001 VL 31 IS 1 BP 28 EP + PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 451LX UT WOS:000169804500003 PM 11464516 ER PT J AU Straus, SE Jaffe, ES Puck, JM Dale, JK Elkon, KB Rosen-Wolff, A Peters, AMJ Sneller, MC Hallahan, CW Wang, J Fischer, RE Jackson, CM Lin, AY Baumler, C Siegert, E Marx, A Vaishnaw, AK Grodzicky, T Fleisher, TA Lenardo, MJ AF Straus, SE Jaffe, ES Puck, JM Dale, JK Elkon, KB Rosen-Wolff, A Peters, AMJ Sneller, MC Hallahan, CW Wang, J Fischer, RE Jackson, CM Lin, AY Baumler, C Siegert, E Marx, A Vaishnaw, AK Grodzicky, T Fleisher, TA Lenardo, MJ TI The development of lymphomas in families with autoimmune lymphoproliferative syndrome with germline Fas mutations and defective lymphocyte apoptosis SO BLOOD LA English DT Article ID NON-HODGKINS-LYMPHOMA; B-CELL LYMPHOMA; CONSECUTIVELY ASCERTAINED SPECIMENS; TUMOR-NECROSIS-FACTOR; CYTOGENETIC ANALYSIS; GENE-MUTATIONS; BCL-2 PROTEIN; MYELOMA CELLS; T-CELLS; CHROMOSOMAL-ABNORMALITIES AB Lymphomas were studied in kindreds with autoimmune lymphoproliferative syndrome (ALPS; Canale-Smith syndrome), a disorder of lymphocyte homeostasis usually associated with germline Fas mutations. Fas (CD95/APO-1) isa ceil surface receptor that initiates programmed cell death, or apoptosis, of activated lymphocytes. Lymphoma phenotype was determined by immunohistochemistry, frequency of CD3(+)CD4(-)CD8(-) T-cell-receptor alpha/beta cells by flow cytometry, nucleotide sequences of the gene encoding Fas (APT1, TNFRSF6), and the percentage of lymphocytes undergoing apoptosis in vitro. Of 223 members of 39 families, 130 individuals possessed heterozygous germline Fas mutations. Eleven B-cell and T-cell lymphomas of diverse types developed in 10 individuals with mutations in 8 families, up to 48 years after lymphoproliferation was first documented. Their risk of non-Hodgkin and Hodgkin lymphomas, respectively, was 14 and 51 times greater; than expected (each P < .001). Investigation of these 10 patients and their relatives with Fas mutations revealed that all had defective lymphocyte apoptosis and most had other features of ALPS. The tumor cells retained the heterozygous Fas mutations found in the peripheral blood and manifested defective Fas-mediated killing, These data implicate a role for Fas-mediated apoptosis in preventing B-cell and T-cell lymphomas, Inherited defects in receptor-mediated lymphocyte apoptosis represents newly appreciated risk factor for lymphomas, (C) 2001 by The American Society of Hematology. C1 NIAID, LCI, NIH, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NCI, Genet Epidemiol Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Ctr Clin, Dept Clin Pathol, Serv Immunol,NIH, Bethesda, MD USA. Natl Human Genome Res Inst, Genet & Mol Biol Branch, NIH, Bethesda, MD USA. Cornell Univ, Weill Med Coll, Dept Med, New York, NY USA. Tech Univ Dresden, Kinderklin, D-8027 Dresden, Germany. Lab Klin Forsch, Dresden, Germany. Univ Freiburg, Childrens Hosp, Freiburg, Germany. Univ Wurzburg, Inst Pathol, D-8700 Wurzburg, Germany. RP Straus, SE (reprint author), NIAID, LCI, NIH, 31 Ctr Dr,Rm 5B-37, Bethesda, MD 20892 USA. FU NIAMS NIH HHS [AR45481] NR 67 TC 246 Z9 251 U1 0 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 2001 VL 98 IS 1 BP 194 EP 200 DI 10.1182/blood.V98.1.194 PG 7 WC Hematology SC Hematology GA 447JK UT WOS:000169568000029 PM 11418480 ER PT J AU Shaughnessy, J Gabrea, A Qi, Y Brents, L Zhan, FH Tian, EM Sawyer, J Barlogie, B Bergsagel, PL Kuehl, M AF Shaughnessy, J Gabrea, A Qi, Y Brents, L Zhan, FH Tian, EM Sawyer, J Barlogie, B Bergsagel, PL Kuehl, M TI Cyclin D3 at 6p21 is dysregulated by recurrent chromosomal translocations to immunoglobulin loci in multiple myeloma SO BLOOD LA English DT Article ID MANTLE-CELL LYMPHOMA; CHRONIC LYMPHOCYTIC-LEUKEMIA; POLYMERASE-CHAIN-REACTION; NON-HODGKINS-LYMPHOMA; TUMOR-CELL; SOMATIC HYPERMUTATION; CLINICAL CORRELATIONS; TRANSGENIC MICE; INHIBITOR P27; D1 BCL-1 AB Reciprocal chromosomal translocations, which are mediated by errors in immunoglobulin heavy chain (IgH) switch recombination or somatic hypermutation as plasma cells are generated in germinal centers, are present in most multiple myeloma (MM) tumors. These translocations dysregulate an oncogene that is repositioned in proximity to a strong IgH enhancer. There is a promiscuous array of nonrandom chromosomal partners land oncogenes), with the 3 most frequent partners (11q13 [cyclin D1]; 4p16 [FGFR3 and MMSET]; 16q23 [c-maf]) involved in nearly half of MM tumors. It is now shown that a novel t(6;14)(p21;q32) translocation is present in 1 of 30 MM cell lines and that this cell line uniquely overexpresses cyclin D3, The cloned breakpoint juxtaposes gamma 4 switch sequences with 6p21 sequences that are located about 65 kb centromeric to the cyclin D3 gene. By metaphase chromosome analysis, the t(6;14) (p21;q32) translocation was identified in 6 of 150 (4%) primary MM tumors. Overexpression of cyclin D3 messenger RNA (mRNA) was identified by microarray RNA expression analysis in 3 of 53 additional primary MM tumors, each of which was found to have a t(6;14) translocation breakpoint by interphase fluorescence in situ hybridization analysis. One tumor has a t(6;22)(p21;q11) translocation, so that cyclin D3 is bracketed by the IgL and IgH breakpoints. These results provide the first clear evidence for primary dysregulation of cyclin D3 during tumorigenesis, It is suggested that the initial oncogenic event for most MM tumors is a primary immunoglobulin translocation that dysregulates cyclin D1, cyclin D3, and other oncogenes to provide a proliferative stimulus to postgerminal center plasma cells. (C) 2001 by The American Society of Hematology. C1 Univ Arkansas Med Sci, Arkansas Canc Res Ctr, Donna D & Donald M Lambert Lab Myeloma Genet, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Arkansas Canc Res Ctr, Myeloma & Transplantat Res Ctr, Little Rock, AR 72205 USA. NCI, Med Branch, Dept Genet, Bethesda, MD 20892 USA. Cornell Univ, Coll Med, Dept Med, Div Hematol & Oncol, New York, NY USA. RP Kuehl, M (reprint author), USN Hosp, Dept Genet, Med Branch, Bldg 8,Rm 5101, Bethesda, MD 20889 USA. RI Bergsagel, Peter/A-7842-2011 OI Bergsagel, Peter/0000-0003-1523-7388 FU NCI NIH HHS [CA74265] NR 60 TC 130 Z9 134 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 2001 VL 98 IS 1 BP 217 EP 223 DI 10.1182/blood.V98.1.217 PG 7 WC Hematology SC Hematology GA 447JK UT WOS:000169568000032 PM 11418483 ER PT J AU Nemeth, MJ Bodine, DM Garrett, LJ Lowrey, CH AF Nemeth, MJ Bodine, DM Garrett, LJ Lowrey, CH TI An erythroid-specific chromatin opening element reorganizes beta-globin promoter chromatin structure and augments gene expression SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article ID LOCUS-CONTROL REGION; DOMINANT CONTROL REGION; HIGH-LEVEL EXPRESSION; HYPERSENSITIVE SITES; TRANSGENIC MICE; ACTIVATION-REGION; TRANSCRIPTIONAL ACTIVATION; ERYTHROLEUKEMIA-CELLS; MINIMAL REQUIREMENTS; ACTIVE GENES AB In erythroid tissues the chromatin structure of the beta -globin gene locus is extensively remodeled, Changes include the formation of DNase I hypersensitive sites (HSs) over the promoters of actively expressed genes. To test the hypothesis that such "opening" of promoter chromatin structure is important for beta -globin gene expression, we placed a 101-bp erythroid-specific hypersensitive-site forming element (HSFE) from the core of LCR HS4 immediately upstream of a minimal beta -globin gene promoter. We then studied the effects of this element alone and in combination with other cis-acting elements on globin gene chromatin structure and gene expression in MEL cells and transgenic mice. Single or tandem HSFEs increased the size of the portion of the promoter accessible to DNase digestion, increased the proportion of promoters in an accessible conformation, and increased gene expression approximately 5-fold. These were equivalent to expression levels attained using a 2.8-kb mu LCR construct. Inclusion of the LCR HS2 enhancer did not increase expression further. In transgenic mouse fetal liver cells the HSFE increased average expression 2.5-fold compared to the minimal promoter alone. These results indicate that a small cis-acting element is capable of remodeling local beta -globin promoter chromatin structure and producing expression similar to that seen with a mu LCR construct. (C) 2001 Academic Press. C1 Dartmouth Coll Sch Med, Dept Pharmacol & Toxicol, Hanover, NH 03755 USA. NHGRI, Hematopoiesis Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. Dartmouth Coll Sch Med, Dept Med, Hanover, NH 03755 USA. Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Lebanon, NH 03756 USA. RP Lowrey, CH (reprint author), Dartmouth Coll Sch Med, Dept Med, Hinman Box 7650, Hanover, NH 03755 USA. FU NHLBI NIH HHS [HL 52243] NR 47 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD JUL-AUG PY 2001 VL 27 IS 4 BP 767 EP 780 DI 10.1006/bcmd.2001.0448 PG 14 WC Hematology SC Hematology GA 488BY UT WOS:000171915900008 PM 11778661 ER PT J AU Burt, RK Fassas, A Snowden, JA van Laar, JM Kozak, T Wulffraat, NM Nash, RA Dunbar, CE Arnold, R Prentice, G Bingham, S Marmont, AM McSweeney, PA AF Burt, RK Fassas, A Snowden, JA van Laar, JM Kozak, T Wulffraat, NM Nash, RA Dunbar, CE Arnold, R Prentice, G Bingham, S Marmont, AM McSweeney, PA TI Collection of hematopoietic stem cells from patients with autoimmune diseases SO BONE MARROW TRANSPLANTATION LA English DT Article DE hematopoietic stem cell transplantation; mobilization; autoimmune disease ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; COLONY-STIMULATING FACTOR; PERIPHERAL-BLOOD STEM; ACTIVE RHEUMATOID-ARTHRITIS; BONE-MARROW-TRANSPLANTATION; PROGRESSIVE MULTIPLE-SCLEROSIS; DOSE IMMUNOSUPPRESSIVE THERAPY; G-CSF; PROGENITOR CELLS; DENDRITIC CELLS AB We reviewed data from 24 transplant centers in Asia, Australia, Europe, and North America to determine the outcomes of stem cell collection including methods used, cell yields, effects on disease activity, and complications in patients with autoimmune diseases. Twenty-one unprimed bone marrow harvests and 174 peripheral blood stem cell mobilizations were performed on 187 patients. Disease indications were multiple sclerosis (76 patients), rheumatoid arthritis (37 patients), scleroderma (26 patients), systemic lupus erythematosus (19 patients), juvenile chronic arthritis (13 patients), idiopathic autoimmune thrombocytopenia (8 patients), Behcet's disease (3 patients), undifferentiated vasculitis (3 patients), polychondritis (1 patient) and polymyositis (1 patient). Bone marrow harvests were used in the Peoples Republic of China and preferred worldwide for children. PBSC mobilization was the preferred technique for adult stem cell collection in America, Australia, and Europe. Methods of PBSC mobilization included G-CSF (5, 10, or 16 mug/kg/day) or cyclophosphamide (2 or 4 g/m(2)) with either G-CSF (5 or 10 mug/kg/day) or GM-CSF (5 mug/kg/day). Bone marrow harvests were without complications and did not affect disease activity. A combination of cyclophosphamide and G-CSF was more likely to ameliorate disease activity than G-CSF alone (P < 0.001). G-CSF alone was more likely to cause disease exacerbation than the combination of cyclophosphamide and G-CSF (P = 0.003). Three patients died as a result of cyclophosphamide-based stem cell collection (2.6% of patients mobilized with cyclophosphamide). When corrected for patient weight and apheresis volume, progenitor cell yields tended to vary by underlying disease, prior medication history and mobilization regimen. Trends in the approaches to, and results of, progenitor cell mobilization are suggested by this survey. While cytokine-based mobilization appears less toxic, it is more likely to result in disease reactivation. Optimization with regard to cell yields and safety are likely to be disease-specific and prospective disease-specific studies of mobilization procedures appear warranted. C1 Northwestern Univ, Med Ctr, Dept Med, Chicago, IL 60611 USA. George Papanicolaou Gen Hosp, Dept Hematol, Thessaloniki, Greece. Univ Hosp Leicester, Leicester, Leics, England. St Vincents Hosp, Sydney, NSW 2010, Australia. Leiden Univ, Med Ctr, Leiden, Netherlands. Univ Hosp Kralovske Vinohrady, Prague, Czech Republic. Univ Med Ctr, Utrecht, Netherlands. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NHLBI, NIH, Hematol Branch, Bethesda, MD 20892 USA. Univ Klinikum, Berlin, Germany. UCL Royal Free & Univ Med Sch, London, England. Leeds Gen Infirm, Leeds, W Yorkshire, England. Osped San Martino Genova, Ctr Trapianti Midollo Osseo, Genoa, Italy. Univ Colorado, Denver, CO 80202 USA. RP Burt, RK (reprint author), Northwestern Univ, Med Ctr, Dept Med, Wesley Pavil,Room 153,250 E Super St, Chicago, IL 60611 USA. RI Kozak, Tomas/K-3561-2012 NR 54 TC 79 Z9 86 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD JUL PY 2001 VL 28 IS 1 BP 1 EP 12 DI 10.1038/sj.bmt.1703081 PG 12 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 456ZC UT WOS:000170111800001 PM 11498738 ER PT J AU Xu, H Lu, YF Rice, KC Ananthan, S Rothman, RB AF Xu, H Lu, YF Rice, KC Ananthan, S Rothman, RB TI SoRI 9409, a non-peptide opioid mu receptor agonist/delta receptor antagonist, fails to stimulate [S-35]-GTP-gamma-S binding at cloned opioid receptors SO BRAIN RESEARCH BULLETIN LA English DT Article DE opioid receptors; analgesics; [S-35]GTP-gamma-S binding ID EFFICACY; BRAIN; DRUGS; SITES AB Recent work suggests that opioids which combine mu agonist and delta antagonist activity may be non-addicting antinociceptive agents. SoRI 9409 (5'-(4-Chlorophenyl)17-(cyclopropylmethyl)-6,7-didehydro-3,14-dihydroxy-4,5 alpha- epoxypyrido-[2',3':6,7]morphinan) is a naltrexone-derived non-peptide ligand which demonstrates partial mu and kappa agonist activity and antagonist activity at delta receptors. Chronic administration of SoRI 9409 to mice failed to produce tolerance to its antinociceptive effect and SoRI 9409 produced less withdrawal signs than naloxone in acute and chronic morphine dependence models. To further characterize SoRI 9409 we determined its effects in the guanosine 5'-O-(3-[S-35]thio)-triphosphate binding assay. SoRI 9409 demonstrated no agonist activity at cloned mu, delta, or kappa receptors. Other experiments demonstrated that SoRI 9409 was a potent and selective delta antagonist (K-i = 0.08 nM) which acted also as an antagonist at mu and kappa receptors. Its profile of activity resembled that of naltrindole (NTI). Viewed collectively, the in vitro data reported here predict that SoRI 9409 should be a mu antagonist in vivo, which is not observed. Resolving these discrepant findings will require additional research. (C) 2001 Elsevier Science Inc. C1 NIDA, Clin Psychopharmacol Sect, DIR, Intramural Res Program,NIH, Baltimore, MD 21224 USA. NIDDKD, Med Chem Lab, Bethesda, MD 20892 USA. So Res Inst, Dept Organ Chem, Birmingham, AL 35255 USA. RP Rothman, RB (reprint author), NIDA, Clin Psychopharmacol Sect, DIR, Intramural Res Program,NIH, POB 5180,5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 16 TC 13 Z9 15 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD JUL 1 PY 2001 VL 55 IS 4 BP 507 EP 511 DI 10.1016/S0361-9230(01)00550-0 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 470YP UT WOS:000170900300009 PM 11543951 ER PT J AU Moody, TW Leyton, J Chan, D Brenneman, DC Fridkin, M Gelber, E Levy, A Gozes, I AF Moody, TW Leyton, J Chan, D Brenneman, DC Fridkin, M Gelber, E Levy, A Gozes, I TI VIP receptor antagonists and chemotherapeutic drugs inhibit the growth of breast cancer cells SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE antagonist; breast cancer; doxorubicin; proliferation; taxol; VIP ID VASOACTIVE-INTESTINAL-PEPTIDE; FUNCTIONAL EXPRESSION; SIGNAL-TRANSDUCTION; MONOCLONAL-ANTIBODY; PACAP RECEPTOR; AMINO-ACIDS; IDENTIFICATION; POLYPEPTIDE; PATHWAY; PROTEIN AB The effects of vasoactive intestinal peptide (VIP) antagonists on breast cancer cells were investigated. (N-stearyl, norleucine(17))VIP hybrid ((SN)VIPhyb) inhibited specific (1)25I-VIP binding to MCF7, SKBR3, T47D ZR75-1 and MDA-MB231 cells with high affinity (IC(5)0 values of 0.03-0.06 muM). (SN)VIPhyb,1 muM, inhibited the ability of 10 nM VIP to cause elevation of cAMP and to increase c-fos mRNA. Micromolar concentrations of (SN)VIPhyb inhibited the proliferation of MDA-MB231 or MCF7 cells using a MTT and clonogenic assay. Using a MTT assay, (SN)VIPhyb enhanced the ability of taxol and doxorubicin to inhibit breast cancer growth. Using nude mice bearing MDA-MB231 xenografts, VIPhyb potentiated the ability of taxol to inhibit proliferation. The results indicate that VIP receptor antagonists increase the ability of chemotherapeutic drugs to kill breast cancer cells. C1 NCI, Cell & Canc Biol Dept, Med Branch, Rockville, MD 20850 USA. Univ Colorado, Ctr Canc, Denver, CO 80262 USA. NICHHD, Dev Neurobiol Lab, Unit Neurochem, Bethesda, MD 20892 USA. Weizmann Inst Sci, Dept Organ Chem, IL-76100 Rehovot, Israel. Sackler Sch Med, Dept Clin Biochem, Tel Aviv, Israel. RP Moody, TW (reprint author), NCI, Cell & Canc Biol Dept, Med Branch, 9610 Med Ctr Dr, Rockville, MD 20850 USA. NR 40 TC 33 Z9 33 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JUL PY 2001 VL 68 IS 1 BP 55 EP 64 DI 10.1023/A:1017994722130 PG 10 WC Oncology SC Oncology GA 471QT UT WOS:000170940600007 PM 11678309 ER PT J AU Shoemaker, RH AF Shoemaker, RH TI High-throughput screening for inhibitors of signaling pathways SO BRITISH JOURNAL OF CANCER LA English DT Meeting Abstract C1 NCI, Screening Technol Branch, Dev Therapeut Program, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JUL PY 2001 VL 85 SU 1 BP 6 EP 6 PG 1 WC Oncology SC Oncology GA 456CH UT WOS:000170065300022 ER PT J AU Epperson, DE Margolis, DA McOlash, L Janczak, T Barrett, AJ AF Epperson, DE Margolis, DA McOlash, L Janczak, T Barrett, AJ TI In vitro T-cell receptor V beta repertoire analysis may identify which T-cell V beta families mediate graft-versus-leukaemia and graft-versus-host responses after human leucocyte antigen-matched sibling stem cell transplantation SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE GVL; GVH; T cell; TCR repertoire; stem cell transplant ID MULTIPLE-SCLEROSIS; MOLECULAR ANALYSIS; BONE-MARROW; LEUKEMIA; DISEASE; EXPANSION; LESIONS AB We studied oligoclonal T-cell expansions of 24 T-cell receptor (TCR) V beta families in normal donor lymphocytes stimulated with patient's cells and in recipient blood after transplant, using a polymerase chain reaction-based assay (spectratyping). T cells from donor blood were incubated with separated myeloid leukaemia cells or T cells from the HLA-identical sibling recipient. In five of the six patients tested, the T-cell V beta skewing pattern observed in vitro was seen in vivo after transplant. After transplant, the myeloid-specific V beta skewing coincided with the disappearance of residual disease in three patients and in one patient skewing was lost at the time of leukaemic relapse. In functional tests, T cells generated against leukaemic cells in vitro produced interferon gamma in response to the leukaemia. Removal of the leukaemia-expanded skewed V beta families significantly decreased cytotoxic killing of the leukaemia. However, while there was a general concordance in the V beta family exhibiting clonal expansion in vitro and in vivo, the exact clonotype expanded in vitro and in vivo differed. These findings suggest that alloresponses involve multiple T-cell clones within a restricted TCR V beta repertoire that undergo different selection pressures in vitro and in vivo. C1 NHLBI, Bone Marrow Transplant Unit, Hematol Branch, NIH, Bethesda, MD 20892 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. RP Barrett, AJ (reprint author), NHLBI, Bone Marrow Transplant Unit, Hematol Branch, NIH, 9000 Rockville Pike,Bldg 10,Room 7C103, Bethesda, MD 20892 USA. FU NCI NIH HHS [K08 CA77330-01A1] NR 15 TC 16 Z9 17 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUL PY 2001 VL 114 IS 1 BP 57 EP 62 DI 10.1046/j.1365-2141.2001.02879.x PG 6 WC Hematology SC Hematology GA 452TR UT WOS:000169875900011 PM 11472345 ER PT J AU Luo, HY Rogers, RD Brechbiel, MW AF Luo, HY Rogers, RD Brechbiel, MW TI A convenient and selective route to a trans-difunctionalized macrocyclic hexadentate N4O2 ligand SO CANADIAN JOURNAL OF CHEMISTRY-REVUE CANADIENNE DE CHIMIE LA English DT Article DE 1,8-difunctionalized; cyclam; copper(II) complex ID CRYSTAL-STRUCTURE; 1,7-DIPROTECTED 1,4,7,10-TETRAAZACYCLODODECANE; REGIOSELECTIVE SYNTHESIS; COPPER(II) COMPLEXES; TETRAAZA MACROCYCLES; NICKEL(II) COMPLEXES; POLYAZA MACROCYCLES; COORDINATING GROUPS; METAL-COMPLEXES; DERIVATIVES AB The synthesis and characterization of a novel difunctionalized tetraaza macrocycle, 1,8-bis(2-hydroxybenzyl)-1,4,8,11 -tetraazacyclotetradecane (abbreviated H(2)bcyclamb), is described. The diprotic hexadentate ligand N4O2 was conveniently synthesized in two steps by the cyclic condensation reaction of 1,4,8,11-tetraazacyclotetradecane (abbreviated cyclam) and salicylaldehyde, followed by NaBH4 reduction of the cyclic hexahydropyrimidine condensate. The difunctionalization was selective and is the first procedure of trans-difunctionalization of a tetraazamacrocycle, without generating mono-, tri-, or tetra-functionalized products, with only 1.8-difunctionalized product being isolated, and with the convenience of the functionalization occurring as a result of deprotection. The trans-arrangement of the two functional groups in H(2)bcyclamb was verified by X-ray crystallographic studies of the copper(II) complex [Cu(H(2)bcyclamb)](OAc)(2). 2H(2)O. The crystal is monoclinic, P2(1)/c, with a = 10.0931(2), b = 13.8820(1), c 10.8752(1) Angstrom, beta = 106.332(1)degrees, V = 1462.26(3) Angstrom (3). The structure of [Cu(H(2)bcyclamb)] (OAc)(2). 2H(2)O also shows the metal ion in an elongated octahedral geometry. C1 NCI, Radioimmune & Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. Univ Alabama, Dept Chem, Tuscaloosa, AL 35487 USA. RP Brechbiel, MW (reprint author), NCI, Radioimmune & Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RI Rogers, Robin/C-8265-2013 OI Rogers, Robin/0000-0001-9843-7494 NR 36 TC 2 Z9 2 U1 0 U2 0 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA, ONTARIO K1A 0R6, CANADA SN 0008-4042 J9 CAN J CHEM JI Can. J. Chem.-Rev. Can. Chim. PD JUL PY 2001 VL 79 IS 7 BP 1105 EP 1109 DI 10.1139/cjc-79-7-1105 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA 473RE UT WOS:000171061200003 ER PT J AU Chu, KC Anderson, WF Fritz, A Ries, LAG Brawley, OW AF Chu, KC Anderson, WF Fritz, A Ries, LAG Brawley, OW TI Frequency distributions of breast cancer characteristics classified by estrogen receptor and progesterone receptor status for eight racial/ethnic groups SO CANCER LA English DT Article DE breast cancer; estrogen receptor (ER); progesterone receptor (PR); white; black; Hispanic; Japanese; Chinese; Filipino; Native Hawaiian; American Indian; and Alaska Native ID HORMONE RECEPTORS AB BACKGROUND. The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) cancer registries have been collecting data regarding estrogen receptor (ER) and progesterone receptor (PR) status in breast cancer since 1990. The current study reports on some of these data for eight racial/ethnic groups. METHODS. Stratified by ER and PR status, the frequency distributions of 112,588 breast cancer cases diagnosed between 1992-1997 in 11 SEER cancer registries were examined by age at diagnosis, stage at diagnosis, histologic grade, and tumor type for white, black, Hispanic, Japanese, Chinese, Filipino, Native Hawaiian, and American Indian and Alaska Native (AI/AN) females. RESULTS. For each racial/ethnic group, the percentage of ER positive (+)/PR+ was > ER-PR- > ER+PR- > ER-PR+ tumors. For the two major ER/PR groups, the ER+PR+ tumors were different from the ER-PR- tumors in several ways. For white females, there were differences in the age distributions, stage at diagnosis, and histologic grade. For black females, the differences involved the age distributions and tumor grades. For Hispanic and Japanese females, there were differences with regard to the age distributions and tumor grades. For Filipino, Chinese, and AI/AN females, the tumor stages and grades differed. For Native Hawaiians, the histologic tumor grades were different. CONCLUSIONS. For each racial/ethnic group, the ER/PR status appeared to divide breast cancer patients into two or more subgroups with unique tumor characteristics. In general, ER status appeared to have the greatest impact on delineating these subgroups, whereas in some cases, PR status was able to modify the subgroups further. It is hoped that reporting these tumor characteristics by ER/PR status for each racial/ethnic group will spur more investigation into the significance of ER/PR status in each racial/ethnic group. Cancer 2001;92:37-45. (C) 2001 American Cancer Society. C1 NCI, Ctr REduce Canc Hlth Dispar, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, Chemoprevent Branch, Bethesda, MD 20892 USA. NCI, Div Canc Control & Populat Sci, Canc Stat Branch, Bethesda, MD 20892 USA. RP Chu, KC (reprint author), NCI, Ctr REduce Canc Hlth Dispar, EPS Room 320,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 19 TC 81 Z9 82 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD JUL 1 PY 2001 VL 92 IS 1 BP 37 EP 45 DI 10.1002/1097-0142(20010701)92:1<37::AID-CNCR1289>3.0.CO;2-F PG 9 WC Oncology SC Oncology GA 449CF UT WOS:000169666200006 PM 11443607 ER PT J AU Kovac, C Chie, L Morin, J Friedman, FK Robinson, R Chung, DL Kanovsky, M Flom, J Brandt-Rauf, PW Yamaizumi, Z Michl, J Pincus, MR AF Kovac, C Chie, L Morin, J Friedman, FK Robinson, R Chung, DL Kanovsky, M Flom, J Brandt-Rauf, PW Yamaizumi, Z Michl, J Pincus, MR TI Plasmid expression of a peptide that selectively blocks oncogenic ras-p21-induced oocyte maturation SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE oncogenic ras-p21; PNC2 plasmid; selective inhibition of oncogenic ras-p21; oocyte maturation ID CHEMOTHERAPEUTIC-AGENTS; KINASE JNK; ACTIVATION; INDUCTION; PROTEINS; GENE; PATHWAY; DESIGN AB Purpose: We have previously found that a synthetic peptide corresponding to ras-p21 residues 96-110 (PNC2) selectively blocks oncogenic (Val 12-containing) ras-p21 protein-induced oocyte maturation. With a view to introducing this peptide into ras-transformed human cells to inhibit their proliferation, we synthesized an inducible plasmid that expressed this peptide sequence. Our purpose was to test this expression system in oocytes to determine if it was capable of causing selective inhibition of oncogenic ras-p21. Methods: We injected this plasmid and a plasmid expressing a control peptide into oocytes either together with oncogenic p21 or in the presence of insulin (that induces maturation that is dependent on normal cellular ras-p21) in the presence and absence of the inducer isopropylthioglucose (IPTG). Results: Microinjection of this plasmid into oocytes together with Val 12-p21 resulted in complete inhibition of maturation in the presence of inducer. Another plasmid encoding the sequence for the unrelated control peptide, X13, was unable to inhibit Val 12-p21-induced maturation. In contrast, PNC2 plasmid had no effect on the ability of insulin-activated normal cellular or wild-type ras-p21 to induce oocyte maturation, suggesting that it is selective for blocking the mitogenic effects of oncogenic (Val 12) ras p21. Conclusion: We conclude that the PNC2 plasmid selectively inhibits oncogenic ras-p21 and may therefore be highly effective in blocking proliferation of ras-induced cancer cells. Also, from the patterns of inhibition, by PNC2 and other ras- and raf-related peptides, of raf- and constitutively activated MEK-induced maturation, we conclude that PNC2 peptide inhibits oncogenic ras p21 downstream of raf. C1 Vet Adm Med Ctr, Dept Pathol & Lab Med, Brooklyn, NY 11209 USA. Long Isl Univ, Dept Biol, Brooklyn, NY 11201 USA. Long Isl Univ, Dept Chem, Brooklyn, NY 11201 USA. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. SUNY Hlth Sci Ctr, Dept Pathol, Brooklyn, NY 11203 USA. Columbia Univ, Sch Publ Hlth, Div Environm Hlth Sci, New York, NY 10032 USA. NCI, Tokyo, Japan. Suny Downstate Med Ctr, Dept Anat & Cell Biol, Brooklyn, NY 11203 USA. Suny Downstate Med Ctr, Dept Microbiol & Immunol, Brooklyn, NY 11203 USA. RP Pincus, MR (reprint author), Vet Adm Med Ctr, Dept Pathol & Lab Med, 800 Poly Pl, Brooklyn, NY 11209 USA. RI Friedman, Fred/D-4208-2016 FU NCI NIH HHS [CA 69243, CA 42500] NR 18 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JUL PY 2001 VL 48 IS 1 BP 9 EP 14 DI 10.1007/s002800100288 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 457PA UT WOS:000170144900002 PM 11488531 ER PT J AU Breslow, RA Ballard-Barbash, R Munoz, K Graubard, BI AF Breslow, RA Ballard-Barbash, R Munoz, K Graubard, BI TI Long-term recreational physical activity and breast cancer in the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID RISK; WOMEN AB Our purpose was to study the association between longterm recreational physical activity and breast cancer in the Epidemiological Follow-up Study (NHEFS) of the first National Health and Nutrition Examination Survey (NHANES I, 1971-1975). The analytic cohort included 6160 women who were free of breast cancer at the first NHEFS follow-up in 1982-1984 and had interview data on recreational physical activity (low, moderate, and high) in 1982-1984 and 10 years earlier, in 1971-1975, We created categories of long-term (1982-1984 + 1971-1975) recreational physical activity: (a) consistently low; (b) moderate/inconsistent; and (c) consistently high. Data were analyzed using Cox proportional hazard regression models. A total of 138 women developed breast cancer between 1982-1984 and 1992. Tn women greater than or equal to 50 years of age in 1982-1984, consistently high (versus consistently low) recreational physical activity was associated with a 67% reduction in breast cancer risk (n = 96 cases; relative risk, 0.33; 95% confidence interval, 0.14-0.82; P for trend = 0.03); in women <50 years of age (n = 42 cases), there was no association. Associations were not modified by body mass index or by weight gain as an adult. High recreational physical activity over the long-term may reduce breast cancer risk in women 50 years of age; in this sample, it did so regardless of weight history. C1 CDCP, Epidemiol & Hlth Serv Branch, Div Canc Prevent & Control, Atlanta, GA 30341 USA. NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Merck Pharmaceut, Whitehouse Stn, NJ 08889 USA. RP Breslow, RA (reprint author), CDCP, Epidemiol & Hlth Serv Branch, Div Canc Prevent & Control, 4770 Buford Highway,MS K-55, Atlanta, GA 30341 USA. NR 17 TC 65 Z9 66 U1 2 U2 6 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL PY 2001 VL 10 IS 7 BP 805 EP 808 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 451CE UT WOS:000169782900011 PM 11440967 ER PT J AU Cui, HM Niemitz, EL Ravenel, JD Onyango, P Brandenburg, SA Lobanenkov, VV Feinberg, AP AF Cui, HM Niemitz, EL Ravenel, JD Onyango, P Brandenburg, SA Lobanenkov, VV Feinberg, AP TI Loss of imprinting of insulin-like growth factor-II in Wilms' tumor commonly involves altered methylation hut not mutations of CTCF or its binding site SO CANCER RESEARCH LA English DT Article ID ENHANCER-BLOCKING ACTIVITY; REDUCED EXPRESSION; GENE; H19; LOCUS; RELAXATION; CANCER; BREAST; IGF2 AB Loss of imprinting (LOI) is the most common molecular abnormality in Wilms' tumor (WT), other embryonal cancers, and most other tumor types. LOI in WT involves activation of the normally silent maternal allele of the insulin-like growth factor-ii (IGF2) gene, silencing of the normally active maternal allele of the H19 gene, and aberrant methylation of a differentially methylated region (DMR) upstream of the maternal copy of H19, Recently, the transcription factor CTCF, which binds to the H19 DMR, has been implicated in the maintenance of H19 and IGF2 imprinting. Here, we show that mutations in the CTCF gene or in the H19 DMR do not occur at significant frequency in WT, nor is there transcriptional silencing of CTCF, We also confirm that methylation of the H19 DMR in WT with LOI includes the CTCF core consensus site. However, some WTs with normal imprinting of IGF2 also show aberrant methylation of CTCF binding sites, indicating that methylation of these sites is necessary but not sufficient for LOI in WT. C1 Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Grad Program Human Genet, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Grad Program Biochem Cell & Mol Biol, Baltimore, MD 21205 USA. NIAID, Bethesda, MD 20892 USA. RP Feinberg, AP (reprint author), Johns Hopkins Univ, Sch Med, Inst Med Genet, 720 Rutland Ave,1064 Ross, Baltimore, MD 21205 USA. RI Cui, Hengmi/A-2598-2008 FU NCI NIH HHS [CA65145] NR 18 TC 108 Z9 115 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 2001 VL 61 IS 13 BP 4947 EP 4950 PG 4 WC Oncology SC Oncology GA 447GJ UT WOS:000169563300003 PM 11431321 ER PT J AU Kobayashi, H Saga, T Kawamoto, S Sato, N Hiraga, A Ishimori, T Konishi, J Togashi, K Brechbiel, MW AF Kobayashi, H Saga, T Kawamoto, S Sato, N Hiraga, A Ishimori, T Konishi, J Togashi, K Brechbiel, MW TI Dynamic micro-magnetic resonance imaging of liver micrometastasis in mice with a novel liver macromolecular magnetic resonance contrast agent DAB-Am64-(1B4M-Gd)(64) SO CANCER RESEARCH LA English DT Article ID GD-EOB-DTPA; SUPERPARAMAGNETIC IRON-OXIDE; I CLINICAL-EVALUATION; MONOCLONAL-ANTIBODY; DENDRIMER; PHARMACOKINETICS; BIODISTRIBUTION; FLEXIBILITY; LESIONS; SYSTEM AB DAB-Am64-(1B4M-Gd)(64) is a newly synthesized macromolecular liver magnetic resonance imaging (MRI) contrast agent with a polypropylenmine diaminobutane (DAB) dendrimer conjugated with a bifunctional diethylenetriaminepentaacetic acid (DTPA) derivative for complexing Gd(III) atoms. The characteristics of DAB-Am64-(1B4M-Gd)(64) which quickly accumulated in the liver, have been reported recently. In the present study, the dynamic micro-MRI with DAB-Am64-(1B4M-Gd)(64) was obtained in the mouse liver metastasis model using colon carcinoma cells to evaluate the ability to visualize the micrometastatic tumors compared with that using Gd-DTPA. The dynamic micro-MRI with DAB-Am64-(1B4M-Gd)(64) was able to homogeneously enhance the normal liver parenchyma and visualize micrometastatic tumors of 0.3-mm diameter in the ii ver of the mice with better contrast than that with Gd-DTPA. In conclusion, DAB-Am64-(1B4M-Gd)(64) is a new liver MRI contrast agent potentially useful for diagnosis of micrometastasis in the liver. C1 Kyoto Univ, Dept Diagnost & Intervent Imagiol, Kyoto 6068507, Japan. Kyoto Univ, Dept Nucl Med & Diagnost Imaging, Kyoto 6068507, Japan. Kyoto Univ, Dept Radiol, Kyoto 6068507, Japan. Otsu Municipal Hosp, Dept Radiol, Otsu, Shiga 5200804, Japan. NCI, Radiat Oncol Branch, Radioimmune & Inorgan Chem Sect, NIH, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), Kyoto Univ, Grad Sch Med, Dept Diagnost & Intervent Radiol, 54 Kawahara Cho, Kyoto 6068507, Japan. NR 31 TC 45 Z9 48 U1 2 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 2001 VL 61 IS 13 BP 4966 EP 4970 PG 5 WC Oncology SC Oncology GA 447GJ UT WOS:000169563300007 PM 11431325 ER PT J AU Sei, S O'Neill, DP Stewart, SK Yang, QE Kumagai, M Boler, AM Adde, MA Zwerski, SL Wood, LV Venzon, DJ Magrath, IT AF Sei, S O'Neill, DP Stewart, SK Yang, QE Kumagai, M Boler, AM Adde, MA Zwerski, SL Wood, LV Venzon, DJ Magrath, IT TI Increased level of stromal cell-derived factor-1 mRNA in peripheral blood mononuclear cells from children with AIDS-related lymphoma SO CANCER RESEARCH LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; NON-HODGKINS-LYMPHOMA; EPSTEIN-BARR-VIRUS; ACUTE LYMPHOBLASTIC-LEUKEMIA; POLYMERASE-CHAIN-REACTION; CENTRAL-NERVOUS-SYSTEM; COMBINATION ANTIRETROVIRAL THERAPY; HIV-1 DISEASE PROGRESSION; CHEMOKINE RECEPTOR GENE; 3' UNTRANSLATED REGION AB A common polymorphism in the 3 ' untranslated region of the stromal cell-derived factor 1 (also called pre-B-cell-stimulating factor) P gene transcript, termed SDF1-3 'A, has been associated with an increased risk of non-Hodgkin's lymphoma (NHL) in HIV-1-infected, but not in uninfected,, individuals. Because the gene variation is located within the 3 ' untranslated region, the SDF1-3 'A may influence the abundance of SDF-1 mRNA, possibly up-regulating the chemokine expression especially in the presence of HIV-1. In the current study, we investigated the levels of SDF-1 mRNA in peripheral blood mononuclear cells and HIV-1 viral Load in 84 HIV-1-infected children (0.7 to 18 years of age; median, 5.8), including 12 children who developed NHL, during their illnesses (AIDS-NHL group; g with SDF1-3 'A, 4 with SDF1-wild-type). High level SDF-1 expression was observed in 15 of 34 children with SDF1-3 'A as compared with 10 of 50 with wild type (P < 0.03), More notably, the children with AIDS-NHL had significantly elevated levels of SDF-1 mRNA in peripheral blood mononuclear cells, obtained at the time of presentation in 10 children and 8.5 to 19.5 months before (median, 15 months) in 7 children, as compared with the children in the non-NHL group (P < 0.00001). The amounts of cell-associated HIV-1 DNA and singly spliced HIV-1 mRNA were significantly greater in children with AIDS-NHL than those with non-NHL AIDS (P = 0.0052 and 0.011, respectively; stratified by antiretroviral treatment regimen), whereas their serum HIV-1 RNA levels were comparable, Overexpression of SDF-1 and aberrant HIV-I expression in circulating lymphocytes appear to be linked to the development of AIDS-lymphoma Additional studies are required to determine whether excessive SDF-1, together with virally encoded factors, is directly involved in the pathogenesis of AIDS-lymphoma. C1 NCI, SAIC Frederick, HIV Clin Interface Lab, Frederick, MD 21702 USA. NCI, Div Clin Sci, AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. NCI, Div Clin Sci, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. NCI, Div Clin Sci, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP NCI, SAIC Frederick, HIV Clin Interface Lab, Bldg 469,Room 105, Frederick, MD 21702 USA. RI Venzon, David/B-3078-2008 FU NCI NIH HHS [N01-CO-56000] NR 102 TC 32 Z9 35 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 2001 VL 61 IS 13 BP 5028 EP 5037 PG 10 WC Oncology SC Oncology GA 447GJ UT WOS:000169563300019 PM 11431337 ER PT J AU Onda, M Nagata, S Tsutsumi, Y Vincent, JJ Wang, QC Kreitman, RJ Lee, B Pastan, I AF Onda, M Nagata, S Tsutsumi, Y Vincent, JJ Wang, QC Kreitman, RJ Lee, B Pastan, I TI Lowering the isoelectric point of the Fv portion of recombinant immunotoxins leads to decreased nonspecific animal toxicity without affecting antitumor activity SO CANCER RESEARCH LA English DT Article ID SINGLE-CHAIN FV; PSEUDOMONAS EXOTOXIN; FRAMEWORK REGIONS; ESCHERICHIA-COLI; FRAGMENTS; PROTEIN; CELL; ANTI-TAC(FV)-PE38; BIODISTRIBUTION; RESPONSES AB Recombinant immunotoxins are genetically engineered proteins in which the Fv portion of an antibody is fused to a toxin, Our laboratory uses a 38-kDa form of Pseudomonas exotoxoin A termed PE38 for this purpose. Clinical studies with immunotoxins targeting CD25 and CD22 have shown that dose-limiting side effects are attributable to liver damage and other inflammatory toxicities. We recently showed that mutating exposed surface neutral residues to acidic residues in the framework region of the Fv portion of an immunotoxin targeting CD25 [anti-Tac-(scFv)-PE38] lowered its isoelectric point (pI) and decreased its toxicity in mice without impairing its cytotoxic or antitumor activities, We have no cu extended these studies and made mutations that change basic residues to neutral or acidic residues, Initially the pi of the mutant Fu (MI) of anti-Tac(scFv)-PE38 was decreased further. Subsequently, mutations were made in tyro other immunotoxins, SS1(dsFv)-PE38 targeting ovarian cancer and B3(dsFv)-PE38 targeting colon and breast cancers. We have found that ah these mutant molecules fully retained specific target cell cytotoxicity and antitumor activity but were considerably less toxic to mice; Therefore, lowering the pI of the Fv may be a general approach to diminish the nonspecific toxicity of recombinant immunotoxins and other Fv fusion proteins without losing antitumor activity. C1 NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, Div Basic Sci, NIH, Bldg 37,Room 4E16,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 30 TC 54 Z9 60 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 2001 VL 61 IS 13 BP 5070 EP 5077 PG 8 WC Oncology SC Oncology GA 447GJ UT WOS:000169563300025 PM 11431343 ER PT J AU Pinilla, C Rubio-Godoy, V Dutoit, V Guillaume, P Simon, R Zhao, YD Houghten, RA Cerottini, JC Romero, P Valmori, D AF Pinilla, C Rubio-Godoy, V Dutoit, V Guillaume, P Simon, R Zhao, YD Houghten, RA Cerottini, JC Romero, P Valmori, D TI Combinatorial peptide libraries as an alternative approach to the identification of ligands for tumor-reactive cytolytic T lymphocytes SO CANCER RESEARCH LA English DT Article ID MELAN-A/MART-1 ANTIGENIC PEPTIDE; HLA-A2 MELANOMAS; CANCER; GENES; MART-1(27-35); RECOGNITION; GENERATION; RESPONSES; RECEPTOR; MIMICS AB The recent identification of molecularly defined human tumor antigens recognized by autologous CTLs has opened new opportunities for the development of antigen-specific cancer vaccines. Despite extensive work, however, the number of CTL-defined tumor antigens that are suitable targets for generic vaccination of cancer patients is still limited, mostly because of the painstaking and lengthy nature of the procedures currently used for their identification. A novel approach is based on the combined use of combinatorial peptide libraries in positional scanning format (positional scanning synthetic combinatorial peptide libraries, PS-SCLs) and tumor-reactive CTL clones. To validate this approach, we herein analyzed in detail the recognition of PS-SCLs by Melan-A-specific CTL clones. Our results indicate that, at least for some clones, most of the amino acids composing the native antigenic peptide can be identified through the use of PS-SCLs, Interestingly, this analysis also allowed the identification of peptide analogues with increased antigenic activity as well as agonist peptides containing multiple amino-acid substitutions. In addition, biometrical analysis of the data generated by PS-SCL screening allowed the identification of the native ligand in a public database. Overall, these data demonstrate the successful use of PS-SCLs for the identification and optimization of tumor-associated CTL epitopes. C1 Torrey Pines Inst Mol Studies & Mixture Sci Inc, San Diego, CA 92121 USA. Univ Hosp, Ludwig Inst Canc Res, Div Clin Oncoimmunol, CH-1011 Lausanne, Switzerland. Univ Hosp, Multidisciplinary Oncol Ctr, CH-1005 Lausanne, Switzerland. NCI, Mol Stat & Bioinformat Sect, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. RP Pinilla, C (reprint author), Hop Orthoped, Div Clin Oncoimmunol, Ave Pierre Decker 4, CH-1005 Lausanne, Switzerland. RI Valmori, Danila/K-2439-2015 NR 30 TC 51 Z9 56 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 2001 VL 61 IS 13 BP 5153 EP 5160 PG 8 WC Oncology SC Oncology GA 447GJ UT WOS:000169563300036 PM 11431354 ER PT J AU Territo, PR French, SA Balaban, RS AF Territo, PR French, SA Balaban, RS TI Simulation of cardiac work transitions, in vitro: effects of simultaneous Ca2+ and ATPase additions on isolated porcine heart mitochondria SO CELL CALCIUM LA English DT Article ID INTRACELLULAR CALCIUM; OXYGEN-CONSUMPTION; OXIDATIVE-PHOSPHORYLATION; RESPIRATORY CONTROL; RUTHENIUM RED; MUSCLE-CELLS; INTACT HEART; RAT HEARTS; P-31 NMR; MYOCYTES AB During increases in cardiac work there are net increases in cytosolic [Ca2+] and ATP hydrolysis by myofiliments and ion transport ATPases. However, it is still unclear what role Ca2+ or the ATP hydrolysis products, ADP and Pi, have on the regulation of mitochondrial ATP production. In this study, work jumps were simulated by simultaneous additions of Ca2+ and ATPase to porcine heart mitochondria. The net effects on the mitochondrial ATP production were monitored by simultaneously monitoring respiration (mVo(2)), [NADH], [ADP] and membrane potential (Delta psi) at 37 degreesC. Addition of exogenous ATPase (300 mlU.ml(-1)) + ATP (3.4 mM) was used to generate a 'resting' background production of ADP. This resting metabolic rate was 200% higher than the quiescent rate while [NADH] and Delta psi were reduced. Subsequent ATPase additions (1.3 IU.ml(-1)) were made with varying amounts of Ca2+ (0 to 535 nM) to simulate step increases in cardiac work. Ca2+ additions increased mVo(2) and depolarized Delta psi, and were consistent with an activation of F-0/F(1)ATPase. In contrast, Ca2+ reduced the [NADH] response to the ATPase addition, consistent with Ca2+-sensitive dehydrogenase activity (CaDH). The calculated free ADP response to ATPase decreased <2-fold in the presence of Ca2+. The addition of 172 nM free Ca2+ + ATPase increased mVo(2) by 300% (P0.05, n = 8) while Delta psi decreased by 14.9 +/- 0.1 mV without changes in [NADH] (P>0.05, n=8), consistent with working heart preparations. The addition of Ca2+ and ATPase combined increased the mitochondrial ATP production rate with changes in Delta psi, NADH and [ADP], consistent with an activation of CaDH and F-0/F(1)ATPase activity. These balancing effects of ATPase activity and [Ca2+] may explain several aspects of metabolic regulation in the heart during work transitions in vivo. (C) 2001 Harcourt Publishers Ltd. C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Territo, PR (reprint author), NHLBI, Cardiac Energet Lab, NIH, Bldg 10,Rm B1D-416, Bethesda, MD 20892 USA. RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 NR 34 TC 33 Z9 35 U1 0 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4160 J9 CELL CALCIUM JI Cell Calcium PD JUL PY 2001 VL 30 IS 1 BP 19 EP 27 DI 10.1054/ceca.2001.0211 PG 9 WC Cell Biology SC Cell Biology GA 449BM UT WOS:000169664500003 PM 11396984 ER PT J AU Wyde, ME Wong, VA Kim, AH Lucier, GW Walker, NJ AF Wyde, ME Wong, VA Kim, AH Lucier, GW Walker, NJ TI Induction of hepatic 8-oxo-deoxyguanosine adducts by 2,3,7,8-tetrachlorodibenzo-p-dioxin in Sprague-Dawley rats is female-specific and estrogen-dependent SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID OXIDATIVE DNA-DAMAGE; CELL-PROLIFERATION; CATECHOL ESTROGENS; DOSE-RESPONSE; OVARIECTOMIZED RATS; MECHANISTIC MODEL; COVALENT BINDING; CHRONIC EXPOSURE; NUCLEAR-DNA; LIVER DNA AB 2,3,7,8-tetrachlorodibenzo-beta -dioxin (TCDD) is a hepatocarcinogen that induces sex-specific hepatic neoplastic alterations in female, but not male, rats. It has been hypothesized that TCDD-induced alterations in estrogen metabolism lead to increased generation of reactive oxygen species. The resulting oxidative damage to DNA may contribute to TCDD-induced tumor promotion and hepatocarcinogenesis. This hypothesis is supported by previous observations of increased 8-oxo-deoxyguanosine (8-oxo-dG) adduct formation in the livers of intact, but not ovariectomized (OVX), rats following chronic exposure to TCDD. The aim of the current study was to more clearly define the roles of hormonal regulation, gender, dose-response, and exposure duration in TCDD induction of 8-oxo-dG adducts. Diethylnitrosamine (DEN)-initiated male and female (both intact and OVX) rats were exposed to TCDD in the presence or absence of 17 beta -estradiol. Following 30 weeks of exposure, hepatic 8-oxo-dG adduct levels were significantly higher in TCDD-treated intact female rats, and TCDD-treated OVX female rats receiving supplemental 17 beta -estradiol, when compared to respective corn oil vehicle controls. In DEN-initiated female rats exposed to a range of TCDD concentrations for 30 weeks, TCDD induced 8-oxo-dG adduct levels in a dose-dependent manner. However, 8-oxo-dG adduct levels were not altered in TCDD-treated male or OVX female rats following 30 weeks of exposure. In noninitiated female rats, the level of 8-oxo-dG adducts 4 days following a single dose of TCDD was not significantly different than in control rats. Additionally, 8-oxo-dG adduct formation was not affected by exposure to TCDD for 20 weeks in intact female rats. These data suggest that the induction of 8-oxo-dG adduct levels by TCDD is likely a response to chronic oxidative imbalance. These studies provide strong evidence that the induction of 8-oxo-dG by TCDD occurs via a chronic, sex-specific, estrogen-dependent mechanism. C1 NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Curriculum Toxicol, Chapel Hill, NC 27709 USA. NIEHS, CIIT Ctr Hlth Res, Res Triangle Pk, NC 27709 USA. RP Walker, NJ (reprint author), NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RI Walker, Nigel/D-6583-2012 OI Walker, Nigel/0000-0002-9111-6855 NR 59 TC 36 Z9 37 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JUL PY 2001 VL 14 IS 7 BP 849 EP 855 DI 10.1021/tx000266j PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 454YP UT WOS:000169999600009 PM 11453731 ER PT J AU Pauly, GT Moschel, RC AF Pauly, GT Moschel, RC TI Mutagenesis by O-6-methyl-, O-6-ethyl-, and O-6-benzylguanine and O-4-methylthymine in human cells: Effects of O-6-alkylguanine-DNA alkyltransferase and mismatch repair SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID 3 O-6-SUBSTITUTED GUANINES; INDUCED DNA DAMAGE; H-RAS GENE; ESCHERICHIA-COLI; MAMMALIAN-CELLS; ALKYLATING-AGENTS; CHROMOSOME-ABERRATIONS; METHYLATING AGENTS; GAPPED PLASMIDS; RAT4 CELLS AB Double-stranded and gapped shuttle vectors were used to study mutagenesis in human cells by O-6-methyl (m(6)G)-, O-6-ethyl (e(6)G)-, and O-6-benzylguanine (b(6)G), and O-4-methylthymine (m(4)T) when these bases were incorporated site-specifically in the ATG initiation codon of a lacZ ' gene. Vectors were transfected into either human kidney cells (293) or colon tumor cells (SO) or into mismatch repair defective human colon tumor cells (H6 and LoVo). Cellular O-6-alkylguanine-DNA alkyltransferase (alkyltransferase) was optionally inactivated by treating cells with O-6-benzylguanine prior to transfection. In alkyltransferase competent cells, the mutagenicity of all the modified bases was substantially higher in gapped plasmids than in double-stranded plasmids. Alkyltransferase inactivation increased mutagenesis by the three O-6-substituted guanines in both double-stranded and gapped plasmids but did not affect m(4)T mutagenesis. In the absence of alkyltransferase, mutagenesis by m(6)G and to a lesser extent e(6)G in double-stranded vectors was higher in the mismatch repair defective H6 and LoVo cells than in SO or 293 cells indicating that e(6)G as well as m(6)G were subject to mismatch repair processing in these cells. The level of mutagenesis by m(4)T and b(6)G was not affected by mismatch repair status. When incorporated in gapped plasmids and in the absence of alkyltransferase, the order of mutagenicity for the modified bases was m(4)T > e(6)G congruent to m(6)G > b(6)G. The O-6-substituted guanines primarily produced G -->A transitions while m(4)T primarily produced T -->C transitions. However, m(4)T also produced a significant number of T -->A transversion mutations in addition to T-C transitions in mismatch repair deficient LoVo cells. C1 NCI, Chem Carcinogenesis Lab, Frederick, MD 21702 USA. RP Moschel, RC (reprint author), NCI, Chem Carcinogenesis Lab, POB B, Frederick, MD 21702 USA. NR 35 TC 40 Z9 41 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JUL PY 2001 VL 14 IS 7 BP 894 EP 900 DI 10.1021/tx010032f PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 454YP UT WOS:000169999600015 PM 11453737 ER PT J AU Hassfjell, S Brechbiel, MW AF Hassfjell, S Brechbiel, MW TI The development of the alpha-particle emitting radionuclides Bi-212 and Bi-213, and their decay chain related radionuclides, for therapeutic applications SO CHEMICAL REVIEWS LA English DT Review ID VASCULAR TARGETED RADIOIMMUNOTHERAPY; BIFUNCTIONAL CHELATING AGENT; THYROID CANCER XENOGRAFT; TAC MONOCLONAL-ANTIBODY; DOSE-LIMITING TOXICITY; B-CELL LYMPHOMAS; GROUP NO 6; MAMMALIAN-CELLS; IN-VIVO; BISPECIFIC ANTIBODY C1 NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Brechbiel, MW (reprint author), NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, 10 Ctr Dr,Bldg 10,Room B3B69, Bethesda, MD 20892 USA. NR 188 TC 81 Z9 83 U1 3 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0009-2665 J9 CHEM REV JI Chem. Rev. PD JUL PY 2001 VL 101 IS 7 BP 2019 EP 2036 DI 10.1021/cr000118y PG 18 WC Chemistry, Multidisciplinary SC Chemistry GA 455TZ UT WOS:000170045000007 PM 11710239 ER PT J AU Pandeya, SN Sriram, D Yogeeswari, P Ananthan, S AF Pandeya, SN Sriram, D Yogeeswari, P Ananthan, S TI Antituberculous activity of norfloxacin Mannich bases with isatin derivatives SO CHEMOTHERAPY LA English DT Article DE isatin; norfloxacin; Mannich bases; antituberculous AB pounds were evaluated in vitro against Mycobacterium tuberculosis H37Rv at 12.5 mug/ml in BACTEC 12B medium using the BACTEC radiometric system. Among the compounds tested, S-10 showed promising activity, with 100% inhibition at a concentration lower Mannich bases of norfloxacin were synthesized by reacting them with formaldehyde and several isatin derivatives. The lower than 6.25 mug/ml. C1 Banaras Hindu Univ, Inst Technol, Dept Pharmaceut, Varanasi 221005, Uttar Pradesh, India. So Res Inst, TAACF, NIAID, Birmingham, AL 35255 USA. RP Pandeya, SN (reprint author), Banaras Hindu Univ, Inst Technol, Dept Pharmaceut, Varanasi 221005, Uttar Pradesh, India. NR 9 TC 20 Z9 20 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0009-3157 J9 CHEMOTHERAPY JI Chemotherapy PD JUL-AUG PY 2001 VL 47 IS 4 BP 266 EP 269 DI 10.1159/000048533 PG 4 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 438RV UT WOS:000169068800006 PM 11399863 ER PT J AU Booth, B Bonner, J Akley, N Macchione, M Adler, K Martin, LD AF Booth, B Bonner, J Akley, N Macchione, M Adler, K Martin, LD TI Interleukin-13, a mediator of subepithelial fibrosis, enhances growth factor production and proliferation in human airway epithelial cells SO CHEST LA English DT Article; Proceedings Paper CT 43rd Annual Thomas L Petty Aspen Lung Conference: Mechanisms of Pulmonary Fribrosis CY MAY 31-JUN 03, 2000 CL ASPEN, COLORADO C1 N Carolina State Univ, Coll Vet Med, Raleigh, NC 27606 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Martin, LD (reprint author), N Carolina State Univ, Coll Vet Med, 4700 Hillsborough St, Raleigh, NC 27606 USA. RI Macchione, Mariangela/C-6696-2012 OI Macchione, Mariangela/0000-0003-3335-2654 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JUL PY 2001 VL 120 IS 1 SU S BP 15S EP 15S DI 10.1378/chest.120.1_suppl.S15 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 453LM UT WOS:000169917400018 ER PT J AU Kagan, E Iwagaki, A Choe, N Zhang, P Wang, YZ Bonner, JC AF Kagan, E Iwagaki, A Choe, N Zhang, P Wang, YZ Bonner, JC TI Tyrosine nitration and mitogen-activated protein kinase activation in asbestosis-induced pulmonary fibrosis SO CHEST LA English DT Article; Proceedings Paper CT 43rd Annual Thomas L Petty Aspen Lung Conference: Mechanisms of Pulmonary Fribrosis CY MAY 31-JUN 03, 2000 CL ASPEN, COLORADO C1 Uniformed Serv Univ Hlth Sci, Dept Pathol, Bethesda, MD 20814 USA. Natl Inst Environm Hlth Sci, Pulm Pathobiol Lab, Res Triangle Pk, NC USA. RP Kagan, E (reprint author), Uniformed Serv Univ Hlth Sci, Dept Pathol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JUL PY 2001 VL 120 IS 1 SU S BP 26S EP 27S DI 10.1378/chest.120.1_suppl.S26 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 453LM UT WOS:000169917400029 ER PT J AU Roberts, AB Piek, E Bottinger, EP Ashcroft, G Mitchell, JB Flanders, KC AF Roberts, AB Piek, E Bottinger, EP Ashcroft, G Mitchell, JB Flanders, KC TI Is Smad3 a major player in signal transduction pathways leading to fibrogenesis? SO CHEST LA English DT Article; Proceedings Paper CT 43rd Annual Thomas L Petty Aspen Lung Conference: Mechanisms of Pulmonary Fribrosis CY MAY 31-JUN 03, 2000 CL ASPEN, COLORADO ID GROWTH-FACTOR-BETA; TGF-BETA; TRANSCRIPTIONAL ACTIVATION; FIBROSIS; PROMOTER; TGF-BETA-1; EXPRESSION; RADIATION; LACKING; THERAPY AB Transforming growth factor (TGF)-beta plays a central role in fibrosis, contributing both to the influx and activation of inflammatory cells, as well as to activation of fibroblasts to elaborate extracellular matrix. In the past few years, new insight has been gained into signal transduction pathways downstream of the TGF-beta receptor serine-threonine kinases with the identification of a family of evolutionarily conserved Smad proteins. Two receptor-activated Smad proteins, Smad2 and Smad3, are phosphorylated by the activated TGF-beta type I receptor kinase, after which they partner with the common mediator, Smad4, and are translocated to the nucleus to where they participate in transcriptional complexes to control expression of target genes, We have shown in wound healing studies of mice null for Smad3, that loss of this key signaling intermediate interferes with the chemotaxis of inflammatory cells to TGF-beta as well as with their ability to autoinduce TGF-beta. Moreover, studies,vith mouse embryo fibroblasts null for Smad3 show that TGF-beta -dependent induction of c-Jun and c-Fos, important in induction of collagen as well as in autoinduction of TGF-beta, is mediated by Smad3. Based on these observations, we hypothesize that loss of Smad3 will confer resistance to fibrosis and result in reduced inflammatory cell infiltrates, reduced autoinduction of TGF-beta, important to sustain the process, and reduced elaboration of collagen. Preliminary observations in a model of radiation-induced fibrosis confirm this hypothesis and suggest that inhibitors of Smad3 might have clinical application both to improve wound healing and to reduce fibrosis. C1 NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. RP Roberts, AB (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Bldg 41,Room C629,41 Lib Dr,MSC 5055, Bethesda, MD 20892 USA. NR 29 TC 74 Z9 86 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JUL PY 2001 VL 120 IS 1 SU S BP 43S EP 47S DI 10.1378/chest.120.1_suppl.S43-a PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 453LM UT WOS:000169917400040 PM 11451911 ER PT J AU Bonner, JC Wang, YZ Zhang, P Rice, A Zhang, LM Adler, K Choe, N Kagan, E AF Bonner, JC Wang, YZ Zhang, P Rice, A Zhang, LM Adler, K Choe, N Kagan, E TI Role of receptor tyrosine kinases and mitogen-activated protein kinases in metal-induced pulmonary fibrosis SO CHEST LA English DT Article; Proceedings Paper CT 43rd Annual Thomas L Petty Aspen Lung Conference: Mechanisms of Pulmonary Fribrosis CY MAY 31-JUN 03, 2000 CL ASPEN, COLORADO C1 NIEHS, Airway Inflammat Grp, Pulm Pathobiol Lab, NIH, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Raleigh, NC 27695 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RP Bonner, JC (reprint author), NIEHS, Airway Inflammat Grp, Pulm Pathobiol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JUL PY 2001 VL 120 IS 1 SU S BP 55S EP 56S DI 10.1378/chest.120.1_suppl.S55 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 453LM UT WOS:000169917400045 ER PT J AU Brennan, MT Pillemer, SR Goldbach-Mansky, R El-Gabalawy, H Schumacher, H Fox, PC AF Brennan, MT Pillemer, SR Goldbach-Mansky, R El-Gabalawy, H Schumacher, H Fox, PC TI Focal sialadenitis in patients with early synovitis SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Article DE early synovitis; focal sialadenitis; salivary glands; rheumatoid arthritis; Sjogren's syndrome ID SJOGRENS-SYNDROME; RHEUMATOID-ARTHRITIS AB Objective To investigate the frequency of sialadenitis on tip biopsy in patients with synovitis of recent onset (ES), and see how sialadenitis relates to clinical and laboratory findings of ES. Methods Joint involvement, laboratory measures and biopsies of the minor salivary glands were evaluated in 10 ES patients. Diagnosis at a one-year follow-up exam was noted. Results Six ES patients (60%) had a positive lip biopsy (mononuclear cell focus score greater than Ij. ES patients with a positively biopsy presented with oligoarthritis, while ES patients with a negative lip biopsy had a more polyarticular presentation. No differences in laboratory measures between patients with a positive and negative lip biopsy were present. Seven ES patients had a diagnosis of rheumatoid arthritis and three had undifferentiated arthritis at the end of one year. Conclusion ES patients had a higher than expected frequency of focal sialadenitis. C1 Carolinas Med Ctr, Dept Oral Med, Charlotte, NC 28232 USA. Natl Inst Arthrit & Musculoskeletal Dis, NIH, Bethesda, MD USA. Univ Penn, Div Rheumatol, Philadelphia, PA 19104 USA. VAMC, Philadelphia, PA USA. Carolinas Med Ctr, Dept Oral Med, Charlotte, NC 28203 USA. RP Brennan, MT (reprint author), Carolinas Med Ctr, Dept Oral Med, 1000 Blythe Blvd,MEB-409, Charlotte, NC 28232 USA. NR 12 TC 2 Z9 3 U1 0 U2 0 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD JUL-AUG PY 2001 VL 19 IS 4 BP 444 EP 446 PG 3 WC Rheumatology SC Rheumatology GA 454XT UT WOS:000169997600013 PM 11491501 ER PT J AU Glass, AG Donis-Keller, H Mies, C Russo, J Zehnbauer, B Taube, S Aamodt, R AF Glass, AG Donis-Keller, H Mies, C Russo, J Zehnbauer, B Taube, S Aamodt, R CA Cooperative Breast Canc Tissue TI The cooperative breast cancer tissue resource: Archival tissue for the investigation of tumor markers SO CLINICAL CANCER RESEARCH LA English DT Article AB Investigators continue to search for reliable markers of prognosis of breast cancer. For many analyses, laboratory techniques permit the use of archival paraffin-embedded tissue collected years previously and readily linked to clinical and follow-up information. Laboratory investigators have often expressed the need for such a tissue resource. We have developed a publicly available resource of archival breast cancer specimens, The pathological material bas been collected and reviewed by investigators at four institutions and currently includes breast cancer specimens from more than 9300 cases. Institutional pathologists reviewed slides and blocks using a common protocol and coding scheme. Clinical information and details of follow-up came from data routinely collected by the institutions ' cancer registries. Coded data are maintained centrally in a single database, A subset of the data may be searched on the World Wide Web to determine the availability of cases with specified characteristics. The material collected by this Cooperative Breast Cancer Tissue Resource is generally representative of breast cancer diagnosed in community hospital settings in the United States. Seventy-two percent of the living cases have been followed for at least 5 years, and follow-up status is updated regularly. Interested laboratory investigators may apply to the Resource for the use of these tissues, This Resource is proving valuable to laboratory investigators who require large numbers of specimens for validation studies of prognostic markers of breast cancer. C1 Kaiser Permanente, Oncol Res, NW Reg, Portland, OR 97227 USA. Washington Univ, St Louis, MO 63110 USA. Univ Miami, Miami, FL 33136 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NCI, Bethesda, MD 20892 USA. RP Glass, AG (reprint author), Kaiser Permanente, Oncol Res, NW Reg, 3600 N Interstate Ave, Portland, OR 97227 USA. FU NCI NIH HHS [5UO1-CA62938, 5UO1-CA62772, 5UO1-CA62773, 5UO1-CA62779] NR 13 TC 21 Z9 21 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL PY 2001 VL 7 IS 7 BP 1843 EP 1849 PG 7 WC Oncology SC Oncology GA 451BZ UT WOS:000169782400004 PM 11448894 ER PT J AU Kruger, EA Figg, WD AF Kruger, EA Figg, WD TI Protein binding alters the activity of suramin, carboxyamidotriazole, and UCN-01 in an ex vivo rat aortic ring angiogenesis assay SO CLINICAL CANCER RESEARCH LA English DT Article ID INDEPENDENT PROSTATE-CANCER; CALCIUM INFLUX INHIBITOR; GROWTH-FACTOR; ANTICANCER DRUG; KINASE-C; PHASE-II; TRIAL; PHARMACOKINETICS; PROLIFERATION; CARCINOMA AB Angiogenesis inhibitors are currently in clinical development for cancer. These agents pose unique developmental challenges: (a) determining maximum biological doses versus maximum tolerated doses; (6) defining response criteria other than objective tumor responses; and (c) defining safe regimens for prolonged, chronic administration. The current in vitro angiogenesis assays used in the screening and preclinical development of antiangiogenic agents each have their own advantages and disadvantages, yet all seem to underestimate the importance and impact of in vivo protein-drug interactions. We have developed a human serum rat aortic ring angiogenesis bioassay that highlights protein binding concerns using three anticancer agents that have documented antiangiogenic activity: suramin, carboxy-amidotriazole, and 7-hydroxystaurosporine. We have determined that the bioassay concentrations of suramin (100 mug/ml) and 7-hydroxyseaurosporine (>1 mug/ml), but not carboxyamidotriazole (greater than or equal to 60 mug/ml), that inhibit microvessel formation are consistent with target plasma levels achievable in the clinic. We conclude that assays such as the human serum rat aortic ring bioassay may prove useful in predicting the concentrations of protein-bound antiangiogenic agents required for free fraction biological activity. C1 NCI, Med Branch, Canc Res Ctr, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Med Branch, Canc Res Ctr, 10 Ctr Dr,Bldg 10,Room 5A-01, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 36 TC 13 Z9 14 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL PY 2001 VL 7 IS 7 BP 1867 EP 1872 PG 6 WC Oncology SC Oncology GA 451BZ UT WOS:000169782400008 PM 11448898 ER PT J AU Figg, WD Dahut, W Duray, P Hamilton, M Tompkins, A Steinberg, SM Jones, E Premkumar, A Linehan, WM Floeter, MK Chen, CC Dixon, S Kohler, DR Kruger, EA Gubish, E Pluda, JM Reed, E AF Figg, WD Dahut, W Duray, P Hamilton, M Tompkins, A Steinberg, SM Jones, E Premkumar, A Linehan, WM Floeter, MK Chen, CC Dixon, S Kohler, DR Kruger, EA Gubish, E Pluda, JM Reed, E TI A randomized phase II trial of thalidomide, an angiogenesis inhibitor, in patients with androgen-independent prostate cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID TUMOR ANGIOGENESIS; ANTIGEN AB Purpose: Thalidomide is a potent teratogen that causes dysmelia in humans. Recently, in vitro data suggested that it inhibits angiogenesis, Prostate cancer is dependent on the recruitment of new blood vessels to grow and metastasize, Based on those data, we initiated a Phase II trial of thalidomide in patients with metastatic androgen-independent prostate cancer. Experimental Design: This was an open-label, randomized Phase II study. Thalidomide was administered either at a dose of 200 mg/day (low-dose arm) or at an initial dose of 200 mg/day that escalated to 1200 mg/day (high-dose arm), Results: A total of 63 patients were enrolled onto the study (50 patients on the low-dose arm and 13 patients on the high-dose arm). Serum prostate-specific antigen (PSA) decline of greater than or equal to 50% was noted in 18% of patients on the low-dose arm and in none of the patients on the high-dose arm. Four patients were maintained for > 150 days. The most prevalent complications were constipation, fatigue, neurocortical, and neurosensory. Conclusion: Thalidomide, an antiangiogenesis agent, has some activity in patients with metastatic prostate cancer who have failed multiple therapies. A total of 27% of all patients had a decline in PSA of greater than or equal to 40%, often associated with an improvement of clinical symptoms. Because our preclinical studies had shown that thalidomide increases PSA secretion, we believe that the magnitude of PSA decline seen in our trial justifies further study. C1 NCI, Ctr Canc Res, Med Branch, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Pathol Lab, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Biostat & Data Management Sect, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Urol Oncol Branch, Bethesda, MD 20892 USA. NCI, Canc Treatment & Evaluat Program, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Radiol, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Nucl Med, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA. Natl Inst Neurol Dis, EMG, Nerve Conduct Sect, Bethesda, MD 20892 USA. EntreMed Inc, Rockville, MD 20850 USA. RP Figg, WD (reprint author), NCI, Ctr Canc Res, Med Branch, Bldg 10,Room 5A01,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Ain, Kenneth/A-5179-2012; Figg Sr, William/M-2411-2016 OI Ain, Kenneth/0000-0002-2668-934X; NR 17 TC 220 Z9 230 U1 1 U2 7 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL PY 2001 VL 7 IS 7 BP 1888 EP 1893 PG 6 WC Oncology SC Oncology GA 451BZ UT WOS:000169782400011 PM 11448901 ER PT J AU Tsilou, E Stratakis, CA Rubin, BI Hay, BN Patronas, N Kaiser-Kupfer, MI AF Tsilou, E Stratakis, CA Rubin, BI Hay, BN Patronas, N Kaiser-Kupfer, MI TI Ophthalmic manifestations of Allgrove syndrome: report of a case SO CLINICAL DYSMORPHOLOGY LA English DT Letter DE adrenal insufficiency; alacrima; achalasia ID ADRENOCORTICAL INSUFFICIENCY; ACHALASIA; DYSFUNCTION; ALACRIMA; CARDIA AB A male patient with the ocular manifestations of Allgrove or triple-A syndrome is described. The need for early diagnosis based on alacrima, anisocoria and optic atrophy of this potentially fatal condition is stressed. Clin Dysmorphol 10: 231-233 (C) 2001 Lippincott Williams & Wilkins. C1 NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Unit Genet & Endocrinol, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NHGRI, NIH, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Tsilou, E (reprint author), NEI, Ophthalm Genet & Visual Funct Branch, NIH, 10 Ctr Dr,MSC-1860,Bldg 10,Room 10N226, Bethesda, MD 20892 USA. NR 5 TC 8 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0962-8827 J9 CLIN DYSMORPHOL JI Clin. Dysmorphol. PD JUL PY 2001 VL 10 IS 3 BP 231 EP 233 DI 10.1097/00019605-200107000-00016 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 448DF UT WOS:000169611400016 PM 11446421 ER PT J AU Altarescu, GM Goldfarb, LG Park, KY Kaneski, C Jeffries, N Litvak, S Nagle, JW Schiffmann, R AF Altarescu, GM Goldfarb, LG Park, KY Kaneski, C Jeffries, N Litvak, S Nagle, JW Schiffmann, R TI Identification of fifteen novel mutations and genotype-phenotype relationship in Fabry disease SO CLINICAL GENETICS LA English DT Article DE alpha-galactosidase A; Fabry disease; genotype; mutation; phenotype ID ALPHA-GALACTOSIDASE-A; GENE REARRANGEMENTS; HETEROZYGOTES; HEMIZYGOTES; FORM AB Fabry disease is an X-linked recessive disorder caused by a deficiency in the lysosomal enzyme alpha -galactosidase A, which results in a progressive multisystem disease. Most families have private mutations and no general correlation between genotype and disease manifestations has. Forty-nine patients (47 males and 2 females) from 36 affected families were selected for the study. Their evaluation included clinical examination, identification of alpha -galactosidase A gene mutations and residual enzymatic activity. For mutation detection, each exon with flanking intronic sequences was amplified by polymerase chain reaction (PCR) from the patient's genomic DNA and sequenced. Analysis of the resulting sequences was conducted to identify structural defects in the gene. Each of the Fabry patients carried a mutation in the alpha -galactosidase A gene. Fifteen mutations were novel. They included missense mutations (M51K, Y123M, G261D), nonsense point mutations (E251X) and small insertions or deletions creating a premature translational termination signal (P6X, D93X, W162X, K240X, H302X, I303X, L403X, S345X, G375X. F396X). Residual alpha -galactosidase A activity was significantly lower in patients with neuropathic pain (p = 0.01) and in patients with mutations leading to a nonconservative amino acid change (p = 0.04). Our findings emphasize the wide variety of genetic mechanisms leading to Fabry disease. A significant genotype-phenotype relationship was found. C1 NINDS, Dev & Metab Neurol Branch, Bethesda, MD 20892 USA. NINDS, Clin Neurogenet Unit, Bethesda, MD 20892 USA. NINDS, Basic Neurosci Program, Bethesda, MD 20892 USA. NINDS, Biometry & Field Studies Branch, Bethesda, MD 20892 USA. RP Schiffmann, R (reprint author), NIH, Bldg 10,Room 3D03,9000 Rockville Pike, Bethesda, MD 20892 USA. OI Kaneski, Christine/0000-0003-1453-2502 NR 31 TC 42 Z9 44 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD JUL PY 2001 VL 60 IS 1 BP 46 EP 51 DI 10.1034/j.1399-0004.2001.600107.x PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 457MT UT WOS:000170141900009 PM 11531969 ER PT J AU Czar, MJ Schwartzberg, PL AF Czar, MJ Schwartzberg, PL TI XLP: One gene, many players SO CLINICAL IMMUNOLOGY LA English DT Editorial Material ID LINKED LYMPHOPROLIFERATIVE-DISEASE; ACTIVATION MOLECULE SLAM; ENCODING GENE; CUTTING EDGE; MUTATIONS; CELLS; 2B4; INFECTION; RECEPTOR; SAP C1 NHGRI, NIH, Bethesda, MD 20892 USA. RP Czar, MJ (reprint author), Curagen Corp, New Haven, CT USA. NR 16 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD JUL PY 2001 VL 100 IS 1 BP 2 EP 3 DI 10.1006/clim.2001.5051 PG 2 WC Immunology SC Immunology GA 449RQ UT WOS:000169701300001 PM 11414739 ER PT J AU Lewis, J Eiben, LJ Nelson, DL Cohen, JI Nichols, KE Ochs, HD Notarangelo, LD Duckett, CS AF Lewis, J Eiben, LJ Nelson, DL Cohen, JI Nichols, KE Ochs, HD Notarangelo, LD Duckett, CS TI Distinct interactions of the X-linked lymphoproliferative syndrome gene product SAP with cytoplasmic domains of members of the CD2 receptor family SO CLINICAL IMMUNOLOGY LA English DT Article DE X-linked lymphoproliferative syndrome; Duncan's disease; SAP; SLAM; CD84 ID EPSTEIN-BARR-VIRUS; TYROSINE-PHOSPHATASE; SIGNAL-TRANSDUCTION; IMMUNE-DEFICIENCY; IG SUPERFAMILY; ENCODING GENE; CUTTING EDGE; SH2 DOMAINS; PROTEIN SAP; KAPPA-B AB X-linked lymphoproliferative syndrome (XLP; Duncan's disease) is a primary immunodeficiency disease that manifests as an inability to regulate the immune response to Epstein-Barr virus (EBV) infection, Here we examine the ability of the product of the gene defective in XLP, SAP (DSHP/SH2D1A), to associate with the cytoplasmic domains of several members of the CD2 subfamily of cell surface receptors, including SLAM, 2B4, and CD84. While recruitment of SAP to SLAM occurred in a phosphorylation-independent manner, SAP was found to bind preferentially to tyrosine-phosphorylated cytoplasmic domains within 2B4 and CD84, Missense or nonsense mutations in the SAP open reading frame were identified in five of seven clinically diagnosed XLP patients from different kindreds, Four of these variants retained the ability to bind to the cytoplasmic tails of SLAM and CD84, While ectopic expression of wild-type SAP was observed to block the binding of SHP-8 to SLAM, mutant SAP derivatives that retained the ability to bind SLAM did not inhibit recruitment of SHP-2 to SLAM, In contrast, SAP binding to CD84 had no effect on the ability of CD84 to recruit SHP-2, but instead displaced SHP-1 from the cytoplasmic tail of CD84, These results suggest that mutations in the gene encoding the XLP protein SAP lead to functional defects in the protein that include receptor binding and SHP-1 and SHP-8 displacement and that SAP utilizes different mechanisms to regulate signaling through the CD2 family of receptors, (C) 2001 Academic Press. C1 NCI, Metab Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. Univ Brescia, Dept Pediat, Ist Med Mol Angelo Nocivelli, Brescia, Italy. Univ Washington, Dept Pediat, Seattle, WA 98195 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. NIAID, Med Virol Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Duckett, CS (reprint author), NCI, Metab Branch, Div Clin Sci, NIH, 10 Ctr Dr,Room 6B-05, Bethesda, MD 20892 USA. RI Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 FU NICHD NIH HHS [HD17427] NR 38 TC 36 Z9 41 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD JUL PY 2001 VL 100 IS 1 BP 15 EP 23 DI 10.1006/clim.2001.5035 PG 9 WC Immunology SC Immunology GA 449RQ UT WOS:000169701300003 PM 11414741 ER PT J AU Monson, NL Foster, SJ Brezinschek, HP Brezinschek, RI Dorner, T Lipsky, PE AF Monson, NL Foster, SJ Brezinschek, HP Brezinschek, RI Dorner, T Lipsky, PE TI The role of CD40-CD40 ligand (CD154) interactions in immunoglobulin light chain repertoire generation and somatic mutation SO CLINICAL IMMUNOLOGY LA English DT Article DE B lymphocytes; immunoglobulin; somatic hypermutation; selection ID HYPER-IGM SYNDROME; X-LINKED IMMUNODEFICIENCY; B-CELL RESPONSES; CD40 LIGAND; GERMINAL CENTER; GENE REPERTOIRE; T-CELL; MOLECULAR MECHANISMS; ANTIBODY-RESPONSES; IMMUNE-RESPONSES AB To determine whether CD40 ligation influences the molecular and selective mechanisms that govern the development of the human Ig light chain repertoire, analysis of the V kappa and V lambda repertoires of CD19(+) B cells obtained from a patient with X-linked hyper IgM syndrome (XHIM) and a nonfunctional CD154 was carried out. The nonproductive V kappa and V lambda repertoires were largely comparable to that of the normals with respect to V gene and J segment distribution as well as CDR3 length and V(L)J(L) joint complexity. Comparison of the nonproductive and productive repertoires indicated that a limited number of V-L genes were positively and negatively selected in the XHIM patient. Although mutations were observed in the XHIM V-L repertoires, the frequency of mutations was significantly lower than in normals. Typical targeting of these mutations into RGYW/WRCY motifs was significantly reduced and subsequent selection of RGYW/WRCY mutations, which is normally observed, was not found. These results indicate that CD40 ligation is not required for generation of the light chain repertoire, positive selection of some Vk rearrangements, negative selection of specific V-L genes, and some degree of somatic mutation. importantly however, targeting of mutations to RGYW/WRCY motifs and subsequent selection of these mutated motifs does not occur in the absence of CD40 ligation. (C) 2001 Academic Press. C1 Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75235 USA. Univ Texas, SW Med Ctr, Harold C Simmons Arthrit Res Ctr, Dallas, TX 75235 USA. RP Lipsky, PE (reprint author), NIAMSD, Bldg 10,Room 9N228,10 Ctr Dr MSC 1820, Bethesda, MD 20892 USA. NR 51 TC 17 Z9 17 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD JUL PY 2001 VL 100 IS 1 BP 71 EP 81 DI 10.1006/clim.2001.5049 PG 11 WC Immunology SC Immunology GA 449RQ UT WOS:000169701300009 PM 11414747 ER PT J AU Nash, TE Ohl, CA Thomas, E Subramanian, G Keiser, P Moore, TA AF Nash, TE Ohl, CA Thomas, E Subramanian, G Keiser, P Moore, TA TI Treatment of patients with refractory giardiasis SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID PYRUVATE-FERREDOXIN OXIDOREDUCTASE; COMMON VARIABLE IMMUNODEFICIENCY; NODULAR LYMPHOID HYPERPLASIA; LINKED-IMMUNOSORBENT-ASSAY; ANTIGIARDIAL ACTIVITY; DRUG SENSITIVITY; LAMBLIA INVITRO; IMMUNE-RESPONSE; T-CELLS; METRONIDAZOLE AB Giardia lamblia is one of the most common parasitic infections. Although standard treatments are usually curative, some immunocompromised patients, including patients with acquired immunodeficiency syndrome as well as healthy patients, have giardiasis that is refractory to recommended regimens. We report our experience with 6 patients with giardiasis, for whom therapy with a combination of quinacrine and metronidazole resulted in cures for 5 of the 6 patients. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Med, Infect Dis Sect, Winston Salem, NC 27103 USA. Univ New Mexico, Dept Med, Albuquerque, NM 87131 USA. Univ Kansas, Sch Med, Dept Internal Med, Wichita, KS 67214 USA. RP Nash, TE (reprint author), NIAID, Parasit Dis Lab, NIH, 9000 Rockville Pike,Bldg 4,Room B1-01, Bethesda, MD 20892 USA. NR 60 TC 47 Z9 51 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL 1 PY 2001 VL 33 IS 1 BP 22 EP 28 DI 10.1086/320886 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 439GB UT WOS:000169101500011 PM 11389490 ER PT J AU Taga, K Taga, H Tosato, G AF Taga, K Taga, H Tosato, G TI Diagnosis of atypical cases of infectious mononucleosis SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID EPSTEIN-BARR-VIRUS; APOPTOTIC CELL-DEATH; LYMPHOCYTES; CHILDREN AB The variable manifestations of infectious mononucleosis rarely cause clinicians to suspect primary Epstein-Barr virus or cytomegalovirus infection; consequently, costly diagnostic tests and unnecessary treatments are undertaken. Seventeen cases of clinically atypical and 11 cases of clinically typical infectious mononucleosis were diagnosed through screening for atypical and apoptotic lymphocytes in the peripheral blood samples by means of an automated hematologic analyzer. Atypical and typical cases did not differ significantly with respect to peripheral white blood cell counts; percentages of lymphocytes, atypical lymphocytes, CD4(+) lymphocytes, human leukocyte antigen-DR positivity in CD3 lymphocytes, or apoptotic cells in blood smear after incubation; or levels of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase. Only the percentage of CD8(+) lymphocytes was significantly higher in patients with typical infectious mononucleosis than it was in patients with atypical infectious mononucleosis. Because certain atypical cases of infectious mononucleosis display laboratory abnormalities that are characteristic of typical infectious mononucleosis, enhanced awareness can help in the diagnosis. C1 NCI, Med Branch, NIH, Div Clin Sci, Bethesda, MD 20892 USA. Neagari Hosp, Dept Pediat, Ishikawa, Japan. Taroda Clin, Ishikawa, Japan. RP Tosato, G (reprint author), NCI, Med Branch, NIH, Div Clin Sci, Bldg 10,Rm 12C-207,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 15 TC 12 Z9 16 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL 1 PY 2001 VL 33 IS 1 BP 83 EP 88 DI 10.1086/320889 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 439GB UT WOS:000169101500020 PM 11389499 ER PT J AU Rex, JH Walsh, TJ Nettleman, M Anaissie, EJ Bennett, JE Bow, EJ Carillo-Munoz, AJ Chavanet, P Cloud, GA Denning, DW de Pauw, BE Edwards, JE Hiemenz, JW Kauffman, CA Lopez-Berestein, G Martino, P Sobel, JD Stevens, DA Sylvester, R Tollemar, J Viscoli, C Viviani, MA Wu, T AF Rex, JH Walsh, TJ Nettleman, M Anaissie, EJ Bennett, JE Bow, EJ Carillo-Munoz, AJ Chavanet, P Cloud, GA Denning, DW de Pauw, BE Edwards, JE Hiemenz, JW Kauffman, CA Lopez-Berestein, G Martino, P Sobel, JD Stevens, DA Sylvester, R Tollemar, J Viscoli, C Viviani, MA Wu, T TI Need for alternative trial designs and evaluation strategies for therapeutic studies of invasive mycoses SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; LIPOSOMAL AMPHOTERICIN-B; PLACEBO-CONTROLLED TRIAL; MULTICENTER RANDOMIZED TRIAL; LIVER-TRANSPLANT RECIPIENTS; FUNGAL-INFECTIONS; DOUBLE-BLIND; CRYPTOCOCCAL MENINGITIS; NEUTROPENIC PATIENTS; DISSEMINATED HISTOPLASMOSIS AB Studies of invasive fungal infections have been and remain difficult to implement. Randomized clinical trials of fungal infections are especially slow and expensive to perform because it is difficult to identify eligible patients in a timely fashion, to prove the presence of the fungal infection in an unequivocal fashion, and to evaluate outcome in a convincing fashion. Because of these challenges, licensing decisions for antifungal agents have to date depended heavily on historical control comparisons and secondary advantages of the new agent. Although the availability of newer and potentially more effective agents makes these approaches less desirable, the fundamental difficulties of trials of invasive fungal infections have not changed. Therefore, there is a need for alternative trial designs and evaluation strategies for therapeutic studies of invasive mycoses, and this article summarizes the possible strategies in this area. C1 Univ Texas, Sch Med, Ctr Study Emerging & Reemerging Pathogens, Dept Internal Med,Div Infect Dis, Houston, TX USA. Univ Texas, MD Anderson Canc Ctr, Dept Bioimmunotherapy, Houston, TX 77030 USA. NCI, Infect Dis Sect, Pediat Branch, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. US FDA, Div Antiviral Drug Prod, Rockville, MD 20857 USA. Virginia Commonwealth Univ, Div Gen Internal Med, Richmond, VA USA. Univ Arkansas Med Sci, Div Hematol Oncol, Little Rock, AR 72205 USA. Univ Alabama, Birmingham, AL USA. Harbor UCLA Med Ctr, Dept Med, Div Infect Dis, Torrance, CA 90509 USA. Stanford Univ, Santa Clara Valley Med Ctr, Div Infect Dis, San Jose, CA USA. Florida Hosp Med Ctr, Walt Disney Mem Canc Inst, Orlando, FL 32803 USA. Vet Adm Med Ctr, Ann Arbor, MI 48105 USA. Wayne State Univ, Sch Med, Harper Hosp, Detroit Med Ctr, Detroit, MI USA. Univ Manitoba, Hlth Sci Ctr, Winnipeg, MB, Canada. Asesoria Cient & Invest Aplicada, Dept Microbiol, Barcelona, Spain. Hosp Bocage, Dept Infect Dis, Dijon, France. Univ Manchester, Sch Med, N Manchester Gen Hosp, Dept Infect & Trop Dis, Manchester, Lancs, England. Univ Nijmegen Hosp, Dept Hematol, NL-6500 HB Nijmegen, Netherlands. Univ La Sapienza, Dept Human Biopathol, Rome, Italy. Univ Genoa, Genoa, Italy. Ist Igiene & Med Prevent, Milan, Italy. European Org Res & Treatment Canc, Cent Off, Brussels, Belgium. Huddinge Univ Hosp, Stockholm, Sweden. RP Rex, JH (reprint author), 6431 Fannin,1728 JFB, Houston, TX 77030 USA. OI Denning, David/0000-0001-5626-2251 NR 108 TC 38 Z9 39 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL 1 PY 2001 VL 33 IS 1 BP 95 EP 106 DI 10.1086/320876 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 439GB UT WOS:000169101500022 PM 11389501 ER PT J AU Powers, JH AF Powers, JH TI Counterpoint: Alternative trial designs for antifungal drugs - Time to talk SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material C1 US FDA, Div Special Pathogen & Immunol Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Powers, JH (reprint author), 9201 Corp Blvd,HFD-590, Rockville, MD 20850 USA. NR 6 TC 6 Z9 6 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL 1 PY 2001 VL 33 IS 1 BP 107 EP 109 DI 10.1086/320895 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 439GB UT WOS:000169101500023 PM 11389502 ER PT J AU Gogate, N Giedd, J Janson, K Rapoport, JL AF Gogate, N Giedd, J Janson, K Rapoport, JL TI Brain imaging in normal and abnormal brain development: new perspectives for child psychiatry SO CLINICAL NEUROSCIENCE RESEARCH LA English DT Article DE brain development; childhood schizophrenia ID ONSET SCHIZOPHRENIA; NEURONAL DENSITY; CEREBRAL-CORTEX; CROHNS-DISEASE; IN-VIVO; ADOLESCENCE; NEUROTROPHINS; PLASTICITY; DISORDER; AGE AB Non-invasive brain imaging permits the study of normal and abnormal brain development in childhood and adolescence. This paper summarizes current knowledge of brain development for healthy adolescents and for patients with childhood-onset schizophrenia (COS), a rare form of the disorder. The implications of these findings are explored. Cross-sectional and longitudinal brain magnetic resonance imaging (MRI) studies are reviewed. The pattern and temporal characteristics of anatomic brain MRI in adult-onset schizophrenia (AOS) and COS are reviewed, and discussed in terms of normal brain development and candidate mechanisms. A consistent, abnormal pattern of childhood brain development is found for COS. Normal children show non-linear regionally specific changs in gray matter volume and linear increase in white matter. COS children have smaller brain volumes due to a 10% decrease in cortical gray matter with white matter sparing. Moreover, there is a progressive loss of regional gray matter particularly in parietal. frontal and temporal regions during adolescence that is more striking for COS than that seen for AOS. In COS, developmental data are consistent with models of time limited diagnostically specific abnormalities of synaptic and dendritic production and pruning. Selected human postmortem brain and developmental animal studies relevant to such models are reviewed. (C) 2001 Association for Research in Nervous and Mental Disease. Published by Elsevier Science B.V. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RP Rapoport, JL (reprint author), NIMH, Child Psychiat Branch, Bldg 10,Room 3N202,10 Ctr Dr MSC 1600, Bethesda, MD 20892 USA. RI Gogtay, Nitin/A-3035-2008; Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 64 TC 13 Z9 14 U1 3 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1566-2772 J9 CLIN NEUROSCI RES JI Clin. Neurosci. Res. PD JUL PY 2001 VL 1 IS 4 BP 283 EP 290 AR PII S1566-2772(01)00014-7 DI 10.1016/S1566-2772(01)00014-7 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 529FC UT WOS:000174288500005 ER PT J AU Shaywitz, BA Shaywitz, SE Pugh, KR Fulbright, RK Mencl, WE Constable, RT Skudlarski, P Fletcher, JM Lyon, GR Gore, JC AF Shaywitz, BA Shaywitz, SE Pugh, KR Fulbright, RK Mencl, WE Constable, RT Skudlarski, P Fletcher, JM Lyon, GR Gore, JC TI The neurobiology of dyslexia SO CLINICAL NEUROSCIENCE RESEARCH LA English DT Article DE dyslexia; reading; functional magnetic resonance imaging; phonology; neurobiology ID POSITRON EMISSION TOMOGRAPHY; READING-DISABILITY; DEVELOPMENTAL DYSLEXIA; WORD IDENTIFICATION; PHONOLOGICAL-CORE; SEX-DIFFERENCES; BRAIN; LANGUAGE; ORGANIZATION; PERFORMANCE AB Within the last two decades overwhelming evidence from many laboratories has converged to indicate the cognitive basis for dyslexia: dyslexia represents a disorder within the language system and more specifically within a particular subcomponent of that system, phonological processing, Recent advances in imaging technology and the development of tasks which sharply isolate the subcomponent processes of reading now allow the localization of phonological processing in brain, and, as a result, provide for the first time, the potential for elucidating a biological signature for reading and reading disability. Converging evidence from a number of laboratories using functional brain imaging indicates a pattern of brain organization in dyslexia different from that seen in nonimpaired readers; specifically these studies show a disruption of left hemisphere posterior brain systems in adult dyslexic readers while performing reading tasks with an additional suggestion for an associated increased reliance on frontal lobe circuits. The discovery of neural systems serving reading has significant implications. At the most fundamental level. it is now possible to investigate specific hypotheses regarding the neural substrate of dyslexia, and to verify, reject or modify suggested cognitive models, From a more clinical perspective. the identification of neural systems for reading offers the promise for more precise identification and diagnosis of dislexia in children, adolescents and adults. (C) 2001 Association for Research in Nervous and Mental Disease. Published by Elsevier Science B.V. All rights reserved. C1 Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. Haskins Labs Inc, New Haven, CT 06511 USA. Yale Univ, Sch Med, Dept Diagnost Radiol, New Haven, CT 06510 USA. Univ Texas, Sch Med, Dept Pediat, Houston, TX USA. NICHHD, Child Behav & Learning Branch, NIH, Bethesda, MD USA. Yale Univ, Dept Appl Phys, New Haven, CT 06520 USA. RP Shaywitz, BA (reprint author), Yale Univ, Sch Med, Dept Pediat, POB 3333, New Haven, CT 06510 USA. NR 85 TC 11 Z9 11 U1 8 U2 19 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1566-2772 J9 CLIN NEUROSCI RES JI Clin. Neurosci. Res. PD JUL PY 2001 VL 1 IS 4 BP 291 EP 299 AR PII S1566-2772(01)00015-9 DI 10.1016/S1566-2772(01)00015-9 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 529FC UT WOS:000174288500006 ER PT J AU Nelson, KB AF Nelson, KB TI Toward a biology of autism: possible role of certain neuropeptides and neurotrophins SO CLINICAL NEUROSCIENCE RESEARCH LA English DT Article DE autism; neuropeptides; neurotrophins ID VASOACTIVE-INTESTINAL-PEPTIDE; SPECTRUM DISORDERS; INFANTILE-AUTISM; VIP; NEURONS; BRAIN; CHILDREN; BDNF; EXPRESSION; GROWTH AB Autism is a behaviorally defined syndrome for which there is no known biologic marker. Although autism is thought to be a disorder of brain development, there have been few efforts to study early regulators of brain development in this disorder. This paper describes a recent study of neonatal blood of children with later-diagnosed of autistic spectrum disorders comparing them with two groups of affected children, those with mental retardation without autism, or with cerebral palsy. and unaffected control children, using recycling immunoaffinity chromatography. We measured concentrations of four neuropeptides and four neurotrophins, finding that neonatal concentrations of the neuropeptides vasoactive intestinal peptide. calcitonin gone-related peptide, and the neurotrophins brain derived neurotrophic factor and neurotrophin 415 were higher in children in the autistic spectrum. and in those with mental retardation without autism, than in children with cerebral palsy or healthy control children. In 99% of children with autism and 97% with mental retardation, levels of at least one of these substances exceeded those of all control children. Concentrations were similar in subgroups of the autistic spectrum (core syndrome with or without mental retardation, other autistic spectrum disorders with or without mental retardation), and in the presence or absence of a history of regression. Two other neuropeptides and two neurotrophins were present in similar concentrations in all groups examined. Thus overexpression of certain neuropeptides and neurotrophins was observed in neonatal blood of children with later diagnoses of autism or cognitive disability. (C) 2001 Association for Research in Nervous and Mental Disease. Published by Elsevier Science B.V. C1 NINCDS, Neuroepidemiol Branch, NIH, Bethesda, MD 20892 USA. RP Nelson, KB (reprint author), NINCDS, Neuroepidemiol Branch, NIH, Bldg 10,Room 5S221, Bethesda, MD 20892 USA. NR 55 TC 5 Z9 5 U1 5 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1566-2772 J9 CLIN NEUROSCI RES JI Clin. Neurosci. Res. PD JUL PY 2001 VL 1 IS 4 BP 300 EP 306 AR PII S1566-2772(01)00016-0 DI 10.1016/S1566-2772(01)00016-0 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 529FC UT WOS:000174288500007 ER PT J AU Mirochnick, M Cooper, E Capparelli, E McIntosh, K Lindsey, J Xu, J Jacobus, D Mofenson, L Bonagura, VR Nachman, S Yogev, R Sullivan, JL Spector, SA AF Mirochnick, M Cooper, E Capparelli, E McIntosh, K Lindsey, J Xu, J Jacobus, D Mofenson, L Bonagura, VR Nachman, S Yogev, R Sullivan, JL Spector, SA TI Population pharmacokinetics of dapsone in children with human immunodeficiency virus infection SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID PNEUMOCYSTIS-CARINII PNEUMONIA; METAANALYSIS; EFFICACY; TOXICITY AB Background: Previous studies of dapsone pharmacokinetics in children have been too small to allow assessment of the relationships between dapsone pharmacokinetic parameters and patient characteristics or markers of efficacy and toxicity. Methods: We used population analysis to estimate dapsone pharmacokinetic parameters in children participating in a phase I/II study of daily and weekly dapsone in children with human immunodeficiency virus (HIV) infection. With use of the program NONMEM and a 1-compartment open model, the influence of demographic and clinical characteristics on oral clearance (CL/F) and oral volume of distribution (V/F) were examined. Measures of drug exposure (area under the concentration-time curve [AUC] and predicted concentrations just before and 2 hours after administration) were estimated for each patient and correlated with markers of efficacy and toxicity. Results: Sixty children (median age, 3 years; age range, 2 months to 12 years) contributed 412 dapsone concentrations collected after 175 study doses. Final parameter estimates were 1.40 L/kg for V/F, 0.0283 L/kg/h for CL/F, and 2.66 for the absorption rate constant. Of the clinical characteristics evaluated, dapsone CL/F was significantly increased by 50% in children taking rifabutin, by 39% in black children, and by 38% in children younger than 2 years old. Although no significant correlations were found between any dapsone exposure parameter and markers of toxicity, increased AUC was associated with a decreased risk of Pneumocystis carinii pneumonia (PCP). Conclusion: Ethnicity, age, and concomitant rifabutin use were associated with dapsone CL/F, with more rapid clearance observed in black children, children younger than 2 years old, and children receiving rifabutin. Dapsone pharmacokinetic parameters were not associated with toxicity, but higher dapsone AUC was associated with decreased risk of PCP. Monitoring of serum dapsone levels may be needed for optimal management of dapsone for PCP prophylaxis in children. C1 Boston Univ, Childrens Hosp, Sch Med, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Jacobus Pharmaceut Co Inc, Princeton, NJ USA. NICHHD, Bethesda, MD 20892 USA. N Shore Long Isl Jewish Hlth Syst, Schneider Childrens Hosp, New Hyde Park, NY USA. SUNY Stony Brook, Stony Brook, NY 11794 USA. Childrens Mem Hosp, Chicago, IL 60614 USA. Univ Massachusetts, Sch Med, Worcester, MA USA. RP Mirochnick, M (reprint author), Boston Med Ctr, Matern 6,1 Boston Med Ctr Pl, Boston, MA 02118 USA. OI Mofenson, Lynne/0000-0002-2818-9808 NR 19 TC 6 Z9 6 U1 0 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JUL PY 2001 VL 70 IS 1 BP 24 EP 32 DI 10.1067/mcp.2001.115891 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 457YN UT WOS:000170166400005 PM 11452241 ER PT J AU Dionne, RA Lepinski, AM Gordon, SM Jaber, L Brahim, JS Hargreaves, KM AF Dionne, RA Lepinski, AM Gordon, SM Jaber, L Brahim, JS Hargreaves, KM TI Analgesic effects of peripherally administered opioids in clinical models of acute and chronic inflammation SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID ARTHROSCOPIC KNEE SURGERY; INTRAARTICULAR MORPHINE; INFLAMED TISSUE; PAIN CONTROL; BUPIVACAINE; HYPERALGESIA; INVOLVEMENT; RECEPTORS; ANALOG; NERVE AB A series of double-blind, placebo-controlled clinical trials demonstrated that low doses of morphine (0.4, 1.2, and 3.6 mg) administered into the intraligamentary space of a chronically inflamed hyperalgesic tooth produced a dose-related naloxone-reversible analgesia. This analgesic effect is mediated by a local mechanism in the inflamed tissue, because subcutaneous administration of a 1.2 mg dose of morphine failed to elicit an analgesic response. In contrast, submucosal administration of 1.2 mg morphine or 50 mug fentanyl to the site of extraction of an impacted third molar after the onset of acute pain failed to elicit an analgesic response despite demonstration of a sensitive bioassay. These data indicate that peripheral opioid analgesia can be evoked in a model of chronic, but not acute, inflammatory pain, suggesting a temporal dependent mechanism needed for the expression of peripheral opiate analgesia during inflammation in humans. C1 Natl Inst Dent & Craniofacial Res, Pain & Neurosensory Mech Branch, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Sch Dent, Minneapolis, MN USA. RP Dionne, RA (reprint author), Natl Inst Dent & Craniofacial Res, Pain & Neurosensory Mech Branch, NIH, Bldg 10,Room 1N-117, Bethesda, MD 20892 USA. RI Hargreaves, Kenneth/F-5308-2010 NR 44 TC 57 Z9 60 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JUL PY 2001 VL 70 IS 1 BP 66 EP 73 DI 10.1067/mcp.2001.116443 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 457YN UT WOS:000170166400010 PM 11452246 ER PT J AU Wood, CM Warne, JM Wang, YX McDonald, MD Balment, RJ Laurent, P Walsh, PJ AF Wood, CM Warne, JM Wang, YX McDonald, MD Balment, RJ Laurent, P Walsh, PJ TI Do circulating plasma AVT and/or cortisol levels control pulsatile urea excretion in the gulf toadfish (Opsanus beta)? SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY LA English DT Article DE gulf toadfish; Opsanus beta; AVT; AVP; isotocin; cortisol; urea; UT-A urea transporter; gills ID MEDULLARY COLLECTING DUCT; ARGININE VASOTOCIN AVT; RAINBOW-TROUT; WATER PERMEABILITY; FRESH-WATER; CARDIORESPIRATORY PHYSIOLOGY; SUBCELLULAR-LOCALIZATION; BATRACHOIDID FISHES; PORICHTHYS-NOTATUS; NITROGEN-EXCRETION AB Previous work has shown that pulsatile urea excretion at the gills of the gulf toadfish is due to periodic activation of a facilitated diffusion transport system with molecular and pharmacological similarity to the UT-A transport system of the mammalian kidney. In mammals, AVP and glucocorticoids are two important endocrine regulators of this system. The present study focused on the potential role of circulating AVT (the teleost homologue of AVP) and cortisol levels as possible triggers for urea pulses. Long-term (34-84 h) monitoring of plasma levels by repetitive sampling at 2-h intervals from chronic cannulae in individual toadfish demonstrated that circulating AVT concentrations are low (10(-12)-10(-11) M), and show no relationship to the occurrence of natural urea pulses. In contrast, plasma cortisol levels decline greatly prior to natural pulses and rise rapidly thereafter. AVT injections into the caudal artery or ventral aorta elicited pulse events, but these were extremely small(1-10%) relative to natural pulses, and occurred only at unphysiological dose levels (10(-9) M in the plasma). AVP was a partial agonist, but isotocin, insulin-like growth factor-1, and atrial natriuretic peptide were without effect at the same concentration. Artificially raising plasma cortisol levels by cortisol injection tended to reduce responsiveness to AVT, Pharmacological reduction of plasma cortisol levels by metyrapone injection elicited small pulses similar to those caused by AVT. Following such pulse events, AVT was ineffective in inducing pulses. We conclude that decreases in circulating cortisol play an important permissive role in urea pulsing, but that circulating AVT levels are not involved. (C) 2001 Elsevier Science Inc. All rights reserved. C1 McMaster Univ, Dept Biol, Hamilton, ON L8S 4K1, Canada. Univ Manchester, Sch Biol Sci, Manchester M13 9PT, Lancs, England. CNRS, Dept Morphol Fonct & Ultrastruct Adaptat, Ctr Ecol & Physiol Energet, F-67037 Strasbourg, France. Univ Waterloo, Dept Kinesiol, Waterloo, ON, Canada. Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NIEHS,Marine & Freshwater Biomed Sci Ctr, Div Marine Biol & Fisheries, Miami, FL 33149 USA. RP Wood, CM (reprint author), Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NIEHS,Marine & Freshwater Biomed Sci Ctr, Div Marine Biol & Fisheries, Miami, FL 33149 USA. EM woodcm@mcmail.cis.mcmaster.ca NR 47 TC 32 Z9 32 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1095-6433 J9 COMP BIOCHEM PHYS A JI Comp. Biochem. Physiol. A-Mol. Integr. Physiol. PD JUL PY 2001 VL 129 IS 4 BP 859 EP 872 DI 10.1016/S1095-6433(01)00340-3 PG 14 WC Biochemistry & Molecular Biology; Physiology; Zoology SC Biochemistry & Molecular Biology; Physiology; Zoology GA 451EQ UT WOS:000169788500013 PM 11440872 ER PT J AU Amundson, SA Bittner, M Meltzer, P Trent, J Fornace, AJ AF Amundson, SA Bittner, M Meltzer, P Trent, J Fornace, AJ TI Physiological function as regulation of large transcriptional programs: the cellular response to genotoxic stress SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY LA English DT Article; Proceedings Paper CT 2000 Great Unknown Symposium CY 2000 CL CAMBRIDGE, ENGLAND DE gene expression; ionizing radiation; cDNA microarray; stress; p53; functional genomics; biomarkers; cancer ID ANTICANCER DRUG SCREEN; DIFFERENTIAL CYTOTOXICITY DATA; NATIONAL-CANCER-INSTITUTE; GENE-EXPRESSION PATTERNS; MOLECULAR PHARMACOLOGY; IONIZING-RADIATION; CDNA MICROARRAY; DIVERSE PANEL; P53; DNA AB The responses to ionizing radiation and other genotoxic environmental stresses are complex and are regulated by a number of overlapping molecular pathways. One such stress signaling pathway involves p53, which regulates the expression of over 100 genes already identified. It is also becoming increasingly apparent that the pattern of stress gene expression has some cell type specificity. It may be possible to exploit these differences in stress gene responsiveness as molecular markers through the use of a combined informatics and functional genomics approach. The techniques of microarray analysis potentially offer the opportunity to monitor changes in gene expression across the entire set of expressed genes in a cell or organism. As an initial step in the development of a functional genomics approach to stress gene analysis, we have recently demonstrated the utility of cDNA microarray hybridization to measure radiation-stress gene responses and identified a number of previously unknown radiation-regulated genes. The responses of some of these genes to DNA-damaging agents vary, widely in cell lines from different tissues of origin and different genetic backgrounds. While this again highlights the importance of a cellular context to genotoxic stress responses, it also raises the prospect of expression-profiling of cell lines, tissues, and tumors. Such profiles may have a predictive value if they can define regions of expression space' that correlate with important endpoints, such as response to cancer therapy regimens, or identification of exposures to environmental toxins. Published by Elsevier Science Inc. C1 NCI, Basic Res Lab, NIH, Bethesda, MD 20892 USA. RP Amundson, SA (reprint author), NCI, Basic Res Lab, NIH, Bethesda, MD 20892 USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 47 TC 38 Z9 39 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1096-4959 J9 COMP BIOCHEM PHYS B JI Comp. Biochem. Physiol. B-Biochem. Mol. Biol. PD JUL PY 2001 VL 129 IS 4 BP 703 EP 710 DI 10.1016/S1096-4959(01)00389-X PG 8 WC Biochemistry & Molecular Biology; Zoology SC Biochemistry & Molecular Biology; Zoology GA 455KM UT WOS:000170026100001 PM 11435125 ER PT J AU Chatterjee, S Dasmahapatra, AK Ghosh, R AF Chatterjee, S Dasmahapatra, AK Ghosh, R TI Disruption of pituitary-ovarian axis by carbofuran in catfish, Heteropneustes fossilis (Bloch) SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY LA English DT Article DE catfish; carbofuran; pituitary; estrogen; vitellogenin ID TROUT ONCORHYNCHUS-MYKISS; PLASMA STEROID-LEVELS; PULP-MILL EFFLUENT; RAINBOW-TROUT; WHITE SUCKER; VITELLOGENIN SYNTHESIS; OOCYTE MATURATION; CLARIAS-BATRACHUS; SALMO-GAIRDNERI; FISH AB We investigated whether carbofuran (CF), a carbamate pesticide, at sub-lethal concentration had any adverse effects on reproductive function of the Indian catfish, Heteropneustes fossilis. 17 beta -Estradiol content of serum and ovary of pre-spawning (P) and spawning (S) fish was reduced after sub-lethal concentration of carbofuran treatment (0.5-2 mg/ml, 30 days). After 30 days of CF treatment, the serum and ovarian vitellogenin levels of fish at the P stage were also reduced but remained unaltered in the S stage. The staining intensity of the pituitary gonadotrophs of the pre-spawning fish was significantly higher in CF-treated fish compared to controls suggesting the inability of the pituitary gonadotrophs to release gonadotropin following CF treatment. CF thus acts as an antiestrogenic, endocrine-disrupting agent in fish, possibly targeting the pituitary-gonad axis. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Bose Inst, Dept Anim Physiol, Kolkata 700054, W Bengal, India. Univ Wisconsin, NIEHS Marine & Freshwater Biomed Sci Ctr, Milwaukee, WI 53204 USA. RP Dasmahapatra, AK (reprint author), Bose Inst, Dept Anim Physiol, P-1-12 CIT Scheme VII-M, Kolkata 700054, W Bengal, India. EM asok@uwm.edu NR 41 TC 10 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1532-0456 EI 1878-1659 J9 COMP BIOCHEM PHYS C JI Comp. Biochem. Physiol. C-Toxicol. Pharmacol. PD JUL PY 2001 VL 129 IS 3 BP 265 EP 273 DI 10.1016/S1532-0456(01)90203-0 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Toxicology; Zoology SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Toxicology; Zoology GA 454BW UT WOS:000169953400007 PM 11461841 ER PT J AU Nicolson, R Lenane, M Brookner, F Gochman, P Kumra, S Spechler, L Giedd, JN Thaker, GK Wudarsky, M Rapoport, JL AF Nicolson, R Lenane, M Brookner, F Gochman, P Kumra, S Spechler, L Giedd, JN Thaker, GK Wudarsky, M Rapoport, JL TI Children and adolescents with psychotic disorder not otherwise specified: A 2-to 8-year follow-up study SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID CHILDHOOD-ONSET SCHIZOPHRENIA; DEFICIT HYPERACTIVITY DISORDER; BIPOLAR DISORDER; NONPSYCHOTIC CHILDREN; EMOTIONAL DISORDERS; HALLUCINATIONS; COMORBIDITY; RELIABILITY; VALIDITY; ILLNESS AB Although psychotic phenomena in children with disruptive behavior disorders are more common than expected, their prognostic significance is unknown. To examine the outcome of pediatric patients with atypical psychoses, a group of 26 patients with transient psychotic symptoms were evaluated with clinical and structured interviews at the time of initial contact (mean age, 11.6 +/- 2.7 years) and at follow-up 2 to 8 years later. Measures of functioning and psychopathology were also completed at their initial assessment. Risk factors associated with adult psychotic disorders (familial psychopathology, eyetracking dysfunction in patients and their relatives, obstetrical complications, and premorbid developmental course in the proband) had been obtained at study entry. On follow-up examination (mean age, 15.7 +/- 3.4 years), 13 patients (50%) met diagnostic criteria for a major axis I disorder: three for schizoaffective disorder, four for bipolar disorder, and six for major depressive disorder. The remaining 13 patients again received a diagnosis of psychotic disorder not other-wise specified (NOS), with most being in remission from their psychotic symptoms. Among this group who had not developed a mood or psychotic disorder, disruptive behavior disorders were exceedingly common at follow-up and were the focus of their treatment. Higher initial levels of psychopathology, lower cognitive abilities, and more developmental motor abnormalities were found in patients with a poor outcome. Obstetrical, educational, and family histories did not differ significantly between the groups. Through systematic diagnostic evaluation, children and adolescents with atypical psychotic disorders can be distinguished from those with schizophrenia, a difference with important treatment and prognostic implications. Further research is needed to delineate the course and outcome of childhood-onset atypical psychoses, but preliminary data indicate improvement in psychotic symptoms in the majority of patients and the development of chronic mood disorders in a substantial subgroup. Copyright (C) 2001 by W.B. Saunders Company. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA. RP Nicolson, R (reprint author), NIMH, Child Psychiat Branch, 10 Ctr Dr,3N202, Bethesda, MD 20892 USA. RI Giedd, Jay/A-3080-2008; Nicolson, Robert/E-4797-2011; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 52 TC 30 Z9 30 U1 1 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD JUL-AUG PY 2001 VL 42 IS 4 BP 319 EP 325 DI 10.1053/comp.2001.24573 PG 7 WC Psychiatry SC Psychiatry GA 453UM UT WOS:000169934900009 PM 11458307 ER PT J AU Kim, W Wilbur, WJ AF Kim, W Wilbur, WJ TI Amino acid residue environments and predictions of residue type SO COMPUTERS & CHEMISTRY LA English DT Article DE protein structures; protein threading; amino acid environment; residue type; naive Bayesian learning; k nearest neighbors; contact energy; precision ID PROTEIN FOLD RECOGNITION; KNOWLEDGE-BASED POTENTIALS; SEQUENCE; MODEL; TERM AB The determination of a protein's structure from the knowledge of its linear chain is one of the important problems that remains as a bottleneck in interpreting the rapidly increasing repository of genetic sequence data. One approach to this problem that has shown promise and given a measure of success is threading. In this approach contact energies between different amino acids are first determined by statistical methods applied to known structures. These contact energies are then applied to a sequence whose structure is to be determined by threading it through various known structures and determining the total threading energy for each candidate structure. That structure that yields the lowest total energy is then considered the leading candidate among all the structures tested. Additional information is often needed in order to support the results of threading studies, as it is well known in the field that the contact potentials used are not sufficiently sensitive to allow definitive conclusions. Here, we investigate the hypothesis that the environment of an amino acid residue realized as all those residues not local to it on the chain but sufficiently close spatially can supply information predictive of the type of that residue that is not adequately reflected in the individual contact energies. We present evidence that confirms this hypothesis and suggests a high order cooperativity between the residues that surround a given residue and how they interact with it. We suggest a possible application to threading. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20892 USA. RP Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Rockville Pike, Bethesda, MD 20892 USA. EM wonkim@ncbi.nlm.nih.gov NR 39 TC 2 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0097-8485 J9 COMPUT CHEM JI Comput. Chem. PD JUL PY 2001 VL 25 IS 4 SI SI BP 411 EP 422 DI 10.1016/S0097-8485(01)00075-4 PG 12 WC Chemistry, Multidisciplinary; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA 451QF UT WOS:000169812200009 PM 11459355 ER PT J AU Rao, GN Peace, TA Hoskins, DE AF Rao, GN Peace, TA Hoskins, DE TI Training could prevent deaths due to rodent gavage procedure SO CONTEMPORARY TOPICS IN LABORATORY ANIMAL SCIENCE LA English DT Letter C1 NIEHS, ACLAM, Res Triangle Pk, NC 27709 USA. NIEHS, ATB, NTP, Res Triangle Pk, NC 27709 USA. Battelle Mem Inst, ACLAM, Columbus, OH 43201 USA. So Res Inst, ACLAM, Birmingham, AL 35255 USA. RP Rao, GN (reprint author), NIEHS, ACLAM, Res Triangle Pk, NC 27709 USA. NR 1 TC 4 Z9 4 U1 0 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1060-0558 J9 CONTEMP TOP LAB ANIM JI Contemp. Top. Lab. Anim. Sci. PD JUL PY 2001 VL 40 IS 4 BP 7 EP 8 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 458KU UT WOS:000170194200002 PM 11488272 ER PT J AU Zheng, X AF Zheng, X TI A novel model for crevice corrosion of lap joints SO CORROSION LA English DT Article; Proceedings Paper CT Corrosion 99 Meeting CY APR 25-30, 1999 CL SAN ANTONIO, TEXAS DE aluminum alloys; crevice corrosion; lap joint; mass transfer ID NUMERICAL-SIMULATION; MATHEMATICAL-MODEL; INITIATION; MECHANISM; METALS AB Lap joints of aging aircraft exhibit serious corrosion because of their crevice structure. A novel model was developed for crevices in aluminum alloys with no large outside cathodes. The most distinguishing difference between lap joint crevice corrosion and conventional crevice corrosion ties in lack of a large outside cathode for a lap joint. Both oxidation and reduction must take place within the lap joint, in contrast to the dominant reduction that occurs at the large outside cathode for conventional crevice corrosion. The model was based on an oxygen reduction control process, and the possible applications of the model include lap joint corrosion of aircraft, automobiles, and building structures. C1 NCI Informat Syst Inc, Fairborn, OH 45324 USA. RP Zheng, X (reprint author), NCI Informat Syst Inc, 3150 Presidential Dr,Bldg 4, Fairborn, OH 45324 USA. NR 21 TC 2 Z9 3 U1 0 U2 1 PU NATL ASSN CORROSION ENG PI HOUSTON PA 1440 SOUTH CREEK DRIVE, HOUSTON, TX 77084-4906 USA SN 0010-9312 J9 CORROSION JI Corrosion PD JUL PY 2001 VL 57 IS 7 BP 634 EP 642 PG 9 WC Materials Science, Multidisciplinary; Metallurgy & Metallurgical Engineering SC Materials Science; Metallurgy & Metallurgical Engineering GA 565EW UT WOS:000176356900008 ER PT J AU Rad, AN Schlom, J Hodge, JW AF Rad, AN Schlom, J Hodge, JW TI Vector-driven hyperexpression of a triad of costimulatory molecules confers enhanced T-cell stimulatory capacity to DC precursors SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY LA English DT Article; Proceedings Paper CT International Conference on Advances in Cancer Immunotherapy CY MAR 02-04, 2000 CL PRINCETON, NEW JERSEY SP Garden State Canc Ctr, Hoechst Marion Roussel Inc, DEC Pharmaceut Co, Immunomedics Inc, Johnson & Johnson, Merck Res Lab, Natl Canc Inst, Natl Inst Hlth, New Jersey Commiss Canc Res, Scher Oncol Biotech DE bone marrow; costimulation; fowlpox; T cells; vaccine; vaccinia ID RECOMBINANT VACCINIA VIRUS; DENDRITIC CELLS; TUMOR-IMMUNITY; PERIPHERAL-BLOOD; LYMPHOCYTES-T; IN-VIVO; GENERATION; ICAM-1; B7; ACTIVATION AB Activation of T cells requires at least two signals: signal 1, via the T-cell receptor, and signal 2, in which a costimulatory molecule on the antigen presenting cell (APC) interacts with a ligand on the T cell. Dendritic cells (DCs) are the most potent APCs in part due to their expression of costimulatory molecules. DCs, however, constitute only a minor percentage of APCs in the body, and the in vitro preparation of DCs is both costly and time consuming. The studies reported here demonstrate that one can utilize other APCs, such as bone marrow progenitor cells (BMPCs) and make them markedly more effective as APCs; this was accomplished by their infection with recombinant poxviruses (either the replication-defective avipox or vaccinial, which contain transgenes for a triad of costimulatory molecules (B7-1, ICAM-1 and LFA-3, designated TRICOM). APCs infected with TRICOM vectors are shown to significantly enhance the activation of both naive and effector CD4(+) and CD8(+) T-cell populations. The use of TRICOM vectors in vaccine strategies is discussed. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, NIH, Room 8B07,10 Ctr Dr, Bethesda, MD 20892 USA. RI Hodge, James/D-5518-2015 OI Hodge, James/0000-0001-5282-3154 NR 29 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1040-8428 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD JUL-AUG PY 2001 VL 39 IS 1-2 BP 43 EP 57 DI 10.1016/S1040-8428(01)00123-8 PG 15 WC Oncology; Hematology SC Oncology; Hematology GA 450DC UT WOS:000169725400006 PM 11418301 ER PT J AU Newton, DL Hansen, HJ Liu, HT Ruby, D Iordanov, MS Magun, BE Goldenberg, DM Rybak, SM AF Newton, DL Hansen, HJ Liu, HT Ruby, D Iordanov, MS Magun, BE Goldenberg, DM Rybak, SM TI Specifically targeting the CD22 receptor of human B-cell lymphomas with RNA damaging agents SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY LA English DT Article; Proceedings Paper CT International Conference on Advances in Cancer Immunotherapy CY MAR 02-04, 2000 CL PRINCETON, NEW JERSEY SP Garden State Canc Ctr, Hoechst Marion Roussel Inc, DEC Pharmaceut Co, Immunomedics Inc, Johnson & Johnson, Merck Res Lab, Natl Canc Inst, Natl Inst Hlth, New Jersey Commiss Canc Res, Scher Oncol Biotech DE antibody; ribonuclease; cancer; immunotoxin; apoptosis ID VASCULAR LEAK SYNDROME; RICIN-A-CHAIN; CYTOTOXIC RIBONUCLEASE; MONOCLONAL-ANTIBODIES; GROWTH-FACTOR; P-30 PROTEIN; ANTITUMOR RIBONUCLEASE; EPITOPE SPECIFICITY; CANCER-THERAPY; N-TERMINUS AB Targeting CD22 on human B-cells with a monoclonal antibody conjugated to a cytotoxic RNAse causes potent and specific killing of the lymphoma cells in vitro. This translates to anti-tumor effects in human lymphoma models in SCID mice. RNA damage caused by RNAses could be an important alternative to standard DNA damaging chemotherapeutics. Moreover, targeted RNAses may overcome problems of toxicity and immunogenicity associated with plant or bacterial toxin containing immunotoxins. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 NCI, Frederick Canc Res & Dev Ctr, Screening Technol Branch, Dev Therapeut Program,Div Canc Treatment & Diag, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Frederick, MD 21702 USA. Immunomed, Morris Plains, NJ 07950 USA. Oregon Hlth Sci Univ, Dept Cell & Dev Biol, Portland, OR 97201 USA. Garden State Canc Ctr, Belleville, NJ 07109 USA. RP Rybak, SM (reprint author), NCI, Frederick Canc Res & Dev Ctr, Screening Technol Branch, Dev Therapeut Program,Div Canc Treatment & Diag, Bldg 567,Room 162, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000, CA-39360]; NIEHS NIH HHS [ES-08456] NR 59 TC 17 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1040-8428 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD JUL-AUG PY 2001 VL 39 IS 1-2 BP 79 EP 86 DI 10.1016/S1040-8428(01)00116-0 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 450DC UT WOS:000169725400009 PM 11418304 ER PT J AU Borst, DE Boatright, JH Si, JS Stodulkova, E Remaley, N Pallansch, LA Nickerson, JM AF Borst, DE Boatright, JH Si, JS Stodulkova, E Remaley, N Pallansch, LA Nickerson, JM TI Structural characterization and comparison of promoter activity of mouse and bovine interphotoreceptor retinoid-binding protein (IRBP) gene 5 ' flanking regions in WERI, Y79, chick retina cells, and transgenic mice SO CURRENT EYE RESEARCH LA English DT Article DE IRBP; promoter activity; retina; transgenic mice; transient transfection ID TISSUE-SPECIFIC EXPRESSION; CHLORAMPHENICOL ACETYLTRANSFERASE; RETINOBLASTOMA CELLS; MAMMALIAN-CELLS; REGULATORY ELEMENTS; MONOLAYER-CULTURES; NEURAL RETINA; RHODOPSIN; FUSION; HYPOMETHYLATION AB Purpose. To determine the sequences of the mouse and bovine interphotoreceptor retinoid-binding protein (IRBP) 5' flanking regions and whether these 5' flanking regions contain functional IRBP promoter activity in multiple cell types using both quantitative and statistical analyses. Methods. We sequenced the bovine and mouse 5' flanking regions of the IRBP gene and compared these sequences to the human gene sequence. To test for functional activity of this region, we used the same DNA construct, p1783, in four different cell types. Mobility shift, DNase footprints, and southwestern blots were used to determine where nuclear protein complexes bind the IRBP 5' flanking region. Results. The 5' Ranking regions of the bovine, human, and mouse IRBP genes exhibit sequence similarity in regions immediately adjacent to the start of transcription (roughly 350 bases in length) and also over a 220 base sequence about 1.25 to 1.50kb upstream of the transcription start site. Two different statistical approaches showed that the IRBP 5' flanking region possesses promoter activity in four different cell types. By using mobility shift, DNase I-protection experiments, and southwestern blotting, a region of about 45 bases at position -300 was identified that specifically binds a protein from the nuclei of bovine retina and Y79 cells. Conclusions. Specific DNA binding events are an essential part of IRBP promoter activity. The conservation of sequences far upstream of the transcription start suggest that unknown physiological processes remain to be understood in IRBP transcriptional regulation. C1 Emory Univ, Dept Ophthalmol, Emory Eye Ctr, Atlanta, GA 30322 USA. Uniformed Univ Hlth Sci, Dept Anat Physiol & Genet, Rockville, MD USA. NEI, Biometry & Epidemiol Program, NIH, Bethesda, MD 20892 USA. So Res Inst, Frederick, MD USA. RP Emory Univ, Dept Ophthalmol, Emory Eye Ctr, Room B5602,1365B Clifton Rd NE, Atlanta, GA 30322 USA. EM litjn@emory.edu FU NEI NIH HHS [R29 EY11726, R01 EY09378, P01 EY06360, F32 EY06403] NR 54 TC 7 Z9 7 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0271-3683 EI 1460-2202 J9 CURR EYE RES JI Curr. Eye Res. PD JUL PY 2001 VL 23 IS 1 BP 20 EP 32 DI 10.1076/ceyr.23.1.20.5419 PG 13 WC Ophthalmology SC Ophthalmology GA 492CG UT WOS:000172149300003 PM 11821982 ER PT J AU Jung, GM Masison, DC AF Jung, GM Masison, DC TI Guanidine hydrochloride inhibits Hsp104 activity in vivo: A possible explanation for its effect in curing yeast prions SO CURRENT MICROBIOLOGY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; PROTEIN HSP104; PROPAGATION; PSI+; THERMOTOLERANCE; DETERMINANT; PSI(+); STRESS; HSP70; SUP35 AB The presence of millimolar concentrations of guanidine hydrochloride (Gdn-HCl) in growth media causes efficient loss of the normally stable [PSI+] element from yeast cells. Although it has become common practice to include 5 mM Gdn-HCl in growth media to cure [PSI+] and other prions of yeast, the biochemical mechanism by which it cures is unknown. We find that 5 mM Gdn-HCl significantly reduces Hsp104-mediated basal and acquired thermotolerance. Gdn-HCl also reduced the ability of Hsp104 to restore activity of thermally denatured luciferase in vivo. The abundance of Hsp104 was not reduced in cells grown in the presence of Gdn-HCl, ruling out negative effects on expression or stability of Hsp104. We therefore conclude that Gdn-HCl inhibits Hsp104 activity in vivo. Since replication of yeast prions is dependent on Hsp104, our results suggest that Gdn-HCl cures prions by inhibiting Hsp104 activity. C1 NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Masison, DC (reprint author), NIDDKD, Lab Biochem & Genet, NIH, Bldg 8,Room 407, Bethesda, MD 20892 USA. NR 19 TC 145 Z9 149 U1 0 U2 4 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0343-8651 J9 CURR MICROBIOL JI Curr. Microbiol. PD JUL PY 2001 VL 43 IS 1 BP 7 EP 10 DI 10.1007/s002840010251 PG 4 WC Microbiology SC Microbiology GA 440LB UT WOS:000169175800002 PM 11375656 ER PT J AU Kundu, M Liu, PP AF Kundu, M Liu, PP TI Function of the inv(16) fusion gene CBFB-MYH11 SO CURRENT OPINION IN HEMATOLOGY LA English DT Article ID ACUTE MYELOID-LEUKEMIA; MYOSIN HEAVY-CHAIN; CBF-BETA-SMMHC; MULTIPLE CHROMOSOMAL TRANSLOCATIONS; FETAL LIVER HEMATOPOIESIS; FACTOR ALPHA-SUBUNIT; BINDING-FACTOR-BETA; TRANSCRIPTION FACTOR; DNA-BINDING; CHIMERIC PROTEIN AB Inv(16)(p13q22) is associated with acute myeloid leukemia subtype M4Eo, which is characterized by the presence of myelomonocytic blasts and atypical eosinophils. This chromosomal rearrangement results in the fusion of CBFB and MYH11 genes. Mouse models indicate that the fusion gene, Cbfb-MYH11, inhibits differentiation of hematopoietic cells. Although expression of Cbfb-MYH11 is not sufficient for leukemogenesis, a combination of Cbfb-MYH11 and additional mutations can lead specifically to the development of myeloid leukemia. Normally, CBF beta interacts with CBF alpha to form a transcriptionally active nuclear complex. In vitro studies indicate that expression of CBFB-MYH11 leads to sequestration of CBF alpha2 in the cytoplasm. It also has been shown to inhibit CBF-mediated transactivation, slow cell cycle progression, delay the apoptotic response to DNA damaging agents, and protect CBF alpha2 from degradation. The importance of these functions in vivo remains to be determined. (C) 2001 Lippincott Williams & Wilkins, Inc. C1 NHGRI, NIH, Bethesda, MD 20892 USA. RP Liu, PP (reprint author), NHGRI, NIH, Room 2A18,Bldg 49,49 Convent Dr, Bethesda, MD 20892 USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 48 TC 17 Z9 17 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1065-6251 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD JUL PY 2001 VL 8 IS 4 BP 201 EP 205 DI 10.1097/00062752-200107000-00004 PG 5 WC Hematology SC Hematology GA 473WD UT WOS:000171071100004 PM 11561156 ER PT J AU Tekki-Kessaris, N Woodruff, R Hall, AC Gaffield, W Kimura, S Stiles, CD Rowitch, DH Richardson, WD AF Tekki-Kessaris, N Woodruff, R Hall, AC Gaffield, W Kimura, S Stiles, CD Rowitch, DH Richardson, WD TI Hedgehog-dependent oligodendrocyte lineage specification in the telencephalon SO DEVELOPMENT LA English DT Article DE telencephalon; hedgehog signalling; oligodendrocyte; rat; mouse ID SPINAL-CORD OLIGODENDROCYTES; CENTRAL-NERVOUS-SYSTEM; PDGF ALPHA-RECEPTOR; SONIC HEDGEHOG; GROWTH-FACTOR; MONOCLONAL-ANTIBODY; PROGENITOR CELLS; NEURAL-TUBE; OPTIC-NERVE; SUBVENTRICULAR ZONE AB In the caudal neural tube, oligodendrocyte progenitors (OLPs) originate in the ventral neuroepithelium under the influence of Sonic hedgehog (SHH), then migrate throughout the spinal cord and brainstem before differentiating into myelin-forming cells, We present evidence that oligodendrogenesis in the anterior neural tube follows a similar pattern, We show that OLPs in the embryonic mouse forebrain express platelet-derived growth factor alpha-receptors (PDGFRA), as they do in more caudal regions, They first appear within a region of anterior hypothalamic neuroepithelunm that co-expresses mRNA encoding SHH, its receptor PTC1 (PTCH) and the transcription factors OLIG1, OLIG2 and SOX10. Pdgfra-positive progenitors later spread through the forebrain into areas where Shh is not expressed, including the cerebral cortex, Cyclopamine inhibited OLP development in cultures of mouse basal forebrain, suggesting that hedgehog (HPI) signalling is obligatory for oligodendrogenesis in the ventral telencephalon, Moreover, Pdgfra-positive progenitors did not appear on schedule in the ventral forebrains of Nkx2.1 null mice, which lack the telencephalic domain of Shh expression. However, OLPs did develop in cultures of Nkx2.1(-/-) basal forebrain and this was blocked by cyclopamine. OLPs also developed in neocortical cultures, even though Shh transcripts could not be detected in the embryonic cortex, Here, too, the appearance of OLPs was suppressed by cyclopamine. In keeping with these findings, we detected mRNA encoding SHH and Indian hedgehog (IHH) in both Nkx2.1(-/-) basal forebrain cultures and neocortical cultures, Overall, the data are consistent with the idea that OLPs in the telencephalon, possibly even some of those in the cortex, develop under the influence of SHH in the ventral forebrain. C1 UCL, Wolfson Inst Biomed Res, London WC1E 6AE, England. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. USDA ARS, Western Reg Res Ctr, Albany, CA 94710 USA. RP Richardson, WD (reprint author), UCL, Wolfson Inst Biomed Res, Cruciform Bldg,Gower St, London WC1E 6AE, England. EM w.richardson@ucl.ac.uk RI Richardson, William/C-1762-2008 OI Richardson, William/0000-0001-7261-2485 NR 65 TC 209 Z9 214 U1 0 U2 5 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD JUL PY 2001 VL 128 IS 13 BP 2545 EP 2554 PG 10 WC Developmental Biology SC Developmental Biology GA 454JE UT WOS:000169968800012 PM 11493571 ER PT J AU Mu, XQ Spanos, SA Shiloach, J Kimmel, A AF Mu, XQ Spanos, SA Shiloach, J Kimmel, A TI CRTF is a novel transcription factor that regulates multiple stages of Dictyostelium development SO DEVELOPMENT LA English DT Article DE transcription factor; development; gene regulation; Dictyostelium ID CELL-FATE SPECIFICATION; CAMP RECEPTOR GENE; SIGNAL-TRANSDUCTION; EXPRESSION; DIFFERENTIATION; DISCOIDEUM; KINASE; GSK3; CAR1; PKA AB During aggregation, Dictyostelium establish nanomolar oscillation waves of extracellular cAMP, but as development progresses, cells become responsive to higher, non-fluctuating concentrations of cAMP, The regulation of the promoter responsible for expression of cAMP receptor subtype 1, CAR1, during aggregation reflects these signaling variations. Transcription of CAR1 from the early, aggregation promoter is activated by cAMP pulsing, but is repressed by continuous exposure to micromolar concentrations of cAMP, Deletion and mutation analyses of this promoter had defined an element essential for cAMP-regulated expression, and mobility shift assay, DNA crosslinking and DNase I footprinting experiments had identified a nuclear protein ((CRTF) with zinc-dependent sequence binding specificity, In our study, CRTF was purified to homogeneity, peptides were sequenced and full-length cDNAs were obtained. The deduced CRTF protein is similar to 100 kDa with a C-terminal, zinc finger-like motif required for DNA binding; CRTF purified from cells, however, represents only a 40 kDa C-terminal fragment that retains DNA-binding activity. As might have been predicted if CRTF were essential for the regulation of CAR1, crtf-null strains fail to develop under standard conditions or to exhibit induced expression of CAR1 or other cAMP-regulated genes. Furthermore, crtf-nulls also fail to sporulate, even under conditions that bypass the dependence on early cAMP signaling pathways. In addition, early developmental events of crtf-null strains could be rescued with exogenous cAMP treatment, constitutive expression of CAR1 or co-development with wild-type cells; however, these treatments were insufficient to promote sporulation, This suggests a cell-autonomous role for CRTF during late development that is separate from its capacity to control CAR1 expression. Finally, ablation of CRTF promotes a precocious induction of certain cAMP-dependent gene expression pathways. We suggest that CRTF may function to help insulate distinct pathways from simultaneous and universal activation by cAMP. CRTF, thus, exhibits multiple complex and independent regulatory functions during Dictyostelium development. C1 NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Kimmel, A (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, MMDS,Bldg 50-3351, Bethesda, MD 20892 USA. RI Mu, Xiuqian/I-9146-2014 OI Mu, Xiuqian/0000-0002-8003-7529 NR 39 TC 7 Z9 9 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD JUL PY 2001 VL 128 IS 13 BP 2569 EP 2579 PG 11 WC Developmental Biology SC Developmental Biology GA 454JE UT WOS:000169968800014 PM 11493573 ER PT J AU Asmus, SE Tian, H Landis, SC AF Asmus, SE Tian, H Landis, SC TI Induction of cholinergic function in cultured sympathetic neurons by periosteal cells: Cellular mechanisms SO DEVELOPMENTAL BIOLOGY LA English DT Article DE osteoblast; periosteum; cholinergic; noradrenergic; LIF; CNTF; autonomic neurons; sympathetic neurons ID LEUKEMIA-INHIBITORY FACTOR; VASOACTIVE-INTESTINAL-PEPTIDE; RAT SWEAT GLANDS; VESICULAR ACETYLCHOLINE TRANSPORTER; NEUROTRANSMITTER PLASTICITY INVIVO; CILIARY NEUROTROPHIC FACTOR; BETA-ADRENERGIC RECEPTORS; FACTOR MESSENGER-RNA; DIFFERENTIATION FACTOR; TYROSINE-HYDROXYLASE AB Periosteum, the connective tissue surrounding bone, alters the transmitter properties of its sympathetic innervation during development in vivo and after transplantation. Initial noradrenergic properties are downregulated and the innervation acquires cholinergic and peptidergic properties. To elucidate the cellular mechanisms responsible, sympathetic neurons were cultured with primary periosteal cells or osteoblast cell lines. Both primary cells and an immature osteoblast cell line, MC3T3-E1, induced choline acetyltransferase (ChAT) activity. In contrast, lines representing marrow stromal cells or mature osteoblasts did not increase ChAT. Growth of periosteal cells with sympathetic neurons in transwell cultures that prevent direct contact between the neurons and periosteal cells or addition of periosteal cell-conditioned medium to neuron cultures induced ChAT, indicating that periosteal cells release a soluble cholinergic inducing factor. Antibodies against LIFR beta, a receptor subunit shared by neuropoietic cytokines, prevented ChAT induction in periosteal cell/neuron cocultures, suggesting that a member of this family is responsible. ChAT activity was increased in neurons grown with periosteal cells or conditioned medium from mice lacking either leukemia inhibitory factor (LIE) or LIF and ciliary neurotrophic factor (CNTF). These results provide evidence that periosteal cells influence sympathetic neuron phenotype by releasing a soluble cholinergic factor that is neither LIF nor CNTF but signals via LIFR beta. C1 Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA. Ctr Coll, Dept Biochem & Mol Biol, Danville, KY 40422 USA. RP Landis, SC (reprint author), Ctr Coll, Dept Biochem & Mol Biol, Danville, KY 40422 USA. FU NINDS NIH HHS [NS09709] NR 84 TC 24 Z9 24 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2001 VL 235 IS 1 BP 1 EP 11 DI 10.1006/dbio.2001.0282 PG 11 WC Developmental Biology SC Developmental Biology GA 449RN UT WOS:000169701100001 PM 11412023 ER PT J AU Hukriede, NA Weeks, DL Dawid, IB AF Hukriede, NA Weeks, DL Dawid, IB TI Functional characterization of the Lim1 gene during gastrulation. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NICHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. Univ Iowa, Dept Biochem, Iowa City, IA 52242 USA. RI Weeks, Daniel/F-6216-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2001 VL 235 IS 1 MA 53 BP 183 EP 183 PG 1 WC Developmental Biology SC Developmental Biology GA 449RN UT WOS:000169701100058 ER PT J AU Mishina, Y Trisha, C Kishigami, S AF Mishina, Y Trisha, C Kishigami, S TI Functional analyses of bone morphogenetic proteins (BMPs) during pattern formation and organogenesis in mouse embryos. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2001 VL 235 IS 1 MA 72 BP 187 EP 187 PG 1 WC Developmental Biology SC Developmental Biology GA 449RN UT WOS:000169701100074 ER PT J AU Chang, W ten Dijke, P Wu, DK AF Chang, W ten Dijke, P Wu, DK TI Chondrogenesis of the otic capsule during the chicken inner ear development. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NIDCD, NIH, Rockville, MD 20850 USA. Netherlands Canc Inst, Div Cellular Biochem, NL-1066 CX Amsterdam, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2001 VL 235 IS 1 MA 99 BP 193 EP 193 PG 1 WC Developmental Biology SC Developmental Biology GA 449RN UT WOS:000169701100100 ER PT J AU Miura, S Tallquist, MD Soriano, P Mishina, Y AF Miura, S Tallquist, MD Soriano, P Mishina, Y TI BMP signaling is important for mesoderm specification and regulation of neurectoderm growth in mouse embryonic development. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NIEHS, Mol Dev Biol Grp, LRDR, NIH, Res Triangle Pk, NC 27709 USA. Fred Hutchinson Canc Res Ctr, Program Dev Biol, Seattle, WA 98109 USA. Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA. RI Soriano, Philippe/E-5797-2015 OI Soriano, Philippe/0000-0002-0427-926X NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2001 VL 235 IS 1 MA 119 BP 198 EP 198 PG 1 WC Developmental Biology SC Developmental Biology GA 449RN UT WOS:000169701100118 ER PT J AU Banumathy, C Tang, Y Fox, C Mishra, B Mishra, L AF Banumathy, C Tang, Y Fox, C Mishra, B Mishra, L TI ITIH-4, a serine protease inhibitor, plays a prominent functional role in IL-6-induced hepatocyte formation. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 DVAMC, Washington, DC USA. Temple Univ, Fels Canc Inst, Philadelphia, PA 19122 USA. NHGRI, CGTB, NIH, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Dept Surg, Washington, DC 20307 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2001 VL 235 IS 1 MA 139 BP 202 EP 202 PG 1 WC Developmental Biology SC Developmental Biology GA 449RN UT WOS:000169701100135 ER PT J AU Isogai, S Lawson, ND Torrealday, S Weinstein, BM AF Isogai, S Lawson, ND Torrealday, S Weinstein, BM TI Intersomitic arteries and intersomitic veins form via distinct mechanisms. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NIH, NICHD, Genet Mol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2001 VL 235 IS 1 MA 172 BP 208 EP 208 PG 1 WC Developmental Biology SC Developmental Biology GA 449RN UT WOS:000169701100160 ER PT J AU Lawson, ND Scheer, N Pham, VN Kim, CH Chitnis, AB Campos-Ortega, JA Weinstein, BM AF Lawson, ND Scheer, N Pham, VN Kim, CH Chitnis, AB Campos-Ortega, JA Weinstein, BM TI Notch signaling is required for arterial differentiation and repression of venous cell fate during embryonic vascular development. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NIH, NICHD, LMG, Bethesda, MD USA. Univ Cologne, Inst Entwicklungsbiol, Cologne, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2001 VL 235 IS 1 MA 173 BP 208 EP 209 PG 2 WC Developmental Biology SC Developmental Biology GA 449RN UT WOS:000169701100161 ER PT J AU Brody, T Stivers, C Kuzin, A Odenwald, WF AF Brody, T Stivers, C Kuzin, A Odenwald, WF TI A cDNA screen for Drosophila genes that are dynamically expressed during the generation of embryonic neural lineages. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NIH, NINDS, Neurogenet Unit, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2001 VL 235 IS 1 MA 204 BP 215 EP 215 PG 1 WC Developmental Biology SC Developmental Biology GA 449RN UT WOS:000169701100189 ER PT J AU Kuzin, A Stivers, C Brody, T Odenwald, WF AF Kuzin, A Stivers, C Brody, T Odenwald, WF TI Nerfin-1, a member of the conserved EIN Zn-finger subfamily, is required for proper cell fate specification in the developing Drosophila nervous system. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NINDS, Neurogenet Unit, Neurochem Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2001 VL 235 IS 1 MA 203 BP 215 EP 215 PG 1 WC Developmental Biology SC Developmental Biology GA 449RN UT WOS:000169701100188 ER PT J AU Stottmann, RW Wiedman, J Mishina, Y Klingensmith, JA AF Stottmann, RW Wiedman, J Mishina, Y Klingensmith, JA TI BMP signaling in the mammalian dorsal neural tube. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA. NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2001 VL 235 IS 1 MA 223 BP 219 EP 219 PG 1 WC Developmental Biology SC Developmental Biology GA 449RN UT WOS:000169701100205 ER PT J AU Tang, Y Fox, C Danovitch, S Fleury, T Mishra, B Sidawy, A Deng, C Mishra, L AF Tang, Y Fox, C Danovitch, S Fleury, T Mishra, B Sidawy, A Deng, C Mishra, L TI Defects in TGF beta signaling by smad 4 and ELF spectrins are associated with gastric carcinogenesis. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 DVAMC, Washington, DC USA. Temple Univ, Fels Inst, Philadelphia, PA 19122 USA. George Washington Univ, Washington, DC USA. Sibley Hosp, Washington, DC USA. NHGRI, CGTB, NIH, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD USA. VA Med Ctr, Dept Surg, Washington, DC USA. Walter Reed Army Med Ctr, Dept Surg, Washington, DC 20307 USA. RI deng, chuxia/N-6713-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2001 VL 235 IS 1 MA 334 BP 243 EP 244 PG 2 WC Developmental Biology SC Developmental Biology GA 449RN UT WOS:000169701100305 ER PT J AU Levashova, ZB Plisov, SY Perantoni, AO AF Levashova, ZB Plisov, SY Perantoni, AO TI Conditionally immortalized cell line of metanephric mesenchyme. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 Natl Canc Inst, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2001 VL 235 IS 1 MA 359 BP 250 EP 250 PG 1 WC Developmental Biology SC Developmental Biology GA 449RN UT WOS:000169701100329 ER PT J AU Vogel, AM Lawson, ND Weinstein, BM AF Vogel, AM Lawson, ND Weinstein, BM TI Sonic hedgehog signaling is required for formation of the dorsal aorta. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NIH, NICHD, Mol Genet Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2001 VL 235 IS 1 MA 384 BP 255 EP 255 PG 1 WC Developmental Biology SC Developmental Biology GA 449RN UT WOS:000169701100350 ER PT J AU Rountree, RB Schoor, M Marks, M Mishina, Y Kingsley, D AF Rountree, RB Schoor, M Marks, M Mishina, Y Kingsley, D TI Tissue-specific knockout shows that BMP signaling is required for articular cartilage maintenance in vertebrate joints. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 Howard Hughes Med Inst, Dept Dev Biol, Stanford, CA 94305 USA. Stanford Univ, Stanford, CA 94305 USA. NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2001 VL 235 IS 1 MA 389 BP 256 EP 256 PG 1 WC Developmental Biology SC Developmental Biology GA 449RN UT WOS:000169701100354 ER PT J AU Loftus, SK Baxter, LL Larson, DM Pavan, WJ AF Loftus, SK Baxter, LL Larson, DM Pavan, WJ TI Expression profile analysis to dissect genetic mechanisms of neural crest development. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NIH, NHGRI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2001 VL 235 IS 1 MA 406 BP 259 EP 259 PG 1 WC Developmental Biology SC Developmental Biology GA 449RN UT WOS:000169701100367 ER PT J AU Luo, T Matsuo-Takasaki, M Sargent, TD AF Luo, T Matsuo-Takasaki, M Sargent, TD TI Regulation of ectodermal patterning in Xenopus by differential sensitivity of Dlx homeodomain genes to BMP signal attenuation. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NIH, NICHD, Genet Mol Lab, Bethesda, MD 20852 USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2001 VL 235 IS 1 MA 423 BP 263 EP 263 PG 1 WC Developmental Biology SC Developmental Biology GA 449RN UT WOS:000169701100382 ER PT J AU Tanaka, TS Ko, MSH AF Tanaka, TS Ko, MSH TI Analysis of genes differentially expressed between morula and blastocyst. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. RI Ko, Minoru/B-7969-2009 OI Ko, Minoru/0000-0002-3530-3015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2001 VL 235 IS 1 MA 440 BP 267 EP 267 PG 1 WC Developmental Biology SC Developmental Biology GA 449RN UT WOS:000169701100399 ER PT J AU Buttitta, LA Tanaka, TS Ko, MS Fan, CM AF Buttitta, LA Tanaka, TS Ko, MS Fan, CM TI Gene expression during somitogenesis. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 Carnegie Inst Washington, Dept Embryol, Washington, DC USA. NIA, Genet Lab, NIH, Bethesda, MD USA. RI Ko, Minoru/B-7969-2009 OI Ko, Minoru/0000-0002-3530-3015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2001 VL 235 IS 1 MA 442 BP 268 EP 268 PG 1 WC Developmental Biology SC Developmental Biology GA 449RN UT WOS:000169701100401 ER PT J AU Belting, HG Hauptmann, G Meyer, D Abdelilah-Seyfried, SA Chitnis, AJ Eschbach, C Thisse, C Thisse, B Soll, I Artinger, KB Driever, W AF Belting, HG Hauptmann, G Meyer, D Abdelilah-Seyfried, SA Chitnis, AJ Eschbach, C Thisse, C Thisse, B Soll, I Artinger, KB Driever, W TI spiel ohne grenzen/pou2 is required for early steps in the establishment of the zebrafish mid-/hindbrain boundary. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 Univ Freiburg, D-79104 Freiburg, Germany. Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA. NICHD, Unit Vertebrate Neural Dev, NIH, Bethesda, MD 20892 USA. IGBMC, F-67404 Illkirch, France. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2001 VL 235 IS 1 MA 482 BP 276 EP 276 PG 1 WC Developmental Biology SC Developmental Biology GA 449RN UT WOS:000169701100437 ER PT J AU Kawahara, A Dawid, IB AF Kawahara, A Dawid, IB TI The Kruppel-like factor biklf mediates erythroid cell differentiation in zebrafish. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2001 VL 235 IS 1 MA 486 BP 277 EP 277 PG 1 WC Developmental Biology SC Developmental Biology GA 449RN UT WOS:000169701100440 ER PT J AU Mueller, K Kelley, MW AF Mueller, K Kelley, MW TI Activation of FGFr3 regulates development of pillar cells in the mammalian cochlea. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NIDCD, Rockville, MD 20850 USA. NIH, Rockville, MD 20850 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2001 VL 235 IS 1 MA 519 BP 285 EP 286 PG 2 WC Developmental Biology SC Developmental Biology GA 449RN UT WOS:000169701100472 ER PT J AU Dabdoub, A Donohue, MJ Kelley, MW AF Dabdoub, A Donohue, MJ Kelley, MW TI Inhibition of protein kinase C induces supernumerary inner hair cells in the developing mammalian cochlea. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 Natl Inst Deafness & Other Commun Disorders, Sect Dev Neurosci, Rockville, MD 20850 USA. NIH, Rockville, MD 20850 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2001 VL 235 IS 1 MA 520 BP 286 EP 286 PG 1 WC Developmental Biology SC Developmental Biology GA 449RN UT WOS:000169701100473 ER PT J AU Shahabuddin, M AF Shahabuddin, M TI Drosophila as a model to study the biology of malaria transmission. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NIH, NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2001 VL 235 IS 1 MA 523 BP 286 EP 287 PG 2 WC Developmental Biology SC Developmental Biology GA 449RN UT WOS:000169701100476 ER PT J AU Roman, BL Pham, VN Childs, S Lekven, AC Neubaum, D Moon, RT Fishman, MC Weinstein, BM AF Roman, BL Pham, VN Childs, S Lekven, AC Neubaum, D Moon, RT Fishman, MC Weinstein, BM TI The zebrafish mutant violet beauregarde exhibits abnormal cranial blood vessel development due to a lesion in alk1, the gene responsible for human hereditary hemorrhagic telangiectasia type II. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NICHD, LMG, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, CVRC, Charlestown, MA 02129 USA. Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2001 VL 235 IS 1 MA 555 BP 293 EP 294 PG 2 WC Developmental Biology SC Developmental Biology GA 449RN UT WOS:000169701100505 ER PT J AU Belachew, S Yuan, XQ Gallo, V AF Belachew, S Yuan, XQ Gallo, V TI Unraveling oligodendrocyte origin and function by cell-specific transgenesis SO DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE 2 '-3 '-cyclic nucleotide 3 '-phosphodiesterase gliogenesis; green fluorescent protein; myelination; oligodendrocyte progenitor; proteolipid protein ID MYELIN PROTEOLIPID PROTEIN; CENTRAL-NERVOUS-SYSTEM; 2',3'-CYCLIC NUCLEOTIDE 3'-PHOSPHODIESTERASE; GREEN FLUORESCENT PROTEIN; VENTRAL NEURAL-TUBE; DM-20 MESSENGER-RNA; BASIC-PROTEIN; SONIC HEDGEHOG; PRECURSOR CELLS; SPINAL-CORD AB Besides the role of mature oligodendrocytes in myelin synthesis during the development of the central nervous system (CNS), the oligodendrocyte lineage also encompasses the largest pool of postnatal proliferating progenitors whose behavior in vivo remains broadly elusive in health and disease. We describe here transgenic models that allow us to track the functions and origins of such cells by using proteolipid protein and 2',3'-cyclic nucleotide T-phosphodiesterase (CNP) gene promoters to direct oligodendroglial expression of different reporters, in particular the green fluorescent protein (GFP). We emphasize that the CNP-GFP mouse, which targets the entire oligodendroglial lineage from embryonic life to adulthood, provides an outstanding tool to study the in vivo properties of oligodendrocyte progenitor cells in normal and damaged CNS. Copyright (C) 2001 S. Karger AG, Basel. C1 NICHHD, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD 20892 USA. RP Belachew, S (reprint author), NICHHD, Lab Cellular & Synapt Neurophysiol, NIH, Bldg 49,R5A-60, Bethesda, MD 20892 USA. NR 98 TC 34 Z9 34 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PD JUL-OCT PY 2001 VL 23 IS 4-5 BP 287 EP 298 DI 10.1159/000048712 PG 12 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 509GK UT WOS:000173137800004 PM 11756744 ER PT J AU Sjogren, K Wallenius, K Liu, JL Bohlooly-Y, M Pacini, G Svensson, L Tornell, J Isaksson, OGP Ahren, B Jansson, JO Ohlsson, C AF Sjogren, K Wallenius, K Liu, JL Bohlooly-Y, M Pacini, G Svensson, L Tornell, J Isaksson, OGP Ahren, B Jansson, JO Ohlsson, C TI Liver-derived IGF-I is of importance for normal carbohydrate and lipid metabolism SO DIABETES LA English DT Article ID GROWTH-FACTOR-I; INSULIN SENSITIVITY; GLUCOSE-TOLERANCE; TRANSGENIC MICE; HORMONE DEFICIENCY; INTRAVENOUS GLUCOSE; POSTNATAL-GROWTH; GENE-EXPRESSION; LARON-SYNDROME; PLASMA LEPTIN AB IGF-I is important for postnatal body growth and exhibits Insulin-like effects on carbohydrate metabolism. The function of liver-derived IGF-I is still not established, although we previously demonstrated that liver-derived IGF-I is not required for postnatal body growth, Mice whose IGF-I gene in the liver was inactivated at 24 days of age were used to investigate the long-term role of liver-derived IGF-I for carbohydrate and lipid metabolism. Serum levels of leptin in these mice were increased by >100% at 3 months of age, whereas the fat mass of the mice was decreased by 25% at 13 months of age. The mice became markedly hyperinsulinemic and yet normoglycemic, indicating an adequately compensated insulin resistance. Furthermore, they had increased serum levels of cholesterol, We conclude that; liver-derived IGF-I is of importance for carbohydrate and lipid metabolism. C1 Sahlgrens Univ Hosp, Dept Internal Med, Res Ctr Endocrinol & Metab, Gothenburg, Sweden. Univ Gothenburg, Dept Physiol, Gothenburg, Sweden. Astrazeneca R&D, Molndal, Sweden. Univ Lund, Dept Med, Malmo, Sweden. NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Natl Res Council, Inst Syst Sci & Biomed Engn, Padua, Italy. RP Isaksson, OGP (reprint author), Sahlgrenska Hosp, Res Ctr Endocrinol & Metab, Dept Internal Med, SE-41345 Gothenburg, Sweden. RI Liu, Jun-Li/A-1501-2008 NR 48 TC 87 Z9 90 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 2001 VL 50 IS 7 BP 1539 EP 1545 DI 10.2337/diabetes.50.7.1539 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 447LX UT WOS:000169575800004 PM 11423474 ER PT J AU Lindsay, RS Krakoff, J Hanson, RL Bennett, PH Knowler, WC AF Lindsay, RS Krakoff, J Hanson, RL Bennett, PH Knowler, WC TI Gamma globulin levels predict type 2 diabetes in the Pima Indians population SO DIABETES LA English DT Article ID INSULIN-RESISTANCE; IMMUNE-SYSTEM; INFLAMMATION; MELLITUS; DISEASE; ATHEROSCLEROSIS; MAGNITUDE; MARKERS; ADULTS; RISK AB It has been proposed that inflammation or infection may contribute to the development of type 2 diabetes. We examined whether serum gamma globulin, a nonspecific measure of the humoral immune system, predicted changes in glucose tolerance in 2,530 members of the Pima Indian population, a group with a marked predisposition to type 2 diabetes. Cross-sectionally, gamma globulin,was positively related to age (r = 0.08, P < 0.0005), BMI (r = 0.09; P < 0.0001), and female sex (P < 0.0001). Gamma globulin concentrations were familial, being positively correlated among siblings (r = 0.23; P < 0.0001) and between parents and their children (mother/child: r = 0.17, P < 0.0001; father/child: r = 0.25, P < 0.0001). Gamma globulin concentrations were higher with greater degrees of American Indian heritage (P < 0.004, with adjustment for age, sex, and BMI) and in the presence of a family history of type 2 diabetes (P < 0.04). Higher gamma globulin levels predicted risk of diabetes. In univariate analysis, a 1 SD difference in gamma globulin was associated with a 20%, higher incidence of diabetes in those who were normal glucose tolerant at baseline (hazard rate ratio 1.20 [CI 1.11-1.30]; P < 0.0001) and remained as a significant predictor of diabetes, even when controlled for effects of sex, BMI,and 2-h glucose as additional predictors (hazard rate ratio for 1 SD difference in gamma globulin, 1.14 [1.05-1.24]; P = 0.002). Gamma globulin was also associated in univariate analysis with later development of impaired glucose tolerance (IGT) (hazard rate ratio 1.15 [1.07-1.23]; P < 0.0001), but not with the transition from IGT to diabetes (hazard rate ratio 1.04 [0.90-1.20]; P = 0.6). Thus, gamma globulin levels predict increased risk of diabetes in the Pima population. We suggest that immune function or activation may play a role in the development of type 2 diabetes. C1 NIDDKD, NIH, Phoenix, AZ 85014 USA. RP Lindsay, RS (reprint author), NIDDKD, NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 28 TC 43 Z9 49 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 2001 VL 50 IS 7 BP 1598 EP 1603 DI 10.2337/diabetes.50.7.1598 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 447LX UT WOS:000169575800011 PM 11423481 ER PT J AU Jovanovic, L Knopp, RH Brown, Z Conley, MR Park, E Mills, JL Metzger, BE Aarons, JH Holmes, LB Simpson, JL AF Jovanovic, L Knopp, RH Brown, Z Conley, MR Park, E Mills, JL Metzger, BE Aarons, JH Holmes, LB Simpson, JL CA Nalt Inst Child Hlth Human Dev Dia TI Declining insulin requirement in the late first trimester of diabetic pregnancy SO DIABETES CARE LA English DT Article ID GLUCOSE-TOLERANCE; WOMEN; INFANTS; MOTHERS AB OBJECTIVE - To investigate whether pregnancies complicated by type 1 diabetes are associated with a decrease in first-trimester insulin requirement. RESEARCH DESIGN AND METHODS - We examined the weekly insulin requirement (as units per kilogram per day) during the first trimester of pregnancy in diabetic women in the Diabetes in Early Pregnancy Study (DIEP) viith accurate gestational dating, regular glucose monitoring, daily insulin-dose recording, and monthly glycohemoglobin measurements. RESULTS - In pregnancies that resulted in live-born full-term singleton infants, a significant 18% increase in mean weekly dosage was observed between weeks 3 and 7 (P = 0.000), followed by a significant 9% decline from week 7 through week 15 (P = 0.000). Further testing localized a significant change in insulin dose in the interval beginning weeks 7-8 and ending weeks 11-12 (P = 0.014). Within this interval, the maximum decrease was between weeks 9 and 10 (mean), 10 and Il (median), and 8 and 9 (most frequent maximal decrease). To determine whether prior poor glucose control exaggerated these trends, we categorized the women based on their glycohemoglobin values: <2 SDs above the mean of a normal population (subgroup 1), 2-4 SDs (subgroup 2), and >4 SDs (subgroup 3) at baseline. Late first-trimester declines in dosage were statistically significant in subgroup 2 (P = 0.002) and subgroups 2 and 3 together (P = 0.003). Similarly, women with BMI > 27.0 had a greater initial insulin rise and then fall compared with leaner women. CONCLUSIONS - Observations in the DIEP cohort disclose a mid-first-trimester decline in insulin requirement in type 1 diabetic pregnant women. Possible explanations include over-insulinization of previously poorly controlled diabetes, a transient decline in progesterone secretion during the late first-trimester luteo-placental shift in progesterone secretion, or other hormonal shifts. Clinicians should anticipate a clinically meaningful reduction in insulin requirement in the 5-week interval between weeks 7 and 12 of gestation. C1 Sansum Med Res Inst, Santa Barbara, CA 93105 USA. Univ Washington, NW Lipid Res Clin, Seattle, WA 98195 USA. Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. NICHHD, Epidemiol Branch, Bethesda, MD 20892 USA. NICHHD, Biometry Branch, Bethesda, MD 20892 USA. Northwestern Univ, Sch Med, Chicago, IL 60611 USA. Univ Pittsburgh, Magee Womens Hosp, Dept Med, Pittsburgh, PA 15213 USA. Massachusetts Gen Hosp, Genet & Teratol Unit, Boston, MA 02114 USA. Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. RP Jovanovic, L (reprint author), Sansum Med Res Inst, 2219 Bath St, Santa Barbara, CA 93105 USA. FU NCRR NIH HHS [RR-00037-28, RR-48]; PHS HHS [CRC R0047] NR 29 TC 36 Z9 39 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUL PY 2001 VL 24 IS 7 BP 1130 EP 1136 DI 10.2337/diacare.24.7.1130 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 446NU UT WOS:000169520000002 PM 11423491 ER PT J AU Galluzzi, JR Cupples, LA Meigs, JB Wilson, PWF Schaefer, EJ Ordovas, JM AF Galluzzi, JR Cupples, LA Meigs, JB Wilson, PWF Schaefer, EJ Ordovas, JM TI Association of the ala54-thr polymorphism in the intestinal fatty acid-binding protein with 2-h postchallenge insulin levels in the Framingham Offspring Study SO DIABETES CARE LA English DT Article ID CORONARY HEART-DISEASE; CANDIDATE GENES; GLUCOSE-TOLERANCE; CODON-54 POLYMORPHISM; DIABETES-MELLITUS; MEXICAN-AMERICANS; JAPANESE SUBJECTS; OBESE SUBJECTS; PIMA-INDIANS; RAT-LIVER AB OBJECTIVE - To investigate the association of variants of the intestinal fatty acid-binding protein gene (FABP2) with Easting and postchallenge glucose and insulin levers, HbA(1c), and prevalence of type 2 diabetes in a separate sample of men and women. RESEARCH DESIGN AND METHODS - Subjects were participants in the Framingham Offspring Study, a long-term community-based prospective observational study of risk factors for cardiovascular disease. The study sample consisted of 762 men and 922 women. RESULTS - In women, carriers of the thr54 allele had significantly higher 2-h postchallenge insulin levels than noncarriers (104.4 +/- 73.0 vs. 93.4 +/- 61.5 muU/ml; P = 0.0139). This relationship remained significant after adjustment for familial relationship, age, BMI, triglycerides, APOE genotype, smoking, alcohol intake, the use of P-blockers, menopausal status, and estrogen therapy. No such significant association was observed in men. In both men and women, there were no statistical associations between the FABP2 polymorphism and BMI, fasting glucose, fasting insulin, 2-h postchallenge glucose levels, HbA(1c), and prevalence of type 2 diabetes. CONCLUSIONS - These results suggest that the FABP2 thr54 allele may have a minor contribution to the insulin resistance syndrome in a white general population. C1 Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Lipid Metab Lab, Boston, MA 02111 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Gen Internal Med, Boston, MA 02114 USA. NHLBI, Framington Heart Study, Framingham, MA USA. RP Galluzzi, JR (reprint author), Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Lipid Metab Lab, 711 Washington St, Boston, MA 02111 USA. OI Ordovas, Jose/0000-0002-7581-5680 FU NHLBI NIH HHS [HL54776]; NIA NIH HHS [AG00209-09] NR 47 TC 33 Z9 33 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUL PY 2001 VL 24 IS 7 BP 1161 EP 1166 DI 10.2337/diacare.24.7.1161 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 446NU UT WOS:000169520000007 PM 11423496 ER PT J AU Kriska, AM Pereira, MA Hanson, RL de Courten, MP Zimmet, PZ Alberti, KGMM Chitson, P Bennett, PH Narayan, KMV Knowler, WC AF Kriska, AM Pereira, MA Hanson, RL de Courten, MP Zimmet, PZ Alberti, KGMM Chitson, P Bennett, PH Narayan, KMV Knowler, WC TI Association of physical activity and serum insulin concentrations in two populations at high risk for type 2 diabetes but differing by BMI SO DIABETES CARE LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; PIMA-INDIANS; FASTING INSULIN; YOUNG-ADULTS; RESISTANCE; WOMEN; SENSITIVITY; INTOLERANCE; INACTIVITY; SECRETION AB OBJECTIVE - Physical activity and insulin sensitivity are related in epidemiological studies, but the consistency of this finding among populations that greatly differ in body size is uncertain. The present multiethnic epidemiological study examined whether physical activity was related to insulin concentrations in two populations at high risk for diabetes that greatly differ by location, ethnic group, and BMI. RESEARCH DESIGN AND METHODS - The study populations consisted of 2,321 nondiabetic Pima Indian men and women aged 15-59 years from Arizona and 2,716 nondiabetic men and women aged 35-54 years from Mauritius. Insulin sensitivity was estimated by mean insulin concentration (average of the fasting and postload insulin), and total (i.e., leisure and occupational) physical activity was assessed by questionnaire. RESULTS - Pima men and women who were more active had significantly (P < 0.05) lower mean insulin concentrations than those less active (BMI and age-adjusted means were 179 vs. 200 and 237 vs. 268 pmol/l). Similar findings were noted in Mauritian men and women (94 vs. 122 and 127 vs. 148 pmol/l). In both populations, activity remained significantly associated with mean insulin concentration controlled for age, BMI, waist-to-thigh or waist-to-hip ratio, and mean glucose concentrations. CONCLUSIONS - Physical activity was negatively associated with insulin concentrations both in the Pima Indians, who tend to be overweight, and in Mauritians, who are leaner. These findings suggest a beneficial role of activity on insulin sensitivity that is separate from any influence of activity on body composition. C1 Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. NIDDKD, Diabet & Arthrit Epidemiol Sect, Phoenix, AZ USA. Univ Newcastle Upon Tyne, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. Ctr Dis Control & Prevent, Atlanta, GA USA. RP Kriska, AM (reprint author), Univ Pittsburgh, GSPH, 130 DeSoto St, Pittsburgh, PA 15261 USA. RI Narayan, K.M. Venkat /J-9819-2012; Hanson, Robert/O-3238-2015; de Courten, Maximilian/B-3300-2012 OI Narayan, K.M. Venkat /0000-0001-8621-5405; Hanson, Robert/0000-0002-4252-7068; de Courten, Maximilian/0000-0001-9997-9359 FU NIDDK NIH HHS [DK-25446, R01 DK-43394-06A1] NR 31 TC 40 Z9 42 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUL PY 2001 VL 24 IS 7 BP 1175 EP 1180 DI 10.2337/diacare.24.7.1175 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 446NU UT WOS:000169520000009 PM 11423498 ER PT J AU Barzilay, JI Spiekerman, CF Kuller, LH Burke, GL Bittner, V Gottdiener, JS Brancati, FL Orchard, TJ O'Leary, DH Savage, PJ AF Barzilay, JI Spiekerman, CF Kuller, LH Burke, GL Bittner, V Gottdiener, JS Brancati, FL Orchard, TJ O'Leary, DH Savage, PJ TI Prevalence of clinical and isolated subclinical cardiovascular disease in older adults with glucose disorders - The Cardiovascular Health Study SO DIABETES CARE LA English DT Article ID ANKLE-ARM INDEX; DIABETES-MELLITUS; RISK FACTOR; MYOCARDIAL-INFARCTION; ARTERY DISEASE; ATHEROSCLEROSIS; ASSOCIATION; MORTALITY AB OBJECTIVE - Clinical cardiovascular disease (CVD) is highly prevalent among people with diabetes. However, there is little information regarding the prevalence of subclinical CVD and its relation to clinical CVD in diabetes and in the glucose disorders that precede diabetes. RESEARCH DESIGN AND METHODS - Participants in the Cardiovascular Health Study, aged greater than or equal to 65 years (n = 5,888), underwent vascular and metabolic testing. Individuals with known disease in the coronary, cerebral, or peripheral circulations were considered to have clinical disease. Those without any clinical disease in whom CVD was detected by ultrasonography, electrocardiography, or ankle arm index in any of the three vascular beds were considered to have isolated subclinical disease. RESULTS - Approximately 30% of the cohort had clinical disease, and similar to 60% of the remainder had isolated subclinical disease. In those with normal glucose status, isolated subclinical disease made up most of the total CVD. With increasing glucose severity, the proportion of total CVD that was clinical disease increased; 75% of men and 66% of women with normal fasting glucose status had either clinical or subclinical CVD. Among those with known diabetes, the prevalence was similar to 88% (odds ratio [OR] 2.46 for men and 4.22 for women, P < 0.0001). There were intermediate prevalences and ORs for those with impaired fasting glucose status and newly diagnosed diabetes. CONCLUSIONS - Isolated subclinical CVD is common among older adults. Glucose disorders are associated with an increased prevalence of total CVD and an increased proportion of clinical disease relative to subclinical disease. C1 Kaiser Permanente Georgia, Div Endocrinol, Tucker, GA 30084 USA. Emory Univ, Sch Med, Div Endocrinol, Atlanta, GA USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27103 USA. Univ Alabama, Dept Cardiovasc Dis, Birmingham, AL USA. St Francis Hosp, Dept Cardiol, Roslyn, NY USA. Johns Hopkins Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Tufts Univ, New England Med Ctr, Dept Radiol, Boston, MA 02111 USA. NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. RP Barzilay, JI (reprint author), Kaiser Permanente Georgia, Div Endocrinol, 200 Crescent Ctr Pkwy, Tucker, GA 30084 USA. OI orchard, trevor/0000-0001-9552-3215 NR 19 TC 61 Z9 65 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUL PY 2001 VL 24 IS 7 BP 1233 EP 1239 DI 10.2337/diacare.24.7.1233 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 446NU UT WOS:000169520000019 PM 11423508 ER PT J AU Hanson, RL Imperatore, G Narayan, KMV Roumain, J Fagot-Campagna, A Pettitt, DJ Bennett, PH Knowler, WC AF Hanson, RL Imperatore, G Narayan, KMV Roumain, J Fagot-Campagna, A Pettitt, DJ Bennett, PH Knowler, WC TI Family and genetic studies of indices of insulin sensitivity and insulin secretion in Pima Indians SO DIABETES-METABOLISM RESEARCH AND REVIEWS LA English DT Article; Proceedings Paper CT 58th Annual Meeting and Scientific Session of the American-Diabetes-Association CY JUN 13-16, 1998 CL CHICAGO, IL SP Amer Diabet Assoc DE diabetes; type 2; genetics; inheritance; insulin sensitivity; insulin secretion; linkage ID DEPENDENT DIABETES-MELLITUS; AUTOSOMAL GENOMIC SCAN; GLUCOSE-TOLERANCE; LINKAGE ANALYSIS; METABOLIC ABNORMALITIES; MATHEMATICAL APPROACH; SUSCEPTIBILITY GENES; VARIANCE-COMPONENTS; COMPLEX TRAITS; NIDDM AB Background The present analyses were conducted to examine the extent to which insulin sensitivity and insulin secretion, assessed using simple indices derived from an oral glucose tolerance test, are influenced by genetic factors, and to assess whether these genetic factors overlap with those influencing susceptibility to type 2 diabetes in Pima Indians. Methods Indices calculated from fasting and 2-h post-load insulin (I(0), I(120)) and glucose (G(0), G(120)) concentrations included insulin sensitivity index [ISI(0) = 10(4)/(I(0).G(0))] and corrected insulin response {CIR(120)=I(120)/[G(120).(G(120)-70mg/dl)]}. Heritability (h(2)) was determined using variance components methods in 1421 non-diabetic individuals from 446 sibships. Among 595 individuals in 186 sibships, genome-wide quantitative trait linkage analyses of ISI(0) and CIR(120) were conducted and affected-sibling analyses of diabetic siblings stratified by prediabetic measurements of ISI(0) and CIR(120) were also performed. Results Both ISI(0) (h(2) = 0.37 +/-0.06) and CIR(120) (h(2) = 0.25 +/-0.07) were moderately heritable. Modest evidence for linkage with CIR120 (logarithm of odds (LOD) = 1.6) was observed on chromosome 1q in a region previously shown to have linkage with young-onset diabetes in Pimas. When diabetic siblings were stratified by CIR120, evidence for linkage in this region was strongest (LOD = 1.5) among those with a low CIR(120). Additional regions with modest evidence for linkage with ISI(0) were observed on chromosomes 9p (LOD = 2.0) and 14p (LOD = 1.7). Conclusions The present analyses suggest that insulin sensitivity and insulin secretion are influenced by genetic factors in Pima Indians. The linkage analyses suggest that the putative diabetes-susceptibility gene on chromosome Iq affects insulin secretion. Published in 2001 by John Wiley & Sons, Ltd. C1 NIDDKD, Diabet & Arthritis Epidemiol Sect, Phoenix, AZ 85014 USA. RP Hanson, RL (reprint author), NIDDKD, Diabet & Arthritis Epidemiol Sect, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. EM rhanson@phx.niddk.nih.gov RI Narayan, K.M. Venkat /J-9819-2012; Hanson, Robert/O-3238-2015 OI Narayan, K.M. Venkat /0000-0001-8621-5405; Hanson, Robert/0000-0002-4252-7068 NR 53 TC 27 Z9 28 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1520-7552 J9 DIABETES-METAB RES JI Diabetes-Metab. Res. Rev. PD JUL-AUG PY 2001 VL 17 IS 4 BP 296 EP 303 DI 10.1002/dmrr.213.abs PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 469TY UT WOS:000170833200007 PM 11544614 ER PT J AU Fetsch, PA Filie, AC Steinberg, SM Abati, A AF Fetsch, PA Filie, AC Steinberg, SM Abati, A TI Comparison of antibodies to MART-1 and MelanA in fine-needle aspiration samples of metastatic malignant melanoma SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Letter ID A103 C1 NCI, Cytopathol Sect, NIH, Bethesda, MD 20892 USA. RP Fetsch, PA (reprint author), NCI, Cytopathol Sect, NIH, Bethesda, MD 20892 USA. NR 7 TC 7 Z9 7 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD JUL PY 2001 VL 25 IS 1 BP 78 EP 79 DI 10.1002/dc.2007 PG 2 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 448YG UT WOS:000169657100012 PM 11466819 ER PT J AU Yamanaka, R Blumenthal, R Lorenzi, MV Tatsumoto, T Miki, T AF Yamanaka, R Blumenthal, R Lorenzi, MV Tatsumoto, T Miki, T TI Ostip2, a novel oncoprotein that associates with the Rho exchange factor Ost SO DNA AND CELL BIOLOGY LA English DT Article ID 2-HYBRID SYSTEM; ONCOGENE; NUCLEOTIDE AB The ost protooncogene encodes a guanine nucleotide exchange factor for the Rho family of small GTPases, RhoA and Cdc42. The N-terminal domain of Ost (Ost-N) appears to negatively regulate the oncogenic activity of the protein, as deletion of this domain drastically increases its transforming activity in NIH 3T3 cells. Using a yeast two-hybrid system, we identified five genes encoding proteins that can interact with Ost-N. One of them, designated OSTIP2 (Ost interacting protein 2), encoded a previously uncharacterized protein. The OSTIP2 product is highly expressed in skeletal muscle as a 1.2-kb transcript. Full-length OSTIP2 cDNA contained an ORF of 193 amino acids. Transcription-coupled translation of OSTIP2 cDNA in reticulocyte lysates revealed a protein product of 20 kDa, which corresponded to the predicted size of the protein. Bacterially expressed glutathione S-transferase (GST)-Ostip2 fusion protein efficiently associated in vitro with baculovirus-expressed Ost. Interestingly, expression of Ostip2 in NIH 3T3 cells efficiently induced foci of morphologically transformed cells. Moreover, inoculation of athymic (nude) mice with OSTIP2 transfectants strongly induced tumor formation. These results suggest that Ostip2 is a novel oncoprotein that can interact with the Rho exchange factor Ost. C1 NCI, Mol Tumor Biol Sect, Basic Res Lab, Bethesda, MD 20892 USA. NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. RP Miki, T (reprint author), NCI, Mol Tumor Biol Sect, Basic Res Lab, Bldg 37,Room 1E24,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 15 TC 1 Z9 1 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD JUL PY 2001 VL 20 IS 7 BP 383 EP 390 DI 10.1089/104454901750361442 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 460EW UT WOS:000170296100001 PM 11506702 ER PT J AU Wall, W Chan, K El Rassi, M AF Wall, W Chan, K El Rassi, M TI Electrically driven microseparation methods for pesticides and metabolites: VI. Surfactant-mediated electrokinetic capillary chromatography of aniline pesticidic metabolites derivatized with 9-fluoroenylmethyl chloroformate and their detection by laser-induced fluorescence SO ELECTROPHORESIS LA English DT Article; Proceedings Paper CT 3rd International Symposium on Capillary Electrophoresis and Related Microscale Techniques (APCE 2000) CY JUN 14-17, 2000 CL HONG KONG, PEOPLES R CHINA DE anilines; pesticidic metabolites; capillary electrophoresis; capillary electrokinetic chromatography; precolumn derivatization; 9-fluoroenylmethyl chloroformate; laser-induced fluorescence ID AMINO-ACIDS; 9-FLUORENYLMETHYL CHLOROFORMATE; ELECTROPHORESIS AB In this report, we describe a surfactant-mediated electrokinetic capillary chromatography (SM-EKC) system for the separation of 9-fluoroenylmethyl chloroformate (FMOC)-derivatized anilines by capillary electrophoresis (CE). The SM-EKC system consisted of dioctyl sulfosuccinate (DOSS)/acetonitrile mixtures and was suited for the CE separation of the relatively hydrophobic FMOC-aniline analytes and other neutral compounds, e.g. alkylphenyl ketones. While the organic modifier acetonitrile (ACN) allowed the solubilization of the hydrophobic solutes and maintained the DOSS surfactant in its monomeric form by inhibiting micellization, the DOSS surfactant associated with the FMOC anilines to a varying degree thus leading to their differential migration and separation. Under these conditions, the FMOC-anilines were readily detected at the 10(-6) M level by UV at 214 nm and at the 10(-8) M level by laser-induced fluorescence (LIF) using a solid-state UV laser operating at 266 nm line as the excitation wavelength. The FMOC precolumn derivatization was also readily performed in lake water spiked with anilines at near the limit of detection (LOD) level. The lake water matrix showed no significant effects on the extent of derivatization at the LOD level as well as on the detection of the analytes due to the selectivity of the FMOC derivatization. The derivatization and detection of spiked lake water necessitated only the removal of microparticles by microfiltration prior to derivatization and detection. C1 Oklahoma State Univ, Dept Chem, Stillwater, OK 74078 USA. NCI, SAIC Frederick, Frederick, MD USA. RP El Rassi, M (reprint author), Oklahoma State Univ, Dept Chem, Stillwater, OK 74078 USA. NR 11 TC 19 Z9 20 U1 1 U2 10 PU WILEY-V C H VERLAG GMBH PI BERLIN PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD JUL PY 2001 VL 22 IS 11 BP 2320 EP 2326 DI 10.1002/1522-2683(20017)22:11<2320::AID-ELPS2320>3.0.CO;2-O PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 458CN UT WOS:000170175800028 PM 11504068 ER PT J AU Esposito, DL Li, YH Cama, A Quon, MJ AF Esposito, DL Li, YH Cama, A Quon, MJ TI Tyr(612) and Tyr(632) in human insulin receptor substrate-1 are important for full activation of insulin-stimulated phosphatidylinositol 3-kinase activity and translocation of GLUT4 in adipose cells SO ENDOCRINOLOGY LA English DT Article ID DEPENDENT DIABETES-MELLITUS; AMINO-ACID POLYMORPHISM; SH2 DOMAINS; IRS-1 GENE; TYROSINE PHOSPHORYLATION; GLUCOSE-TRANSPORT; YMXM MOTIFS; BETA-CELLS; MICE; EXPRESSION AB To examine contributions of specific YXXM motifs in human insulin receptor substrate-1 (IRS-1) to mediating the metabolic actions of insulin, we studied IRS-1 mutants containing various substitutions of Phe for Tyr. In transfected NIH-3T3(IR) cells, insulin stimulation caused a 5-fold increase in phosphatidylinositol 3-kinase (PI3K) activity coimmunoprecipitated with wild-type IRS-1. No PI3K activity was associated with IRS1-F6 (Phe substituted for Tyr at positions 465, 612, 632, 662, 941, and 989). Adding back both Tyr(612) and Tyr(632) fully restored IRS-l-associated PI3K activity, whereas adding back either Tyr(612) or Tyr(632) alone was associated with intermediate PI3K activity. In rat adipose cells transfected with epitope-tagged GLUT4, insulin stimulation caused a a-fold increase in cell surface GLUT4-HA. Cotransfection of cells with GLUT4-HA and either wild-type IRS-1 or IRS1-Y612/Y632 increased basal cell surface GLUT4-HA (in the absence of insulin) to approximately 80% of the levels seen in insulin-stimulated control cells, whereas overexpression of IRS1-F6 had no effect on the insulin dose-response curve. Overexpression of IRS1-Y612 or IRS1-Y632 caused intermediate effects. Thus, both Tyr(612) and Tyr(632) are important for IRS-1 to fully activate PI3K and mediate translocation of GLUT4 in response to insulin. C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. Univ G Dannunzio, Dept Oncol & Neurosci, I-66013 Chieti, Italy. RP Quon, MJ (reprint author), NHLBI, Cardiol Branch, NIH, Bldg 10,Room 8C-218,10 Ctr Dr,MSC 1755, Bethesda, MD 20892 USA. RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 NR 48 TC 96 Z9 99 U1 0 U2 4 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 2001 VL 142 IS 7 BP 2833 EP 2840 DI 10.1210/en.142.7.2833 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 445XX UT WOS:000169484800014 PM 11416002 ER PT J AU Javitt, NB Lee, YC Shimizu, C Fuda, H Strott, CA AF Javitt, NB Lee, YC Shimizu, C Fuda, H Strott, CA TI Cholesterol and hydroxycholesterol sulfotransferases: Identification, distinction from dehydroepiandrosterone sulfotransferase, and differential tissue expression SO ENDOCRINOLOGY LA English DT Article ID HUMAN CYTOSOLIC SULFOTRANSFERASES; PROTEIN-KINASE-C; MOLECULAR-CLONING; HUMAN LIVER; CDNA CLONING; HYDROXYSTEROID SULFOTRANSFERASE; MITOCHONDRIAL CYTOCHROME-P-450; FUNCTIONAL-CHARACTERIZATION; STRUCTURAL CHARACTERIZATION; ESTROGEN SULFOTRANSFERASE AB In humans, the biotransformation of cholesterol and its hydroxylated metabolites (oxysterols) by sulfonation is a fundamental process of great importance. Nevertheless, the sulfotransferase enzyme(s) that carries out this function has never been clearly identified. Cholesterol is a relatively poor substrate for the previously cloned hydroxysteroid sulfotransferase (HST), i.e. dehydroepiandrosterone (DHEA) sulfotransferase (HST1). Recently, cloning of a single human gene that encodes for two proteins related to HST1 was reported. These newly cloned sulfotransferases (HST2a and HST2b), while exhibiting sequence similarity to other members of the soluble sulfotransferase superfamily, also contain unique structural features. This latter aspect prompted an examination of their substrate specificity for comparison with HST1. Thus, HST1, HST2a, and HST2b were overexpressed as fusion proteins and purified. Furthermore, a novel procedure for the isolation of cholesterol and oxysterol sulfonates was developed that was used in association with HPLC to resolve specific sterol sulfonates. HST1 preferentially sulfonated DHEA and, to a lesser extent, oxysterols: whereas cholesterol was a negligible substrate. The reverse, however, was the case for the HST2 isoforms, particularly HST2b, which preferentially sulfonated cholesterol and oxysterols, in contrast to DHEA, which served as a poor substrate for this enzyme. RT-PCR analysis revealed distinct patterns of HST1, HST2a, and HST2b expression. It was particularly notable that both HST2 isoforms, but not HST1, were expressed in skin, a tissue where cholesterol sulfonation plays an important role in normal development of the skin barrier. In conclusion, substrate specificity and tissue distribution studies strongly suggest that HST2a and HST2b, in contrast to HST1, represent normal human cholesterol and oxysterol sulfotransferases. Furthermore, this study represents the first example of the sulfonation of oxysterols by a specific human HST. C1 NICHHD, Sect Steroid Regulat, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Strott, CA (reprint author), NICHHD, Sect Steroid Regulat, Endocrinol & Reprod Res Branch, NIH, Bldg 49,Room 6A36, Bethesda, MD 20892 USA. NR 72 TC 65 Z9 66 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 2001 VL 142 IS 7 BP 2978 EP 2984 DI 10.1210/en.142.7.2978 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 445XX UT WOS:000169484800032 PM 11416019 ER PT J AU Abylkassimova, Z Land, C Hartshome, M Crooks, L Luckyanov, N Bouville, A Simon, S Weinstock, B Romanyukha, A Fillmore, CM Gusev, B Zhumadilov, Z Chaizhunusova, N AF Abylkassimova, Z Land, C Hartshome, M Crooks, L Luckyanov, N Bouville, A Simon, S Weinstock, B Romanyukha, A Fillmore, CM Gusev, B Zhumadilov, Z Chaizhunusova, N TI Fallout exposure in Kazakhstan and thyroid disease prevalence SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Vet Adm Med Ctr, Albuquerque, NM 87108 USA. Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2001 VL 12 IS 4 MA 451 BP S83 EP S83 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 443GZ UT WOS:000169334500410 ER PT J AU Alavanja, M Blomeke, B Welsh, J Harns, C Bennett, W AF Alavanja, M Blomeke, B Welsh, J Harns, C Bennett, W TI Genes, vegetables, residential radon and risk of lung cancer in non-smoking women SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Rhein Westfal TH Aachen, Dept Dermatol, D-5100 Aachen, Germany. NCI, Div Basic Sci, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. City Hope Beckman Res Inst, Div Mol Med, Duarte, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2001 VL 12 IS 4 MA 251 BP S52 EP S52 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 443GZ UT WOS:000169334500226 ER PT J AU Ayotte, JD Baris, D Robinson, GP Lubin, J Cantor, KP Silverman, DT Grauman, D Hoover, RN Fraumeni, JF AF Ayotte, JD Baris, D Robinson, GP Lubin, J Cantor, KP Silverman, DT Grauman, D Hoover, RN Fraumeni, JF TI Relation of bladder cancer mortality rates in New England to water use data SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2001 VL 12 IS 4 MA 542 BP S97 EP S97 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 443GZ UT WOS:000169334500492 ER PT J AU Bell, EM Alavanja, MCR Sandler, DP AF Bell, EM Alavanja, MCR Sandler, DP TI High pesticide exposure events (HPEE) among pesticide applicators enrolled in the agricultural health study SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2001 VL 12 IS 4 MA 440 BP S81 EP S81 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 443GZ UT WOS:000169334500400 ER PT J AU David-Beabes, G London, S AF David-Beabes, G London, S TI Genetic polymorphism of XRCC1 and lung cancer risk among African-Americans and Caucasians SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2001 VL 12 IS 4 MA 527 BP S95 EP S95 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 443GZ UT WOS:000169334500478 ER PT J AU De Roos, AJ Ward, MH Lynch, CF Cantor, KP AF De Roos, AJ Ward, MH Lynch, CF Cantor, KP TI Nitrate in community water supplies and the risk of colon cancer SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Iowa, Dept Prevent Med & Environm Hlth, Iowa City, IA 52242 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2001 VL 12 IS 4 MA 338 BP S65 EP S65 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 443GZ UT WOS:000169334500307 ER PT J AU De Roos, AJ Zahm, SH Cantor, KP Weisenburger, DD Homes, FF Burmeister, LF Blair, A AF De Roos, AJ Zahm, SH Cantor, KP Weisenburger, DD Homes, FF Burmeister, LF Blair, A TI Integrative assessment of multiple pesticide exposures in farming as risk factors for non-Hodgkin's lymphoma in men SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Univ Nebraska, Lincoln, NE 68583 USA. Univ Kansas, Lawrence, KS 66045 USA. Univ Iowa, Iowa City, IA 52242 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2001 VL 12 IS 4 MA 291 BP S58 EP S58 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 443GZ UT WOS:000169334500263 ER PT J AU Dosemeci, M Alavanje, M Rowland, A Mage, D Zahm, S Thoms, K Lubin, J Hoppin, J Sandler, D Blair, A AF Dosemeci, M Alavanje, M Rowland, A Mage, D Zahm, S Thoms, K Lubin, J Hoppin, J Sandler, D Blair, A TI A quantitative approach for estimating exposure to pesticides in the agricultural health study SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NIEHS, Res Triangle Pk, NC 27709 USA. US EPA, Res Triangle Pk, NC 27711 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2001 VL 12 IS 4 MA 80 BP S25 EP S25 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 443GZ UT WOS:000169334500075 ER PT J AU Hauptmann, M Pohlabeln, H Lubin, JH Joeckel, KH Ahrens, W Brueske-Hohlfeld, I Wichmann, HE AF Hauptmann, M Pohlabeln, H Lubin, JH Joeckel, KH Ahrens, W Brueske-Hohlfeld, I Wichmann, HE TI On the exposure-time-response-relationship between occupational asbestos exposure and lung cancer in two german case-control studies SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Bremen Inst Prevent Res & Social Med, Bremen, Germany. Univ Essen Gesamthsch, Inst Med Informat, Essen, Germany. GSF, Natl Res Ctr Environm & Hlth, Inst Epidemiol, Neuherberg, Germany. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2001 VL 12 IS 4 MA 318 BP S62 EP S62 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 443GZ UT WOS:000169334500288 ER PT J AU Heineman, E AF Heineman, E TI Geographic information system for the Long Island Breast Cancer Study Project SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2001 VL 12 IS 4 MA 435 BP S81 EP S81 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 443GZ UT WOS:000169334500396 ER PT J AU Landi, MT Baccarelli, A Calista Grossman, L AF Landi, MT Baccarelli, A Calista Grossman, L TI UV-exposure, DNA repair and dysplastic nevi in the genesis of melanoma: A case-control study in Italy. SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. Bufalini Hosp, Cesena, Italy. Johns Hopkins Sch Publ Hlth, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2001 VL 12 IS 4 MA 431 BP S80 EP S80 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 443GZ UT WOS:000169334500393 ER PT J AU London, S Gauderman, W Avol, E Rappaport, E Peters, J AF London, S Gauderman, W Avol, E Rappaport, E Peters, J TI Family history and the risk of early onset persistent, early onset transient and late onset asthma SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. Univ So Calif, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2001 VL 12 IS 4 MA 529 BP S95 EP S95 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 443GZ UT WOS:000169334500480 ER PT J AU Lubin, JH Garcia-Closas, M Rothman, N AF Lubin, JH Garcia-Closas, M Rothman, N TI Case-control studies of gene-environment interactions: Sample size, power, misclassification and the case-only design alternative SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2001 VL 12 IS 4 MA 449 BP S83 EP S83 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 443GZ UT WOS:000169334500408 ER PT J AU McGuinness, BM Buck, GM Weiner, JM Vena, JE AF McGuinness, BM Buck, GM Weiner, JM Vena, JE TI Environmental pollutants and menstrual cycle length in a prospective pregnancy cohort SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 SUNY Buffalo, Buffalo, NY 14260 USA. NICHHD, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2001 VL 12 IS 4 MA 452 BP S83 EP S83 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 443GZ UT WOS:000169334500411 ER PT J AU Mohan, A Hauptmann, M Doody, M Freedman, D Alexander, B Boice, JA Mandel, J Correa-Villasenor, A Matanoski, G Linet, M AF Mohan, A Hauptmann, M Doody, M Freedman, D Alexander, B Boice, JA Mandel, J Correa-Villasenor, A Matanoski, G Linet, M TI Breast cancer mortality among radiologic technologists in the United States SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Univ Minnesota, Minneapolis, MN USA. Int Epidemiol Inst Ltd, Rockville, MD USA. Exponent, Menlo Pk, CA USA. Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2001 VL 12 IS 4 MA 349 BP S67 EP S67 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 443GZ UT WOS:000169334500318 ER PT J AU Mohan, AK Matanoski, GM Hauptmann, M Doody, MM Freedman, DM Alexander, BH Linet, MS AF Mohan, AK Matanoski, GM Hauptmann, M Doody, MM Freedman, DM Alexander, BH Linet, MS TI Risk for hematopoietic malignancies among radiologic technologists in the United States SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD USA. Univ Minnesota, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2001 VL 12 IS 4 MA 128 BP S32 EP S32 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 443GZ UT WOS:000169334500113 ER PT J AU Nuckols, JR Miller, R Gunier, R Reynolds, P Hertz, A Ward, M AF Nuckols, JR Miller, R Gunier, R Reynolds, P Hertz, A Ward, M TI Use of a geographic information system (GIS) for assessment of exposure to agricultural chemicals in the State of California, USA SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Colorado State Univ, Ft Collins, CO 80523 USA. Calif Dept Hlth Serv, Oakland, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2001 VL 12 IS 4 MA 344 BP S66 EP S66 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 443GZ UT WOS:000169334500313 ER PT J AU Parks, C Cooper, G Nylander-French, L Archer, J Storm, J AF Parks, C Cooper, G Nylander-French, L Archer, J Storm, J TI Measuring silica dust exposure from farm work in a population-based study of systemic lupus erythematosus SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. UNC, Sch Publ Hlth Environm Sci & Engn, Chapel Hill, NC USA. N Carolina State Univ, Dept Toxicol, Raleigh, NC 27695 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2001 VL 12 IS 4 MA 354 BP S68 EP S68 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 443GZ UT WOS:000169334500322 ER PT J AU Parks, C Cooper, G Nylander-French, L Sanderson, W Dement, J Hoppin, J Savitz, D AF Parks, C Cooper, G Nylander-French, L Sanderson, W Dement, J Hoppin, J Savitz, D TI Crystalline silica and risk of systemic lupus erythematosus: A population-based case-control study in the southeastern United States SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 NIEHS, Durham, NC USA. Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. NIOSH, Cincinnati, OH 45226 USA. Duke Univ, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2001 VL 12 IS 4 MA 351 BP S67 EP S67 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 443GZ UT WOS:000169334500320 ER PT J AU Ronckers, CM Land, CE Verduijn, PG Hayes, RB Stovall, M van Leeuwen, FE AF Ronckers, CM Land, CE Verduijn, PG Hayes, RB Stovall, M van Leeuwen, FE TI Late health effects of nasopharyngeal radium irradiation: Cancer incidence SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 Reinaert Klin Maastricht, Maastricht, Netherlands. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands. RI Schouten, Leo/G-3713-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2001 VL 12 IS 4 MA 356 BP S68 EP S68 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 443GZ UT WOS:000169334500324 ER PT J AU Ronckers, CM Schouten, LJ Verduijn, PG Land, CE Hayes, RB van Leeuwen, FE AF Ronckers, CM Schouten, LJ Verduijn, PG Land, CE Hayes, RB van Leeuwen, FE TI Assessment of cancer incidence in a cohort study: Self-report versus cancer registry linkage SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 Reinaert Klin Maastricht, Maastricht, Netherlands. Maastricht Univ, Dept Epidemiol, Maastricht, Netherlands. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands. RI Schouten, Leo/G-3713-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2001 VL 12 IS 4 MA 357 BP S68 EP S68 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 443GZ UT WOS:000169334500325 ER PT J AU Salo, PM Xia, J Avol, E Li, Y Johnson, CA Yang, J London, SJ AF Salo, PM Xia, J Avol, E Li, Y Johnson, CA Yang, J London, SJ TI Respiratory symptoms in relation to coal burning and smoking in the home among early adolescents in Wuhan, China SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. Wuhan Publ Hlth & Antiepidem Stn, Wuhan, Peoples R China. Univ So Calif, Keck Sch Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2001 VL 12 IS 4 MA 528 BP S95 EP S95 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 443GZ UT WOS:000169334500479 ER PT J AU Thomas, D Avol, E Berhane, K Gauderman, J Gilliland, F London, S Lurman, F Margolis, H McConnell, R Peters, J AF Thomas, D Avol, E Berhane, K Gauderman, J Gilliland, F London, S Lurman, F Margolis, H McConnell, R Peters, J TI Chronic respiratory effects of air pollution on Southern California children SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 Univ So Calif, Los Angeles, CA 90089 USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2001 VL 12 IS 4 MA 430 BP S80 EP S80 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 443GZ UT WOS:000169334500392 ER PT J AU Ward, MH Cantor, KP Lynch, C Merkle, SK AF Ward, MH Cantor, KP Lynch, C Merkle, SK TI Nitrate in public water supplies and risk of bladder cancer in Iowa, USA SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Iowa, Iowa City, IA 52242 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2001 VL 12 IS 4 MA 481 BP S88 EP S88 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 443GZ UT WOS:000169334500438 ER PT J AU Yeargin-Allsopp, M AF Yeargin-Allsopp, M CA Longitudinal Cohort Study Interage TI The longitudinal cohort study of environmental effects on child health and development SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 Ctr Dis Control & Prevent, Atlanta, GA USA. NIH, Bethesda, MD USA. US EPA, Res Triangle Pk, NC 27711 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2001 VL 12 IS 4 MA 232 BP S49 EP S49 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 443GZ UT WOS:000169334500209 ER PT J AU Ahern, GL Sollers, JJ Lane, RD Labiner, DM Herring, AM Weinand, ME Hutzler, R Thayer, JF AF Ahern, GL Sollers, JJ Lane, RD Labiner, DM Herring, AM Weinand, ME Hutzler, R Thayer, JF TI Heart rate and heart rate variability changes in the intracarotid sodium amobarbital test SO EPILEPSIA LA English DT Article DE autonomic nervous system; heart rate; heart rate variability; intracarotid sodium amobarbital test; wada test ID AUTONOMIC CONTROL; EEG; MECHANISMS; DEPRESSION; EPILEPSY; SEIZURES; STROKE; SYSTEM; DEATH AB Purpose: Changes in heart rate and heart rate variability have been found in prior studies performed during the intracarotid sodium amobarbital (ISA) test. However, these results. are not entirely consistent with current models of differential cerebral involvement in the modulation of the heart. This study was designed to re-investigate this topic with a larger N than has heretofore been used. Methods:. The electrocardiogram was recorded during left and right ISAs in 73 subjects. Raw heart rate and heart rate variability were calculated. Results: Raw heart rate increased during inactivation of either hemisphere, but more so for the right hemisphere. Heart rate variability changes consistent with decreasing parasympathetic tone also were found to occur during either ISA, but to a significant degree, only during right ISA. Conclusions: The right hemisphere appears to have a greater role in cerebral regulation of cardiac function, perhaps by virtue of the modification of parasympathetic effects. C1 Univ Arizona, Hlth Sci Ctr, Dept Neurol, Tucson, AZ 85724 USA. Univ Arizona, Hlth Sci Ctr, Dept Psychiat, Tucson, AZ 85724 USA. Univ Arizona, Hlth Sci Ctr, Neurosurg Sect, Dept Surg, Tucson, AZ 85724 USA. Univ Arizona, Hlth Sci Ctr, Arizona Comprehens Epilepsy Program, Tucson, AZ 85724 USA. NIA, Gerontol Res Ctr, LPC, Baltimore, MD 21224 USA. RP Ahern, GL (reprint author), Univ Arizona, Hlth Sci Ctr, Dept Neurol, 1501 N Campbell Ave, Tucson, AZ 85724 USA. NR 45 TC 106 Z9 107 U1 4 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD JUL PY 2001 VL 42 IS 7 BP 912 EP 921 DI 10.1046/j.1528-1157.2001.042007912.x PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 466TE UT WOS:000170661000015 PM 11488892 ER PT J AU Devin, A Nogueira, V Leverve, X Guerin, B Rigoulet, M AF Devin, A Nogueira, V Leverve, X Guerin, B Rigoulet, M TI Allosteric activation of pyruvate kinase via NAD(+) in rat liver cells SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE NAD(+) pyruvate kinase; isolated hepatocytes ID MITOCHONDRIA; METABOLISM; GLUCONEOGENESIS; HEPATOCYTES; GLYCOLYSIS; SUBSTRATE; GLYCEROL; OXYGEN; STATE; ATP AB In isolated rat hepatocytes, it has previously been reported that a rise in the ATP content induces a proportional increase in cytosolic NAD(+) concentration [Devin, A., Guerin, B. & Rigoulet, M. (1997) FEBS Lett. 410, 329-332]. This occurs under physiological conditions such as various substrates or different energetic states. To investigate the effect of a physiological rise in cytosolic [NAD(+)] per se on glycolysis and gluconeogenesis, an increase in [NAD(+)] induced by exogenous nicotinamide addition was obtained without a change in redox potential, ATP/ADP ratio and ATP concentration. Using dihydroxyacetone as substrate, we found that an increase in cytosolic [NAD(+)] decreases gluconeogenesis and enhances glycolysis without significant alteration of dihydroxyacetone consumption rate. These modifications are the consequence of an allosteric activation of pyruvate kinase via cytosolic NAD(+) content. Thus, in addition to the well-known thermodynamic control of glycolysis by pyridine-nucleotide redox status, our study points to a new mechanism of glycolytic flux regulation by NAD(+) concentration at the level of pyruvate kinase activity. C1 Univ Bordeaux 2, CNRS, Inst Biochim & Genet Cellulaires, F-33077 Bordeaux, France. NCI, NIH, Bethesda, MD 20892 USA. Univ Grenoble 1, Lab Bioenerget Fondamentale & Appl, Grenoble, France. RP Rigoulet, M (reprint author), Univ Bordeaux 2, CNRS, Inst Biochim & Genet Cellulaires, 1 Rue Camille St Saens, F-33077 Bordeaux, France. NR 27 TC 10 Z9 10 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD JUL PY 2001 VL 268 IS 14 BP 3943 EP 3949 DI 10.1046/j.1432-1327.2001.02306.x PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 458EG UT WOS:000170179800009 PM 11453987 ER PT J AU Rabkin, CS AF Rabkin, CS TI AIDS and cancer in the era of highly active antiretroviral therapy (HAART) SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Kaposi's sarcoma; non-Hodgkin's lymphoma; HAART; AIDS-related malignancy; Epstein-Barr virus; human herpesvirus-8 ID HUMAN-IMMUNODEFICIENCY-VIRUS; CENTRAL-NERVOUS-SYSTEM; NON-HODGKINS-LYMPHOMA; EPSTEIN-BARR-VIRUS; KAPOSIS-SARCOMA; HIV-INFECTION; COHORT; RISK; INITIATION; ILLNESSES AB Combination therapy with protease inhibitors and nucleoside analogues dramatically suppresses plasma HIV-1 RNA and delays progression to AIDS, but the impact on HIV-associated malignancy remains to be established. Observational and time-trend data indicate that the incidence of Kaposi's sarcoma (KS) and primary brain lymphoma have decreased, but suggest that current therapies have nor had a proportionate effect on systemic non-Hodgkin's lymphomas (NHL). As opportunistic infection and mortality are yielding to advances in antiretroviral therapy, lymphoma may increase in importance as a cause of AIDS-related morbidity and mortality. Further improvements in the long-term consequences of HIV infection will depend on better prevention and treatment of this serious malignant complication. (C) 2001 Published by Elsevier Science Ltd. C1 NCI, Viral Epidemiol Branch, Bethesda, MD 20892 USA. RP Rabkin, CS (reprint author), NCI, Viral Epidemiol Branch, Bethesda, MD 20892 USA. NR 30 TC 48 Z9 49 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JUL PY 2001 VL 37 IS 10 SI SI BP 1316 EP 1319 DI 10.1016/S0959-8049(01)00104-6 PG 4 WC Oncology SC Oncology GA 448UN UT WOS:000169648500015 PM 11423263 ER PT J AU Byrnes, AA Ma, XJ Cuomo, P Park, K Wahl, L Wolf, SF Zhou, HF Trinchieri, G Karp, CL AF Byrnes, AA Ma, XJ Cuomo, P Park, K Wahl, L Wolf, SF Zhou, HF Trinchieri, G Karp, CL TI Type I interferons and IL-12: convergence and cross-regulation among mediators of cellular immunity SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE IL-12; IFN-alpha/beta; monocyte/macrophage; Th1/Th2; IFN-gamma ID CHRONIC HEPATITIS-C; BLOOD MONONUCLEAR-CELLS; P40 GENE PROMOTER; HUMAN T-CELLS; NF-KAPPA-B; MULTIPLE-SCLEROSIS; IFN-GAMMA; DENDRITIC CELLS; VIRUS-INFECTION; VIRAL-INFECTION AB Therapeutic use of type I IFN (IFN-alpha/beta) has become common. Many of the diverse diseases targeted are marked: by pathogenetic abnormalities in cell-mediated immunity (CMI), these cellular immune responses either causing injury to the host, lacking sufficient vigor for virus or tumor clearance, or both, in general, therapeutic efficacy is limited. It is thus notable that the pleiotropic effects of type I IFN on CMI remain poorly understood. We characterized the effects of type I IFN on the production of IL-12, the central immunoregulatory cytokine of the CD4(+) T cell arm of CMI. We show that type I IFN are potent inhibitors of IL-12 production by human monocytes/macrophages. The underlying mechanism involves transcriptional inhibition of the IL-12p40 gene, marked by down-regulation of PU.1 binding activity at the upstream Ets site of the IL-12p40 promoter. Type I IFN have previously been shown to be able to substitute for IL-12 in: driving IFN-gamma production from T and NK cells. The ability of IFN-alpha/beta to suppress IL-12 production white up-regulating IFN-gamma production suggests a possible mechanistic basis; for the difficulties of employing these cytokines in diseases involving abnormalities of CMI. C1 Johns Hopkins Univ, Dept Med, Baltimore, MD USA. Wistar Inst, Philadelphia, PA 19104 USA. Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. Genet Inst, Andover, MA USA. RP Karp, CL (reprint author), Univ Cincinnati, Childrens Hosp Res Fdn, 3333 Burnet Ave, Cincinnati, OH 45229 USA. OI Karp, Christopher/0000-0002-0832-2659 FU NIAID NIH HHS [AI45899]; NIDDK NIH HHS [DK56415]; NINDS NIH HHS [NS39435] NR 62 TC 62 Z9 62 U1 0 U2 3 PU WILEY-V C H VERLAG GMBH PI BERLIN PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUL PY 2001 VL 31 IS 7 BP 2026 EP 2034 DI 10.1002/1521-4141(200107)31:7<2026::AID-IMMU2026>3.3.CO;2-L PG 9 WC Immunology SC Immunology GA 452DJ UT WOS:000169841600010 PM 11449355 ER PT J AU McHugh, RS Shevach, EM Margulies, DH Natarajan, K AF McHugh, RS Shevach, EM Margulies, DH Natarajan, K TI A T cell receptor transgenic model of severe, spontaneous organ-specific autoimmunity SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE gastritis; H/K ATPase; transgenic; autoimmune model ID BETA-SUBUNIT; MICE; PATHOGENESIS; EXPRESSION; GASTRITIS; ENCEPHALOMYELITIS; TOLERANCE; REQUIREMENT; REPERTOIRE; OOPHORITIS AB The, development of mouse models of human organ-specific autoimmune diseases has been hampered by the need to immunize mice with autoantigens in potent adjuvants. Even autoantigen-specific T cell receptor transgenic models of autoimmunity have proven to be complex as the transgenic mice frequently fair to develop disease spontaneously. We have isolated a CD4(+) T cell clone (TxA23) that recognizes the gastric parietal cell antigen, H/K ATPase alpha -chain(630-641), from a mouse with autoimmune gastritis that developed after thymectomy on day 3 of life. The T cell receptor alpha and beta genes from this clone were used to generate A23 transgenic mice. All A23 transgenic animals spontaneously developed severe autoimmune gastritis, and evidence of disease was detected as early as day 10 of life. Gastritis could be transferred to immunocompromised mice with a limited number of transgenic thymocytes (10(3)), but as many as 10(7) induced only mild disease in wild-type animals. Due to the complete penetrance of spontaneous disease, identity of the auto-antigen, susceptibility to immunoregulation, and close relation to autoimmune gastritis in man, A23 transgenic mice represent a unique CD4(+) T cell-mediated disease model far understanding the multiple factors regulating organ-specific autoimmunity. C1 NIAID, Immunol Lab, NIH, Cellular Immunol Sect, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Mol Biol Sect, Bethesda, MD 20892 USA. RP Shevach, EM (reprint author), NIAID, Immunol Lab, NIH, Cellular Immunol Sect, Bldg 10 Rm 11N311,10 Ctr Dr-MSC 1892, Bethesda, MD 20892 USA. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 NR 32 TC 60 Z9 60 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI BERLIN PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUL PY 2001 VL 31 IS 7 BP 2094 EP 2103 DI 10.1002/1521-4141(200107)31:7<2094::AID-IMMU2094>3.0.CO;2-S PG 10 WC Immunology SC Immunology GA 452DJ UT WOS:000169841600018 PM 11449363 ER PT J AU Lipska, BK Khaing, ZZ Weickert, CS Weinberger, DR AF Lipska, BK Khaing, ZZ Weickert, CS Weinberger, DR TI BDNF mRNA expression in rat hippocampus and prefrontal cortex: effects of neonatal ventral hippocampal damage and antipsychotic drugs SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE animal model; clozapine; haloperidol; neurotrophin; schizophrenia ID CHRONIC HALOPERIDOL TREATMENT; NEUROTROPHIC FACTOR; SYNAPTIC-TRANSMISSION; ANTEROGRADE TRANSPORT; GLUTAMATE RECEPTORS; GENE-EXPRESSION; REPEATED STRESS; ANIMAL-MODEL; BRAIN; SCHIZOPHRENIA AB Brain-derived neurotrophic factor (BDNF) plays an important role in development, synapse remodelling and responses to stress and injury. Its abnormal expression has been implicated in schizophrenia, a neuropsychiatric disorder in which abnormal neural development of the hippocampus and prefrontal cortex has been postulated. To clarify the effects of antipsychotic drugs used in the therapy of schizophrenia on BDNF mRNA, we studied its expression in rats treated with clozapine and haloperidol and in rats with neonatal lesions of the ventral hippocampus, used as an animal model of schizophrenia. Both antipsychotic drugs reduced BDNF expression in the hippocampus of control rats, but did not significantly lower its expression in the prefrontal cortex. The neonatal hippocampal lesion itself suppressed BDNF mRNA expression in the dentate gyrus and tended to reduce its expression in the prefrontal cortex. These results indicate that, unlike antidepressants, antipsychotics down-regulate BDNF mRNA, and suggest that their therapeutic properties are not mediated by stimulation of this neurotrophin. To the extent that the lesioned rat models some pathophysiological aspects of schizophrenia, our data suggest that a neurodevelopmental insult might suppress expression of the neurotrophin in certain brain regions. C1 NIMH, Clin Brain Disorders Branch, Intramural Res Program, Bethesda, MD 20892 USA. RP Lipska, BK (reprint author), NIMH, Clin Brain Disorders Branch, Intramural Res Program, Bethesda, MD 20892 USA. EM lipskab@intra.nimh.nih.gov RI Shannon Weickert, Cynthia/G-3171-2011; Lipska, Barbara/E-4569-2017 NR 66 TC 126 Z9 130 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD JUL PY 2001 VL 14 IS 1 BP 135 EP 144 DI 10.1046/j.1460-9568.2001.01633.x PG 10 WC Neurosciences SC Neurosciences & Neurology GA 462JY UT WOS:000170418000015 PM 11488957 ER PT J AU Mitchell, JB Krishna, MC Kuppusamy, P Cook, JA Russo, A AF Mitchell, JB Krishna, MC Kuppusamy, P Cook, JA Russo, A TI Protection against oxidative stress by nitroxides SO EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article; Proceedings Paper CT Free Radical Mechanisms of Cellular Injury Symposium CY FEB, 1997 CL WASHINGTON, D.C. SP Soc Experiment Bio & Med, District Columbia Sect, Oxygen Club Great Washington D.C ID SUPEROXIDE; TEMPOL; DAMAGE; MODEL C1 NCI, Div Clin Sci, Radiat Biol Branch, Bethesda, MD 20892 USA. Johns Hopkins Univ, Div Cardiol, Baltimore, MD 21205 USA. RP Mitchell, JB (reprint author), NCI, Div Clin Sci, Radiat Biol Branch, Bethesda, MD 20892 USA. NR 10 TC 25 Z9 25 U1 0 U2 0 PU SOC EXPERIMENTAL BIOLOGY MEDICINE PI MAYWOOD PA 195 WEST SPRING VALLEY AVE, MAYWOOD, NJ 07607-1727 USA SN 0037-9727 J9 EXP BIOL MED JI Exp. Biol. Med. PD JUL PY 2001 VL 226 IS 7 BP 620 EP 621 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 446PV UT WOS:000169522400003 PM 11444094 ER PT J AU Wink, DA Miranda, KM Espey, MG AF Wink, DA Miranda, KM Espey, MG TI Cytotoxicity related to oxidative and nitrosative stress by nitric oxide SO EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article; Proceedings Paper CT Free Radical Mechanisms of Cellular Injury Symposium CY FEB, 1997 CL WASHINGTON, D.C. SP Soc Experiment Bio & Med, District Columbia Sect, Oxygen Club Great Washington D.C C1 NCI, Radiat Biol Branch, Bethesda, MD 20892 USA. RP Wink, DA (reprint author), NCI, Radiat Biol Branch, Bethesda, MD 20892 USA. RI Miranda, Katrina/B-7823-2009 NR 3 TC 35 Z9 40 U1 0 U2 2 PU SOC EXPERIMENTAL BIOLOGY MEDICINE PI MAYWOOD PA 195 WEST SPRING VALLEY AVE, MAYWOOD, NJ 07607-1727 USA SN 0037-9727 J9 EXP BIOL MED JI Exp. Biol. Med. PD JUL PY 2001 VL 226 IS 7 BP 621 EP 623 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 446PV UT WOS:000169522400004 PM 11444095 ER PT J AU Brechbiel, MW AF Brechbiel, MW TI Chelated metal ions for therapeutic and diagnostic applications SO EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article; Proceedings Paper CT Free Radical Mechanisms of Cellular Injury Symposium CY FEB, 1997 CL WASHINGTON, D.C. SP Soc Experiment Bio & Med, District Columbia Sect, Oxygen Club Great Washington D.C AB Use of radiolabeled monoclonal antibodies (mAb's) that localize and bind to malignant cells continues to be an attractive mechanism for targeting and delivering either an imagable isotope, be it a y-emitter or B+-emitter, or a particle emitter such as a B--emitter or an a-emitter for therapeutic applications. C1 NCI, DCS, Radioimmune & Inorgan Chem Sect, NIH, Bethesda, MD 20892 USA. RP Brechbiel, MW (reprint author), NCI, DCS, Radioimmune & Inorgan Chem Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SOC EXPERIMENTAL BIOLOGY MEDICINE PI MAYWOOD PA 195 WEST SPRING VALLEY AVE, MAYWOOD, NJ 07607-1727 USA SN 0037-9727 J9 EXP BIOL MED JI Exp. Biol. Med. PD JUL PY 2001 VL 226 IS 7 BP 627 EP 628 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 446PV UT WOS:000169522400008 PM 11444098 ER PT J AU Chen, NH White, IM Wise, SP AF Chen, NH White, IM Wise, SP TI Neuronal activity in dorsomedial frontal cortex and prefrontal cortex reflecting irrelevant stimulus dimensions SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE visually guided movement; supplementary eye field; frontal cortex; medial eye field; monkey ID SUPPLEMENTARY EYE FIELD; RHESUS-MONKEY; MOTOR CORTEX; MOVEMENTS; TASK; SACCADES; SELECTIVITY; FIXATION; SIGNALS; CUES AB Previous studies of the dorsomedial frontal cortex (DMF) and the prefrontal cortex (PF) have shown that, when monkeys respond to nonspatial features of a discriminative stimulus (e.g., color) and the stimulus appears at a place unrelated to the movement target, neurons nevertheless encode stimulus location. This observation could support the idea that these neurons always encode stimulus location, regardless of its relevance to an instrumentally conditioned behavior. Past studies, however, leave open the possibility that activity observed during one operant task might reflect the contingencies of a different task, performed at different times. To test these alternatives, we examined the activity of DMF and PF neurons in two rhesus monkeys conditioned to perform an operant eye-movement task in which only the color and shape of visual stimuli served as salient discriminative features. Each of eight stimuli was associated with a response to a different eye-movement target. The location of these stimuli varied from trial to trial but was of no behavioral relevance, and the monkeys did not perform any operant task in which stimulus location controlled behavior. A substantial minority of neurons in both DMF and PF nevertheless encoded stimulus location, which indicates that this property does not depend on its relevance in an instrumentally conditioned behavior. C1 NIMH, Sect Neurophysiol, Lab Syst Neurosci, NIH, Bethesda, MD 20892 USA. KunMing Inst Zool, Kunming 650223, YunNan, Peoples R China. Swiss Fed Inst Technol, Inst Toxicol, CH-8603 Schwerzenbach, Switzerland. RP Wise, SP (reprint author), NIMH, Sect Neurophysiol, Lab Syst Neurosci, NIH, 49 Convent Dr,MSC 4401,Bldg 49,Room B1EE17, Bethesda, MD 20892 USA. NR 25 TC 10 Z9 10 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD JUL PY 2001 VL 139 IS 1 BP 116 EP 119 DI 10.1007/s002210100760 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 448UF UT WOS:000169647800013 PM 11482838 ER PT J AU Ikawa, H Kameda, H Kamitani, H Baek, SJ Nixon, JB Hsi, LC Eling, TE AF Ikawa, H Kameda, H Kamitani, H Baek, SJ Nixon, JB Hsi, LC Eling, TE TI Effect of PPAR activators on cytokine-stimulated cyclooxygenase-2 expression in human colorectal carcinoma cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE COX-2; PPAR; TNF-alpha; colorectal cells ID INFLAMMATORY-BOWEL-DISEASE; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; PROSTAGLANDIN-H SYNTHASE-2; HUMAN COLON-CANCER; RECEPTOR-GAMMA; PEROXISOME PROLIFERATORS; EPITHELIAL-CELLS; GENE-EXPRESSION; MESSENGER-RNA; ASPIRIN USE AB Cyclooxygenase-2 (COX-2) expression is up-regulated in colorectal cancer tissue. Peroxisome proliferator-activated receptors (PPARs) are expressed in human colorectal tissue and activation of PPARs can alter COX-2 expression. In macrophages, activation of PPARs down-regulates COX-2 expression. We examined the effect of PPAR alpha and PPAR gamma ligands on untreated and TNF-alpha -induced COX-2 expression in the human colorectal epithelial cell line HT-29. The expression of PPAR alpha and PPAR gamma was confirmed in these cells. TNF-alpha, an inflammatory cytokine, increased COX-2 expression via the NF kappaB pathway. In the absence of TNF-alpha, WY14643 (PPAR alpha activator) caused an increase, while BRL49653 (PPAR gamma activator) did not alter COX-2 expression. When HT-29 cells were incubated with TNF-alpha and WY14643, a further increase in COX-2 expression was detected, Incubation with TNF-alpha and BRL49653 caused an additional twofold increase in COX-2 expression. Our results suggest that both PPAR alpha signaling and TNF-alpha signaling increase COX-2 expression by independent pathways, while PPAR gamma stimulates COX-2 expression by up-regulation of the TNF-alpha pathway. C1 NIEHS, Mol Carcinogenesis Lab, Eicosanoid Biochem Sect, NIH, Res Triangle Pk, NC 27709 USA. RP Eling, TE (reprint author), NIEHS, Mol Carcinogenesis Lab, Eicosanoid Biochem Sect, NIH, POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. OI Baek, Seung/0000-0001-7866-7778 NR 41 TC 31 Z9 32 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JUL 1 PY 2001 VL 267 IS 1 BP 73 EP 80 DI 10.1006/excr.2001.5233 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 447YK UT WOS:000169599900007 PM 11412039 ER PT J AU Ingram, DK Nakamura, E Smucny, D Roth, GS Lane, MA AF Ingram, DK Nakamura, E Smucny, D Roth, GS Lane, MA TI Strategy for identifying biomarkers of aging in long-lived species SO EXPERIMENTAL GERONTOLOGY LA English DT Article; Proceedings Paper CT 2nd European Congress on Biogerontology: From Molecules to Humans CY AUG 25-28, 2000 CL ST PETERSBURG, RUSSIA SP Russian Acad Sci, Gerontol Soc DE lifespan; rodents; monkeys; calorie restriction; dehydroepiandrosterone ID GENETICALLY HETEROGENEOUS MICE; SENESCENCE; AGE AB If effective anti-aging interventions are to be identified for human application, then the development of reliable and valid biomarkers of aging are essential for this progress. Despite the apparent demand for such gerotechnology, biomarker research has become a controversial pursuit. Much of the controversy has emerged from a lack of consensus on terminology and standards for evaluating the reliability and validity of candidate biomarkers. The initiation of longitudinal studies of aging in long-lived non-human primates has provided an opportunity for establishing the reliability and validity of biomarkers of aging potentially suitable for human studies. From the primate study initiated in 1987 at the National Institute on Aging (NIA), the following criteria for defining a biomarker of aging have been offered: (1) significant cross-sectional correlation with age; (2) significant longitudinal change in the same direction as the cross-sectional correlation (3) significant stability of individual differences over time. These criteria relate to both reliability and validity. However, the process of validating a candidate biomarker requires a greater standard of proof. Ideally, the rate of change in a biomarker of aging should be predictive of lifespan. In short-lived species, such as rodents, populations differing in lifespan can be identified, such as different strains of rodents or groups on different diets, such as those subjected to calorie restriction (CR), which Live markedly longer. However, in the NIA primate study, the objective is to demonstrate that CR retards the rate of aging and increases lifespan. In the absence of lifespan data associated with CR in primates, validation of biomarkers of aging must rely on other strategies of proof. With this challenge, we have offered the following strategy: If a candidate biomarker is a valid measure of the rate of aging, then the rate of age-related change in the biomarker should be proportional to differences in lifespan among related species. Thus, for example, the rate of change in a candidate biomarker of aging in chimpanzees should be twice that of humans (60 vs 120 years maximum Lifespan); in rhesus monkeys three times that of humans (40 vs 120 years maximum lifespan). The realization of this strategy will be aided by developing a primate aging database, a project that was recently launched in cooperation with the NIA, the National Center for Research Resources, and the University of Wisconsin Regional Primate Research Center. Published by Elsevier Science Inc. C1 NIA, Neurosci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Kyoto Univ, Div Life Sci, Sakyo Ku, Kyoto 60601, Japan. Univ Wisconsin, Wisconsin Reg Primate Res Ctr, Madison, WI 53715 USA. RP Ingram, DK (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 24 TC 45 Z9 48 U1 2 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD JUL PY 2001 VL 36 IS 7 BP 1025 EP 1034 DI 10.1016/S0531-5565(01)00110-3 PG 10 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 450AB UT WOS:000169718400007 PM 11404048 ER PT J AU Fujino, T Yamazaki, Y Largaespada, DA Jenkins, NA Copeland, NG Hirokawa, K Nakamura, T AF Fujino, T Yamazaki, Y Largaespada, DA Jenkins, NA Copeland, NG Hirokawa, K Nakamura, T TI Inhibition of myeloid differentiation by Hoxa9, Hoxb8, and Meis homeobox genes SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID ACUTE MYELOGENOUS LEUKEMIA; BONE-MARROW CELLS; HOMEODOMAIN PROTEINS; DNA-BINDING; NUCLEAR IMPORT; EXPORT SIGNALS; PBX PROTEINS; EXPRESSION; TRANSLOCATION; EXTRADENTICLE AB Objective. The homeobox gene Hoxb8 is activated in the murine myelomonocytic cell line WEHI-3B as a result of intracisternal A particle integration. Cooperative activation between Hoxa9 and Meis1 is induced by retroviral integration in BXH2 murine myeloid leukemias and the myeloid leukemia cell line M1, The present study was conducted to examine possible Meis gene activation and cooperative DNA binding of homeobox proteins in WENI-3R and to reveal the specific role of Hox and Meis genes in myeloid differentiation. Materials and Methods. Northern blot analysis and reverse transcriptase polymerase chain reaction were performed to examine homeobox genes expression. Electrophoretic mobility shift assay was performed to evaluate DNA binding of homeobox proteins. Myeloid differentiation of 32Dc13 was induced by granulocyte colony-stimulating factor, Results. Meis2 was coactivated with Herbs in WEHI-3B cells. DNA-protein complexes including Hox, Meis, and Pbx were observed in WEHI-3B and 32Dc13, Expression and the DNA-binding complex of Hoxa9, Hoxb8, Meis1, and Meis2 were down-regulated during myeloid differentiation of 32Dc13 cells. Enforced expression of Hox or Meis genes inhibited myeloid differentiation of 32Dc13, Conclusion, The results indicate that Meis2 is an important Meis gene for myeloid leukemogenesis and that Hox and Meis are important genes for myeloid leukemogenesis through differentiation block, (C) 2001 International Society for Experimental Hematology. Published by Elsevier Science Inc. C1 Japanese Fdn Canc Res, Inst Canc, Dept Carcinogenesis, Tokyo 1708455, Japan. NCI, Frederick Canc Res & Dev Ctr, Mouse Canc Genet Program, Frederick, MD USA. Univ Minnesota, Ctr Canc, Dept Genet Cell Biol & Dev, Minneapolis, MN USA. Tokyo Med & Dent Univ, Grad Sch, Div Gerontol & Gerodontol, Dept Pathol & Immunol, Tokyo, Japan. RP Nakamura, T (reprint author), Japanese Fdn Canc Res, Inst Canc, Dept Carcinogenesis, 1-37-1 Kami Ikebukuro, Tokyo 1708455, Japan. NR 31 TC 53 Z9 58 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 2001 VL 29 IS 7 BP 856 EP 863 DI 10.1016/S0301-472X(01)00655-5 PG 8 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 455ZJ UT WOS:000170057400007 PM 11438208 ER PT J AU Gao, ZG Fackler, MJ Leung, W Lumkul, R Ramirez, M Theobald, N Malech, HL Civin, CI AF Gao, ZG Fackler, MJ Leung, W Lumkul, R Ramirez, M Theobald, N Malech, HL Civin, CI TI Human CD34(+) cell preparations contain over 100-fold greater NOD/SCID mouse engrafting capacity than do CD34(-) cell preparations SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID HEMATOPOIETIC STEM-CELLS; BONE-MARROW CELLS; LETHALLY IRRADIATED BABOONS; TERM LYMPHOHEMATOPOIETIC RECONSTITUTION; COMBINED IMMUNODEFICIENT MICE; MOBILIZED PERIPHERAL-BLOOD; COLONY-STIMULATING FACTOR; IN-VIVO; PROGENITOR CELLS; MONOCLONAL-ANTIBODY AB Objective. The CD34 cell surface marker is used widely for stem/progenitor cell isolation. Since several recent studies reported that CD34 cells also have in vivo engrafting capacity, we quantitatively compared the engraftment potential of CD34' vs CD34 cell preparations from normal human placental/umbilical cord blood (CB), bone marrow (BM), and mobilized peripheral blood (PBSC) specimens, using the nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse model, Methods. CD34(+) and CD34 cell preparations were purified by four different approaches in 14 individual experiments involving 293 transplanted NOD/SCID mice. In most experiments, CD34(+) cells were depleted twice (CD34(-)) in order to obtain efficient depiction of CD34 cells from the CD34(-) cell preparations. Results. Dose-dependent levels of human hematopoietic cells were observed after transplantation of CD34(+) cell preparations. To rigorously assess the complementary CD34(-) cell preparations, cell doses 10- to 1000-fold higher than the minimum dose of the CD34 cell preparations necessary for engraftment were transplanted. Nevertheless, of 125 NOD/SCID mice transplanted with CD34 cell preparations purified from the same starting cells, only sis mice had detectable human hematopoiesis, by flow cytometric or PCR assay. Conclusions. CD34 cells provide only a minor contribution to hematopoietic engraftment in this in vivo model system, as compared to CD34(+) cells from the same samples of noncultured human cells. Hematopoiesis derived from actual CD34 cells is difficult to distinguish from that due to CD34+ cells potentially contaminating the preparations, (C) 2001 International Society for Experimental Hematology. Published by Elsevier Science Inc. C1 Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. NIAID, Genet Immunotherapy Sect, Bethesda, MD 20892 USA. RP Civin, CI (reprint author), Johns Hopkins Oncol Ctr, Bunting Blaustein Canc Res Bldg,Room 27MM,1650 Or, Baltimore, MD 21231 USA. RI Ramirez, Manuel/H-7710-2015 OI Ramirez, Manuel/0000-0003-0332-6973 FU NCI NIH HHS [P01 CA70970] NR 72 TC 40 Z9 43 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 2001 VL 29 IS 7 BP 910 EP 921 DI 10.1016/S0301-472X(01)00654-3 PG 12 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 455ZJ UT WOS:000170057400013 PM 11438214 ER PT J AU Lu, CB Mattson, MP AF Lu, CB Mattson, MP TI Dimethyl sulfoxide suppresses NMDA- and AMPA-induced ion currents and calcium influx and protects against excitotoxic death in hippocampal neurons SO EXPERIMENTAL NEUROLOGY LA English DT Article DE DMSO; fura-2; glutamate; ischemia; pain; patch clamp ID LONG-TERM POTENTIATION; GLUTAMATE RECEPTORS; CEREBRAL-ISCHEMIA; REDOX MODULATION; BRAIN-FUNCTION; DMSO; MECHANISM; TRANSMISSION; PLASTICITY; APOPTOSIS AB Dimethyl sulfoxide (DMSO) is widely used in neuroscience research as a solvent for various pharmacological agents in both cell culture and in vivo studies and is also used in humans to treat musculoskeletal problems and pain. We now report that concentrations of DMSO to which neurons are typically exposed in experimental studies and in human patients (0.5-1.5%) inhibit glutamate responses in hippocampal neurons. DMSO suppresses, in a rapidly reversible manner, electrophysiological responses and calcium in influx induced by glutamate, N-methyl-D-aspartate, and alpha -amino-3-hydroxy-5-methylisoxazole-4-prop Moreover, DMSO can prevent excitotoxic death of the neurons. These findings have important implications for the use of DMSO as a solvent in studies that involve glutamatergic neurotransmission. Our data also identify a mechanism that might explain clinical effects of DMSO on both peripheral and CNS neurons and suggest a potential use for DMSO in the treatment of excitotoxic neurodegenerative conditions. C1 NIA, Neurosci Lab, Gerontol Res Ctr 4F01, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr 4F01, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 37 TC 50 Z9 56 U1 4 U2 9 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD JUL PY 2001 VL 170 IS 1 BP 180 EP 185 DI 10.1006/exnr.2001.7686 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 452CW UT WOS:000169840400017 PM 11421595 ER PT J AU Schiller, JT Lowy, DR AF Schiller, JT Lowy, DR TI Papillomavirus-like particle based vaccines: cervical cancer and beyond SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Review DE auto-antibodies; human papillomavirus; immunity; papillomavirus; self-antigens; vaccine; virus-like particles ID VIRUS-LIKE PARTICLES; NEUTRALIZING ANTIBODIES; CAPSID PROTEIN; IN-VITRO; L1 PROTEIN; SACCHAROMYCES-CEREVISIAE; IMMUNE-RESPONSE; CELL RESPONSES; B-LYMPHOCYTES; SELF PROTEIN AB Non-infectious human papillomavirus-like particles (VLP), composed of the Ll major capsid protein, are under active development as vaccines to prevent cervical cancer. They would presumably function primarily by generating virion-neutralising antibodies against the genital human papillomavirus (HPV) types that are the principal cause of most cervical cancers. Early phase clinical studies indicate that the VLP vaccines are well tolerated and able to consistently induce high titres of virus type-specific neutralising antibodies. Two types of second-generation VLP-based subunit vaccines with therapeutic implications, both related and unrelated to papillomavirus infection, are in preclinical development. One type seeks to induce cell-mediated immune responses, especially cytotoxic lymphocytes (CTL) against non-structural papillomavirus proteins, proteins of other viruses, or tumour associated antigens. The target antigen is incorporated into the VLPs as a fusion protein of L1 or the L2 minor capsid protein. In mouse models, this approach has generated potent CTL responses after low dose vaccination in the absence adjuvant. The second type of therapeutic VLP-based vaccine seeks to generate autoantibodies to self-antigens. The display of self polypeptides in the context of the highly ordered array of repetitive elements on the papillomavirus VLP surface abrogates the ability of the humoral immune system to functionally distinguish between foreign and self. High titre and high avidity auto-reactive IgG antibodies have been induced to both soluble (TNF-alpha) and cell surface (CCR5) central self-antigens. Vaccines based on this approach could potentially be effective alternatives to monoclonal antibody (mAb)-based therapies for a variety of disease targets. C1 NCI, Bethesda, MD 20892 USA. RP Schiller, JT (reprint author), NCI, Bethesda, MD 20892 USA. NR 77 TC 46 Z9 50 U1 0 U2 2 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1471-2598 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD JUL PY 2001 VL 1 IS 4 BP 571 EP 581 PG 11 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 493XX UT WOS:000172249700002 PM 11727495 ER PT J AU Stowers, A Carter, R AF Stowers, A Carter, R TI Current developments in malaria transmission-blocking vaccines SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Review DE malaria; Plasmodium falciparum; Plasmodium vivax; transmission-blocking vaccines ID PARASITE PLASMODIUM-FALCIPARUM; GAMETE SURFACE PROTEIN; SEXUAL-STAGE; MONOCLONAL-ANTIBODIES; MINIMAL VARIATION; RECOMBINANT PROTEINS; CANDIDATE PFS48/45; TARGET ANTIGENS; IMMUNITY; PFS230 AB Malaria is still a leading cause of morbidity and mortality in human populations. Problems, including drug-resistant parasites and insecticide resistant mosquitoes, ensure the continued hold of malaria in the tropics and sub-tropics. Each year around 100 million cases of malaria result in at least 50,000 deaths outside of sub-Saharan Africa; within sub-Saharan Africa itself, malaria causes around one million child deaths per year. New approaches for malaria control are badly needed and much effort has gone to develop malaria vaccines. In addition to giving personal protection, most such vaccines would also tend to reduce the transmission of malaria. One class of vaccine is being developed specifically for this purpose - the malaria transmission-blocking vaccines (TBV). TBVs are based upon antigens expressed on the surface of the sexual and mosquito mid-gut stages of malaria parasites. These antigens are the targets of antibodies induced by vaccination of the host and ingested with the parasites in a mosquito blood meal. The antibodies act by inhibiting the parasite's development within the mosquito itself and they thereby prevent the onward transmission of the parasites. TBVs could contribute to the total interruption of malaria transmission in many locations with relatively low transmission rates, mostly outside sub-Saharan Africa. Under almost all transmission rates, however, TBVs would help reduce malaria incidence and malaria-related morbidity and mortality. Promising recombinant TBV candidate antigens for the two main human malaria parasite species, Plasmodium falciparum and Plasmodium vivax, have been produced and tested in the laboratory, one has undergone early clinical trials. C1 NIAID, Malaria vaccine Dev Unit, Parasit Dis Lab, NIH, Rockville, MD 20852 USA. Univ Edinburgh, Div Biol Sci, Edinburgh EH9 3JT, Midlothian, Scotland. RP Stowers, A (reprint author), NIAID, Malaria vaccine Dev Unit, Parasit Dis Lab, NIH, 5640 Fishers Lane, Rockville, MD 20852 USA. NR 70 TC 47 Z9 50 U1 0 U2 8 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1471-2598 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD JUL PY 2001 VL 1 IS 4 BP 619 EP 628 PG 10 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 493XX UT WOS:000172249700005 PM 11727498 ER PT J AU Howard, OMZ Yoshimura, T AF Howard, OMZ Yoshimura, T TI Inhibitors of monocyte chemoattractant protein-1/CC ligand 2 and its receptor CCR2 SO EXPERT OPINION ON THERAPEUTIC PATENTS LA English DT Review DE atherogenic disease; CCL2; CCR2; inflammation; monocyte chemoattractant proteins; tumour AB Chemoattractant cytokines (chemokines) have been shown to be pro-inflammatory and are thus likely targets for therapeutic intervention. An agent that interferes with directed migration of leukocytes to an inflammatory site is potentially a candidate anti-inflammatory drug. A specific chemokine, monocyte chemoattractant protein (MCP)-1 or CC ligand 2 (CCL2), and its receptor, CC-chemokine receptor 2 (CCR2), have been implicated in both acute and chronic inflammatory and autoimmune diseases associated with infiltration of monocytes, macrophages, dendritic cells, NK cells, basophils and memory T-cells. Genetic modification of CCL2 and CCRZ in murine models has demonstrated the potential for antagonists to prevent atherogenic vascular disease and autoimmune inflammatory diseases. Modified CCL2 peptides, which still bind but no longer activate CCR2, demonstrated the therapeutic potential of CCL2 inhibitors in animal models of arthritis. Several classes of small molecular weight CCL2 inhibitors have also been shown to inhibit chemotaxis in response to CCL2 in vitro and in animal models. However, more work is needed to establish the clinical efficacy of these CCL2 inhibitors. C1 NCI, Mol Immunoregulat Lab, Canc Res Ctr, Frederick, MD 21702 USA. RP Howard, OMZ (reprint author), Bld 560,Rm 31 19, Frederick, MD 21702 USA. RI Howard, O M Zack/B-6117-2012 OI Howard, O M Zack/0000-0002-0505-7052 NR 7 TC 4 Z9 4 U1 0 U2 4 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1354-3776 J9 EXPERT OPIN THER PAT JI Expert Opin. Ther. Patents PD JUL PY 2001 VL 11 IS 7 BP 1147 EP 1151 DI 10.1517/13543776.11.7.1147 PG 5 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 450DX UT WOS:000169727200006 ER PT J AU Avis, I Hong, SH Martinez, A Moody, T Choi, YH Trepel, J Das, R Jett, M Mulshine, JL AF Avis, I Hong, SH Martinez, A Moody, T Choi, YH Trepel, J Das, R Jett, M Mulshine, JL TI Five-lipoxygenase inhibitors can mediate apoptosis in human breast cancer cell lines through complex eicosanoid interactions SO FASEB JOURNAL LA English DT Article DE breast cancer; leukotrienes; 5-lipoxygenase pathway; peroxisome proliferator-activated receptor; apoptosis ID PROLIFERATOR-ACTIVATED RECEPTORS; 5-LIPOXYGENASE-ACTIVATING PROTEIN FLAP; LEUKOTRIENE C-4 SYNTHASE; IN-VITRO GROWTH; PPAR-GAMMA; ARACHIDONIC-ACID; CYCLOOXYGENASE-2 EXPRESSION; PEROXISOME PROLIFERATORS; INFLAMMATORY RESPONSES; GENE-EXPRESSION AB Many arachidonic acid metabolites function in growth signaling for epithelial cells, and we previously reported the expression of the major arachidonic acid enzymes in human breast cancer cell lines. To evaluate the role of the 5-lipoxygenase (5-LO) pathway on breast cancer growth regulation, we exposed cells to insulinlike growth factor-1 or transferrin, which increased the levels of the 5-LO metabolite, 5(S)-hydrooxyeicosa-6E,8C,11Z,14Z-tetraenoic acid (5-HETE), by radioimmunoassay and high-performance liquid chromatography. Addition of 5-HETE to breast cancer cells resulted in growth stimulation, whereas selective biochemical inhibitors of 5-LO reduced the levels of 5-HETE and related metabolites. Application of 5-LO or 5-LO activating protein-directed inhibitors, but not a cyclooxygenase inhibitor, reduced growth, increased apoptosis, down-regulated bcl-2, up-regulated bax, and increased G1 arrest. Exposure of breast cancer cells to a 5-LO inhibitor up-regulated peroxisome proliferator-activated receptor (PPAR)alpha and PPAR gamma expression, and these same cells were growth inhibited when exposed to relevant PPAR agonists. These results suggest that disruption of the 5-LO signaling pathway mediates growth arrest and apoptosis in breast cancer cells. Additional experiments suggest that this involves the interplay of several factors, including the loss of growth stimulation by 5-LO products, the induction of PPAR gamma, and the potential activation of PPAR gamma by interactions with shunted endoperoxides. C1 NCI, Dept Cell & Canc Biol, Med Branch, Div Clin Sci, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Div Pathol, Washington, DC 20307 USA. RP Mulshine, JL (reprint author), NCI, Intervent Sect, CCB,MB, DCS,NIH,Clin Ctr, B10,12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. EM mulshinj@mail.nih.gov RI Martinez, Alfredo/A-3077-2013 OI Martinez, Alfredo/0000-0003-4882-4044 NR 74 TC 129 Z9 136 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL PY 2001 VL 15 IS 9 BP 2007 EP + DI 10.1096/fj.00-0866fje PG 30 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 460PV UT WOS:000170318500024 PM 11511519 ER PT J AU Haseman, J Melnick, R Tomatis, L Huff, J AF Haseman, J Melnick, R Tomatis, L Huff, J TI Carcinogenesis bioassays: study duration and biological relevance SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE rodent carcinogenicity bioassay; time-to-tumor; National Toxicology Program; study duration; relevance to humans ID RODENT CARCINOGENICITY; EXPERIMENTAL-ANIMALS; IARC MONOGRAPHS; CANCER; CHEMICALS; PREVENTION; PROGRAM; HUMANS; UPDATE AB Criticisms of the scientific value of rodent carcinogenicity bioassays have focused on the arguments that the studies are too long and that most organ-specific carcinogenic effects observed in experimental animals have little or no relevance to humans. For example, Davies et al. (Davies, T.S., Lynch, B.S., Monro, A.M., Munro, I.C., Nestmann, E.R., 2000. Rodent carcinogenicity tests need be no longer than 18 months: an analysis based on 210 chemicals in the IARC Monographs. Food and Chemical Toxicology 38, 219-235) concluded that the duration of rodent bioassays should be no more than 18 months, based on their analysis of 210 International Agency for Research on cancer (IARC) rodent carcinogens in which they report that most chemicals "tumorigenic effects;'' at or before 12 months. However, many of these "tumorigenic effects" reflect the occurrence of a single neoplasm, with most tumors occurring much later in the study. Reliance on a single tumor at an early time point as providing definitive evidence of rodent carcinogenicity is a dangerous practice that could produce both false positive and false negative outcomes. An extensive evaluation of the NTP database reveals that many rodent carcinogens produce later-appearing tumors that would not be detected as statistically significant in a 12-18 month study. Such a shortened duration study would be roughly equivalent to evaluating human cancer in subjects 30-50 years of age, which would, result in markedly reduced study sensitivity. In fact, many investigators recommend extending the duration of rodent studies to 30 months or to a true lifetime to increase study sensitivity. We also do not agree with the second conclusion of Davies et al. (2000) that the mode of action of rodent carcinogenesis is sufficiently well understood to justify discounting the majority of organ-specific carcinogenic effects found in these studies. The consequences of performing rodent carcinogenicity studies with inadequate sensitivity, and then discounting most of the carcinogenic effects that are observed will be that potential human carcinogens will not be detected, thus forcing near total reliance on human studies for this purpose. This is not prudent public health policy. Published by Elsevier Science Ltd. All rights reserved. C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Haseman, J (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 27 TC 35 Z9 35 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD JUL PY 2001 VL 39 IS 7 BP 739 EP 744 DI 10.1016/S0278-6915(01)00010-2 PG 6 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 442VQ UT WOS:000169306000011 PM 11397520 ER PT J AU Carper, D John, M Chen, ZG Subramanian, S Wang, RR Ma, WC Spector, A AF Carper, D John, M Chen, ZG Subramanian, S Wang, RR Ma, WC Spector, A TI Gene expression analysis of an H2O2-resistant lens epithelial cell line SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE differential display; gene expression; hydrogen peroxide; lens cell line; RT-PCR; free radicals ID ALPHA-B-CRYSTALLIN; OXIDATIVE STRESS; LIPID-PEROXIDATION; HYDROGEN-PEROXIDE; ULTRAVIOLET-RADIATION; DIFFERENTIAL DISPLAY; MOLECULAR CHAPERONE; OXYGEN-TOXICITY; CATALASE GENE; CATARACT AB Gene expression patterns were examined in lens epithelial cells conditioned to grow in 125 muM hydrogen peroxide in order to define the protective mechanisms that may be involved in survival during oxidative stress. RNA was extracted from normal and hydrogen peroxide-resistant alpha TN4 mouse lens epithelial cells. Gene expression was evaluated using Differential Display (DD) and RT-PCR. Upregulation of mRNAs for antioxidant and cellular defense enzymes was observed. The highest elevation detected was a 14-fold increase in catalase in the hydrogen peroxide-resistant cells. Glutathione peroxidase. ferritin. and alphaB-crystallin were upregulated 2-fold, and reticulocalbin was upregulated 6-fold in the resistant cells. alphaA-crystallin was downregulated 5-fold, while aldose reductase and mitochondrial gene products were unchanged. Thus, in the alpha TN4 mouse lens cell line, long-term exposure to high levels of hydrogen peroxide elicited an upregulation of transcripts for enzymes involved in hydrogen peroxide degradation, metal binding, and chaperone function, Since mitochondrial gene transcription is sensitive to hydrogen peroxide, the presence of normal levels of mitochondrial transcripts, in this study, demonstrates the effectiveness of the antioxidant defense systems. (C) 2001 Elsevier Science Inc. C1 NEI, Lab Mechanisms Ocular Dis, NIH, Bethesda, MD 20892 USA. Columbia Univ, Dept Ophthalmol, New York, NY 10027 USA. RP Carper, D (reprint author), NEI, Lab Mechanisms Ocular Dis, NIH, Bldg 6,Room 232,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 62 TC 30 Z9 33 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD JUL 1 PY 2001 VL 31 IS 1 BP 90 EP 97 DI 10.1016/S0891-5849(01)00561-5 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 451GN UT WOS:000169793100011 PM 11425494 ER PT J AU Bisaglia, M Venezia, V Mancini, F Milanese, C Schettini, G AF Bisaglia, M. Venezia, V. Mancini, F. Milanese, C. Schettini, G. TI Acetaminophen protects hippocampal and PC12 cultures from amyloid beta-peptides induced oxidative stress and NF-kappa B activation SO FUNDAMENTAL & CLINICAL PHARMACOLOGY LA English DT Meeting Abstract C1 [Bisaglia, M.; Venezia, V.; Schettini, G.] Univ Genoa, Natl Canc Inst, Genoa, Italy. [Bisaglia, M.; Venezia, V.; Schettini, G.] Univ Genoa, Adv Biotechnol Ctr, Genoa, Italy. [Bisaglia, M.; Schettini, G.] Univ Genoa, Dept Oncol, Pharmacol Sect, Genoa, Italy. [Mancini, F.; Milanese, C.] ACRAF Angelini Ric, Rome, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0767-3981 J9 FUND CLIN PHARMACOL JI Fundam. Clin. Pharmacol. PD JUL PY 2001 VL 15 SU 1 BP 34 EP 34 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA V23AR UT WOS:000208316200195 ER PT J AU Luo, DL Broad, LM Bird, GS Putney, JW AF Luo, D. L. Broad, L. M. Bird, G. St J. Putney, J. W., Jr. TI Mutual antagonism of calcium entry by capacitative and arachidonic acid-mediated calcium entry pathways SO FUNDAMENTAL & CLINICAL PHARMACOLOGY LA English DT Meeting Abstract C1 [Luo, D. L.] Harbin Med Univ, Harbin 150086, Peoples R China. [Broad, L. M.; Putney, J. W., Jr.] NIEHS, NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0767-3981 J9 FUND CLIN PHARMACOL JI Fundam. Clin. Pharmacol. PD JUL PY 2001 VL 15 SU 1 BP 42 EP 42 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA V23AR UT WOS:000208316200247 ER PT J AU Bisaglia, M Piccioli, P Stanzione, S Porcile, C Schettini, G AF Bisaglia, M. Piccioli, P. Stanzione, S. Porcile, C. Schettini, G. TI Activity-dependent neurotrophic factor-9 rescues cerebellar granule cells from apoptosis: involvement of protein-kinases and reactive oxygen species SO FUNDAMENTAL & CLINICAL PHARMACOLOGY LA English DT Meeting Abstract C1 [Bisaglia, M.; Piccioli, P.; Stanzione, S.; Porcile, C.; Schettini, G.] Natl Canc Inst, Genoa, Italy. [Bisaglia, M.; Schettini, G.] Univ Genoa, Dept Oncol, Pharmacol Sect, Genoa, Italy. [Bisaglia, M.; Piccioli, P.; Stanzione, S.; Porcile, C.; Schettini, G.] Adv Biotechnol Ctr, Genoa, Italy. NR 1 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0767-3981 J9 FUND CLIN PHARMACOL JI Fundam. Clin. Pharmacol. PD JUL PY 2001 VL 15 SU 1 BP 98 EP 98 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA V23AR UT WOS:000208316200573 ER PT J AU Shao, RG Cao, CX Pommier, Y AF Shao, R. G. Cao, C. X. Pommier, Y. TI Abrogation cell cycle checkpoint and inhibition of Chk1 kinase by UCN-01 in cancer cells treated with ara-C and other anticancer agents SO FUNDAMENTAL & CLINICAL PHARMACOLOGY LA English DT Meeting Abstract C1 Chinese Acad Med Sci, Inst Med Biotechnol, Beijing 100050, Peoples R China. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0767-3981 J9 FUND CLIN PHARMACOL JI Fundam. Clin. Pharmacol. PD JUL PY 2001 VL 15 SU 1 BP 147 EP 147 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA V23AR UT WOS:000208316200862 ER PT J AU Wassarman, KM Repoila, F Rosenow, C Storz, G Gottesman, S AF Wassarman, KM Repoila, F Rosenow, C Storz, G Gottesman, S TI Identification of novel small RNAs using comparative genomics and microarrays SO GENES & DEVELOPMENT LA English DT Article DE Hfq; rpoS; antisense regulation ID ESCHERICHIA-COLI K-12; SMALL NUCLEAR RIBONUCLEOPROTEINS; OMPA MESSENGER-RNA; HOST FACTOR-I; STATIONARY-PHASE; RPOS TRANSLATION; PHYSICAL MAP; SIGMA-FACTOR; HF-I; GENE AB A burgeoning list of small RNAs with a variety of regulatory functions has been identified in both prokaryotic and eukaryotic cells. However, it remains difficult to identify small RNAs by sequence inspection. We used the high conservation of small RNAs among closely related bacterial species, as well as analysis of transcripts detected by high-density oligonucleotide probe arrays, to predict the presence of novel small RNA genes in the intergenic regions of the Escherichia coli genome. The existence of 23 distinct new RNA species was confirmed by Northern analysis. Of these, six are predicted to encode short ORFs, whereas 17 are likely to be novel functional small RNAs. We discovered that many of these small RNAs interact with the RNA-binding protein Hfq, pointing to a global role of the Hfq protein in facilitating small RNA function. The approaches used here should allow identification of small RNAs in other organisms. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Affymetrix, Santa Clara, CA 95051 USA. RP Gottesman, S (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. OI Storz, Gisela/0000-0001-6698-1241 NR 44 TC 449 Z9 467 U1 2 U2 22 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JUL 1 PY 2001 VL 15 IS 13 BP 1637 EP 1651 DI 10.1101/gad.901001 PG 15 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 451WD UT WOS:000169824600006 PM 11445539 ER PT J AU Golubovsky, MD Konev, AY Walter, MF Biessmann, H Mason, JM AF Golubovsky, MD Konev, AY Walter, MF Biessmann, H Mason, JM TI Terminal retrotransposons activate a subtelomeric white transgene at the 2L telomere in Drosophila SO GENETICS LA English DT Article ID BROKEN CHROMOSOME ENDS; SACCHAROMYCES-CEREVISIAE; P-ELEMENT; HET-A; CHROMATIN STRUCTURE; LENGTH REGULATION; YEAST TELOMERE; DNA-SEQUENCES; MELANOGASTER; GENE AB Genetically marked P elements inserted into the subtelomeric satellites of Drosophila show repression and variegation of the reporter gene. One such white(+) reporter, inserted between the subtelomeric satellite and the terminal HeT-A array in the left arm of chromosome 2 (2L), is sensitive to its context; changes in the structure of the telomere region can be identified by changes in eye color. Addition of HeT-A or TART elements to the 2L terminus increases w(+) expression, and loss of sequence from the end decreases expression. This indicates that the telomeric retrotransposons in Drosophila have an activating influence on the repressed subterminal reporter gene. Changes in eye color due to altered expression of the transgene also allow the detection of interactions between homologous telomeres. The 2L arms that terminate in long HeT-A/TART arrays showed increased expression of the subterminal w(+) transgene when the terminal repeats on the homologue are absent or markedly shorter. We propose that the chromatin structure of the terminal HeT-A/TART array and the activity of a putative promoter/enhancer element on HeT-A are affected by telomeric interactions. Such trans-activation may reflect control over HeT-A transcription and, thus, transposition activity. C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. Univ Calif Irvine, Ctr Dev Biol, Irvine, CA 92697 USA. RP Mason, JM (reprint author), NIEHS, Mol Genet Lab, 111 Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. RI Konev, Alexander/J-4401-2015 OI Konev, Alexander/0000-0002-4497-6377 FU NIGMS NIH HHS [GM-56729] NR 50 TC 51 Z9 53 U1 0 U2 0 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD JUL PY 2001 VL 158 IS 3 BP 1111 EP 1123 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 453VF UT WOS:000169936600017 PM 11454760 ER PT J AU Robin, NH Biesecker, LG AF Robin, NH Biesecker, LG TI Considerations for a multiaxis nomenclature system for medical genetics SO GENETICS IN MEDICINE LA English DT Article ID CYSTIC-FIBROSIS; CRANIOSYNOSTOSIS; GENES C1 Case Western Reserve Univ, Univ Hosp Cleveland, Sch Med, Dept Genet, Cleveland, OH 44106 USA. Case Western Reserve Univ, Univ Hosp Cleveland, Sch Med, Dept Pediat, Cleveland, OH 44106 USA. Case Western Reserve Univ, Univ Hosp Cleveland, Sch Med, Dept Otolaryngol, Cleveland, OH 44106 USA. Case Western Reserve Univ, Univ Hosp Cleveland, Sch Med, Dept Reprod Biol, Cleveland, OH 44106 USA. NHGRI, NIH, Bethesda, MD 20892 USA. RP Robin, NH (reprint author), Ctr Human Genet, Lakeside 1500, Cleveland, OH 44106 USA. NR 16 TC 21 Z9 21 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD JUL-AUG PY 2001 VL 3 IS 4 BP 290 EP 293 DI 10.1097/00125817-200107000-00004 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 468UX UT WOS:000170777500004 PM 11478529 ER PT J AU Dean, M Rzhetsky, A Allikmets, R AF Dean, M Rzhetsky, A Allikmets, R TI The human ATP-binding cassette (ABC) transporter superfamily SO GENOME RESEARCH LA English DT Review ID FAMILIAL INTRAHEPATIC CHOLESTASIS; MULTIDRUG-RESISTANCE GENE; DROSOPHILA-WHITE GENE; CYSTIC-FIBROSIS GENE; P-GLYCOPROTEIN; DIETARY-CHOLESTEROL; MOLECULAR-CLONING; DEATH PROCESS; HUMAN HOMOLOG; MUTATIONS AB The ATP-binding cassette (ABC) transporter superfamily contains membrane proteins that translocate a variety of substrates across extra- and intra-cellular membranes. Genetic variation in these genes is the cause of or contributor to a wide variety of human disorders with Mendelian and complex inheritance, including cystic Fibrosis, neurological disease, retinal degeneration, cholesterol and bile transport defects, anemia, and drug response. Conservation of the ATP-binding domains of these genes has allowed the identification of new members of the superfamily based on nucleotide and protein sequence homology. Phylogenetic analysis is used to divide all 48 known ABC transporters into seven distinct subfamilies of proteins. For each gene, the precise map location on human chromosomes, expression data, and localization within the superfamily has been determined. These data allow predictions to be made as to potential functions or disease phenotypes associated with each protein. In this paper, we review the current state of knowledge on all human ABC genes in inherited disease and drug resistance. In addition, the availability of the complete Drosophila genome sequence allows the comparison of the known human ABC genes with those in the fly genome. The combined data enable an evolutionary analysis of the superfamily. Complete characterization of all ABC from the human genome and from model organisms will lead to important insights into the physiology and the molecular basis of many human disorders. C1 NCI, Human Genet Sect, Lab Genom Divers, Frederick, MD 21702 USA. Columbia Univ, Dept Med Informat, New York, NY 10032 USA. Columbia Univ, Dept Ophthalmol, New York, NY 10032 USA. Columbia Univ, Dept Pathol, New York, NY 10032 USA. Columbia Univ, Columbia Genome Ctr, New York, NY 10032 USA. RP Dean, M (reprint author), NCI, Human Genet Sect, Lab Genom Divers, Frederick, MD 21702 USA. EM dean@nclfcrf.gov RI rzhetsky, andrey/B-6118-2012; Dean, Michael/G-8172-2012; Marion-Poll, Frederic/D-8882-2011 OI Dean, Michael/0000-0003-2234-0631; Marion-Poll, Frederic/0000-0001-6824-0180 NR 70 TC 970 Z9 1014 U1 25 U2 164 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD JUL PY 2001 VL 11 IS 7 BP 1156 EP 1166 DI 10.1101/gr.GR-1649R PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 448VF UT WOS:000169650100004 PM 11435397 ER PT J AU Mohlke, KL Lange, EM Valle, TT Ghosh, S Magnuson, VL Silander, K Watanabe, RM Chines, PS Bergman, RN Tuomilehto, A Collins, FS Boehnke, M AF Mohlke, KL Lange, EM Valle, TT Ghosh, S Magnuson, VL Silander, K Watanabe, RM Chines, PS Bergman, RN Tuomilehto, A Collins, FS Boehnke, M TI Linkage disequilibrium between microsatellite markers extends beyond 1 cM on chromosome 20 in Finns SO GENOME RESEARCH LA English DT Article ID DEPENDENT DIABETES-MELLITUS; ISOLATED POPULATIONS; GENETICS FUSION; MAPPING GENES; FINLAND; GENOME; CONCORDANCE; REGIONS; TWINS; SCAN AB Linkage disequilibrium (LD) is a proven tool for evaluating population structure and localizing genes for monogenic disorders. LD-based methods may also help localize genes for complex traits. We evaluated marker-marker LD using 43 microsatellite markers spanning chromosome 20 with an average density of 2.3 cM. We studied 837 individuals affected with type 2 diabetes and 386 mostly unaffected spouse controls. A test of homogeneity between the affected individuals and their spouses showed no difference, allowing the 1223 individuals to be analyzed together. Significant (P < 0.01) LD was observed using a likelihood ratio test in all (11/11) marker pairs within 1 cM, 78% (25/32) of pairs 1-3 cM apart, and 39% (7/18) of pairs 3-4 cM apart, but for only 12 of 842 pairs more than 4 cM apart. We used the human genome project working draft sequence to estimate kilobase (kb) intermarker distances, acid observed highly significant LD (P < 10(-10)) for all six marker pairs up to 350 kb apart, although the correlation of LD with cM is slightly better than the correlation with megabases. These data suggest that microsatellites present at 1-cM density are sufficient to observe marker-marker LD in the Finnish population. C1 Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. NHGRI, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Diabet & Genet Epidemiol Unit, Helsinki, Finland. Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA. Univ Helsinki, Dept Publ Hlth, Helsinki, Finland. RP Boehnke, M (reprint author), Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. FU NHGRI NIH HHS [HG00376, HG00040]; NIDDK NIH HHS [DK09525] NR 26 TC 44 Z9 44 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD JUL PY 2001 VL 11 IS 7 BP 1221 EP 1226 DI 10.1101/gr.173201 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 448VF UT WOS:000169650100011 PM 11435404 ER PT J AU Randel, L Pearson, SD Sabin, JE Hyams, T Emanuel, EJ AF Randel, L Pearson, SD Sabin, JE Hyams, T Emanuel, EJ TI How managed care can be ethical SO HEALTH AFFAIRS LA English DT Article AB The growth of managed care in the United States has been paralleled by a rising tide of anti-managed care sentiment. The "managed care problem" is understood generally as the need to protect individuals against large companies that care more about their bottom line than about people. The premise of the BEST (Best Ethical Strategies for Managed Care) project is that the "managed care problem" is best understood as an ethical problem - a conflict of Values that arises as the country changes from a patient-centered to a population-centered approach to health care. The BEST project team worked with nine managed care organizations to identify their most intractable problems. The team redefined these problems in terms of ethical dilemmas, then studied each organization in search of innovative, exemplary approaches. These exemplary approaches are being shared publicly with the aim that they be adapted and adopted by other organizations facing similar difficulties and by regulators and legislators hoping to improve the health care system. C1 NIH, Warren G Magnuson Clin Ctr, Dept Clin Bioeth, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Ctr Eth Managed Care, Cambridge, MA 02138 USA. Harvard Univ, Pilgrim Hlth Care, Cambridge, MA 02138 USA. RP Randel, L (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Clin Bioeth, Bethesda, MD 20892 USA. NR 12 TC 13 Z9 13 U1 1 U2 1 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD JUL-AUG PY 2001 VL 20 IS 4 BP 43 EP 56 DI 10.1377/hlthaff.20.4.43 PG 14 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 453PQ UT WOS:000169925400004 PM 11463089 ER PT J AU Murphy, DA Stein, JA Schlenger, W Maibach, E AF Murphy, DA Stein, JA Schlenger, W Maibach, E CA Natl Inst Mental Hlth Multisite Hl TI Conceptualizing the multidimensional nature of self-efficacy: Assessment of situational context and level of behavioral challenge to maintain safer sex SO HEALTH PSYCHOLOGY LA English DT Article DE self-efficacy; HIV/AIDS; assessment; structural equation modeling (SEM) ID MODEL; ADOLESCENTS AB A. Bandura (1991) argued that self-efficacy measurement should be specific both to the situation in which the behavior occurs and level of challenge in that situation. Measures consistent with the 2 dimensions were developed with graded challenge levels and differing gender-appropriate situations. Participants were 1,496 controls in the National Institute of Mental Health Multisite HIV Prevention Trial recruited from STD clinics and health service centers (925 women and 571 men). The authors tested 4 separate-sex confirmatory factor analysis models as follows: (a) Condom negotiation efficacy as a unitary construct across situations and gradation of difficulty; (b) situation as preeminent, which transfers across skills whatever the gradation of difficulty; (c) skill as predominant, irrespective of situation; and (d) a multidimensional design that simultaneously accounts for both situation and graded difficulty. Consistent with Bandura's theory, the multidimensional model provided the best fit for both samples. C1 Univ Calif Los Angeles, Res Ctr, Hlth Risk Reduct Projects, Dept Psychiat, Los Angeles, CA 90025 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90025 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27706 USA. Porter Novelli, Washington, DC USA. NIMH, Multisite HIV Prevent Trial Grp, NIH, Bethesda, MD USA. RP Murphy, DA (reprint author), Univ Calif Los Angeles, Res Ctr, Hlth Risk Reduct Projects, Dept Psychiat, 1640 S Sepulveda Blvd,Suite 200, Los Angeles, CA 90025 USA. OI Maibach, Edward/0000-0003-3409-9187 FU NIDA NIH HHS [DA01070]; NIMH NIH HHS [U01 MH49059] NR 30 TC 24 Z9 24 U1 1 U2 4 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD JUL PY 2001 VL 20 IS 4 BP 281 EP 290 DI 10.1037//0278-6133.20.4.281 PG 10 WC Psychology, Clinical; Psychology SC Psychology GA 472HC UT WOS:000170977100005 PM 11515740 ER PT J AU Factor, V Oliver, AL Panta, GR Thorgeirsson, SS Sonenshein, GE Arsura, M AF Factor, V Oliver, AL Panta, GR Thorgeirsson, SS Sonenshein, GE Arsura, M TI Roles of Akt/PKB and IKK complex in constitutive induction of NF-kappa B in hepatocellular carcinomas of transforming growth factor alpha/c-myc transgenic mice SO HEPATOLOGY LA English DT Article ID CASEIN KINASE-II; NECROSIS-FACTOR-ALPHA; C VIRUS-INFECTION; TRANSCRIPTION FACTOR; CORE PROTEIN; MOUSE MODEL; CELL-LINES; TYROSINE PHOSPHORYLATION; EMBRYONIC LETHALITY; SIGNAL-TRANSDUCTION AB NF-kappaB regulates liver cell death during development, regeneration, and neoplastic transformation. For example, we showed that oncogenic Ras- or Raf-mediated transformation of rat liver epithelial cells (RLEs) led to altered NF-kappaB regulation through IKK complex activation, which rendered these cells more resistant to TGF-beta1-induced apoptosis. Thus, based on these findings, we sought to determine whether NF-kappaB could also be involved in tumor growth of liver cells in vivo. Hepatocellular carcinomas (HCCs) derived from bitransgenic mice harboring TGF-alpha and c-myc transgenes targeted specifically to the liver were compared with HCCs from c-myc single transgenic mice. Tumors from bitransgenic mice are characterized by a higher frequency of appearance, lower apoptotic index, and a higher rate of cell proliferation. Here we show that NF-kappaB is activated in HCCs of double TGF-alpha /c-myc transgenic mice, but not of c-myc single transgenic mice, suggesting that TGF-alpha mediates induction of NF-kappaB. Activation of the IKK complex was observed in the HCCs of double TGF-alpha /c-myc transgenic mice, implicating this pathway in NF-kappaB induction. Lastly, activation of the Akt/ protein kinase B (PKB), which has recently been implicated in NF-kappaB activation by PDGF, TNF-alpha, and Ras, was also observed. Importantly, human HCC cell lines similarly displayed NF-kappaB activation. Thus, these studies elucidate an anti-apoptotic mechanism by a TGF-alpha -Akt/PKB-IKK pathway, which likely contributes to survival and proliferation, thereby accelerating c-myc-induced liver neoplastic development in vivo. C1 Univ Tennessee, Coll Med, Dept Pharmacol, Memphis, TN 38163 USA. NCI, Expt Carcinogenesis Lab, Div Basic Sci, Bethesda, MD USA. Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. RP Arsura, M (reprint author), Univ Tennessee, Coll Med, Dept Pharmacol, 874 Union Ave, Memphis, TN 38163 USA. FU NCI NIH HHS [CA36355, CA78616] NR 74 TC 62 Z9 65 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUL PY 2001 VL 34 IS 1 BP 32 EP 41 DI 10.1053/jhep.2001.25270 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 445YG UT WOS:000169485700006 PM 11431731 ER PT J AU Kloehn, S Otte, C Korsanke, M Arendt, T Clemens, A Glasow, A Bornstein, SR Folsch, UR Monig, H AF Kloehn, S Otte, C Korsanke, M Arendt, T Clemens, A Glasow, A Bornstein, SR Folsch, UR Monig, H TI Expression and distribution of the prolactin receptor in normal rat liver and in experimental liver cirrhosis SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE prolactin; fibrogenesis; regeneration factor; metabolic zoning ID PROTEIN-KINASE-C; ORNITHINE DECARBOXYLASE ACTIVITY; GROWTH-HORMONE; GENE-EXPRESSION; PLACENTAL-LACTOGEN; HEPATIC MITOGEN; PRL RECEPTOR; CELLS; DEPENDENCE; MICE AB Recent results have suggested a role for prolactin (PRL) as a regeneration factor in the liver. In order to investigate the involvement of prolactin in the pathogenesis of liver cirrhosis, we studied the expression of the prolactin receptor (PRLR) and PRL during the development of cirrhosis in an animal model. 30 male rats were exposed to CCl4 by inhalation. Phenobarbitone was added to the drinking water to accelerate the formation of toxic metabolites by enzyme induction. Two control groups of 30 animals each were treated with phenobarbitone only or received no treatment. 10 animals of each group were sacrificed 35, 55, and 70 days after initiation of treatment. Liver tissue was subjected to histological examination, which demonstrated fibrosis of different grades and cirrhosis in the CCl4-treated rats. Expression of PRLR mRNA was investigated by mRNA extraction, RT-PCR and computer-supported densitometric evaluation. Compared to control liver, PRLR mRNA was expressed at a higher level in fibrotic and cirrhotic liver specimens. In normal tissue, immunohistochemical staining showed a high concentration of PRLR around the central vein and in the epithelium of the bile ducts. This pattern of distribution was lost in fibrosis and cirrhosis. An accumulation of PRLR was demonstrated within the damaged cells. Neither PRL nor PRL mRNA was detectable in normal, fibrotic, or cirrhotic liver. We conclude that PRLR is distributed in normal rat liver in a typical pattern which is lost with increasing fibrosis. PRL is not produced by rat liver, indicating that PRL does not act through autocrine or paracrine mechanisms. C1 Univ Kiel, Dept Med, Kiel, Germany. Univ Kiel, Dept Pathol, D-2300 Kiel, Germany. Univ Leipzig, Dept Internal Med 3, D-7010 Leipzig, Germany. NICHHD, Bethesda, MD 20892 USA. RP Kloehn, S (reprint author), CAU Kiel, Med Klin 1, Schittenhelmstr 12, D-24105 Kiel, Germany. NR 54 TC 8 Z9 9 U1 0 U2 1 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD JUL PY 2001 VL 33 IS 7 BP 394 EP 401 DI 10.1055/s-2001-16229 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 460LK UT WOS:000170308900003 PM 11507675 ER PT J AU Breitbart, E Lomnitski, L Nyska, A Malik, Z Bergman, M Sofer, Y Haseman, JK Grossman, S AF Breitbart, E Lomnitski, L Nyska, A Malik, Z Bergman, M Sofer, Y Haseman, JK Grossman, S TI Effects of water-soluble antioxidant from spinach, NAO, on doxorubicin-induced heart injury SO HUMAN & EXPERIMENTAL TOXICOLOGY LA English DT Article DE antioxidants; cardiotoxicity; doxorubicin; oxidative stress; polyphenols ID INDUCED CARDIOTOXICITY; SUPEROXIDE-DISMUTASE; LIPID-PEROXIDATION; ANTICANCER DRUG; ADRIAMYCIN; MICE; RAT; TOXICITY; CARDIOMYOPATHY; PREVENTION AB Doxorubicin (DOX) produces clinically restorative responses innumerous human cancers, butits cardiotoxicity has limited its usefulness. Because reactive oxygen species may affect DOX-induced antitumor activity and cardiotoxicity, we evaluated the prophylactic effect of spinach natural antioxidant (NAO) on DOX-induced cardiotoxicity and oxidative stress in female Balb/c mice using histological, electron microscopical and biochemical parameters. Mice were treated with NAO for 7 days prior to and/or for 6 days after DOX administration. Pretreatment with NAO (cumulative dose: 130 mg/kg) did not hinder the effectiveness of DOX. Light and electron microscopy of DOX-treated heart revealed myocardial degeneration. When administered combined before and after DOX, NAO conferred the most significant cardiac protection. The effects of NAO on the lipid peroxidation product, malondialdehyde, and on H(2)O(2)/hydroperoxides were examined on day 6 following DOX administration; levels of both were elevated in DOX-treated mice, compared to control. Pretreatment with NAO prevented these changes. Pretreatment with NAO before DOX administration decreased catalase and increased superoxide dismutase activities compared to the DOX group. Our results suggest usage of NAO in combination with DOX as a prophylactic strategy to protect heart muscle from DOX-induced cellular damage. C1 Bar Ilan Univ, Fac Life Sci, IL-52900 Ramat Gan, Israel. NIEHS, Res Triangle Pk, NC 27709 USA. Coll Judea & Samaria, Ariel, Israel. RP Grossman, S (reprint author), Bar Ilan Univ, Fac Life Sci, IL-52900 Ramat Gan, Israel. NR 43 TC 18 Z9 18 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0960-3271 J9 HUM EXP TOXICOL JI Hum. Exp. Toxicol. PD JUL PY 2001 VL 20 IS 7 BP 337 EP 345 DI 10.1191/096032701680350604 PG 9 WC Toxicology SC Toxicology GA 463ZL UT WOS:000170507200003 PM 11530832 ER PT J AU Hoque, ATMS Baccaglini, L Baum, BJ AF Hoque, ATMS Baccaglini, L Baum, BJ TI Hydroxychloroquine enhances the endocrine secretion of adenovirus-directed growth hormone from rat submandibular glands in vivo SO HUMAN GENE THERAPY LA English DT Article ID MEDIATED GENE-TRANSFER; PRIMARY SJOGRENS-SYNDROME; SALIVARY-GLANDS; IN-VIVO; INTRACELLULAR TRAFFICKING; RHEUMATOID-ARTHRITIS; T-CELLS; CHLOROQUINE; PROTEINS; EXPRESSION AB Use of gene transfer technology for treating single protein deficiency disorders requires delivery of therapeutic levels of the transgene product. We have suggested that salivary glands may provide a potentially valuable target site for certain systemic applications of gene therapeutics (He et al., Gene Ther. 1998; 5:537-541). However, the ability of salivary glands to deliver therapeutic proteins to either the upper gastrointestinal tract via saliva or to the bloodstream, as required, must be carefully evaluated. In the anterior pituitary gland, human growth hormone (hGH) is secreted into the bloodstream via the regulated secretory pathway. However, when expressed from an adenoviral vector delivered to salivary glands, most hGH follows the regulated, tissue-specific, exocrine secretory pathway into saliva, where it is not therapeutically useful. We tested the hypothesis that the commonly used, FDA-approved drug hydroxychloroquine (HCQ) can divert adenovirus-directed hGH from this regulated secretory pathway in rat submandibular glands and enhance delivery into the bloodstream. In untreated rats, there was similar to 20-fold more vector-directed hGH in saliva than in serum. Administration of HCQ led to a shift of hGH secretion into the bloodstream. When delivered at doses of 1 or 10 mg/kg body weight, via intraperitoneal injection plus intraductal infusion, the saliva: serum hGH ratio was similar to2:1. Such HCQ delivery did not significantly alter the total amount of hGH measured, but increased the serum level of hGH 5- to 6-fold. Also, HCQ had no significant effects on serum chemistries or hematological parameters. We conclude that HCQ is able to significantly enhance hGH secretion from salivary glands into the bloodstream and may be useful to facilitate clinical applications of gene therapeutics via salivary glands. C1 NIDCR, GTTB, NIH, Bethesda, MD 20892 USA. RP Baum, BJ (reprint author), NIDCR, GTTB, NIH, Bldg 10,Room 1N113,MSC-1190, Bethesda, MD 20892 USA. NR 36 TC 31 Z9 31 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JUL PY 2001 VL 12 IS 10 BP 1333 EP 1341 DI 10.1089/104303401750270986 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 451HV UT WOS:000169797300009 PM 11440626 ER PT J AU Orioli, IM Castilla, EE Ming, JE Nazer, J de Aguiar, MJB Llerena, JC Muenke, M AF Orioli, IM Castilla, EE Ming, JE Nazer, J de Aguiar, MJB Llerena, JC Muenke, M TI Identification of novel mutations in SHH and ZIC2 in a South American (ECLAMC) population with holoprosencephaly SO HUMAN GENETICS LA English DT Article ID SONIC-HEDGEHOG GENE; CALIFORNIA POPULATION AB Holoprosencephaly (HPE) is genetically heterogeneous with four genes, SIX3, SHH, TGIF, and ZIC2 that have been identified to date and that are altered in 12% of patients. To analyze this prevalence in a South American population-based sample (57 HPE cases in 244,511 live and still births or 1 in 4300), we performed a mutational study of these genes in 30 unrelated children (26 newborns and 4 non-newborns) with HPE being ascertained by ECLAMC (Latin American Collaborative Study of Congenital Malformations). We identified three novel mutations: two were missense mutations of the SHH gene (Cys183--->Phe; His140->Pro); the third mutation was a 2-bp deletion in the zinc-finger region of the ZIC2 gene. These molecular results explained 8% (2/26 newborn samples) of the HPE cases in this South American population-based sample, a proportion similar to our previously published data from a collection of cases. C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Dept Pediat & Genet, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Inst Oswaldo Cruz, Dept Genet, ECLAMC, BR-20001 Rio De Janeiro, Brazil. Cemic, ECLAMC, Buenos Aires, DF, Argentina. Univ Chile, Hosp Clin, Unidad Neonatol, Santiago, Chile. Univ Fed Minas Gerais, Hosp Clin, Serv Especial Genet, Belo Horizonte, MG, Brazil. Fiocruz MS, Inst Fernandes Figueira, BR-21045900 Rio De Janeiro, Brazil. RP NHGRI, Med Genet Branch, NIH, 10 Ctr Dr,MSC 1852,Bldg 10,10C101, Bethesda, MD 20892 USA. EM muenke@nih.gov FU NICHD NIH HHS [HD01218, HD29862] NR 15 TC 36 Z9 38 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 EI 1432-1203 J9 HUM GENET JI Hum. Genet. PD JUL PY 2001 VL 109 IS 1 BP 1 EP 6 DI 10.1007/s004390100537 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 461WE UT WOS:000170386000001 PM 11479728 ER PT J AU Muller, S Wienberg, J AF Muller, S Wienberg, J TI "Bar-coding" primate chromosomes: molecular cytogenetic screening for the ancestral hominoid karyotype SO HUMAN GENETICS LA English DT Article ID IN-SITU HYBRIDIZATION; POLYMERASE CHAIN-REACTION; GENOMIC REORGANIZATION; INSITU HYBRIDIZATION; DNA PROBES; GREAT APES; YAC CLONES; FLUORESCENCE; EVOLUTION; PHYLOGENY AB Two recently introduced multicolor FISH approaches, cross-species color banding (also termed Rx-FISH) and multiplex FISH using painting probes derived from somatic cell hybrids retaining fragments of human chromosomes, were applied in a comparative molecular cytogenetic study of higher primates. We analyzed these "chromosome bar code" patterns to obtain an overview of chromosomal rearrangements that occurred during higher primate evolution. The objective was to reconstruct the ancestral genome organization of hominoids using the macaque as outgroup species. Approximately 160 individual and discernible molecular cytogenetic markers were assigned in these species. Resulting comparative maps allowed us to identify numerous intra-chromosomal rearrangements, to discriminate them from previous contradicting chromosome banding interpretations and to propose an ancestral karyotype for hominoids. From 25 different chromosome forms in an ancestral karyotype for all hominoids of 2N=48 we propose 21. Probes for chromosomes 2p, 4, 9 and Y were not informative in the present experiments. The orangutan karyotype was very similar to the proposed ancestral organization and conserved 19 of the 21 ancestral forms; thus most chromosomes were already present in early hominoid evolution, while African apes and human show various derived changes. C1 NCI, Basic Res Lab, Ft Detrick, MD 21702 USA. LMU Munchen, Inst Anthropol & Humangenet, D-80333 Munich, Germany. RP Wienberg, J (reprint author), NCI, Basic Res Lab, Bldg 560,Room 11-75, Ft Detrick, MD 21702 USA. NR 31 TC 61 Z9 65 U1 1 U2 4 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD JUL PY 2001 VL 109 IS 1 BP 85 EP 94 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 461WE UT WOS:000170386000012 PM 11479739 ER PT J AU Papageorgiou, TC Hearns-Stokes, RM Leondires, MP Miller, BT Chakraborty, P Cruess, D Segars, J AF Papageorgiou, TC Hearns-Stokes, RM Leondires, MP Miller, BT Chakraborty, P Cruess, D Segars, J TI Training of providers in embryo transfer: what is the minimum number of transfers required for proficiency? SO HUMAN REPRODUCTION LA English DT Article DE assisted reproduction; embryo transfer; Fellows training; learning-curve; pregnancy rate ID IN-VITRO FERTILIZATION; PREGNANCY RATES; INVITRO FERTILIZATION; PROGRAM; TIME AB BACKGROUND: Embryo transfer represents one of the most critical procedures in the practice of assisted reproduction. The objective of this study was to identify retrospectively the minimum number of embryo transfers required to train providers properly in this skill. METHODS AND RESULTS: The study group consisted of 204 patients who received embryo transfers between January 1996 and March 2000 in a university-based programme of assisted reproduction. The main outcome measure was clinical pregnancies per embryo transfer. Five Fellow trainees performed a total of 204 embryo transfers for an overall pregnancy rate of 45.5% per embryo transfer (93/204), In comparison, the programme pregnancy rate per transfer for experienced providers was 47.3% (560/1179). A chronological graph of each individual trainee's experience for the first 50 embryo transfers performed suggested a lower initial pregnancy rate for three of the five trainees, To determine whether a learning curve might exist, results of the first 25 transfers were compared as a subgroup with the second 25 transfers. Pregnancy rates were lower for the 1-25 transfer subgroup than in the 26-50 subgroup for three of the five Fellow trainees, although the difference was not statistically significant. CONCLUSION: Clinical pregnancy rates of Fellows-in-training were indistinguishable statistically from those of experienced staff by 50 transfers. C1 NICHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Dept Obstet & Gynecol, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. RP Segars, J (reprint author), NICHD, Pediat & Reprod Endocrinol Branch, NIH, Bldg 10,Room 9D42, Bethesda, MD 20892 USA. NR 15 TC 27 Z9 27 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD JUL PY 2001 VL 16 IS 7 BP 1415 EP 1419 DI 10.1093/humrep/16.7.1415 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 451QD UT WOS:000169812000019 PM 11425822 ER PT J AU Pacak, K Eisenhofer, G Carrasquillo, JA Chen, CC Li, ST Goldstein, DS AF Pacak, K Eisenhofer, G Carrasquillo, JA Chen, CC Li, ST Goldstein, DS TI 6-[F-18]fluorodopamine positron emission tomographic (PET) scanning for diagnostic localization of pheochromocytoma SO HYPERTENSION LA English DT Article DE fluorodopamine; pheochromocytoma; positron emission tomography; metanephrines ID CARDIAC SYMPATHETIC INNERVATION; PLASMA METANEPHRINES; METAIODOBENZYLGUANIDINE; SCINTIGRAPHY AB The diagnosis and treatment of pheochromocytoma depend critically on effective means to localize the tumor. Computed tomography and magnetic resonance imaging have good sensitivity but poor specificity for detecting pheochromocytoma, and nuclear imaging approaches such as I-131-metaiodobenzylguanidine scintigraphy have limited sensitivity. Here we report initial results using 6-[F-18]fluorodopamine positron emission tomography (PET) scanning in the diagnostic localization of pheochromocytoma. Twenty-eight patients with known or clinically suspected pheochromocytoma underwent PET scanning after intravenous injection of 6-[F-18]fluorodopamine. Of the 28 patients, 9 had surgical confirmation of the tumor, 8 had previously diagnosed metastatic pheochromocytoma, and I I had plasma levels of metanephrines that were within normal limits. All 9 patients with surgically proven pheochromocytoma had abnormal 6-[F-18]fluorodopamine PET scans that identified the tumors. All 8 patients with metastatic pheochromocytoma had extra-adrenal sites of 6-[F-18]fluorodopamine-derived activity. Of the I I patients with normal plasma levels of metanephrines, 9 had negative 6-[F-18]fluorodopamine PET scans, I had extra-adrenal foci of 6-[F-18]fluorodopamine-derived activity, and I had symmetric uptake of 6-[F-18]fluorodopamine in the region of the adrenal glands. In patients with known disease, 6-[F-18]fluorodopamine PET scanning can detect and localize pheochromocytomas with high sensitivity. In patients in whom the diagnosis of pheochromocytoma is considered but excluded because of negative plasma metanephrine results, 6-[F-18]fluorodopamine PET scans are consistently negative. These findings justify a clinical trial of 6-[F-18]fluorodopamine PET scanning as a diagnostic tool. C1 Nichhd, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD 20892 USA. RP Pacak, K (reprint author), Nichhd, Pediat & Reprod Endocrinol Branch, NIH, Bldg 10 Room 9D42,10 Ctr Dr, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010; OI Carrasquillo, Jorge/0000-0002-8513-5734 NR 17 TC 116 Z9 118 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUL PY 2001 VL 38 IS 1 BP 6 EP 8 PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 458EH UT WOS:000170179900003 PM 11463751 ER PT J AU Funakoshi, Y Ichiki, T Shimokawa, H Egashira, K Takeda, K Kaibuchi, K Takeya, M Yoshimura, T Takeshita, A AF Funakoshi, Y Ichiki, T Shimokawa, H Egashira, K Takeda, K Kaibuchi, K Takeya, M Yoshimura, T Takeshita, A TI Rho-kinase mediates angiotensin II-induced monocyte chemoattractant protein-1 expression in rat vascular smooth muscle cells SO HYPERTENSION LA English DT Article DE angiotensin II; peptides; muscle, smooth, vascular; receptors, angiotensin; kinase ID GROWTH-FACTOR RECEPTOR; FACTOR-KAPPA-B; CARDIAC MYOCYTES; ACTIVATION; INVOLVEMENT; CYTOKINE; ATHEROSCLEROSIS; INFILTRATION; INHIBITION; GTPASES AB Recently, it was shown that Rho-kinase plays an important role in blood pressure regulation. However, it is not known whether Rho-kinase is involved in atherogenesis. Monocyte chemoattractant protein-1 (MCP-1) is an important chemokine that regulates monocyte recruitment and atherogenesis. Therefore, we examined the role of Rho and Rho-kinase in the angiotensin (Ang) II-induced expression of MCP-1. Ang II dose- and time-dependently enhanced the expression of MCP-1 mRNA and the protein production in vascular smooth muscle cells. CV 11974, an Ang I type 1 receptor (AT(1)-R) specific antagonist inhibited the enhancement of MCP-1 expression by Ang II, suggesting that the effect of Ang II is mediated by the AT(1)-R. Botulinum C3 exotoxin, a specific inhibitor of Rho, suppressed Ang II-induced MCP-1 production. To examine the role of Rho-kinase in Ang II-induced MCP-1 expression, we used adenovirus-mediated overexpression of the dominant negative mutant of Rho-kinase (AdDNRhoK) or Y-27632, a specific inhibitor of Rho-kinase. Both AdDNRhoK and Y-27632 strongly inhibited Ang II-induced MCP-1 expression. Although inhibition of extracellular signal-regulated protein kinase (ERK) by PD 098,059 also inhibited Ang II-induced MCP-1 expression, Y-27632 did not affect Ang II-induced activation of ERK. These results indicate that Rho-kinase plays a critical role in Ang II-induced MCP-1 production independent of ERK. The Rho-Rho-kinase pathway may be a novel target for the inhibition of Ang II signaling and the treatment of atherosclerosis. C1 Kyushu Univ, Grad Sch Med Sci, Dept Cardiovasc Med, Higashi Ku, Fukuoka 8128582, Japan. Kumamoto Univ, Sch Med, Dept Pathol 2, Kumamoto 860, Japan. NCI, Frederick Canc Res & Dev Ctr, Immunopathol Sect, Immunobiol Lab, Frederick, MD USA. RP Ichiki, T (reprint author), Kyushu Univ, Grad Sch Med Sci, Dept Cardiovasc Med, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan. RI U-ID, Kyushu/C-5291-2016 NR 30 TC 128 Z9 141 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUL PY 2001 VL 38 IS 1 BP 100 EP 104 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 458EH UT WOS:000170179900020 PM 11463768 ER PT J AU Schmidt, R Schmidt, H Fazekas, F Launer, LJ Niederkorn, K Kapeller, P Lechner, A Kostner, GM AF Schmidt, R Schmidt, H Fazekas, F Launer, LJ Niederkorn, K Kapeller, P Lechner, A Kostner, GM TI Angiotensinogen polymorphism M235T, carotid atherosclerosis, and small-vessel disease-related cerebral abnormalities SO HYPERTENSION LA English DT Article DE angiotensinogen; genetics; carotid arteries; atherosclerosis; vessels ID NHLBI FAMILY HEART; AUSTRIAN STROKE PREVENTION; CONVERTING ENZYME; MYOCARDIAL-INFARCTION; RISK; GENE; HYPERTENSION; WHITE; ASSOCIATIONS AB The angiotensinogen M235T polymorphism has been linked to hypertension and cardiovascular disease. We studied the role of this polymorphism as a risk factor for carotid atherosclerosis and small-vessel disease-related brain abnormalities. A total of 431 randomly selected community-dwelling subjects without clinical evidence for strokes underwent angiotensinogen genotyping and carotid Duplex scanning, 1.5-T brain magnetic resonance imaging (MRI) was done in 396 individuals. At 3-year follow-up, we reexamined 343 and 267 study participants by ultrasound and brain MRI, respectively. Carotid atherosclerosis was graded on a 5-point scale. Small-vessel disease-related brain abnormalities were deep or subcortical white matter lesions or lacunes. Progression of carotid atherosclerosis and MRI findings was rated by direct imaging comparison by 3 independent raters. The M/M, M/T, and T/T genotypes were seen in 20.9%, 52.9%, and 18.1% of subjects, respectively. The M235T polymorphism was neither associated with baseline carotid findings nor with progression of carotid atherosclerosis. There was a trend toward more frequent small-vessel disease-related MRI abnormalities in the T/T than in the other genotypes at the baseline examination. Progression of brain lesions occurred significantly more commonly in T/T than in M/M and M/T carriers (P <0.001). Logistic regression analysis identified the T/T genotype (odds ratio, 3.19; P=0.002) and arterial hypertension (odds ratio, 3.06; P=0.03) as significant independent predictors of lesion progression. These data suggest that the angiotensinogen T/T genotype at position 235 is a genetic marker for brain lesions from and progression of small vessel disease but not for extracranial carotid atherosclerosis. C1 Karl Franzens Univ Graz, Dept Neurol, A-8036 Graz, Austria. Karl Franzens Univ Graz, Inst Med Biochem & Med Mol Biol, A-8036 Graz, Austria. Karl Franzens Univ Graz, MRI Ctr, A-8036 Graz, Austria. NIA, NIH, Bethesda, MD 20892 USA. RP Schmidt, R (reprint author), Karl Franzens Univ Graz, Dept Neurol, Auenbruggerpl 22, A-8036 Graz, Austria. NR 24 TC 43 Z9 45 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUL PY 2001 VL 38 IS 1 BP 110 EP 115 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 458EH UT WOS:000170179900022 PM 11463770 ER PT J AU Schmidt, K Sokoloff, L AF Schmidt, K Sokoloff, L TI A computationally efficient algorithm for determining regional cerebral blood flow in heterogeneous tissues by positron emission tomography SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE brain; blood flow; least squares methods; positron emission tomography ID WEIGHTED INTEGRATION METHOD; ERROR ANALYSIS; COMPUTED-TOMOGRAPHY; INTRAVENOUS (H2O)-O-15; PARTITION-COEFFICIENT; INPUT FUNCTION; O-15 WATER; PET; QUANTITATION; IMAGES AB nclusion of brain tissues with different rates of blood flow and metabolism within a voxel or region of interest is an unavoidable problem with positron emission tomography due to its limited spatial resolution. Because regional cerebral blood flow (rCBF) is higher in gray matter than in white matter, the partial volume effect leads to underestimation of rCBF in gray matter when rCBF in the region as a whole is determined. Furthermore, weighted-average rCBF itself is underestimated if the kinetic model used in the analysis fails to account for the tissue heterogeneity. We have derived a computationally efficient method for estimating both gray matter and weighted-average rCBF in heterogeneous tissues and validated the method in simulation studies. The method is based on a model that represents a heterogeneous tissue as a weighted mixture of two homogeneous tissues. A linear least squares algorithm is used to estimate the model parameters. C1 NIMH, Lab Cerebral Metab, Bethesda, MD 20892 USA. RP NIMH, Lab Cerebral Metab, Bldg 36,Room 36,Room 1A-07,9000 Rockville Pike, Bethesda, MD 20892 USA. EM kathy@shiloh.nimh.nih.gov NR 33 TC 3 Z9 3 U1 0 U2 3 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 EI 1558-254X J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD JUL PY 2001 VL 20 IS 7 BP 618 EP 632 DI 10.1109/42.932746 PG 15 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 449UQ UT WOS:000169705900007 PM 11465468 ER PT J AU Kim, HP Kelly, J Leonard, WJ AF Kim, HP Kelly, J Leonard, WJ TI The basis for IL-2-induced IL-2 receptor a chain gene regulation: Importance of two widely separated IL-2 response elements SO IMMUNITY LA English DT Article ID INTERLEUKIN-2 RECEPTOR; ALPHA-GENE; IMMUNOGLOBULIN-KAPPA; T-CELLS; HTLV-I; EXPRESSION; PROTEINS; BINDING; ENHANCER; HMG-I(Y) AB The interleukin-2 receptor alpha (IL-2R alpha) chain is an essential component of high-affinity IL-2 receptors. Accordingly, lL-2R alpha expression helps to regulate T cell growth and other lymphoid functions. Lineage-restricted and activation-dependent IL-2R alpha transcription is controlled by three upstream positive regulatory regions (PRRs). We now describe an additional IL-2 response element, PRRIV, within intron 1, in humans and mice. PRRIV activity requires GAS motifs that bind Stat5 proteins and additional upstream HMG-I(Y) binding sites. Moreover, IL-2 induces the binding of HMG-I(Y), Stat5a, and Stat5b in vivo to PRRIV and PRRIII, which also functions as an IL-2 response element. Thus, the IL-2 inducibility of the lL-2Ra gene is unexpectedly mediated by two widely separated regulatory Stat5-dependent elements, located both upstream and downstream of the transcription initiation sites. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 42 TC 80 Z9 82 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JUL PY 2001 VL 15 IS 1 BP 159 EP 172 DI 10.1016/S1074-7613(01)00167-4 PG 14 WC Immunology SC Immunology GA 457TQ UT WOS:000170153300016 PM 11485747 ER PT J AU Furuya, T Salstrom, JL Joe, B Hashiramoto, A Dobbins, DE Wilder, RL Remmers, EF AF Furuya, T Salstrom, JL Joe, B Hashiramoto, A Dobbins, DE Wilder, RL Remmers, EF TI Polymorphisms of the tumor necrosis factor receptor type 1 locus among autoimmune susceptible and resistant inbred rat strains SO IMMUNOGENETICS LA English DT Article DE TNFRI; single nucleotide polymorphism; SNP; autoimmunity; rats ID COLLAGEN-INDUCED ARTHRITIS; RHEUMATOID-ARTHRITIS; TNF RECEPTOR; MICE; DISSECTION; EXPRESSION; DEFICIENT; DISEASES C1 NIAMSD, Arthrit & Rheumat Branch, Inflammatory Joint Dis Sect, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. RP Remmers, EF (reprint author), NIAMSD, Arthrit & Rheumat Branch, Inflammatory Joint Dis Sect, NIH, 9000 Rockville Pike,Bldg 10,Room 9N228, Bethesda, MD 20892 USA. NR 15 TC 1 Z9 2 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD JUL PY 2001 VL 53 IS 5 BP 427 EP 429 DI 10.1007/s002510100338 PG 3 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 465VD UT WOS:000170609900009 PM 11486281 ER PT J AU Lee, JK Back, TC Komschlies, KL Ruscetti, FW Young, HA Wiltrout, RH AF Lee, JK Back, TC Komschlies, KL Ruscetti, FW Young, HA Wiltrout, RH TI Hematopoietic switch from lymphoid to granulocytic development in 3LL tumor-bearing mice SO IN VIVO LA English DT Article DE hematopoiesis; granulocytosis; splenomegaly; N-ras; 3LL ID COLONY-STIMULATING ACTIVITY; SQUAMOUS-CELL CARCINOMA; MARKED GRANULOCYTOSIS; C57BL/6 MICE; ADENOCARCINOMA; INHIBITION; LINE AB A significant splenomegaly and lymphadenopathy develops during the progressive growth of Lewis Lung (3LL) tumors in mice. Enlarged spleen and lymph nodes occur because of a pronounced increase in granulocytes in these organs. This granulocytosis in spleen and lymph node was not simply due to recruitment of granulocytes from peripheral blood to spleen and lymph nodes, but also a result of development and/or differentiation of granulocytes from the bone marrow. There was a marked increase in development of myeloid lineage cells, whereas lymphoid populations including T cells and B cells, were dramatically decreased in bone marrow and peripheral blood of 3LL tumor-beating mice. These data demonstrate that host hematopoiesis shifts from lymphoid to granulocytic development in the 3LL tumor-beating mice. Interestingly, a somatic mutation of N-Ras gene was found in 3LL tumor cells at codon 61, suggesting that mutated N-Ras may contribute to induction of granulocytosis in 3LL tumor-bearing mice. C1 NCI, Expt Therapeut Sect, LEI, Frederick, MD 21702 USA. NCI, Lab Leukocyte Biol, Frederick, MD 21701 USA. SAIC Frederick, Intramural Res Support Program, Frederick, MD USA. RP Wiltrout, RH (reprint author), NCI, Expt Therapeut Sect, LEI, Bldg 560,Room 31-93, Frederick, MD 21702 USA. NR 29 TC 3 Z9 3 U1 0 U2 1 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0258-851X J9 IN VIVO JI In Vivo PD JUL-AUG PY 2001 VL 15 IS 4 BP 255 EP 263 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 487JJ UT WOS:000171871600001 PM 11695215 ER PT J AU Kullberg, MC Rothfuchs, AG Jankovic, D Caspar, P Wynn, TA Gorelick, PL Cheever, AW Sher, A AF Kullberg, MC Rothfuchs, AG Jankovic, D Caspar, P Wynn, TA Gorelick, PL Cheever, AW Sher, A TI Helicobacter hepaticus-induced colitis in interleukin-10-deficient mice: Cytokine requirements for the induction and maintenance of intestinal inflammation SO INFECTION AND IMMUNITY LA English DT Article ID HAPTEN-INDUCED COLITIS; RIBOSOMAL-RNA GENE; CROHNS-DISEASE; T-CELLS; DEFICIENT MICE; SCHISTOSOMA-MANSONI; GRANULOMA-FORMATION; IN-VIVO; MONOCLONAL-ANTIBODIES; IL-10-DEFICIENT MICE AB We have previously shown that specific-pathogen-free interleukin-10 (IL-10)-deficient (IL-10 KO) mice reconstituted with Helicobacter hepaticus develop severe colitis associated with a Th1-type cytokine response. In the present study, we formally demonstrate that IL-12 is crucial for disease induction, because mice deficient for both IL-10 and IL-12 p40 show no intestinal pathology following H, hepaticus infection. By using monoclonal antibodies (MAbs) to IL-12, gamma interferon (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha), we have further analyzed the role of these cytokines in the maintenance of the Th1 response and inflammation in IL-10 KO mice with established H. hepaticus-induced colitis. Treatment of infected colitic IL-10 KO mice with anti-IL-12 p40 resulted in markedly reduced intestinal inflammation, colonic IFN-gamma, TNF-alpha, and inducible nitric oxide synthase (iNOS) mRNA levels, and H, hepaticus-specific IFN-gamma secretion by mesenteric lymph node (MLN) cells compared to the findings in control MAb-treated mice. Moreover, the diminished pathology was associated with decreased numbers of colonic CD3(+) T cells and significantly reduced frequencies of Helicobacter-reactive CD4(+) Th1 cells in MLN, In contrast, anti-IFN-gamma and/or anti-TNF-alpha had no effect on intestinal inflammation in IL-IO KO mice with established colitis, Using IL-10/IFN-gamma double-deficient mice, we further show that IFN-gamma is not required for the development of colitis following H, hepaticus infection. MLN cells from infected IL-10/IFN-gamma KO animals secreted elevated amounts of IL-12 and TNF-alpha following bacterial antigen stimulation, indicating alternative pathways of disease induction. Taken together, our results demonstrate a crucial role for IL-12 in both inducing and sustaining intestinal inflammation through recruitment and maintenance of a pool of pathogenic Th1 cells. C1 NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Schistosomiasis Immunol & Pathol Unit, Parasit Dis Lab, Bethesda, MD 20892 USA. NCI, Anim Hlth Diagnost Lab, Lab Anim Sci Program, Frederick Canc Res & Dev Ctr,Sci Applicat Int Cor, Ft Detrick, MD 21702 USA. Biomed Res Inst, Rockville, MD 20852 USA. RP Kullberg, MC (reprint author), NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bldg 4,Room 126,4 Ctr Dr, Bethesda, MD 20892 USA. RI Wynn, Thomas/C-2797-2011; Rothfuchs, Antonio/F-5981-2013 OI Rothfuchs, Antonio/0000-0001-6001-7240 NR 50 TC 94 Z9 98 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 2001 VL 69 IS 7 BP 4232 EP 4241 DI 10.1128/IAI.69.7.4232-4241.2001 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 443HL UT WOS:000169335700006 PM 11401959 ER PT J AU Wang, L Richie, TL Stowers, A Nhan, DH Coppel, RL AF Wang, L Richie, TL Stowers, A Nhan, DH Coppel, RL TI Naturally acquired antibody responses to Plasmodium falciparum merozoite surface protein 4 in a population living in an area of endemicity in Vietnam SO INFECTION AND IMMUNITY LA English DT Article ID HUMORAL IMMUNE-RESPONSES; RHOPTRY-ASSOCIATED PROTEIN-1; IMMUNOGLOBULIN G3 SUBCLASS; CARBOXY-TERMINAL FRAGMENT; FACTOR-LIKE DOMAIN; MALARIA TRANSMISSION; MONOCLONAL-ANTIBODY; CLINICAL IMMUNITY; UNSTABLE MALARIA; SERUM ANTIBODIES AB Merozoite surface protein 4 (MSP4) of Plasmodium falciparum is a glycosylphosphatidylinositol-anchored integral membrane protein that is being developed as a component of a subunit vaccine against malaria. We report here the measurement of naturally acquired antibodies to MSP4 in a population of individuals living in the Khanh-Hoa region of Vietnam, an area where malaria is highly endemic. Antibodies to MSP4 were detected in 94% of the study population at titers of 1:5,000 or greater. Two forms of recombinant MSP4 produced in either Escherichia call or Saccharomyces cerevisiae were compared as substrates in the enzyme-linked immunosorbent assay. There was an excellent correlation between reactivity measured to either, although the yeast substrate was recognized by a higher percentage of sera. Four different regions of MSP 1 were recognized by human antibodies, demonstrating that there are at least four distinct epitopes in this protein, In the carboxyl terminus, where the single epidermal growth factor-like domain is located, the reactive epitope(s) was shown to be conformation dependent, as disruption of the disulfide bonds almost completely abolished reactivity with human antibodies. The anti-MSP4 antibodies were mainly of the immunoglobulin G1 (IgG1) and IgG3 subclasses, suggesting that such antibodies may play a role in opsonization and complement-mediated lysis of free merozoites. Individuals in the study population were drug-cured and followed up for 6 months; no significant correlation was observed between the anti-MSP1 antibodies and the absence of parasitemia during the surveillance period. As a comparison, antibodies to MSPI19 a leading vaccine candidate, were measured, and no correlation with protection was observed in these individuals. The anti-MSP1(19) antibodies were predominantly of the IgG1 isotype, in contrast to the IgG3 predominance noted for MSP4. C1 Monash Univ, Dept Microbiol, Clayton, Vic 3800, Australia. USN, Med Res Ctr, Malaria Program, Silver Spring, MD 20910 USA. NIAID, Malaria Vaccine Dev Unit, NIH, Rockville, MD 20852 USA. Inst Microbiol Parasitol & Entomol, Hanoi, Vietnam. RP Coppel, RL (reprint author), Monash Univ, Dept Microbiol, Clayton, Vic 3800, Australia. RI Coppel, Ross/A-6626-2008; Richie, Thomas/A-8028-2011 OI Coppel, Ross/0000-0002-4476-9124; NR 42 TC 37 Z9 38 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 2001 VL 69 IS 7 BP 4390 EP 4397 DI 10.1128/IAI.69.7.4390-4397.2001 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 443HL UT WOS:000169335700025 PM 11401978 ER PT J AU Price, BM Liner, AL Park, S Leppla, SH Mateczun, A Galloway, DF AF Price, BM Liner, AL Park, S Leppla, SH Mateczun, A Galloway, DF TI Protection against anthrax lethal toxin challenge by genetic immunization with a plasmid encoding the lethal factor protein SO INFECTION AND IMMUNITY LA English DT Article ID BACILLUS-ANTHRACIS; EUKARYOTIC CELLS; MAMMALIAN-CELLS; DNA VACCINES; EXOTOXIN-A; ANTIGEN; SEQUENCE; PURIFICATION; MACROPHAGES; ANTIBODIES AB The ability of genetic vaccination to protect against a lethal challenge of anthrax toxin was evaluated, BALB/c mice were immunized via gene gun inoculation with eucaryotic expression vector plasmids encoding either a fragment of the protective antigen (PA) or a fragment of lethal factor (LF), Plasmid pCLF4 contains the N-terminal region (amino acids [aa] 10 to 254) of Bacillus anthracis LF cloned into the pCI expression plasmid, Plasmid pCPA contains a biologically active portion (aa 175 to 764) of B, anthracis PA cloned into the pCI expression vector, One-micrometer-diameter gold particles were coated with plasmid pCLF4 or pCPA or a 1:1 mixture of both and injected into mice via gene gun (I mug of plasmid DNA/injection) three times at 2-week intervals. Sera were collected and analyzed for antibody titer as well as antibody isotype, Significantly, titers of antibody to both PA and LF from mice immunized with the combination of pCPA and pCLF4 were four to five times greater than titers from mice immunized with either gene alone. Two weeks following the third and final plasmid DNA boost, all mice were challenged with 5 50% lethal doses of lethal toxin (PA plus LF) injected intravenously into the tail vein. All mice immunized with pCLF4, pCPA, or the combination of both survived the challenge, whereas all unimmunized mice did not survive. These results demonstrate that DNA-based immunization alone can provide protection against a lethal toxin challenge and that DNA immunization against the LF antigen alone provides complete protection. C1 Ohio State Univ, Dept Microbiol, Columbus, OH 43017 USA. Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. NMRC, Biol Def Res Directorate, Silver Spring, MD 20910 USA. RP Galloway, DF (reprint author), Ohio State Univ, Dept Microbiol, Columbus, OH 43017 USA. NR 35 TC 105 Z9 108 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 2001 VL 69 IS 7 BP 4509 EP 4515 DI 10.1128/IAI.69.7.4509-4515.2001 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 443HL UT WOS:000169335700040 PM 11401993 ER PT J AU Shaw, JH Grund, VR Durling, L Caldwell, HD AF Shaw, JH Grund, VR Durling, L Caldwell, HD TI Expression of genes encoding Th1 cell-activating cytokines and lymphoid homing chemokines by chlamydia-pulsed dendritic cells correlates with protective immunizing efficacy SO INFECTION AND IMMUNITY LA English DT Article ID OUTER-MEMBRANE PROTEIN; ECTOPIC PREGNANCY; TRACHOMATIS; VACCINATION; INFECTION; TRAFFICKING; VACCINES AB We studied the expression of cytokines, chemokines, and chemokine receptors by the RNase protection assay in chlamydia-pulsed dendritic cells to better understand their potent anti-chlamydial immunizing properties. We found that chlamydia-pulsed dendritic cells express a complex profile of inflammatory and immunomodulatory molecules. These include CCR-7, interleukin-12, and interferon-induced protein LO, molecules that might influence the homing of pulsed dendritic cells to the site of chlamydial infection and the induction of a local protective CD4(+) Th1 cellular immunity. C1 NIAID, Rocky Mt Lab, Intracellular Parasites Lab, NIH, Hamilton, MT 59840 USA. Univ Montana, Dept Pharmaceut Sci, Missoula, MT 59801 USA. RP Caldwell, HD (reprint author), NIAID, Rocky Mt Lab, Intracellular Parasites Lab, NIH, 903 S 4th St, Hamilton, MT 59840 USA. NR 21 TC 31 Z9 32 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 2001 VL 69 IS 7 BP 4667 EP 4672 DI 10.1128/IAI.69.7.4667-4672.2001 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 443HL UT WOS:000169335700060 PM 11402013 ER PT J AU Ahlers, JD Belyakov, IM Matsui, S Berzofsky, JA AF Ahlers, JD Belyakov, IM Matsui, S Berzofsky, JA TI Mechanisms of cytokine synergy essential for vaccine protection against viral challenge SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE cytokines; cytotoxic T lymphocyte; T(h)1 cells; viral immunity ID CYTOTOXIC T-LYMPHOCYTES; COLONY-STIMULATING FACTOR; HELPER PHENOTYPE DEVELOPMENT; PRIMARY IMMUNE-RESPONSE; HIV-1 PEPTIDE VACCINE; DENDRITIC CELLS; IN-VIVO; INFLUENZA-VIRUS; NEUTRALIZING-ANTIBODY; ANTIVIRAL PROTECTION AB The ability of cytokines to steer CD4(+) T-h cell responses toward a T(h)1 or T(h)2 phenotype and enhance the magnitude of both CD8(+) cytotoxic T lymphocytes (CTL) and antibody responses has clearly been demonstrated by our lab and others, but the influence of cytokines on protective immune responses is much less clear. Here we show an essential role for CD4(+) TO helper cell induction and IFN-gamma production in protection from viral challenge with a recombinant vaccinia virus expressing HIV-1MN viral envelope glycoprotein gp160. Complete protection from viral challenge is achieved only when the triple combination of exogenous cytokines granulocyte macrophage colony stimulating factor (GM-CSF), IL-12 and tumor necrosis factor (TNF)-alpha are co-administered with the peptide vaccine. In vivo depletion of CD4(+) cells or immunization of IFN-gamma -deficient mice abrogates protection. GM-CSF, IL-12 and TNF-alpha also synergize for the enhanced induction of CTL; however, adoptive transfer of a CD8(+) CTL line afforded only partial protection in this viral challenge model. As a possible mechanism of in vivo protection we show that GM-CSF increases the percentage and activity of antigen-presenting dendritic cells in draining lymph nodes where the immune response is initiated. We further demonstrate synergy between IL-12 and the proinflammatory cytokine TNF-alpha in driving IFN-gamma production. Thus, a combination of IL-12 and TNF-alpha is essential for the optimal development of T(h)1 responses and help for CTL induction in BALB/c mice, and is complemented by a third cytokine, GM-CSF, which enhances antigen presentation. C1 NCI, Metab Branch, Mol Immunogenet & Vaccine Res Sect, NIH, Bethesda, MD 20892 USA. RP Berzofsky, JA (reprint author), NCI, Metab Branch, Mol Immunogenet & Vaccine Res Sect, NIH, Bldg 10,Rm 6B-12,MSC 1578, Bethesda, MD 20892 USA. NR 88 TC 59 Z9 60 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD JUL PY 2001 VL 13 IS 7 BP 897 EP 908 DI 10.1093/intimm/13.7.897 PG 12 WC Immunology SC Immunology GA 457TR UT WOS:000170153400007 PM 11431420 ER PT J AU Kanai, H Barrett, JC Metzler, M Tsutsui, T AF Kanai, H Barrett, JC Metzler, M Tsutsui, T TI Cell-transforming activity and estrogenicity of bisphenol-A and 4 of its analogs in mammalian cells SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE SHE cells; bisphenol-A; estrogenicity ID HAMSTER EMBRYO CELLS; RECEPTOR-ALPHA; ANEUPLOIDY; ESTRADIOL; BETA AB Estrogenicity is an important mechanism in hormonal carcinogenesis but not sufficient to explain the carcinogenic activity of all estrogens. Additional mechanisms, related to genetic alterations, in conjunction with estrogenicity mediated through the estrogen receptor, have been suggested, An environmental estrogen bisphenol-A (BP-A) and its analogs are widespread in our living environment. Because of the potential for human exposure, the possible relationship between carcinogenicity and estrogenicity of these bisphenols was studied using mammalian cells. We quantitatively compared the cell-transforming activity of BP-A and 4 of its analogs (BP-2, BP-3, BP-4 and BP-5) in Syrian hamster embryo (SHE) cells lacking estrogen-receptor expression. The transforming activity determined by the morphological transformation frequencies in SHE cells treated with the bisphenols ranked: BP-4 > BP-5 > BP-3 > BP-A > BP-2, We also compared the estrogenicity of the 5 bisphenols in MCF7 human breast cancer cells as determined by cell proliferation or progesterone receptor (PgR) expression assayed by RT-PCR, When MCF7 cells were treated with the bisphenols, the proliferative potency ranked: BP-A > BP-5 > BP-4 > BP-3 = BP-2. The level of mRNA for PgR in cells treated with the bisphenols was BE-A > BP-5 > BP-4 > BP-3 > BP-2, These indicate that the transforming activity does not correlate with the estrogenicity of the bisphenols, except for BP-2 that has the weakest activity at the both endpoints, In addition, our results suggest that bisphenols with few, if any, transforming and estrogenic activities could be altered by a modification of the chemical structure, Published 2001 Wiley-Liss, Inc.(dagger). C1 NIEHS, Res Triangle Pk, NC 27709 USA. Nippon Dent Univ, Dept Pharmacol, Tokyo, Japan. NCI, Bethesda, MD 20892 USA. Univ Karlsruhe, Inst Food Chem, Karlsruhe, Germany. RP Barrett, JC (reprint author), NIEHS, POB 12233,MD C2-15, Res Triangle Pk, NC 27709 USA. NR 18 TC 15 Z9 16 U1 1 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 1 PY 2001 VL 93 IS 1 BP 20 EP 25 DI 10.1002/ijc.1303 PG 6 WC Oncology SC Oncology GA 436BP UT WOS:000168916900004 PM 11391616 ER PT J AU Kim, SN Ahn, YH Kim, SG Park, SD Yoon, SCC Hong, SH AF Kim, SN Ahn, YH Kim, SG Park, SD Yoon, SCC Hong, SH TI 8-Cl-cAMP induces cell cycle-specific apoptosis ln human cancer cells SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE 8-Cl-cAMP; apoptosis; protein kinase A; cell cycle; human cancer cells ID PROTEIN-KINASE-A; RII(BETA) REGULATORY SUBUNIT; HUMAN NEUROBLASTOMA-CELLS; HL-60 LEUKEMIA-CELLS; RI-ALPHA-SUBUNIT; GROWTH-INHIBITION; AMP ANALOGS; CAMP; DIFFERENTIATION; SITE AB 8-Cl-cyclic adenosine monophosphate (8-Cl-cAMP) has been known to induce growth inhibition and differentiation in a variety of cancer cells by differential modulation of protein kinase A isozymes, To understand the anticancer activity of 8-Cl-cAMP further, we investigated the effect of 8-Cl-cAMP on apoptosis in human cancer cells. Most of the tested human cancer cells exhibited apoptosis upon treatment with 8-Cl-cAMP, albeit with different sensitivity. Among them, SH-SY5Y neuroblastoma cells and HL60 leukemic cells showed the most extensive apoptosis, The effect of 8-Cl-cAMP was not reproduced by other cAMP analogues or cAMP-elevating agents, showing that the effect of 8-Cl-cAMP was not caused by simple activation of protein kinase A (PKA), However, competition experiments showed that the binding of 8-Cl-cAMP to the cAMP receptor was essential for the induction of apoptosis, After the treatment of 8-Cl-cAMP, cells initially accumulated at the S and G2/M phases of the cell cycle and then apoptosis began to occur among the population of cells at the S/G2/M cell cycle phases, indicating that the 8-Cl-cAMP-induced apoptosis is closely related to cell cycle control. In support of this assumption, 8-Cl-cAMP-induced apoptosis was blocked by concomitant treatment with mimosine, which blocks the cell cycle at early S phase. Interestingly, 8-Cl-cAMP did not induce apoptosis in primary cultured normal cells and non-transformed cell lines, showing that 8-CI-cAMP-induced apoptosis is specific to transformed cells. Taken together, our results show that the induction of apoptosis is one of the mechanisms through which 8-Cl-cAMP exerts anticancer activity. (C) 2001 Wiley-Liss, Inc. C1 Seoul Natl Univ, Inst Mol Biol & Genet, Seoul 151742, South Korea. Seoul Natl Univ, Coll Nat Sci, Sch Biol Sci, Seoul, South Korea. NCI, Cellular Biochem Sect, Tumor Immunol & Biol Lab, NIH, Bethesda, MD USA. RP Hong, SH (reprint author), Seoul Natl Univ, Inst Mol Biol & Genet, Seoul 151742, South Korea. NR 25 TC 44 Z9 46 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 1 PY 2001 VL 93 IS 1 BP 33 EP 41 DI 10.1002/ijc.1308 PG 9 WC Oncology SC Oncology GA 436BP UT WOS:000168916900006 PM 11391618 ER PT J AU Dhillon, PK Farrow, DC Vaughan, TL Chow, WH Risch, HA Gammon, MD Mayne, ST Stanford, JL Schoenberg, JB Ahsan, H Dubrow, R West, AB Rotterdam, H Blot, WJ Fraumeni, JF AF Dhillon, PK Farrow, DC Vaughan, TL Chow, WH Risch, HA Gammon, MD Mayne, ST Stanford, JL Schoenberg, JB Ahsan, H Dubrow, R West, AB Rotterdam, H Blot, WJ Fraumeni, JF TI Family history of cancer and risk of esophageal and gastric cancers in the United States SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE esophageal neoplasm; stomach neoplasm; case-control study; family history; United States ID SQUAMOUS-CELL CARCINOMA; STOMACH-CANCER; SOCIOECONOMIC-FACTORS; HELICOBACTER-PYLORI; COLORECTAL-CANCER; SHANXI-PROVINCE; ADENOCARCINOMA; TOBACCO; CARDIA; ALCOHOL AB The worldwide rates for histology- and subsite-specific types of esophageal and gastric cancer reveal strikingly divergent patterns. The contribution of environmental and genetic factors has been explored in several high-incidence areas, but data on genetic influences are scarce for Western countries. Using data from a multicenter, population-based, case-control study on 1,143 cases and 695 controls in the United States, we evaluated whether a family history of digestive or other cancers was associated with an increased risk of esophageal adenocarcinoma (n = 293), esophageal squamous cell carcinoma (n = 221), gastric cardia adenocarcinoma(n = 261) or non-cardia gastric adenocarcinoma (n = 368). After adjusting for other risk factors, individuals reporting a family history of digestive cancers experienced no increased risk of either type of esophageal cancer but they were prone to adenocarcinomas of the gastric cardia [odds ratio (OR) = 1.34, 95% confidence interval (CI) 0.91-1.97] and non-cardia segments (OR = 1.46, 95% CI 1.03-2.08). This familial tendency, particularly for non-cardia gastric tumors, was largely explained by an association with family history of stomach cancer (OR = 2.52, 95% CI 1.50-4.23), In addition, family history of breast cancer was associated with increased risks of esophageal adenocarcinoma (OR = 1.74, 95% CI 1.07-2.83) and non-cardia gastric adenocarcinoma (OR = 1.76, 95% CI 1.09-2.82). Also seen were non-significant familial associations of esophageal squamous-cell cancer with prostate cancer as well as non-cardia gastric cancer with leukemia and brain tumors, though these relationships must be interpreted with caution. Our data point to the role of familial susceptibility to gastric cancer, but not to any form of esophageal cancer, in the United States. (C) 2001 Wiley-Liss, Inc. C1 Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98109 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. New Jersey Dept Hlth & Senior Serv, Off Canc Epidemiol, Trenton, NJ USA. Columbia Univ, Joseph L Mailman Sch Publ Hlth, Div Epidemiol, New York, NY USA. Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. Columbia Univ, Coll Phys & Surg, Dept Pathol, New York, NY USA. Int Epidemiol Inst, Rockville, MD USA. RP Farrow, DC (reprint author), Fred Hutchinson Canc Res Ctr, Program Epidemiol, 1100 Fairview Ave N,POB 19024,MP-474, Seattle, WA 98109 USA. FU NCI NIH HHS [5U01-CA57923, N01-CN-05230, N02-CP-40501, U01-CA57949, U01-CA57983]; NIDDK NIH HHS [R01-DK58834] NR 42 TC 78 Z9 82 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 1 PY 2001 VL 93 IS 1 BP 148 EP 152 DI 10.1002/ijc.1294 PG 5 WC Oncology SC Oncology GA 436BP UT WOS:000168916900023 PM 11391635 ER PT J AU Oppenheim, JJ AF Oppenheim, JJ TI Cytokines: Past, present, and future SO INTERNATIONAL JOURNAL OF HEMATOLOGY LA English DT Article DE cytokines; interleukins; receptors; immunoregulation; chemotaxis; hematopoiesis ID NEUTROPHIL CHEMOTACTIC FACTOR; TUMOR NECROSIS FACTOR; MOLECULAR-CLONING; INTERLEUKIN-2 RECEPTOR; LEUKOCYTIC PYROGEN; COMPLEMENTARY-DNA; LYMPHOCYTE-T; EXPRESSION; CDNA; CELLS AB This review provides an historical account of the discovery and development of cytokines. Cytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell growth, differentiation, cell death, angiogenesis, and development and repair processes aimed at the restoration of homeostasis. Although cytokines are occasionally produced constitutively, they are usually produced by virtually every nucleated cell type in response to injurious stimuli. Cytokines act on cells expressing complementary receptors. Cytokines have been assigned to various family groups based on the structural homologies of their receptors. This review shows how cytokine research evolved from phenomenological to molecular stages and from a focus on ligands to characterization of cytokine receptors. The advent of molecular biology, monoclonal antibodies, and microsequencing made it possible to obtain pure recombinant cytokine preparation for experimental and therapeutic applications. The development of targeted gene .deletions revealed many cytokines to have unexpected pathophysiological functions. The identification of "virokines," homologues that mimic cytokine ligands and receptors, has provided impetus to the founding of biotechnology companies aimed at developing cytokine agonists and antagonists for therapeutic applications. The discipline of cytokinology is now endowed with several journals, multiple annual meetings, and many devoted investigators. The explosion in cytokine information over the past 40 years has been enormous and full of surprises. If past be prologue, with the advent of genomics and proteomics the future should witness even greater progress. (C) 2001 The Japanese Society of Hematology. C1 NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, Div Basic Sci, Frederick, MD 21702 USA. RP Oppenheim, JJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, Div Basic Sci, Bldg 560,Room 21-89A, Frederick, MD 21702 USA. NR 62 TC 92 Z9 94 U1 1 U2 12 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0925-5710 J9 INT J HEMATOL JI Int. J. Hematol. PD JUL PY 2001 VL 74 IS 1 BP 3 EP 8 DI 10.1007/BF02982543 PG 6 WC Hematology SC Hematology GA 466HV UT WOS:000170640900002 PM 11530802 ER PT J AU Ruscetti, FW Bartelmez, SH AF Ruscetti, FW Bartelmez, SH TI Transforming growth factor beta, pleiotropic regulator of hematopoietic stem cells: Potential physiological and clinical relevance SO INTERNATIONAL JOURNAL OF HEMATOLOGY LA English DT Article DE transforming growth factor-beta 1; hematopoiesis; autocrine; paracrine; stem cells ID HUMAN MARROW CULTURES; HUMAN-BONE-MARROW; TGF-BETA; PROGENITOR CELLS; GENE-TRANSFER; RETROVIRAL TRANSDUCTION; STROMAL CELLS; CYCLE STATUS; IN-VIVO; TGF-BETA-1 AB Transforming growth factor beta (TGF-beta) is a pleiotropic regulator of all stages of hematopoieis. Depending on the differentiation stage of the target cell, the local environment, and the concentration of TGF-beta, TGF-beta can be proproliferative or antiproliferative, proapoptotic or antiapoptotic, and/or prodifferentiative or antidifferentiative. TGF-beta is the major regulator of stem cell quiescence and can act directly or indirectly through effects on the marrow microenvironment. In addition, paracrine and autocrine actions of TGF-beta have overlapping but distinct regulatory effects on hematopoietic stem/progenitor cells. Neutralization of autocrine TGF-beta has therapeutic potential. (C) 2001 The Japanese Society of Hematology. C1 NCI, Frederick Canc Res & Dev Ctr, Leukocyte Biol Sect, Basic Res Lab,Ctr Canc Res, Frederick, MD 21702 USA. Univ Washington, Sch Publ Hlth, Dept Pathobiol, Seattle, WA 98195 USA. RP Ruscetti, FW (reprint author), NCI, Frederick Canc Res & Dev Ctr, Leukocyte Biol Sect, Basic Res Lab,Ctr Canc Res, Bldg 567,Rm 251, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 45 TC 18 Z9 21 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0925-5710 J9 INT J HEMATOL JI Int. J. Hematol. PD JUL PY 2001 VL 74 IS 1 BP 18 EP 25 DI 10.1007/BF02982545 PG 8 WC Hematology SC Hematology GA 466HV UT WOS:000170640900004 PM 11530800 ER PT J AU Lin, YW Hamahata, K Watanabe, K Adachi, S Akiyama, Y Kubota, M Nakahata, T AF Lin, YW Hamahata, K Watanabe, K Adachi, S Akiyama, Y Kubota, M Nakahata, T TI Repetitious appearance and disappearance of different kinds of clonal cytogenetic abnormalities after allogeneic bone marrow transplantation SO INTERNATIONAL JOURNAL OF HEMATOLOGY LA English DT Article DE cytogenetic abnormality; BMT; MDS; genomic instability ID ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; MYELODYSPLASIA; CHILDHOOD; LYMPHOMA; CHILDREN AB We report a childhood case that showed the repeated appearance and disappearance of various kinds of cytogenetic abnormalities (CA) for 5.5 years after allogeneic bone marrow transplantation (BMT). The patient underwent allogeneic BMT from an HLA-matched unrelated donor during the second complete remission of acute lymphoblastic leukemia. The conditioning regimen for BMT consisted of etoposide, cyclophosphamide. anti-human thymocyte immunoglobulin, and total body irradiation. There were no leukemic relapses or secondary acute myeloid leukemia/myelodysplastic syndrome (AML/MDS) since the BMT. The CA occurred from residual recipient cells, which were damaged by chemotherapy or radiation prior to BMT. Although previous studies about post-BMT CA had reported the continuous emergence of identical clones, the present case showed the appearance of one different type of clone after another. Although the appearance of different types of CA may mean that these clones did not obtain any growth advantages, it may be a sign of genomic instability, which is probably a risk factor for the development of secondary AML/MDS. (C) 2001 The Japanese Society of Hematology. C1 Kyoto Univ, Fac Med, Dept Pediat, Kyoto 606, Japan. S Kyoto Natl Hosp, Dept Pediat, Kyoto, Japan. Kobe City Gen Hosp, Dept Pediat, Kobe, Hyogo, Japan. RP Lin, YW (reprint author), NCI, Ctr Adv Technol, NIH, 8717 Grovemont Circle, Gaithersburg, MD 20877 USA. NR 16 TC 9 Z9 9 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0925-5710 J9 INT J HEMATOL JI Int. J. Hematol. PD JUL PY 2001 VL 74 IS 1 BP 86 EP 89 DI 10.1007/BF02982555 PG 4 WC Hematology SC Hematology GA 466HV UT WOS:000170640900014 PM 11530811 ER PT J AU Kawate, S Ohwada, S Hamada, K Koyama, T Takenoshita, S Morishita, Y Hagiwara, K AF Kawate, S Ohwada, S Hamada, K Koyama, T Takenoshita, S Morishita, Y Hagiwara, K TI Mutational analysis of the Smad6 and Smad7 genes in hepatocellular carcinoma SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE Smad; TGF-beta; hepatocellular carcinoma; mutation; polymorphism ID GROWTH-FACTOR-BETA; MAD-RELATED PROTEIN; II RECEPTOR GENE; TGF-BETA; INTRON PRIMERS; GENOMIC DNA; DPC4 GENE; SUPERFAMILY; INHIBITION; ANTAGONIST AB Resistance to the transforming growth factor-beta (TGF-beta) is a frequently found phenotype in human malignancies. The recent identification of Smad6 and Smad7, both anti-Smads which inhibit TGF-beta signaling, raises a possibility that constitutive activation of the anti-Smads by a somatic mutation may impair the TGF-beta signaling pathway. We tested this hypothesis by screening the entire coding sequences of these anti-Smads for mutations in 52 hepatocellular carcinoma (HCC) samples using polymerase chain reaction - single strand confomation polymorphism analysis. We detected no mutations, but found 3 single nucleotide polymorphisms (SNPs) in the Smad6 gene and 2 SNPs in the Smad7 gene. These results suggest that mutations of the Smad6 and Smad7 genes are not the main cause of the TGF-beta resistance in human HCC. C1 Gunma Univ, Fac Med, Dept Surg 2, Maebashi, Gumma 3718511, Japan. NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Fukushima Med Coll, Dept Surg 2, Fukushima 9601295, Japan. RP Ohwada, S (reprint author), Gunma Univ, Fac Med, Dept Surg 2, Maebashi 3-39-22, Maebashi, Gumma 3718511, Japan. NR 23 TC 15 Z9 18 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD JUL PY 2001 VL 8 IS 1 BP 49 EP 52 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 445PH UT WOS:000169466100006 PM 11408948 ER PT J AU Klus, GT Rokaeus, N Bittner, ML Chen, YD Korz, DM Sukumar, S Schick, A Szallasi, Z AF Klus, GT Rokaeus, N Bittner, ML Chen, YD Korz, DM Sukumar, S Schick, A Szallasi, Z TI Down-regulation of the desmosomal cadherin desmocollin 3 in human breast cancer SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE down-regulation; desmocollin 3; breast cancer; desmosome; gene expression ID MAMMARY EPITHELIAL-CELLS; GENE-EXPRESSION PATTERNS; CARCINOMA; DIFFERENTIATION; ISOFORMS; BEHAVIOR AB In previous studies using cDNA microarray analysis, we have identified an expressed sequence tag which is consistently down-regulated in six human breast tumor cell lines. In the current study, we have determined this tag to be part of the mRNA sequence of human desmocollin 3, a member of the cadherin superfamily of proteins and an integral component of desmosomes. Desmosomes are sites of adhesion between adjacent cells in layers of epithelia, as well as in some non-epithelial tissues, and play an important role in the maintenance of tissue structure. Northern analysis, quantitative real-time polymerase chain reaction assay and Western blot analysis showed that desmocollin 3 is present in normal and immortalized human mammary epithelial cells, but consistently exhibits a significant, and often complete, down-regulation in breast cancer cell lines and primary breast tumors, both at the mRNA and protein levels. C1 Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Bethesda, MD 20814 USA. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Oncol Ctr, Baltimore, MD 21231 USA. RP Szallasi, Z (reprint author), Uniformed Serv Univ Hlth Sci, Dept Pharmacol, 4301 Jones Bridge Rd,Room C-2027, Bethesda, MD 20814 USA. NR 20 TC 22 Z9 24 U1 0 U2 1 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD JUL PY 2001 VL 19 IS 1 BP 169 EP 174 PG 6 WC Oncology SC Oncology GA 446QR UT WOS:000169524400024 PM 11408939 ER PT J AU Zhou, DH Yu, T Chen, G Brown, SA Yu, ZF Mattson, MP Thompson, JS AF Zhou, DH Yu, T Chen, G Brown, SA Yu, ZF Mattson, MP Thompson, JS TI Effects of NF-kappa B1 (p50) targeted gene disruption on ionizing radiation-induced NF-kappa-B activation and TNF alpha, IL-1 alpha, IL-1 beta and IL-6 mRNA expression in vivo SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; VERSUS-HOST DISEASE; TOTAL-BODY IRRADIATION; MESSENGER-RNA LEVELS; BONE-MARROW TRANSPLANTATION; NORMAL RAT ASTROCYTES; GAMMA-IRRADIATION; INTERLEUKIN-1-BETA GENE; IMMUNE-RESPONSES; MICE LACKING AB Purpose: To investigate the role of the NF-kappaB] (p50) gene in ionizing radiation (IR)-induced NF-kappaB activation and TNF alpha, IL- 1 alpha, IL-1 beta and IL-6 mRNA expression in vivo. Materials and methods: NF-kappaB activation was analysed by the gel shift/supershift assay and the levels or TNF alpha, IL-1 alpha, IL-1 beta and IL-6 mRNA were measured using RNase protection assay (RPA). Various tissues from BALB/c, B6,129P-Nfkb1 (NF-kappa B1 or p50 gene knockout, p50(-/-)) and B6,129PF2 (wild-type, p50(+/+)) mice were analysed before or after exposure to a lethal dose (8.5 Gy) of total-body gamma -irradiation. Results: Exposure of BALB/c mice to total-body IR selectively activated NF-kappaB in the spleen, mesenteric lymph nodes (LN) and bone marrow (BM). Gel supershift assay using polyclonal antibodies against NF-kappaB p50, p65 or c-Rel protein revealed that the NF-kappaB p50 subunit is a critical component of the NF-kappaB complexes activated by IR in vivo. Discretely augmented TNF alpha, IL-1 alpha, IL-1 beta and IL-6 mRNA expression was found in the spleen, LN and BM after BALB/c mice received IR. However, mice lacking the p50 gene (p50(-/-)) showed a significant reduction in IR-induced activation of NF-kappaB and increases in TNF alpha, IL-1 alpha IL-1 beta and IL-6 mRNA expression, as compared with that of wild-type mice (p50(+/+)). Conclusions:The NF-kappaB p50 subunit is a critical component of the NF-kappaB complexes activated by IR and it plays an important role in mediating IR-induced TNF alpha, IL-1 alpha, IL-1 beta and IL-6 mRNA expression in vivo. C1 Univ Kentucky, Sanders Brown Res Ctr Aging, Div Rheumatol Allergy & Immunol, Dept Internal Med, Lexington, KY 40536 USA. Vet Adm Med Ctr, Lexington, KY 40511 USA. NIA, Gerontol Res Ctr, Neurosci Lab, Baltimore, MD 21224 USA. Med Univ S Carolina, Dept Pathol, Div Res, Charleston, SC 29425 USA. RP Zhou, DH (reprint author), Univ Kentucky, Sanders Brown Res Ctr Aging, Div Rheumatol Allergy & Immunol, Dept Internal Med, Lexington, KY 40536 USA. RI Mattson, Mark/F-6038-2012 FU NCI NIH HHS [CA78688]; NIMH NIH HHS [MH55058] NR 49 TC 52 Z9 52 U1 0 U2 4 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 0955-3002 J9 INT J RADIAT BIOL JI Int. J. Radiat. Biol. PD JUL PY 2001 VL 77 IS 7 BP 763 EP 772 PG 10 WC Biology; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 450PE UT WOS:000169751700001 PM 11454276 ER PT J AU de Bruyn, G Adams, GJ Teeter, LD Soini, H Musser, JM Graviss, EA AF de Bruyn, G Adams, GJ Teeter, LD Soini, H Musser, JM Graviss, EA TI The contribution of ethnicity to Mycobacterium tuberculosis strain clustering SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE LA English DT Article DE M tuberculosis; epidemiology; RFLP; minorities ID HUMAN-IMMUNODEFICIENCY-VIRUS; EXTENSIVE TRANSMISSION; RECEPTOR GENE; SAN-FRANCISCO; SUSCEPTIBILITY; OUTBREAK; EPIDEMIOLOGY; INFECTION; AFRICANS; POLYMORPHISM AB OBJECTIVE: Descriptive study of molecular epidemiologic patterns of tuberculosis cases among ethnic minorities in Houston, Texas. DESIGN: Population-based, prospective, active surveillance, and molecular epidemiology study. PATIENTS: Tuberculosis cases reported to the City of Houston Tuberculosis Control Office between October 1995 and September 1998. RESULTS: During the study period, 1133 culture-positive patients were enrolled for whom isolates of their culture specimen were available. Of these, 310 were part of an ethnic minority. Molecular characterization identified 689 of 1139 isolates to be clonally related. Factors significantly associated with tuberculosis strain clustering in a multivariable logistic regression analysis were: birth in the United States, a history of homelessness, infection with the human immunodeficiency virus (HIV), pulmonary disease, infection with a tuberculosis strain from principal genetic group 1 or 3, living in a residence with five or more persons present, and use of public transportation more than once weekly. Asian ethnicity and increasing age were associated with decreased odds of clustering. CONCLUSIONS: Ethnicity was not a significant covariate for strain clustering after adjustments for factors related to socio-economic status. C1 Baylor Coll Med, Dept Pathol 209 E, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA. NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. RP Graviss, EA (reprint author), Baylor Coll Med, Dept Pathol 209 E, 1 Baylor Plaza, Houston, TX 77030 USA. FU NIAID NIH HHS [N01-AO-02738]; NIDA NIH HHS [DA-09238] NR 43 TC 7 Z9 7 U1 0 U2 2 PU INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D) PI PARIS PA 68 BOULEVARD SAINT-MICHEL,, 75006 PARIS, FRANCE SN 1027-3719 J9 INT J TUBERC LUNG D JI Int. J. Tuberc. Lung Dis. PD JUL PY 2001 VL 5 IS 7 BP 633 EP 641 PG 9 WC Infectious Diseases; Respiratory System SC Infectious Diseases; Respiratory System GA 449FH UT WOS:000169673300007 PM 11469256 ER PT J AU Lee, J Jiao, XD Hejtmancik, JF Kaiser-Kupfer, M Gahl, WA Markello, TC Guo, JR Chader, GJ AF Lee, J Jiao, XD Hejtmancik, JF Kaiser-Kupfer, M Gahl, WA Markello, TC Guo, JR Chader, GJ TI The metabolism of fatty acids in human bietti crystalline dystrophy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; DOCOSAHEXAENOIC ACID; BINDING; RETINA; PHOSPHOLIPIDS; PROTEINS; CULTURE; LIPIDS; TISSUE; CELLS AB PURPOSE. TO investigate the role of abnormal lipid metabolism in Bietti crystalline dystrophy. METHODS. Cultured human lymphocytes and fibroblasts from patients with Bietti crystalline dystrophy (BCD) were incubated in the presence of [C-14]18:3n-3 or [C-14]18:2n-6. Incorporation into the cellular lipid pools and further metabolism by desaturation or elongation were monitored by thin-layer chromatography and HPLC. Results were compared with those in normal control subjects and patients with Wolman disease (WD). RESULTS. Pulse-chase experiments with labeled fatty acids in all groups showed that, after 1 hour, radioactivity was largely confined to the triacylglyceride (TG) and choline phosphoglyceride (CPG) pools. However, after several hours, radioactivity was transferred from the TG and CPG pools, some going to the serine and ethanolamine phosphoglyceride (SPG and EPG) pools. Fibroblasts from all groups showed direct transfer of fatty acids (FAs) into CPG and EPG. Incorporation of labeled FAs into the EPG pool paralleled extensive desaturation and elongation of 18:2n-6 to 22:5n-6 and 18:3n-3 to 22:6n-3. Fibroblasts from patients with WD (a lysosomal acid lipase deficiency characterized by excessive lipid accumulation), showed higher incorporation of 18:2n-6 into TGs than did normal or BCD fibroblasts. Conversely, fibroblasts from patients with BCD showed lower conversion of 18:3n-3, but not of 18:2n6, into polyunsaturated FAs (PUFAs) than those of normal subjects or patients with WD. This was true for total FAs, CPGs, and EPGs. Similar results were found in both fibroblasts and lymphocytes; however, unlike fibroblasts, lymphocytes from normal subjects showed similar levels of incorporation of FAs into EPGs and CPGs. In contrast, incorporation of 18:3n-3 into EPGs was decreased in lymphocytes from patients with BCD. CONCLUSIONS. BCD is characterized by a lower than normal conversion of FA precursors into n-3 PUFA, whereas there is a higher than normal level of nd and n-3 FAs incorporation into TGs in cells from patients with WD. These findings raise the possibility that abnormal lipid metabolism associated with BCD is the result of deficient lipid binding, elongation, or desaturation in contrast to the lysosomal acid lipase deficiency found in Wolman disease. C1 NEI, OGVFB, NIH, Bethesda, MD 20892 USA. NICHHD, NIH, Bethesda, MD 20892 USA. Fdn Fighting Blindness, Hunt Valley, MD USA. RP Hejtmancik, JF (reprint author), NEI, OGVFB, NIH, Bldg 10,Room 10B10,10 Ctr Dr MSC 1860, Bethesda, MD 20892 USA. NR 25 TC 40 Z9 46 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUL PY 2001 VL 42 IS 8 BP 1707 EP 1714 PG 8 WC Ophthalmology SC Ophthalmology GA 451JG UT WOS:000169798500008 PM 11431432 ER PT J AU Finkel, T AF Finkel, T TI Reactive oxygen species and signal transduction SO IUBMB LIFE LA English DT Review DE glutathione; NADPH oxidase; reactive oxygen species; signal transduction ID HYDROGEN-PEROXIDE; GENERATION; RAC1; CELLS; EXPRESSION; OXIDASE; H2O2 AB Increasing evidence suggests a role for intracellular reactive oxygen species (ROS) as mediators of normal and pathological signal transduction pathways. In particular, a growing list of recent reports have demonstrated a rapid and significant increases in intracellular ROS following growth factor or cytokine stimulation. These ROS appear essential for a host of downstream signaling events. Biochemical characterization of this ligand-activated ROS production has revealed important information regarding the molecular composition of the cellular oxidases and the regulation of their activity by small GTPases. Work is proceeding on identifying strategies to identify how ROS might specifically regulate signaling pathways by altering the activity of direct target molecules. This review will focus on the progress in the rapid emerging area of oxidant or redox-dependent signal transduction and speculate how these insights might alter our view and treatment of diseases thought to be caused by oxidative stress. C1 NHLBI, Mol Biol Lab, NIH, Bethesda, MD 20814 USA. RP Finkel, T (reprint author), NHLBI, Mol Biol Lab, NIH, Bldg 10,6N-240,10 Ctr Dr, Bethesda, MD 20814 USA. RI Bell, Tiffany/F-4403-2010 NR 22 TC 189 Z9 194 U1 2 U2 16 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1521-6543 J9 IUBMB LIFE JI IUBMB Life PD JUL PY 2001 VL 52 IS 1-2 BP 3 EP 6 DI 10.1080/15216540252774694 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 509ER UT WOS:000173133800002 PM 11795590 ER PT J AU Rhee, SG Kang, SW Chang, TS Jeong, W Kim, K AF Rhee, SG Kang, SW Chang, TS Jeong, W Kim, K TI Peroxiredoxin, a novel family of peroxidases SO IUBMB LIFE LA English DT Review ID THIOL-SPECIFIC ANTIOXIDANT; ONE-CONSERVED CYSTEINE; SACCHAROMYCES-CEREVISIAE; MAMMALIAN PEROXIREDOXIN; THIOREDOXIN PEROXIDASE; HYDROGEN-PEROXIDE; CRYSTAL-STRUCTURE; RAT-LIVER; CLONING; PROTEIN C1 NHLBI, NIH, Lab Cell Signaling, Bethesda, MD 20892 USA. Chonnam Natl Univ, Coll Home Econ, Dept Food & Nutr, Kwangju, South Korea. RP Rhee, SG (reprint author), NHLBI, NIH, Lab Cell Signaling, Bldg 50,Rm 3523, Bethesda, MD 20892 USA. NR 40 TC 351 Z9 382 U1 0 U2 19 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1521-6543 J9 IUBMB LIFE JI IUBMB Life PD JUL PY 2001 VL 52 IS 1-2 BP 35 EP 41 DI 10.1080/15216540252774748 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 509ER UT WOS:000173133800007 PM 11795591 ER PT J AU Matsumoto, Y Takano, H Kunishio, K Nagao, S Fojo, T AF Matsumoto, Y Takano, H Kunishio, K Nagao, S Fojo, T TI Expression of drug resistance genes in VP-16 and mAMSA-selected human carcinoma cells SO JAPANESE JOURNAL OF CANCER RESEARCH LA English DT Article DE topoisomerase II; MRP; cMOAT; CKII; MDR-1 ID DNA TOPOISOMERASE-II; HUMAN TUMOR-CELLS; CASEIN KINASE-II; MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; NIH-3T3 CELLS; OVEREXPRESSION; FORMS; LINE; ACCUMULATION AB The cell lines described in the present study were isolated as part of an effort to understand resistance to topoisomerase (topo) II inhibitors. To that end, 50 sublines were isolated from four human breast cancer cell lines, i.e., MCF-7, T47D, MDA-MB-231, and ZR-75B. As an initial step, a concentration that would be lethal to the majority of cells (IC99) was selected for both VP-16 and mAMSA, for each cell line. The identification of an increasing number of putative drug resistance-related proteins provided the opportunity to examine expression of the corresponding genes in the selected cell lines. Northern blot analysis revealed different responses to the selecting agents in the different cell lines. Previous studies examining expression of multidrug resistance (MDR)-1 in resistant cell lines had found undetectable levels in all cells. In the ZR-75B sublines, increased expression of MDR-associated protein (NW) and canalicular multispecific organic anion transporter (c-MOAT) was observed, and when the relative levels of overexpression were compared, a high correlation was found. In contrast, increased expression of MR-P was observed in some of the MDA-MB-231 sublines, without a concomitant increase in cMOAT expression. Finally, in both T47D and MCF-7 sublines, increased expression of cMOAT or MRP was observed infrequently, and where it occurred, was of a much smaller magnitude. In the analysis of expression of MRP, the highest levels were found in the ZR-75B and MDA-MB-231 sublines, with lower levels in the MCF-7 and T47D clones. Similarly, differences in the expression of topo II alpha were observed among the sublines. Although the differences in expression appear to depend on the parental cell line from which the resistant sublines were derived, a strong correlation was observed between the expression of MRP and the levels of topo II alpha. Cell lines with low levels of MRP had lower levels of topo II alpha, while those with high levels of MRP maintained higher levels of topo Ha. While a reduced topo II alpha level was common, there did not appear to be a compensating increase in the expression of topo II beta or topo I or casein kinase (CK) II alpha in any of the cell lines. While the possibility that such compensation could occur has been discussed and even reported in some cell lines, such an adaptation was not observed in the present study, suggesting that it is not common. C1 Kagawa Med Univ, Dept Neurol Surg, Miki, Kagawa 7610793, Japan. NCI, Med Branch, DCS, NIH, Bethesda, MD 20892 USA. RP Matsumoto, Y (reprint author), Kagawa Med Univ, Dept Neurol Surg, 1750-1 Ikenobe, Miki, Kagawa 7610793, Japan. NR 36 TC 9 Z9 11 U1 0 U2 0 PU BUSINESS CENTER ACADEMIC SOCIETIES JAPAN PI TOKYO PA 5-16-9 HONKOMAGOME, BUNKYO-KU, TOKYO, 113-8633, JAPAN SN 0910-5050 J9 JPN J CANCER RES JI Jpn. J. Cancer Res. PD JUL PY 2001 VL 92 IS 7 BP 778 EP 784 PG 7 WC Oncology SC Oncology GA 457JK UT WOS:000170133600009 PM 11473729 ER PT J AU Matsumoto, Y Takano, H Kunishio, K Nagao, S Fojo, T AF Matsumoto, Y Takano, H Kunishio, K Nagao, S Fojo, T TI Hypophosphorylation of topoisomerase II alpha in etoposide (VP-16)-resistant human carcinoma cell lines associated with carboxy-terminal truncation SO JAPANESE JOURNAL OF CANCER RESEARCH LA English DT Article DE topoisomerase II; nuclear localization; acquired drug resistance; etoposide; topoisomerase II poisons ID CASEIN KINASE-II; DNA TOPOISOMERASE; RESISTANCE; DOMAIN; GENE; PHOSPHORYLATION; EXPRESSION; REGION; AGENTS; CYCLE AB Topoisomerase II alpha is a target for many chemotherapeutic agents in clinical use. To define mechanisms of resistance and regions crucial for the function of topoisomerase II alpha drug-resistant cell lines have been isolated following exposure to topoisomerase II poisons. Two resistant sublines, T47D-VP and MCF-7-VP, were isolated from human carcinoma cell lines following exposure to 300 or 500 ng/ml etoposide (VP-16). Cytotoxicity studies confirmed resistance to etoposide and other topoisomerase II poisons. KCl-sodium dodecyl sulfate (K-SDS) precipitation assays using intact cells showed reduced DNA-topoisomerase II complex formation following VP-16 or amsacrine (m-AMSA). RNAse protection analysis identified a deletion of 200 base pairs in the topoisomerase II alpha cDNA of T47D-VP and "AA insertion" in the topoisomerase II alpha cDNA of MCF-7-VP. Reduced topoisomerase II alpha mRNA and protein levels were observed in both cell lines. It was somewhat surprising to find that nuclear extracts from T47D-VP and MCF-7-VP cells had comparable topoisomerase II activity to that of parental cells. Analysis of the extent of phosphorylation demonstrated that topoisomerase II alpha from the resistant cells was relatively hypophosphorylated compared to that of parental cells. In these cell lines, hypophosphorylation secondary to loss of a portion of the C-terminal domain of topoisomerase II alpha mediated the restored activity, despite a fall in topoisomerase II alpha mRNA and protein, and this resulted in cross resistance to topoisomerase II poisons. C1 Kagawa Med Univ, Dept Neurol Surg, Miki, Kagawa 7610793, Japan. NCI, Med Branch, DCS, NIH, Bethesda, MD 20892 USA. RP Matsumoto, Y (reprint author), Kagawa Med Univ, Dept Neurol Surg, 1750-1 Ikenobe, Miki, Kagawa 7610793, Japan. NR 22 TC 2 Z9 2 U1 0 U2 0 PU BUSINESS CENTER ACADEMIC SOCIETIES JAPAN PI TOKYO PA 5-16-9 HONKOMAGOME, BUNKYO-KU, TOKYO, 113-8633, JAPAN SN 0910-5050 J9 JPN J CANCER RES JI Jpn. J. Cancer Res. PD JUL PY 2001 VL 92 IS 7 BP 799 EP 805 PG 7 WC Oncology SC Oncology GA 457JK UT WOS:000170133600012 PM 11473732 ER PT J AU Miyata, M Furukawa, M Takahashi, K Gonzalez, FJ Yamazoe, Y AF Miyata, M Furukawa, M Takahashi, K Gonzalez, FJ Yamazoe, Y TI Mechanism of 7,12-dimethylbenz[alpha]anthracene-induced immunotoxicity: Role of metabolic activation at the target organ SO JAPANESE JOURNAL OF PHARMACOLOGY LA English DT Article DE 7,12-dimethylbenz[alpha]anthracene; immunotoxicity; microsomal epoxide hydrolase; spleen; null-mouse ID ARYL-HYDROCARBON RECEPTOR; PREB CELL APOPTOSIS; POLYCYCLIC AROMATIC-HYDROCARBONS; MICROSOMAL EPOXIDE HYDROLASE; B6C3F1 MICE; 7,12-DIMETHYLBENZANTHRACENE EXPOSURE; INTRACELLULAR CALCIUM; ALPHA-NAPHTHOFLAVONE; CYTOCHROME P4501B1; AH-RECEPTOR AB The polycyclic aromatic hydrocarbon, 7,12-dimethylbenz[a]anthracene (I)MBA), is an immunosuppressor as well as a potent organ-specific carcinogen. To understand the organ-specific mechanism of DMBA-induced lymphoid toxicity, aryl hydrocarbon-nonresponsive mice and microsomal epoxide hydrolase (mEH)-null mice were analyzed. DMBA caused a dose-dependent decrease in spleen weights, but not the thymus weights in aryl hydrocarbon-nonresponsive mice. On the other hand, both spleen and thymus weights were decreased to less than a half in wild-type mice exposed to 30 mg/kg of DMBA. In contrast, no decrease was detected in spleen weights of mEH-null mice exposed to up to 100 mg/kg of DMBA, while thymus weights were markedly lower. Responses to the B-cell mitogen lipopolysaccharide and to T-cell mitogen phytohemagglutinin were nearly completely abolished in splenocytes isolated from wild-type mice treated with 100 mg/kg of DMBA. These responses were decreased, but maintained in splenocytes isolated from mEH-null mice treated with DMBA. Two DMBA metabolites dependent on mEH including DMBA-3,4-diol were detected in an HPLC chromatogram of spleen microsomes isolated from wild-type mice, but not those from ni-EH-mill mice. These results suggest the involvement of mEH in splenic activation of DMBA for immunotoxicity and the difference for the DMBA-induced lymphoid toxicity between spleen and thymus. C1 Tohoku Univ, Grad Sch Pharmaceut Sci, Div Drug Metab & Mol Toxicol, Aoba Ku, Sendai, Miyagi 9808578, Japan. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Miyata, M (reprint author), Tohoku Univ, Grad Sch Pharmaceut Sci, Div Drug Metab & Mol Toxicol, Aoba Ku, Sendai, Miyagi 9808578, Japan. NR 39 TC 44 Z9 46 U1 1 U2 3 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 0021-5198 J9 JPN J PHARMACOL JI Jpn. J. Pharmacol. PD JUL PY 2001 VL 86 IS 3 BP 302 EP 309 DI 10.1254/jjp.86.302 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 457JR UT WOS:000170134200006 PM 11488430 ER PT J AU Sher, L AF Sher, L TI Relationship between mood disorders and coronary artery disease: possible role of the immune system and infection SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Letter ID HEART-DISEASE; PSYCHOLOGICAL-FACTORS; DEPRESSION; STRESS C1 NIMH, Sect Biol Rhythms, Bethesda, MD 20892 USA. RP Sher, L (reprint author), NIMH, Sect Biol Rhythms, Bldg 10,Room 3S-231,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 17 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD JUL PY 2001 VL 65 IS 2 BP 195 EP 196 DI 10.1016/S0165-0327(00)00214-7 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 438WU UT WOS:000169077900013 PM 11417519 ER PT J AU Roca-Ferrer, J Mullol, J Xaubet, A Benitez, P Bernal-Sprekelsen, M Shelhamer, J Picado, C AF Roca-Ferrer, J Mullol, J Xaubet, A Benitez, P Bernal-Sprekelsen, M Shelhamer, J Picado, C TI Proinflammatory cytokines and eosinophil cationic protein on glandular secretion from human nasal mucosa: Regulation by corticosteroids SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE nasal mucosa; glandular secretion; lactoferrin; budesonide; eosinophil cationic protein; IL-1 beta; TNF-alpha; GM-CSF; IL-10 ID OBSTRUCTIVE PULMONARY-DISEASE; TOPICAL ANTIINFLAMMATORY DRUGS; NECROSIS-FACTOR-ALPHA; HUMAN AIRWAYS INVITRO; GM-CSF SECRETION; EPITHELIAL-CELLS; ALLERGIC RHINITIS; TNF-ALPHA; GLYCOCONJUGATE SECRETION; GLYCOPROTEIN-SECRETION AB Background: Airway hypersecretion is a common finding in rhinitis and asthma in which proinflammatory cytokines are upregulated. The effect of inflammation on glandular secretion remains unclear. Objective: We sought to investigate the effect of proinflammatory cytokines and eosinophil products in in vitro lactoferrin glandular secretion from human nasal mucosa and the role of corticosteroids and IL-10 in modulating this effect. Methods: Nasal explants from patients undergoing turbinectomies were incubated in a controlled atmosphere (50% N-2, 5% CO2, and 45% O-2) at 37 degreesC. Nasal explants were incubated with or without IL-1 beta, IL-4, IL-5, IL-8, eotaxin, GM-CSF, TNF-alpha, eosinophil cationic protein (ECP), IL-10, and budesonide in a time-course and dose-response fashion. Lactoferrin concentrations in culture supernatants were measured by means of ELISA. Results: ECP (up to 30%) caused a dose-related stimulation of lactoferrin secretion. TNF-alpha (20 ng/mL) induced a significant increase of lactoferrin release from 8 hours (27.7 % +/- 17.8 %, P < .05) to 24 hours (40.8% +/- 17.2%, P < .01) compared with that found in media-treated explants. At 24 hours, TNF-alpha caused a dose-related stimulation of lactoferrin secretion (up to 35%). IL-1 beta (65.3% +/- 15.2%, P < .05) and GM-CSF (15.7% +/- 6.7%, P < .05), both at 20 ng/mL, exerted a stimulatory effect only at 24 hours, and IL-4, IL-5, IL-8, and eotaxin had no significant effect. Budesonide caused a dose-related inhibition of lactoferrin secretion induced by IL-1 beta (down to -76%) and TNF-alpha (down to -70%), whereas IL-10 had no effect. Conclusions: ECP and some proinflammatory cytokines (IL-1 beta, TNF-alpha, and GM-CSF) may contribute to glandular hypersecretion in the inflamed nose. Corticosteroids may reduce nasal hypersecretion by blocking the direct effect of proinflammatory cytokines on glandular output. C1 Univ Barcelona, Hosp Clin, Dept Med, Serv Pneumol, E-08036 Barcelona, Catalonia, Spain. IDIBAPS, Fundacio Clin Recerca Biomed, Barcelona, Catalonia, Spain. Gen Hosp, Serv Otorinolaringol, Barcelona, Catalonia, Spain. NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. RP Picado, C (reprint author), Univ Barcelona, Hosp Clin, Dept Med, Serv Pneumol, Villarroel 170, E-08036 Barcelona, Catalonia, Spain. NR 55 TC 14 Z9 14 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUL PY 2001 VL 108 IS 1 BP 87 EP 93 DI 10.1067/mai.2001.115485 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 458AN UT WOS:000170171200012 PM 11447387 ER PT J AU Mueller, SO Korach, KS AF Mueller, SO Korach, KS TI Immortalized testis cell lines from estrogen receptor (ER) alpha knock-out and wild-type mice expressing functional ER alpha or ER beta SO JOURNAL OF ANDROLOGY LA English DT Article DE immortalization; HPV E6/E7; in vitro models; alpha ERKO; Sertoli cells; Leydig cells ID SULFATED GLYCOPROTEIN-1 PROSAPOSIN; MESSENGER-RIBONUCLEIC-ACID; MALE REPRODUCTIVE-SYSTEM; ANTI-MULLERIAN HORMONE; HUMAN EPITHELIAL-CELLS; RAT SERTOLI CELLS; TARGETED DISRUPTION; GENE DISRUPTION; LEYDIG-CELLS; TISSUE DISTRIBUTION AB The surprising findings that male mice lacking the estrogen receptor (ER) alpha (olERKO) have atrophic testis and are infertile proved that ER alpha is involved in normal testicular function. To obtain compatible in vitro model systems for alpha ERKO male mice, we immortalized different cell lines from the testis of alpha ERKO and wild-type (C57BL/6) mice with the human papilloma virus E6/E7 genes. The established cell lines were characterized for Sertoli, Leydig, and peritubular cell markers by means of messenger RNA expression and functional assays. One wild-type-derived cell line showed Leydig cell-specific marker gene expression and produced testosterone after stimulation with cyclic adenosine monophosphate. Most wild-type cell lines expressed androgen receptor and a functional ER alpha as shown by high estrogenic activity in a luciferase-based transactivation assay. Most notably, the wild-type-derived WL3, and the ES4 cell line derived from alpha ERKO mice expressed ER beta and showed ER-mediated transcriptional activity, but no ER alpha protein expression. These cell lines with and without functional ER alpha or ER beta enable the analyses of ER subtype-specific responses and their function in testicular cell signaling, morphogenesis, and neoplasia. C1 NIEHS, Reprod & Dev Toxicol Lab, Receptor Biol Grp, NIH, Res Triangle Pk, NC 27709 USA. RP Mueller, SO (reprint author), Knoll AG, MPR, PTE, POB 210805, D-67008 Ludwigshafen, Germany. OI Korach, Kenneth/0000-0002-7765-418X NR 56 TC 12 Z9 12 U1 0 U2 2 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA SN 0196-3635 J9 J ANDROL JI J. Androl. PD JUL-AUG PY 2001 VL 22 IS 4 BP 652 EP 664 PG 13 WC Andrology SC Endocrinology & Metabolism GA 449XQ UT WOS:000169712800018 PM 11451363 ER PT J AU Repoila, F Gottesman, S AF Repoila, F Gottesman, S TI Signal transduction cascade for regulation of RpoS: Temperature regulation of DsrA SO JOURNAL OF BACTERIOLOGY LA English DT Article ID COLD-SHOCK RESPONSE; ESCHERICHIA-COLI; TRANSCRIPTIONAL CONTROL; BACTERIAL VIRULENCE; GENE-REGULATION; SMALL RNA; EXPRESSION; TRANSLATION; PROMOTER; PROTEIN AB Many environmental parameters modulate the amount of the RpoS sigma factor in Escherichia coli, Temperature control of RpoS depends on the untranslated RNA DsrA. DsrA activates RpoS translation by pairing with the Leader of the mRNA, We find that temperature affects both the rate of transcription initiation of the dsrA gene and the stability of DsrA RNA. Both are increased at low temperature (25 degreesC) compared to 37 or 42 degreesC, The combination of these results is 25-fold-Less DsrA at 37 degreesC and 30-fold Less at 42 degreesC than at 25 degreesC. Using an adapted lacZ-based reporter system, we show that temperature control of transcription initiation of dsrA requires only the minimal promoter of 36 bp. Overall, transcription responses to temperature lead to a sixfold increase in DsrA synthesis at 25 degreesC over that at 42 degreesC. Furthermore, two activating regions and a site for LeuO negative regulation were identified in the dsrA promoter, The activating regions also activate transcription in vitro. DsrA decays with a half-life of 23 min at 25 degreesC and 4 min at 37 and 42 degreesC, These results demonstrate that the dsrA promoter and the stability of DsrA RNA are the thermometers for RpoS temperature sensing. Multiple inputs to DsrA accumulation allow sensitive modulation of changes in the synthesis of the downstream targets of DsrA such as RpoS. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Gottesman, S (reprint author), NCI, Mol Biol Lab, NIH, 37 Convent Dr,Bldg 37,Room 2E18, Bethesda, MD 20892 USA. OI Repoila, Francis/0000-0001-5149-9698 NR 52 TC 103 Z9 105 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JUL PY 2001 VL 183 IS 13 BP 4012 EP 4023 DI 10.1128/JB.183.13.4012-4023.2001 PG 12 WC Microbiology SC Microbiology GA 442DH UT WOS:000169269600024 PM 11395466 ER PT J AU Markus, MA Triantafillidou, D Choli-Papadopoulou, T Torchia, DA AF Markus, MA Triantafillidou, D Choli-Papadopoulou, T Torchia, DA TI Letter to the Editor: H-1, N-15, and C-13 assignments and secondary structure identification for full-length ribosomal protein L11 from Thermus thermophilus SO JOURNAL OF BIOMOLECULAR NMR LA English DT Letter DE antibiotic target; chemical shift assignments; ribosomal protein; RNA-protein interaction; secondary structure ID RNA; RESOLUTION; BINDING C1 Natl Inst Dent & Craniofacial Res, Struct Mol Biol Unit, Bethesda, MD 20892 USA. Aristotelian Univ Salonika, Sch Chem, Biochem Lab, GR-54006 Salonika, Greece. RP Torchia, DA (reprint author), Natl Inst Dent & Craniofacial Res, Struct Mol Biol Unit, 30 Convent Dr, Bethesda, MD 20892 USA. NR 8 TC 5 Z9 5 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD JUL PY 2001 VL 20 IS 3 BP 293 EP 294 DI 10.1023/A:1011275602138 PG 2 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 456AW UT WOS:000170060800011 PM 11519754 ER PT J AU Taaffe, DR Cauley, JA Danielson, M Nevitt, MC Lang, TF Bauer, DC Harris, TB AF Taaffe, DR Cauley, JA Danielson, M Nevitt, MC Lang, TF Bauer, DC Harris, TB TI Race and sex effects on the association between muscle strength, soft tissue, and bone mineral density in healthy elders: The Health, Aging, and Body Composition Study SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE bone; muscle; fat; strength; sex; race ID NORMAL POSTMENOPAUSAL WOMEN; D-ENDOCRINE SYSTEM; FAT MASS; HIP FRACTURE; PREMENOPAUSAL WOMEN; LUMBAR SPINE; LEAN MASS; VITAMIN-D; RACIAL-DIFFERENCES; FEMORAL-NECK AB Two factors generally reported to influence bone density are body composition and muscle strength. However, it is unclear if these relationships are consistent across race and sex, especially in older persons. If differences do exist by race and/or sex, then strategies to maintain bone mass or minimize bone loss in older adults may need to be modified accordingly. Therefore, we examined the independent effects of bone mineral-free lean mass (LM), fat mass (FM), and muscle strength on regional and whole body bone mineral density (BMD) in a cohort of 2619 well-functioning older adults participating in the Health, Aging, and Body Composition (Health ABC) Study with complete measures. Participants included 738 white women, 599 black women, 827 white men, and 455 black men aged 70-79 years. BMD (g/cm(2)) of the femoral neck, whole body, upper and lower limb, and whole body and upper limb bone mineral-free LM and FM was assessed by dual-energy X-ray absorptiometry (DXA). Handgrip strength and knee extensor torque were determined by dynamometry. In analyses stratified by race and sex and adjusted for a number of confounders, LM was a significant (p < 0.001) determinant of BMD, except in white women for the lower limb and whole body. In women, FM also was an independent contributor to BMD at the femoral neck, and both PM and muscle strength contributed to limb BMD. The following were the respective Beta-weights (regression coefficients for standardized data, Std beta) and percent difference in BMD per unit (7.5 kg) LM: femoral neck, 0.202-0.386 and 4.7-6.9 %; lower limb,.0.209-0.357 and 2.9-3.5%; whole body, 0.239-0.484 and 3.0-4.7 %; and upper limb (unit = 0.5 kg), 0.231-0.407 and 3.1-3.4%. Adjusting for bone size (bone mineral apparent density [BMAD]) or body size BMD/height) diminished the importance of LM, and the contributory effect of FM became more pronounced. These results indicate that LM and FM were associated with bone mineral depending on the bone site and bone index used. Where differences did occur, they were primarily by sex not race. To preserve BMD, maintaining or increasing LM in the elderly would appear to be an appropriate strategy, regardless of race or sex. C1 NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. RP Taaffe, DR (reprint author), Univ Queensland, Fac Hlth Sci, Sch Human Movement Studies, Connell Bldg, Brisbane, Qld 4072, Australia. RI Lang, Thomas/B-2685-2012; Cauley, Jane/N-4836-2015 OI Lang, Thomas/0000-0002-3720-8038; Cauley, Jane/0000-0003-0752-4408 FU NIA NIH HHS [N01-AG-6-2102, N01-AG-6-2103, N01-AG-6-2106] NR 74 TC 125 Z9 128 U1 2 U2 5 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JUL PY 2001 VL 16 IS 7 BP 1343 EP 1352 DI 10.1359/jbmr.2001.16.7.1343 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 446AQ UT WOS:000169491100018 PM 11450711 ER PT J AU Lathrop, DA Spooner, PM AF Lathrop, DA Spooner, PM TI On the neural connection SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Editorial Material DE autonomic neural system; neuropeptides; remodeling; arrhythmia; therapy ID ATRIAL-FIBRILLATION; DENERVATION; HEART AB Discoveries concerning cardiac neural-electrical modulation and local neural remodeling provide powerful new approaches for the development of novel antiarrhythmic strategies. This "view" of developments in this emerging field highlights recent advances and suggests that additional neurally targeted investigations have considerable potential for prevention of arrhythmic diseases. C1 NHLBI, Div Heart & Vasc Dis, Bethesda, MD 20892 USA. RP Spooner, PM (reprint author), NHLBI, Div Heart & Vasc Dis, 2 Rockledge Ctr,SUite 9192,6701 Rockledge Dr,MSC, Bethesda, MD 20892 USA. RI LATHROP, David/A-2758-2008 NR 12 TC 13 Z9 14 U1 0 U2 1 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD JUL PY 2001 VL 12 IS 7 BP 841 EP 844 DI 10.1046/j.1540-8167.2001.00841.x PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 448XC UT WOS:000169654400024 PM 11469441 ER PT J AU Bivalacqua, TJ Champion, HC De Witt, BJ Saavedra, JE Hrabie, JA Keefer, LK Kadowitz, PJ AF Bivalacqua, TJ Champion, HC De Witt, BJ Saavedra, JE Hrabie, JA Keefer, LK Kadowitz, PJ TI Analysis of vasodilator responses to novel nitric oxide donors in the hindquarters vascular bed of the cat SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY LA English DT Article DE diazeniumdiolate; feline; NO donors; regional vascular bed ID CONTROLLED BIOLOGICAL RELEASE; SMOOTH-MUSCLE RELAXATION; RELAXING FACTOR; COMPLEXES; MECHANISM; NUCLEOPHILES; PHARMACOLOGY; NONOATES; ARTERY; AGENTS AB Controlled release of nitric oxide (NO.) may be useful in the treatment of a variety of vascular disorders. NO. donors of the diazeniumdiolate family with different rates of spontaneous NO. release have been synthesized. In the current study responses to seven diazeniurndiolate NO. donors (DEA/NO., DETA/NO., OXI/NO., PIPERAZI/NO., PROLT/NO., SPER/NO., and SULFI/NO.) were investigated in the hindquarters vascular bed of the cat. Intravenous injections of all NO. donors caused dose-dependent decreases in systemic arterial pressure and the rank order of potency was SNP > DEA/NO. > PIPERAZI/NO. > SPER/NO. > PROLI/NO. > OXI/NO., Injections of all NO. donors into the hindlimb perfusion circuit caused dose-related decreases in hindquarters perfusion pressure that were similar to the order of potency in decreasing systemic arterial pressure. The rank order of the time required for the response to return to 50% of the maximal decrease in pressure (T-1/2) and total duration of action of the NO. donors was SPER/NO. > PIPERAZI/NO. > DEA/NO. > OXVNO. > DETA/NO. > PROLI/NO. > SULFI/NO.. After treatment with the NO. synthase inhibitor, N-omega-nitro-L-arginine methyl ester (100 mg/kg, i.v.), hindlimb vasodilator responses to the NO. donors were not significantly different, but vasodilator responses to acetylcholine were significantly reduced. After treatment with zaprinast (2 mg/kg, i.v.), a type V cyclic 3 ', 5 ' -guanosine monophosphate-specific phosphodiesterase inhibitor, the duration of vasodilator responses to the NO. donors, as measured by T-1/2, was increased significantly, whereas the duration of the response to the beta (2)-adrenergic receptor agonist albuterol was unchanged. These data suggest that diazeniumdiolate NO. donors are endothelium-independent, directly stimulate soluble guanylate cyclase, and decrease vascular resistance by increasing cyclic 3 ', 5 ' -guanosine monophosphate levels in the hindquarters vascular bed of the cat. C1 Tulane Univ, Sch Med, Dept Pharmacol, New Orleans, LA 70112 USA. NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Frederick, MD USA. SAIC Frederick, Frederick, MD USA. RP Kadowitz, PJ (reprint author), Tulane Univ, Sch Med, Dept Pharmacol, 1430 Tulane Ave,SL83, New Orleans, LA 70112 USA. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU NCI NIH HHS [N01-CO-56000]; NHLBI NIH HHS [HL-62000] NR 28 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0160-2446 J9 J CARDIOVASC PHARM JI J. Cardiovasc. Pharmacol. PD JUL PY 2001 VL 38 IS 1 BP 120 EP 129 DI 10.1097/00005344-200107000-00013 PG 10 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 445ED UT WOS:000169444400013 PM 11444495 ER PT J AU Yamada, KM Araki, M AF Yamada, KM Araki, M TI Tumor suppressor PTEN: modulator of cell signaling, growth, migration and apoptosis SO JOURNAL OF CELL SCIENCE LA English DT Article DE tumor suppressor; migration; adhesion; cytoskeleton; integrin; anoikis ID FOCAL ADHESION KINASE; PROTEIN-TYROSINE PHOSPHATASES; GTPASE-ACTIVATING PROTEINS; PHOSPHOINOSITIDE 3-KINASE; CYCLE ARREST; GLIOBLASTOMA CELLS; PROSTATE-CANCER; GLIOMA-CELLS; PHOSPHOLIPID PHOSPHATASE; PTEN/MMAC1 PSEUDOGENE AB PTEN (also known as MMAC-1 or TEP-1) is one of the most frequently mutated tumor suppressors in human cancer. It is also essential for embryonic development. PTEN functions primarily as a lipid phosphatase to regulate crucial signal transduction pathways; a key target is phosphatidylinositol 3,4,5-trisphosphate. In addition, it displays weak tyrosine phosphatase activity, which may downmodulate signaling pathways that involve focal adhesion kinase (FAK) or She. Levels of PTEN are regulated in embryos and adult organisms, and gene-targeting studies demonstrate that it has a crucial role in normal development. Functions for PTEN have been identified in the regulation of many normal cell processes, including growth, adhesion, migration, invasion and apoptosis. PTEN appears to play particularly important roles in regulating anoikis (apoptosis of cells after loss of contact with extracellular matrix) and cell migration. Gene targeting and transient expression studies have provided insight into the specific signaling pathways that regulate these processes. Characterization of the diverse signaling networks modulated by PTEN, as well as the regulation of PTEN concentration, enzymatic activity, and coordination with other phosphatases, should provide intriguing new insight into the biology of normal and malignant cells. C1 Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, Bethesda, MD 20892 USA. RP Yamada, KM (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, Bethesda, MD 20892 USA. OI Yamada, Kenneth/0000-0003-1512-6805 NR 85 TC 288 Z9 328 U1 6 U2 24 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD JUL PY 2001 VL 114 IS 13 BP 2375 EP 2382 PG 8 WC Cell Biology SC Cell Biology GA 456HN UT WOS:000170077200003 PM 11559746 ER PT J AU Quirion, R Hyde, T AF Quirion, R Hyde, T TI Special issue on human brain (part 2) - Introduction SO JOURNAL OF CHEMICAL NEUROANATOMY LA English DT Editorial Material C1 McGill Univ, Douglas Hosp, Res Ctr, Dept Psychiat, Verdun, PQ H4H 1R3, Canada. NIMH, Clin Brain Disorders Branch, IRP, NIH, Bethesda, MD 20892 USA. RP Quirion, R (reprint author), McGill Univ, Douglas Hosp, Res Ctr, Dept Psychiat, 6875 LaSalle Blvd, Verdun, PQ H4H 1R3, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0891-0618 J9 J CHEM NEUROANAT JI J. Chem. Neuroanat. PD JUL PY 2001 VL 22 IS 1-2 BP 1 EP 1 DI 10.1016/S0891-0618(01)00134-X PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 468FC UT WOS:000170746600001 ER PT J AU Hyde, TM Crook, JM AF Hyde, TM Crook, JM TI Cholinergic systems and schizophrenia: primary pathology or epiphenomena? SO JOURNAL OF CHEMICAL NEUROANATOMY LA English DT Article DE cholinergic systems; schizophrenia; epiphenomena ID MUSCARINIC ACETYLCHOLINE-RECEPTOR; NEURONAL NICOTINIC RECEPTORS; RADIAL-ARM MAZE; NUCLEUS BASALIS; HUMAN-BRAIN; IN-VIVO; ALPHA-BUNGAROTOXIN; CAUDATE-PUTAMEN; ACETYLTRANSFERASE IMMUNOHISTOCHEMISTRY; CORTICAL ACETYLCHOLINE AB Post mortem schizophrenia research has been driven first by the dopamine and then the glutamate hypotheses. These hypotheses posit primary pathology in pathways dependent upon dopamine or glutamate neurotransmission. Although the dopamine and glutamate hypotheses retain considerable theoretical strength, neurobiological findings of altered dopamine or glutamate activity in schizophrenia do not explain all features of this disorder. A more synthetic approach would suggest that focal pathological change in either the prefrontal cortex or mesial temporal lobe leads to neurochemical changes in multiple neurotransmitter systems. Despite the limited experimental evidence for abnormal cholinergic neurotransmission in psychiatric disorders, increased understanding of the role of acetylcholine in the human brain and its relationship to other neurotransmitter systems has led to a rapidly growing interest in the cholinergic system in schizophrenia. This review focuses on the basic anatomy of the mammalian cholinergic system, and its possible involvement in the neurobiology of schizophrenia. Summaries of cholinergic cell groups, projection pathways, and receptor systems, in the primate and human brain, are followed by a brief discussion of the functional correlations between aberrant cholinergic neurotransmission and the signs and symptoms of schizophrenia. (C) 2001 Elsevier Science B.V. All rights reserved. C1 NIMH, Clin Brain Disorders Branch, IRP, NIH, Bethesda, MD 20892 USA. RP NIMH, Clin Brain Disorders Branch, IRP, NIH, Bethesda, MD 20892 USA. EM hydet@intra.nimh.nih.gov NR 98 TC 70 Z9 73 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0891-0618 EI 1873-6300 J9 J CHEM NEUROANAT JI J. Chem. Neuroanat. PD JUL PY 2001 VL 22 IS 1-2 BP 53 EP 63 DI 10.1016/S0891-0618(01)00101-6 PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 468FC UT WOS:000170746600005 PM 11470554 ER PT J AU Kuperman, H Damiani, D Chrousos, GP Dichtchekenian, V Della Manna, T Odone, V Setian, N AF Kuperman, H Damiani, D Chrousos, GP Dichtchekenian, V Della Manna, T Odone, V Setian, N TI Evaluation of the hypothalamic-pituitary-adrenal axis in children with leukemia before and after 6 weeks of high-dose glucocorticoid therapy SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE; SHORT-TERM; SUPPRESSION; RECOVERY; RESPONSES; CORTICOSTEROIDS; INSUFFICIENCY; WITHDRAWAL AB Among the adverse effects arising from chronic high-dose glucocorticoid treatment, adrenal insufficiency secondary to suppression of the hypothalamic-pituitary-adrenal (HPA) axis is a cause for concern. Glucocorticoid-induced adrenal suppression is related to the duration of therapy, type of steroid used and dosage, and schedule of glucocorticoid administration. To evaluate the suppression and recovery time of the HPA axis in children with acute leukemia, we performed the ovine CRH (oCRH) stimulation test in 15 patients, who were given high doses of dexamethasone as part of their induction chemotherapy for 42 days. The oCRH tests were performed before, and 7 and 14 days after, discontinuation of the glucocorticoid. The ACTH levels were not significantly different among the 3 tests. The cortisol levels, however, were significantly (albeit mildly) lower, both basally and after oCRH, 1 and 2 weeks post treatment than before therapy. Six patients had cortisol values that remained suppressed 2 weeks after discontinuation of therapy. One of these patients had manifestations of mild adrenal insufficiency, 6-8 days after discontinuation of therapy, but required no glucocorticoid coverage. We conclude that up to 2 weeks after discontinuation of 6 weeks of high-dose dexamethasone administration, the HPA axis of patients with acute leukemia is mildly suppressed but infrequently associated with clinical manifestations of adrenal insufficiency. This may indicate that major stress, when concurrent with glucocorticoid treatment, may prevent clinically significant adrenal suppression. C1 Univ Sao Paulo, Sch Med, Childrens Hosp, Dept Pediat Endocrinol,Fac Med, BR-01232010 Sao Paulo, Brazil. Univ Sao Paulo, Sch Med, Childrens Hosp, Dept Oncol, BR-01232010 Sao Paulo, Brazil. NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Kuperman, H (reprint author), Univ Sao Paulo, Sch Med, Childrens Hosp, Dept Pediat Endocrinol,Fac Med, Rua Conselheiro Brotero 1182,Apt 182, BR-01232010 Sao Paulo, Brazil. EM hkuperman@terra.com.br NR 33 TC 34 Z9 34 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2001 VL 86 IS 7 BP 2993 EP 2996 DI 10.1210/jc.86.7.2993 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 452BY UT WOS:000169838300014 PM 11443157 ER PT J AU Mantzoros, CS Ozata, M Negrao, AB Suchard, MA Ziotopoulou, M Caglayan, S Elashoff, RM Cogswell, RJ Negro, P Liberty, V Wong, ML Veldhuis, J Ozdemir, IC Gold, PW Flier, JS Licinio, J AF Mantzoros, CS Ozata, M Negrao, AB Suchard, MA Ziotopoulou, M Caglayan, S Elashoff, RM Cogswell, RJ Negro, P Liberty, V Wong, ML Veldhuis, J Ozdemir, IC Gold, PW Flier, JS Licinio, J TI Synchronicity of frequently sampled thyrotropin (TSH) and leptin concentrations in healthy adults and leptin-deficient subjects: Evidence for possible partial TSH regulation by leptin in humans SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; FASTING-INDUCED SUPPRESSION; MESSENGER-RIBONUCLEIC-ACID; PULSATILE SECRETION; THYROID-FUNCTION; NEUROENDOCRINE REGULATION; STIMULATING-HORMONE; LUTEINIZING-HORMONE; MISSENSE MUTATION; ARCUATE NUCLEUS AB Leptin signals the status of energy reserves to the brain. Leptin stimulates biosynthesis of TRH in vitro and influences the activity of the hypothalamic-pituitary-thyroid axis in vivo in rodents. Because blood levels of both leptin and TSH: display diurnal variation with a distinct nocturnal rise, we sought to determine whether a relationship exists between fluctuations in circulating leptin and TSH. We measured serum leptin and TSH levels every 7 min for 24h in five healthy men and found that both leptin and TSH levels are highly organized and pulsatile. A similar pattern of leptin and TSH rhythms was observed, with TSH and leptin levels reaching a nadir in late morning and a peak, in the early morning hours. Importantly, cosinor analysis on the absolute leptin and TSH levels revealed a statistically significant fit for a 24-h period and the two hormones showed similar probabilities of rhythm and superimposable peak values. Further-more, this study shows a strong positive Pearson correlation between the 24-h patterns of variability of leptin and TSH in healthy subjects. Finally, the ultradian fluctuations in leptin levels showed pattern synchrony with those of TSH as determined by cross-correlation analysis, by cross-approximate enthropy and Bayessian analysis applied independently. To further explore whether these associations could reflect: an underlying regulation of TSH secretion by leptin, we also studied frequently sampled leptin and TSH levels in four brothers, members of a family with leptin deficiency tone normal homozygote, two heterozygotes, and one leptin-deficient homozygote,. Leptin levels of the homozygous leptin-deficient subject are detectable but bioinactive, and the rhythm of his TSH is disorganized, 24-h pattern of leptin and TSH variability in the heterozygous subjects, although significantly correlated, showed a weaker correlation compared with the strong correlation in the normal subjects. These data are consistent with the: possibility that leptin may regulate TSH pulsatility and circadian rhythmicity, but interventional studies are needed to definitively prove whether leptin regulates the minute-to-minute oscillations and ultradian rhythm of TSH levels. C1 Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Biomath, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Clin Pharmacol Program, Los Angeles, CA 90095 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol & Metab,Harvard Thorndike Lab, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Charles A Dana Res Inst, Boston, MA 02215 USA. Gulhane Sch Med, Dept Endocrinol & Metab, TR-06018 Ankara, Turkey. NIH, Clin Neuroendocrinol Branch, Bethesda, MD 20892 USA. Univ Virginia, Hlth Sci Ctr, Dept Med, Charlottesville, VA 22908 USA. Univ Virginia, Hlth Sci Ctr, Gen Clin Res Ctr, Charlottesville, VA 22908 USA. RP Licinio, J (reprint author), Univ Calif Los Angeles, Gonda Ctr 3357A, Dept Psychiat, 695 Charles Young Dr S, Los Angeles, CA 90095 USA. EM licinio@ucla.edu RI Wong, Ma-Li/D-7903-2011; Negrao, Andre Brooking/C-9526-2014; OI Negrao, Andre Brooking/0000-0002-8133-6723; Licinio, Julio/0000-0001-6905-5884 FU NCRR NIH HHS [M01-RR01032]; NIDDK NIH HHS [P30-DK-46200]; NIGMS NIH HHS [GM08042] NR 57 TC 134 Z9 137 U1 1 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2001 VL 86 IS 7 BP 3284 EP 3291 DI 10.1210/jc.86.7.3284 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 452BY UT WOS:000169838300061 PM 11443202 ER PT J AU Roth, GS Lesnikov, V Lesnikov, M Ingram, DK Lane, MA AF Roth, GS Lesnikov, V Lesnikov, M Ingram, DK Lane, MA TI Dietary caloric restriction prevents the age-related decline in plasma melatonin levels of rhesus monkeys SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BLOOD-CHEMISTRY; HEMATOLOGY; BIOMARKERS; PRIMATE AB Rhesus monkeys exhibit an age-associated decrease in peak. plasma melatonin levels analogous to that reported for humans. This decrease is essentially abolished in monkeys subjected to a 30% reduction in caloric intake over a 12-yr period. The caloric restriction (CR) effect does not seem to be a reversal, but rather a long-term prevention, of the age-related decline in hormone concentrations. The age effect does not seem to be due to a phase shift in the peak of melatonin secretions, as has been observed in some populations of aged humans. It is also extremely unlikely that; the CR effect simply reflects a phase shift, since old monkeys on the diet have nocturnal melatonin levels equal to or greater than adult fully fed controls Thus, if peak times (approximately 0200 h) were actually shifted, maximal levels in old CR monkeys would be even higher. These findings, coupled with previous observations in humans, suggest that peak plasma melatonin levels may represent a possible candidate "biomarker of aging" in primates. Moreover, this index of age-associated physiological decrement seems to be inhibited by dietary CR. C1 NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Jean Choay Inst Biomed Res, CH-6826 Riva San Vitale, Switzerland. RP Roth, GS (reprint author), NIA, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 23 TC 32 Z9 36 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2001 VL 86 IS 7 BP 3292 EP 3295 DI 10.1210/jc.86.7.3292 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 452BY UT WOS:000169838300062 PM 11443203 ER PT J AU Charmandari, E Pincus, SM Matthews, DR Dennison, E Fall, CHD Hindmarsh, PC AF Charmandari, E Pincus, SM Matthews, DR Dennison, E Fall, CHD Hindmarsh, PC TI Joint growth hormone and cortisol spontaneous secretion is more asynchronous in older females than in their male counterparts SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE; MESSENGER-RNA LEVELS; SEXUAL-DIMORPHISM; HYPOTHALAMIC SOMATOSTATIN; (GH)-RELEASING HORMONE; LUTEINIZING-HORMONE; APPROXIMATE ENTROPY; GH RELEASE; RATS; INHIBITION AB In humans, cortisol and GH are secreted in a pulsatile manner, and an interaction between GH and the hypothalamic-pituitary-adrenal axis has been established. Ln view of the sexually dimorphic pattern in GH secretion, we investigated the GH-cortisol bihormonal secretory dynamics in male and female healthy older individuals. We studied the GH and cortisol secretory patterns in 83 healthy subjects (45 men and 38 women; age range, 59.4-73.0 yr) by determining serum GH and cortisol concentrations at 20-min intervals for 24 h. The irregularity of GH and cortisol secretion was assessed using approximate entropy (ApEn), a scale- and model-independent statistic. The synchrony of joint GH-cortisol spontaneous secretion was quantified using the cross-ApEn statistic. Cross-correlation analysis of GH and cortisol patterns was computed at various time lags covering the 24-h period. Mean 24-h serum GH concentrations were significantly higher in females (mean, 1.31mU/L; sn, 0.87) than in males (mean, 0.88 mU/L; so, 0.42; P = 0.009), whereas mean 24-h serum total cortisol concentrations were higher in males (mean, 9.0 mug/dL; SD, 1.4) than in females (mean, 7.3 mug/dL; so, 1.4;P = 0.0001). GH secretion was more irregular in females (mean ApEn, 0.81; sn, 0.23) than in males (mean ApEn, 0.60; so, 0.20; P < 0.001). No significant difference in the regularity of cortisol secretion was noted between sexes. Cross-ApEn values of paired GH-cortisol were higher in females (mean, 1.15; sn, 0.18) than in males (mean, 1.01; sn, 0.16; P = 0.0003). Stepwise multiple linear regression analysis indicated that estradiol and insulin-like growth factor-binding protein-3 concentrations were independently related to GH ApEn values (P = 0.14; P = 0.01), whereas cross-ApEn values of paired GH-cortisol were best predicted by FSH concentrations (r(2) = 0.37; P = 0.003). Cross-correlation analysis revealed a significant positive correlation between GH and cortisol, peaking at lag time of 4.7 h in males (r = 0.30; P < 0.0001) and 4.3 h in females (r = 0.14; P < 0.0001), with GH leading cortisol by these time intervals. In addition, a significant negative correlation between the two hormones was noted over time, peaking at 4.7 h in males (r = -0.21; P < 0.0001) and 6.3 h in females (r = -0.25; P < 0.0001), with cortisol leading GH by these time intervals. The above results indicate that in the elderly, females have a more disordered GH secretory pattern and a more asynchronous joint GH-cortisol secretion than their male counterparts. These observations most likely reflect bidirectional interactions between the GH and hypothalamic-pituitary-adrenal ards in humans as well as diminution of subsystem integrity and synchronous control of interconnected hormonal systems with advancing age. C1 UCL, London Ctr Pediat Endocrinol, London W1T 3AA, England. Radcliffe Infirm, Diabet Res Labs, Oxford OX2 6HE, England. MRC, Environm Epidemiol Unit, Southampton SO16 6YD, Hants, England. RP Charmandari, E (reprint author), NICHHD, Pediat & Reprod Endocrinol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 9D42, Bethesda, MD 20892 USA. RI Hindmarsh, Peter/C-4964-2008; Charmandari, Evangelia/B-6701-2011 NR 44 TC 8 Z9 9 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2001 VL 86 IS 7 BP 3393 EP 3399 DI 10.1210/jc.86.7.3393 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 452BY UT WOS:000169838300075 PM 11443216 ER PT J AU Kitazono, M Robey, R Zhan, ZR Sarlis, NJ Skarulis, MC Aikou, T Bates, S Fojo, T AF Kitazono, M Robey, R Zhan, ZR Sarlis, NJ Skarulis, MC Aikou, T Bates, S Fojo, T TI Low concentrations of the histone deacetylase inhibitor, depsipeptide (FR901228), increase expression of the Na(+)/I(-) symporter and iodine accumulation in poorly differentiated thyroid carcinoma cells SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID DOXORUBICIN PLUS CISPLATIN; ANAPLASTIC CARCINOMA; CANCER; LINES; PAPILLARY; QUANTITATION; RETINOIDS; THERAPY; TRIAL AB Thyroid carcinoma accounts for the majority of deaths from endocrine cancers. A major cause of treatment failure is the inability to trap iodine. Chemotherapeutic agents with differentiating properties have been tried in an attempt to increase iodine uptake. We examined the ability of the novel histone deacetylase (HDAC) inhibitor, depsipeptide (FR901228), to modulate the expression of thyroid-specific genes. Four cell lines, two derived from follicular thyroid carcinomas (FTC 133 and FTC 236)and two derived from anaplastic thyroid carcinomas (SW-1736 and KAT-4) were used. In these four cell lines, a very low concentration of depsipeptide (1 ng/mL) increased histone acetylation and expression of both thyroglobulin and the Na(+)/I(-) symporter messenger RNAs. After 3 days, messenger RNA levels approached those of a normal thyroid control. Depsipeptide induced increases in (125)I accumulation indicated that a functional Na(+)/I(-)symporter protein was induced. Transient transfections indicate that the effects are mediated at least in part by a trans-activating factor. These in vitro results suggest that depsipeptide or other histone deacetylase inhibitors might be used clinically in thyroid carcinomas that are unable to trap iodine as an adjunct to radioiodine therapy. C1 NCI, Med Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Kagoshima Univ, Fac Med, Dept Surg 1, Kagoshima 8908520, Japan. RP Fojo, T (reprint author), NCI, Med Branch, NIH, Bldg 10,Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. EM tfojo@helix.nih.gov RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 26 TC 120 Z9 129 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2001 VL 86 IS 7 BP 3430 EP 3435 DI 10.1210/jc.86.7.3430 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 452BY UT WOS:000169838300079 PM 11443220 ER PT J AU Blazevic, V Mac Trubey, C Shearer, GM AF Blazevic, V Mac Trubey, C Shearer, GM TI Analysis of the costimulatory requirements for generating human virus-specific in vitro T helper and effector responses SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE costimulatory molecules; cytokines; T lymphocytes; human ID INTERFERON-GAMMA PRODUCTION; IFN-GAMMA; CYTOKINE PRODUCTION; LYMPHOCYTES-T; CELLS; CTLA-4; INTERLEUKIN-12; INDUCTION; IMMUNITY; ANTIGEN AB The present study analyzes the role of CD28-B7-mediated costimulation during in vitro human peripheral blood memory T cell activation by influenza A virus. Inhibition studies using the B7-binding fusion protein CTLA41g and antibodies against CD80 and CD86 demonstrate that CTLA41g and anti-CD86 inhibited influenza-specific T cell proliferation, interleukin (IL)-2 and interferon (IFN)-gamma production, and generation of influenza-specific CD8+ CTL. The production of IL-10 and IL-18, which are known to modulate T cell immune responses, were not affected by blocking the CD28-B7 costimulatory pathway. Inhibition of diverse influenza-specific T cell functions could be reversed by the addition of exogenous IL-2 or IL-12 but not by the addition of IFN-gamma or IL-18. Although IL-2 is known to overcome CD28-B7 costimulatory requirements, this is the first report showing that exogenous IL-12 is able to bypass CD28-B7 costimulatory blockade induced by CTLA41g in vitro. The induction of IFN-gamma production with the recently described IFN-gamma inducing cytokine IL-18 was not detected. In conclusion, these results demonstrate that CD86 represents a major costimulatory signal for the activation of resting peripheral blood memory T cells with recall antigens. These observations may have important implications for the development of immunotherapeutic strategies in diverse immunodeficiency diseases as well as in tumor immunotherapy. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Intramural Res Support Program, Frederick, MD USA. RP Blazevic, V (reprint author), Univ Tampere, Inst Med Technol, Lenkkeilijankatu 6, FIN-33101 Tampere, Finland. FU NCI NIH HHS [N01-CO-56000] NR 42 TC 6 Z9 6 U1 0 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD JUL PY 2001 VL 21 IS 4 BP 293 EP 302 DI 10.1023/A:1010987426835 PG 10 WC Immunology SC Immunology GA 457KN UT WOS:000170136300008 PM 11506200 ER PT J AU Wigginton, JM Gruys, E Geiselhart, L Subleski, J Komschlies, KL Park, JW Wiltrout, TA Nagashima, K Back, TC Wiltrout, RH AF Wigginton, JM Gruys, E Geiselhart, L Subleski, J Komschlies, KL Park, JW Wiltrout, TA Nagashima, K Back, TC Wiltrout, RH TI IFN-gamma and Fas/FasL are required for the antitumor and antiangiogenic effects of IL-12/pulse IL-2 therapy SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CELL-MEDIATED CYTOTOXICITY; NATURAL-KILLER-CELLS; MURINE RENAL-CANCER; FAS LIGAND; TUMOR-CELLS; IN-VIVO; STIMULATORY FACTOR; INTERFERON-GAMMA; PHASE-I; INTERLEUKIN-12 AB Systemic administration of IL-12 and intermittent doses of IL-2 induce complete regression of metastatic murine renal carcinoma. Here, we show that overt tumor regression induced by IL-12/pulse IL-2 is preceded by recruitment of CD8(+) T cells, vascular injury disrupted tumor neovascularization, and apoptosis of both endothelial and tumor cells. The IL-12/IL-2 combination synergistically enhances cell surface FasL expression on CD8(+) T lymphocytes in vitro and induces Fas and FasL expression within tumors via an IFN-gamma -dependent mechanism in vivo. This therapy also inhibits tumor neovascularization and induces tumor regression by mechanisms that depend critically on endogenous IFN-gamma production and an intact Fas/FasL pathway. The ability of IL-12/pulse IL-2 to induce rapid destruction of rumor-associated endothelial cells and regression of established metastatic tumors is ablated in mice with a dysregulated Fas/FasL pathway. The common, critical role for endogenous IFN-gamma and the Fas/FasL pathway in early antiangiogenic effects and in antitumor responses suggests that early, cytokine-driven innate immune mechanisms and CD8(+) T cell-mediated responses are interdependent. Definition of critical early molecular events engaged by IL-12/IL-2 may provide new perspective into optimal therapeutic engagement of a productive host-antitumor immune response. C1 NCI, Expt Immunol Lab, Ctr Canc Res, Frederick, MD 21702 USA. NCI, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. Sci Applicat Int Corp, Intramural Res Support Program, Frederick, MD USA. RP Wiltrout, RH (reprint author), NCI, Expt Immunol Lab, Ctr Canc Res, Bldg 560,Room 31-93, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 48 TC 104 Z9 114 U1 0 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2001 VL 108 IS 1 BP 51 EP 62 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 449HX UT WOS:000169679900009 PM 11435457 ER PT J AU Apasov, SG Blackburn, MR Kellems, RE Smith, PT Sitkovsky, MV AF Apasov, SG Blackburn, MR Kellems, RE Smith, PT Sitkovsky, MV TI Adenosine deaminase deficiency increases thymic apoptosis and causes defective T cell receptor signaling SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID S-ADENOSYLHOMOCYSTEINE HYDROLASE; EXTRACELLULAR ADENOSINE; COMBINED IMMUNODEFICIENCY; PURINERGIC RECEPTOR; FLOW-CYTOMETRY; ACTIVATION; MICE; INHIBITION; THYMOCYTES; EXPRESSION AB Adenosine deaminase (ADA) deficiency in humans results in a severe combined immunodeficiency (SCID). This immunodeficiency is associated with severe disturbances in purine metabolism chat are thought to mediate lymphotoxicity. The recent generation of ADA-deficient (ADA(-/-)) mice has enabled the in vivo examination of mechanisms that may underlie the SCID resulting from ADA deficiency. We demonstrate severe depletion of T and B lymphocytes and defects in T and B cell development in ADA(-/-) mice. T cell apoptosis was abundant in thymi of ADA(-/-) mice, but no increase in apoptosis was detected in the spleen and lymph nodes of these animals, suggesting that the defect is specific to developing thymocytes. Studies of mature T cells recovered from spleens of ADA(-/-) mice revealed that ADA deficiency is accompanied by TCR activation defects of T cells in vivo. Furthermore, ex vivo experiments on ADA(-/-) T cells demonstrated that elevated adenosine is responsible for this abnormal TCR signaling. These findings suggest that the metabolic disturbances seen in ADA(-/-) mice affect various signaling pathways that regulate thymocyte survival and function. Experiments with thymocytes ex vivo confirmed that ADA deficiency reduces tyrosine phosphorylation of TCR-associated signaling molecules and blocks TCR-triggered calcium increases. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Univ Texas, Houston Med Sch, Dept Biochem & Mol Biol, Houston, TX USA. RP Sitkovsky, MV (reprint author), NIAID, Immunol Lab, NIH, 10-11N311,10 Ctr Dr, Bethesda, MD 20892 USA. OI Blackburn, Michael/0000-0002-1394-9966 FU NHLBI NIH HHS [HL61888]; NIAID NIH HHS [AI43572, R01 AI043572]; NIDDK NIH HHS [R01 DK046207, DK54443, DK46207] NR 37 TC 70 Z9 72 U1 0 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2001 VL 108 IS 1 BP 131 EP 141 DI 10.1172/JCI10360 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 449HX UT WOS:000169679900017 PM 11435465 ER PT J AU Wang, XY Masilamani, S Nielsen, J Kwon, TH Brooks, HL Nielsen, S Knepper, MA AF Wang, XY Masilamani, S Nielsen, J Kwon, TH Brooks, HL Nielsen, S Knepper, MA TI The renal thiazide-sensitive Na-Cl cotransporter as mediator of the aldosterone-escape phenomenon SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID THICK ASCENDING LIMB; SODIUM-CHANNEL; RAT-KIDNEY; AQUAPORINS; ENAC AB The kidneys "escape" from the Na-retaining effects of aldosterone when circulating levels of aldosterone are inappropriately elevated in the setting of normal or expanded extracellular fluid volume, e.g., in primary aldosteronism. Using a targeted proteomics approach, we screened renal protein extracts with rabbit polyclonal antibodies directed to each of the major Na transporters expressed along the nephron to determine whether escape from aldosterone-mediated Na retention is associated with decreased abundance of one or more of renal Na transporters. The analysis revealed that the renal abundance of the thiazide-sensitive Na-Cl cotransporter (NCC) was profoundly and selectively decreased. None of the other apical solute-coupled Na transporters displayed decreases in abundance, nor were the total abundances of the three ENaC subunits significantly altered. Immunocytochemistry showed a strong decrease in NCC labeling in distal convoluted tubules of aldosterone-escape rats with no change in the cellular distribution of NCC, Ribonuclease protection assays (RPAs) revealed that the decrease in NCC protein abundance was not associated with altered NCC mRNA abundance. Thus, the thiazide-sensitive Na-Cl cotransporter of the distal convoluted tubule appears to be the chief molecular target for regulatory processes responsible for mineralocorticoid escape, decreasing in abundance via a posttranscriptional mechanism. C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. Univ Aarhus, Dept Cell Biol, Inst Anat, Aarhus, Denmark. RP Knepper, MA (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bldg 10,Room 6N260,10 Ctr Dr,MSC 1603, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999]; NHLBI NIH HHS [Z01-HL-01282] NR 29 TC 76 Z9 77 U1 0 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2001 VL 108 IS 2 BP 215 EP 222 DI 10.1172/JCI10366 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 452QY UT WOS:000169871300009 PM 11457874 ER PT J AU Cannon, RO Schechter, AN Panza, JA Ognibene, FP Pease-Fye, ME Waclawiw, MA Shelhamer, JH Gladwin, MT AF Cannon, RO Schechter, AN Panza, JA Ognibene, FP Pease-Fye, ME Waclawiw, MA Shelhamer, JH Gladwin, MT TI Effects of inhaled oxide on regional blood flow are consistent with intravascular nitric oxide delivery SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID RESPIRATORY-DISTRESS SYNDROME; BIOLOGICAL-SYSTEMS; L-ARGININE; XANTHINE OXIDOREDUCTASE; CORONARY CIRCULATION; S-NITROSOHEMOGLOBIN; ENDOTHELIAL-CELLS; CARBON-MONOXIDE; RELAXING FACTOR; HEMOGLOBIN AB Nitric oxide (NO) may be stabilized by binding to hemoglobin, by nitrosating thiol-containing plasma molecules, or by conversion to nitrite, all reactions potentially preserving its bioactivity in blood. Here we examined the contribution of blood-transported NO to regional vascular tone in humans before and during NO inhalation. While breathing room air and then room air with NO at 80 parts per million, forearm blood flow was measured in 16 subjects at rest and after blockade of forearm NO synthesis with N(G)-monomethyl-L-arginine (L-NMMA) followed by forearm exercise stress. L-NMMA reduced blood flow by 25% and increased resistance by 50%, an effect that was blocked by NO inhalation. With NO inhalation, resistance was significantly lower during L-NMMA infusion, both at rest and during repetitive hand-grip exercise. S-nitrosohemoglobin and plasma S-nitrosothiols did not change with NO inhalation. Arterial nitrite levels increased by 11% and arterial nitrosyl(heme)hemoglobin levels increased tenfold to the micromolar range, and both measures were consistently higher in the arterial than in venous blood. S-nitrosohemoglobin levels were in the nanomolar range, with no significant artery-to-vein gradients. These results indicate that inhaled NO during blockade of regional NO synthesis can supply intravascular NO to maintain normal vascular function. This effect may have application for the treatment of diseases characterized by endothelial dysfunction. C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Biol Chem Lab, Bethesda, MD 20892 USA. NHLBI, Dept Crit Care Med, Ctr Clin, NIH, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. RP Cannon, RO (reprint author), NHLBI, Cardiol Branch, NIH, Bldg 10,Room 7B-15,10 Ctr Dr,MSC 1650, Bethesda, MD 20892 USA. EM cannonr@nih.gov OI Schechter, Alan N/0000-0002-5235-9408 NR 51 TC 192 Z9 195 U1 0 U2 4 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2001 VL 108 IS 2 BP 279 EP 287 DI 10.1172/JCI12761 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 452QY UT WOS:000169871300016 PM 11457881 ER PT J AU Vaisman, BL Lambert, G Amar, M Joyce, C Ito, T Shamburek, RD Cain, WJ Fruchart-Najib, J Neufeld, ED Remaley, AT Brewer, HB Santamarina-Fojo, S AF Vaisman, BL Lambert, G Amar, M Joyce, C Ito, T Shamburek, RD Cain, WJ Fruchart-Najib, J Neufeld, ED Remaley, AT Brewer, HB Santamarina-Fojo, S TI ABCA1 overexpression leads to hyperalphalipoproteinemia and increased biliary cholesterol excretion in transgenic mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ATP-BINDING CASSETTE; DENSITY-LIPOPROTEIN CHOLESTEROL; APOLIPOPROTEIN-A-I; TANGIER-DISEASE; CELLULAR CHOLESTEROL; PLASMA HDL; TARGETED MUTATION; SELECTIVE UPTAKE; SR-BI; GENE AB The discovery of the ABCA1 lipid transporter has generated interest in modulating human plasma HDL levels and atherogenic risk by enhancing ABCA1 gene expression. To determine if increased ABCA1 expression modulates HDL metabolism in vivo, we generated transgenic mice that overexpress human ABCA1 (hABCA1-Tg). Hepatic and macrophage expression of hABCA1 enhanced macrophage cholesterol efflux to apoA-I; increased plasma cholesterol, cholesteryl esters (CEs), free cholesterol, phospholipids, HDL cholesterol, and apoA-I and apoB levels; and led to the accumulation of apoE-rich HDL1. ABCA1 transgene expression delayed I-125-apoA-I catabolism in both liver and kidney, leading to increased plasma apoA-I levels, but had no effect on apoB secretion after infusion of Triton WR1339. Although the plasma clearance of HDL-CE was not significantly altered in hABCA1-Tg mice, the net hepatic delivery of exogenous 3H-CEt-HDL, which is dependent on the HDL pool size, was increased 1.5-fold. In addition, the cholesterol and phospholipid concentrations in hABCA1-Tg bile were increased 1.8-fold. These studies show that steady-state overexpression of ABCA1 in vivo (a) raises plasma apoB levels without altering apoB secretion and (b) raises plasma HDL-C and apoA-I levels, facilitating hepatic reverse cholesterol transport and biliary cholesterol excretion. Similar metabolic changes may modify atherogenic risk in humans. C1 NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Delaware, Newark, DE USA. Inst Pasteur, Dept Atherosclerosis, F-59019 Lille, France. RP Vaisman, BL (reprint author), NHLBI, Mol Dis Branch, NIH, Bldg 10,Room 7N115,10 Ctr Dr, Bethesda, MD 20892 USA. NR 47 TC 180 Z9 200 U1 0 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2001 VL 108 IS 2 BP 303 EP 309 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 452QY UT WOS:000169871300018 PM 11457883 ER PT J AU Conville, PS Witebsky, FG AF Conville, PS Witebsky, FG TI Lack of usefulness of carbon utilization tests for identification of Mycobacterium mucogenicum SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID RAPIDLY GROWING MYCOBACTERIA; CHELONAE-LIKE ORGANISM; FORTUITUM COMPLEX; CHROMATOGRAPHY; SUSCEPTIBILITY; AMPLIFICATION; PATTERNS; GENE AB Carbon utilization tests have proven to be useful for the identification of some species of rapidly growing mycobacteria and have been described as one of the few tests useful for the differentiation of Mycobacterium mucogenicum from other rapid growers, We have found the carbon utilization tests to be unreliable for the identification of patient isolates of this species. In this study, using 28 isolates of rapidly growing mycobacteria, we examined several variables which might have an effect on results of citrate, inositol, and mannitol utilization: inoculum concentration, incubation temperature, and medium manufacturer. None of these variables affected results obtained for most species of rapid growers or for ATCC strains of M. mucogenicum. Results for patient isolates of M. mucogenicum were found to be inconsistent regardless of the methodology employed and resulted in an ambiguous identification of these isolates or an incorrect identification as Mycobacterium chelonae. Molecular or cell wall analysis may be the best technique to employ for accurate identification of M. mucogenicum. C1 Warren Grant Magnuson Clin Ctr, Microbiol Serv, Dept Lab Med, NIH, Bethesda, MD 20892 USA. RP Conville, PS (reprint author), Warren Grant Magnuson Clin Ctr, Microbiol Serv, Dept Lab Med, NIH, 10 Ctr Dr MSC 1508, Bethesda, MD 20892 USA. NR 13 TC 10 Z9 10 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUL PY 2001 VL 39 IS 7 BP 2725 EP 2728 DI 10.1128/JCM.39.7.2725-2728.2001 PG 4 WC Microbiology SC Microbiology GA 447RN UT WOS:000169586400066 PM 11427607 ER PT J AU Marques, AR Stock, F Gill, V AF Marques, AR Stock, F Gill, V TI Culture of Borrelia burgdorferi - Author's reply SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Letter C1 NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NIH, Dept Clin Pathol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Marques, AR (reprint author), NIAID, Clin Invest Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUL PY 2001 VL 39 IS 7 BP 2747 EP 2747 PG 1 WC Microbiology SC Microbiology GA 447RN UT WOS:000169586400075 ER PT J AU Kim, JS Nafziger, AN Gaedigk, A Dickmann, LJ Rettie, AE Bertino, JS AF Kim, JS Nafziger, AN Gaedigk, A Dickmann, LJ Rettie, AE Bertino, JS TI Effects of oral vitamin K on S- and R-Warfarin pharmacokinetics and pharmacodynamics: Enhanced safety of warfarin as a CYP2C9 probe SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article; Proceedings Paper CT 101st Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 15-17, 2000 CL LOS ANGELES, CALIFORNIA SP Amer Soc Clin Pharmacol & Therapeut ID HUMAN LIVER-MICROSOMES; CYTOCHROME-P450 2C9; ALLELIC VARIANT; JAPANESE PATIENTS; O-DEMETHYLATION; METABOLISM; (S)-WARFARIN; ENANTIOMERS; TOLBUTAMIDE; 4'-HYDROXYLATION AB Evidence for the selectivity of S-warfarin metabolism by CYP2C9 is substantial, suggesting that warfarin may be a potential CYP2C9 phenotyping probe. It is, however, limited by its ability to elevate the international normalized ratio (INR) and potentially cause bleeding. The effect of vitamin K to attenuate the elevation of INR may enable the safe use of warfarin as a probe. The objective of this study was to investigate the pharmacokinetics and pharmacodynamics of S- and B-warfarin in plasma following the administration of warfarin alone versus warfarin and vitamin K in CYP2C9 XI homozygotes. Healthy adults received, in a randomized crossover fashion in a fasted state, warfarin 10 mg orally or warfarin 10 mg plus vitamin K 10 mg orally. Blood samples were obtained over 5 days during each phase. INR measurements were obtained at baseline and day 2 in each phase. INR, AUC(0-infinity), and t(1/2) of plasma S- and R-warfarin were examined. Eleven CYP2C9*1 homozygotes (3 men, 8 women) were enrolled. INR at day 2 following warfarin 10 mg was 1.18 +/-0.19, which differed significantly from baseline (INR = 1.00 +/-0.05) and warfarin with vitamin K (INR = 1.06 +/-0.07). INR at baseline was not significantly different from warfarin with vitamin K. t(1/2) and AUC(0-infinity) of both enantiomers did not significantly differ between the phases. It was concluded that INR is apparently attenuated by concomitant administration of a single dose of vitamin K without affecting the pharmacokinetics of either warfarin stereoisomer. Warfarin 10 mg may be safely used as a CYP2C9 probe in *1 homozygotes when given concomitantly with 10 mg of oral vitamin K. C1 Bassett Healthcare, Dept Pharm Serv, Cooperstown, NY 13326 USA. Bassett Healthcare, Clin Pharmacol Res Ctr, Cooperstown, NY 13326 USA. Bassett Healthcare, Dept Med, Cooperstown, NY 13326 USA. Childrens Mercy Hosp, NICHD, Pediat Pharmacol Res Unit Lab, Kansas City, MO USA. Univ Washington, Dept Med Chem, Seattle, WA 98195 USA. RP Bertino, JS (reprint author), Bassett Healthcare, Dept Pharm Serv, 1 Atwell Rd, Cooperstown, NY 13326 USA. FU NICHD NIH HHS [HD31313-07]; NIGMS NIH HHS [GM32165] NR 27 TC 23 Z9 25 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD JUL PY 2001 VL 41 IS 7 BP 715 EP 722 DI 10.1177/00912700122010618 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 448WQ UT WOS:000169653300002 PM 11452703 ER PT J AU Herscovitch, P AF Herscovitch, P TI Can [O-15]water be used to evaluate drugs? SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID CEREBRAL BLOOD-FLOW; POSITRON-EMISSION-TOMOGRAPHY; GLUCOSE-UTILIZATION; ENERGY-METABOLISM; FUNCTIONAL-ACTIVITY; INTRAVENOUS (H2O)-O-15; ELECTRICAL-STIMULATION; SYNAPTIC ACTIVITY; WORKING-MEMORY; BRAIN ACTIVITY C1 NCI, Ctr Clin, PET Dept, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Herscovitch, P (reprint author), NCI, Ctr Clin, PET Dept, Warren Grant Magnuson Clin Ctr, Bldg 10,Rm 1C401,10 Ctr DR MSC 1180, Bethesda, MD 20892 USA. NR 63 TC 4 Z9 4 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD JUL PY 2001 SU S BP 11S EP 20S PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 450FC UT WOS:000169730000004 ER PT J AU Harris, KJ Ahluwalia, JS Okuyemi, KS Turner, JR Woods, MN Backinger, CL Resnicow, K AF Harris, KJ Ahluwalia, JS Okuyemi, KS Turner, JR Woods, MN Backinger, CL Resnicow, K TI Addressing cultural sensitivity in a smoking cessation intervention: Development of the kick it at swope project SO JOURNAL OF COMMUNITY PSYCHOLOGY LA English DT Article; Proceedings Paper CT 20th Annual Meeting of the Society-for-Behavioral-Medicine CY MAR, 1999 CL SAN DIEGO, CALIFORNIA SP Soc Behav Med ID CANCER INFORMATION-SERVICE; AFRICAN-AMERICAN SMOKERS; HEALTH PROMOTION; BLACK-WOMEN; PREVENTION; IMPACT; DESIGN; QUIT AB There are marked and growing disparities in the health status among different racial/ethnic groups. Most researchers and practitioners agree health interventions that are tailored for specific populations are ethically important and more likely to succeed, get there are few models for how to tailor interventions. This article outlines three phases and eight activities conducted to increase the cultural sensitivity of a clinical trial assessing the efficacy of bupropion for smoking cessation among African Americans. Early in the project development (Phase I) a strong partnership was built with a community-based clinic, two Advisory Boards were formed (Community and Scientific), and materials were developed. Formative research (Phase II) included a survey to assess smoking cessation needs of clinic patients and exploratory focus groups. Through Pilot testing (Phase III), clinic patients tested the intervention components and, in follow-up focus groups, discussed their experiences. Over 13 months the project successfully recruited 523 African Americans into a randomized trial, and preliminary analysis suggest acceptable follow-up rates. Successful recruitment and retention suggests the activities are promising and Potentially generalizable. Discussions of these activities illustrate concrete steps researchers and practitioners can take to increase the cultural sensitivity of health promotion and prevention interventions and clinical trials. (C) 2001 John Wiley & Sons, Inc. C1 Univ Kansas, Sch Med, Dept Prevent Med, Kansas City, KS 66160 USA. NCI, NIH, Bethesda, MD 20892 USA. Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. RP Harris, KJ (reprint author), Univ Kansas, Sch Med, Dept Prevent Med, 3901 Rainbow Blvd, Kansas City, KS 66160 USA. NR 35 TC 16 Z9 16 U1 1 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0090-4392 J9 J COMMUNITY PSYCHOL JI J. Community Psychol. PD JUL PY 2001 VL 29 IS 4 BP 447 EP 458 DI 10.1002/jcop.1028 PG 12 WC Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Social Work SC Public, Environmental & Occupational Health; Psychology; Social Work GA 442RH UT WOS:000169298400006 ER PT J AU Foreman, KE Friborg, J Chandran, B Katano, H Sata, T Mercader, M Nabel, GJ Nickoloff, BJ AF Foreman, KE Friborg, J Chandran, B Katano, H Sata, T Mercader, M Nabel, GJ Nickoloff, BJ TI Injection of human herpesvirus-X in human skin engrafted on SCID mice induces Kaposi's sarcoma-like lesions SO JOURNAL OF DERMATOLOGICAL SCIENCE LA English DT Article DE AIDS; angiogenesis; animal model; Kaposi's sarcoma-associated herpesvirus; viral pathogenesis ID SPINDLE-SHAPED CELLS; POLYMERASE CHAIN-REACTION; URACIL DNA GLYCOSYLASE; ENDOTHELIAL-CELLS; PERIPHERAL-BLOOD; FACTOR-XIIIA; TUMOR-CELLS; EXPRESSION; HUMAN-HERPESVIRUS-8; INFECTION AB Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV-8) has been implicated in the development of Kaposi's sarcoma (KS) and several B-cell lymphoproliferative diseases. Serologic and molecular genetic association data has implicated HHV-8 as the causal agent of KS, but its role in the development of KS lesions is not understood. To examine the etiology of KS, HHV-8 was injected into normal human skin transplanted onto SCID mice. Injection of HHV-8 induced lesion formation that is morphologically and phenotypically consistent with KS, including the presence of angiogenesis and spindle-shaped cells latently infected with HHV-8. These findings suggest that HHV-8 is indeed the etiologic agent of KS, and that the virus plays an important role in initiation of this disease. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Loyola Univ, Med Ctr, Dept Pathol, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Skin Canc Res Labs, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA. NIH, Vaccine Res Ctr, Bethesda, MD USA. Univ Kansas, Med Ctr, Dept Microbiol Mol Genet & Immunol, Kansas City, KS 66103 USA. Natl Inst Infect Dis, Dept Pathol, Ctr AIDS Res, Tokyo, Japan. RP Nickoloff, BJ (reprint author), Loyola Univ, Med Ctr, Dept Pathol, Cardinal Bernardin Canc Ctr, Room 301,2160 S 1st Ave, Maywood, IL 60153 USA. FU NCI NIH HHS [CA76951, CA75893, CA86435] NR 42 TC 21 Z9 23 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0923-1811 J9 J DERMATOL SCI JI J. Dermatol. Sci. PD JUL PY 2001 VL 26 IS 3 BP 182 EP 193 DI 10.1016/S0923-1811(01)00087-1 PG 12 WC Dermatology SC Dermatology GA 445WB UT WOS:000169480600004 PM 11390203 ER PT J AU Gustafson, DH Hawkins, R Pingree, S McTavish, F Arora, NK Mendenhall, J Cella, DF Serlin, RC Apantaku, FM Stewart, J Salner, A AF Gustafson, DH Hawkins, R Pingree, S McTavish, F Arora, NK Mendenhall, J Cella, DF Serlin, RC Apantaku, FM Stewart, J Salner, A TI Effect of computer support on younger women with breast cancer SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE breast cancer; quality of life; patient participation; computer; patient education; disadvantaged; Digital Divide ID QUALITY-OF-LIFE; FUNCTIONAL ASSESSMENT; INFORMATION; ONCOLOGY; THERAPY; SYSTEM; RELIABILITY; VALIDITY; HIGHWAY AB OBJECTIVE: Assess impact of a computer-based patient support system on quality of life in younger women with breast cancer, with particular emphasis on assisting the underserved. DESIGN: Randomized controlled trial conducted between 1995 and 1998. SETTING: Five sites: two teaching hospitals (Madison, Wis, and Chicago, Ill), two nonteaching hospitals (Chicago, Ill), and a cancer resource center (Indianapolis, Ind). The latter three sites treat many underserved patients. PARTICIPANTS: Newly diagnosed breast cancer patients (N = 246) under age 60. INTERVENTIONS: Experimental group received Comprehensive Health Enhancement Support System (CHESS), a home-based computer system providing information, decision-making, and emotional support. MEASUREMENTS AND MAIN RESULTS: Pretest and two posttest surveys (at two- and five-month follow-up) measured aspects of participation in care, social/information support, and quality of life. At two-month follow-up, the CHESS group was significantly more competent at seeking information. more comfortable participating In care, and had greater confidence in doctor(s). At five-month follow-up, the CHESS group had significantly better social support and also greater information competence. In addition, experimental assignment interacted with several Indicators of medical under-service (race, education, and lack of insurance), such that CHESS benefits were greater for the disadvantaged than the advantaged group. CONCLUSIONS: Computer-based patient support systems such as CHESS may benefit patients by providing information and social support, and increasing their participation in health care. These benefits may be largest for currently underserved populations. C1 Univ Wisconsin, Ctr Hlth Syst Res & Anal, Madison, WI 53705 USA. Univ Wisconsin, Dept Ind Engn, Madison, WI 53705 USA. Univ Wisconsin, Dept Prevent Med, Madison, WI 53705 USA. Univ Wisconsin, Sch Journalism & Mass Commun, Madison, WI 53705 USA. Univ Wisconsin, Dept Life Sci Commun, Madison, WI 53705 USA. Univ Wisconsin, Dept Educ Psychol, Madison, WI 53705 USA. Univ Wisconsin, Dept Clin Oncol, Madison, WI 53705 USA. Univ Wisconsin, Dept Psychiat & Behav Sci, Madison, WI 53705 USA. Univ Wisconsin, Dept Radiat Oncol, Madison, WI 53705 USA. Univ Wisconsin, Canc Program, Madison, WI 53705 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD USA. Evanston NW Healthcare, Evanston, IL USA. Univ Illinois, Natl Black Leadership Initiat Canc, Chicago, IL USA. Hartford Hosp, Hartford, CT 06115 USA. RP Gustafson, DH (reprint author), Univ Wisconsin, Ctr Hlth Syst Res & Anal, Room 1119,610 Walnut St, Madison, WI 53705 USA. FU NICHD NIH HHS [5R01HD32922] NR 41 TC 207 Z9 212 U1 2 U2 9 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2001 VL 16 IS 7 BP 435 EP 445 DI 10.1046/j.1525-1497.2001.016007435.x PG 11 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 458DV UT WOS:000170178700002 PM 11520380 ER PT J AU Tyska, MJ Huang, JD Skowron, J Jenkins, NA Copeland, NG Mooseker, MS AF Tyska, MJ Huang, JD Skowron, J Jenkins, NA Copeland, NG Mooseker, MS TI Characterization of mice lacking brush border myosin-I SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract C1 Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT USA. NCI, Mouse Canc Genet Program, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JUL PY 2001 VL 118 IS 1 MA 14 BP 6A EP 7A PG 2 WC Physiology SC Physiology GA 451CD UT WOS:000169782800025 ER PT J AU Sellers, JR Wang, F Chen, LF Meng, HP Hammer, JA AF Sellers, JR Wang, F Chen, LF Meng, HP Hammer, JA TI Structure and function of myosin V and X SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JUL PY 2001 VL 118 IS 1 MA 27 BP 13A EP 13A PG 1 WC Physiology SC Physiology GA 451CD UT WOS:000169782800038 ER PT J AU Yu, LC Gu, J Xu, S AF Yu, LC Gu, J Xu, S TI Distribution of myosin heads attached to actin filaments in the weakly bound states of A center dot M center dot ATP and A center dot M center dot ADP center dot P-i in skinned psoas muscle fibers SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JUL PY 2001 VL 118 IS 1 MA 33 BP 15A EP 16A PG 2 WC Physiology SC Physiology GA 451CD UT WOS:000169782800044 ER EF