Datasets:

---

siddharthtumre

/

Revised-JNLPBA

like 0

[ "Cosmid", "probe", "of", "BCL6", "hybridized", "to", "14q11", "and", "3q27", "by", "fluorescence", "in", "situ", "hybridization", "(", "FISH", ")", "." ]

[ 0, 0, 0, 1, 0, 0, 1, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "Although", "the", "band", "14q11", "is", "a", "locus", "of", "T-cell", "receptor", "alpha-", "and", "delta-chains", "(", "TCR", "alpha/delta", ")", ",", "lymphoma", "cells", "expressed", "B-cell", ",", "IgGk", "phenotype", "." ]

[ 0, 0, 0, 1, 0, 0, 0, 0, 9, 10, 10, 0, 9, 0, 9, 10, 0, 0, 7, 8, 0, 7, 0, 9, 0, 0 ]

[ "The", "findings", "suggest", "that", "a", "novel", "proto-oncogene", "in", "the", "vicinity", "of", "TCR", "alpha/delta", "is", "involved", "in", "this", "translocation", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 0, 0, 0, 0, 0, 0 ]

[ "Transgenic", "expression", "of", "PML/RARalpha", "impairs", "myelopoiesis", "." ]

[ 0, 0, 0, 9, 0, 0, 0 ]

[ "The", "translocation", "found", "in", "acute", "promyelocytic", "leukemia", "rearranges", "the", "promyelocytic", "leukemia", "gene", "(", "PML", ")", "on", "chromosome", "15", "with", "the", "retinoic", "acid", "receptor", "alpha", "(", "RARalpha", ")", "on", "chromosome", "17", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 2, 0, 1, 0, 0, 1, 2, 0, 0, 1, 2, 2, 2, 0, 1, 0, 0, 1, 2, 0 ]

[ "This", "yields", "a", "fusion", "transcript", ",", "PML/RARalpha", ",", "a", "transcription", "factor", "with", "reported", "dominant", "negative", "functions", "in", "the", "absence", "of", "hormone", "." ]

[ 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "Clinical", "remissions", "induced", "with", "all-trans", "retinoic", "acid", "(", "RA", ")", "treatment", "in", "acute", "promyelocytic", "leukemia", "are", "linked", "to", "PML/RARalpha", "expression", "in", "leukemic", "cells", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 9, 0, 0, 7, 8, 0 ]

[ "To", "evaluate", "the", "PML/RARalpha", "role", "in", "myelopoiesis", ",", "transgenic", "mice", "expressing", "PML/RARalpha", "were", "engineered", "." ]

[ 0, 0, 0, 9, 0, 0, 0, 0, 0, 0, 0, 9, 0, 0, 0 ]

[ "A", "full-length", "PML/RARalpha", "cDNA", "driven", "by", "the", "CD11b", "promoter", "was", "expressed", "in", "transgenic", "mice", "." ]

[ 0, 0, 1, 2, 0, 0, 0, 1, 2, 0, 0, 0, 0, 0, 0 ]

[ "Expression", "was", "confirmed", "in", "the", "bone", "marrow", "with", "a", "reverse", "transcription", "PCR", "assay", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "Basal", "total", "white", "blood", "cell", "and", "granulocyte", "counts", "did", "not", "appreciably", "differ", "between", "PML/RARalpha", "transgenic", "and", "control", "mice", "." ]

[ 0, 0, 7, 8, 8, 0, 7, 0, 0, 0, 0, 0, 0, 9, 0, 0, 0, 0, 0 ]

[ "Cell", "sorter", "analysis", "of", "CD11b+", "bone", "marrow", "cells", "revealed", "similar", "CD11b+", "populations", "in", "transgenic", "and", "control", "mice", "." ]

[ 0, 0, 0, 0, 0, 7, 8, 8, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "However", ",", "in", "vitro", "clonal", "growth", "assays", "performed", "on", "peripheral", "blood", "from", "transgenic", "versus", "control", "mice", "revealed", "a", "marked", "reduction", "of", "myeloid", "progenitors", ",", "especially", "in", "those", "responding", "to", "granulocyte/", "macrophage", "colony-stimulating", "factor", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 7, 8, 0, 0, 0, 0, 0, 0, 9, 10, 10, 10, 0 ]

[ "Granulocyte/macrophage", "colony-stimulating", "factor", "and", "kit", "ligand", "cotreatment", "did", "not", "overcome", "this", "inhibition", "." ]

[ 9, 10, 10, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "Impaired", "myelopoiesis", "in", "vivo", "was", "shown", "by", "stressing", "these", "mice", "with", "sublethal", "irradiation", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "Following", "irradiation", ",", "PML/RARalpha", "transgenic", "mice", ",", "as", "compared", "with", "controls", ",", "more", "rapidly", "depressed", "peripheral", "white", "blood", "cell", "and", "granulocyte", "counts", "." ]

[ 0, 0, 0, 9, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 7, 8, 8, 8, 0, 7, 0, 0 ]

[ "As", "expected", ",", "nearly", "all", "control", "mice", "(", "94.4", "%", ")", "survived", "irradiation", ",", "yet", "this", "irradiation", "was", "lethal", "to", "45.8", "%", "of", "PML/RARalpha", "transgenic", "mice", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 9, 0, 0, 0 ]

[ "Lethality", "was", "associated", "with", "more", "severe", "leukopenia", "in", "transgenic", "versus", "control", "mice", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "Retinoic", "acid", "treatment", "of", "irradiated", "PML/RARalpha", "mice", "enhanced", "granulocyte", "recovery", "." ]

[ 0, 0, 0, 0, 0, 9, 0, 0, 7, 0, 0 ]

[ "These", "data", "suggest", "that", "abnormal", "myelopoiesis", "due", "to", "PML/RARalpha", "expression", "is", "an", "early", "event", "in", "oncogenic", "transformation", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 9, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "C/EBP", "activators", "are", "required", "for", "HIV-1", "replication", "and", "proviral", "induction", "in", "monocytic", "cell", "lines", "." ]

[ 9, 10, 0, 0, 0, 0, 0, 0, 0, 0, 0, 5, 6, 6, 0 ]

[ "Previous", "work", "has", "shown", "that", "C/EBP", "sites", "and", "C/EBP", "transcriptional", "activators", "are", "necessary", "for", "HIV-1", "LTR", "activity", "in", "monocytes/macrophages", "." ]

[ 0, 0, 0, 0, 0, 1, 2, 0, 9, 10, 10, 0, 0, 0, 1, 2, 0, 0, 7, 0 ]

[ "We", "have", "investigated", "the", "role", "that", "C/EBP", "proteins", "play", "in", "induction", "and", "replication", "of", "HIV-1", "." ]

[ 0, 0, 0, 0, 0, 0, 9, 10, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "Ectopic", "expression", "of", "the", "dominant", "negative", "C/EBP", "protein", "LIP", "inhibited", "HIV-1", "mRNA", "and", "virus", "production", "in", "activated", "U1", "cells", ",", "demonstrating", "that", "C/EBP", "proteins", "are", "required", "for", "provirus", "induction", "." ]

[ 0, 0, 0, 0, 0, 0, 9, 10, 10, 0, 0, 0, 0, 0, 0, 0, 0, 5, 6, 0, 0, 0, 9, 10, 0, 0, 0, 0, 0, 0 ]

[ "U1", "lines", "overexpressing", "C/EBP", "activator", "NF-IL-6", "produced", "more", "viral", "mRNA", "and", "virus", "particles", "following", "cellular", "activation", "than", "control", "lines", ",", "demonstrating", "that", "C/EBP", "proteins", "are", "limiting", "for", "virus", "transcription", "." ]

[ 5, 6, 0, 9, 10, 10, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 9, 10, 0, 0, 0, 0, 0, 0 ]

[ "HIV-1", "harboring", "mutations", "within", "two", "C/EBP", "sites", "were", "crippled", "in", "their", "ability", "to", "replicate", "in", "U937", "promonocytic", "cells", ",", "indicating", "that", "these", "sites", "are", "required", "for", "replication", "." ]

[ 0, 0, 0, 0, 0, 1, 2, 0, 0, 0, 0, 0, 0, 0, 0, 5, 6, 6, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "These", "data", "identify", "C/EBP", "proteins", "as", "regulators", "of", "HIV-1", "expression", "in", "monocytes/macrophages", "." ]

[ 0, 0, 0, 9, 10, 0, 0, 0, 0, 0, 0, 7, 0 ]

[ "Epstein-Barr", "virus", "nuclear", "antigen", "2", "and", "latent", "membrane", "protein", "independently", "transactivate", "p53", "through", "induction", "of", "NF-kappaB", "activity", "." ]

[ 9, 10, 10, 10, 10, 0, 0, 0, 0, 0, 0, 9, 0, 0, 0, 9, 0, 0 ]

[ "B-cell", "immortalization", "by", "Epstein-Barr", "virus", "(", "EBV", ")", "is", "dependent", "on", "permanent", "control", "of", "the", "cellular", "processes", "which", "normally", "regulate", "cell", "division", "and", "apoptosis", ",", "functions", "possessed", "by", "p53", "in", "a", "number", "of", "normal", "cell", "types", "." ]

[ 7, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 9, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "In", "studies", "initiated", "to", "evaluate", "relationships", "between", "EBV", "latent", "genes", "and", "p53", ",", "p53", "levels", "were", "found", "to", "increase", "approximately", "10-fold", "4", "to", "5", "days", "after", "EBV", "infection", "of", "purified", "resting", "human", "B", "cells", ";", "the", "induced", "p53", "was", "transcriptionally", "active", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 9, 0, 9, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 7, 8, 8, 0, 0, 0, 9, 0, 0, 0, 0 ]

[ "Latent", "membrane", "protein", "1", "and", ",", "to", "a", "lesser", "extent", ",", "EBV", "nuclear", "antigen", "2", "mediated", "the", "increase", "in", "p53", "levels", "via", "activation", "of", "the", "NF-kappaB", "transcription", "factor", "." ]

[ 9, 10, 10, 10, 0, 0, 0, 0, 0, 0, 0, 9, 10, 10, 10, 0, 0, 0, 0, 9, 0, 0, 0, 0, 0, 9, 10, 10, 0 ]

[ "Cooperation", "between", "core", "binding", "factor", "and", "adjacent", "promoter", "elements", "contributes", "to", "the", "tissue-specific", "expression", "of", "interleukin-3", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 9, 0 ]

[ "Tissue-specific", "expression", "of", "interleukin-3", "(", "IL-3", ")", "is", "mediated", "via", "cis-acting", "elements", "located", "within", "315", "base", "pairs", "of", "the", "transcription", "start", "." ]

[ 0, 0, 0, 9, 0, 9, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "This", "is", "achieved", "in", "part", "through", "the", "positive", "activities", "of", "the", "AP-1", "and", "Elf-1", "sites", "in", "the", "IL-3", "promoter", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 1, 2, 0, 0, 1, 2, 0 ]

[ "The", "contribution", "to", "T", "cell-specific", "expression", "by", "other", "promoter", "sites", "was", "assessed", "in", "a", "transient", "expression", "assay", "with", "IL-3", "promoter", "constructs", "linked", "to", "a", "luciferase", "gene", ",", "focusing", "initially", "on", "the", "core", "binding", "factor", "(", "CBF", ")", "site", ",", "which", "is", "footprinted", "in", "vivo", "upon", "T", "cell", "activation", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 2, 0, 0, 0, 1, 2, 0, 0, 0, 0, 0, 1, 2, 2, 2, 2, 2, 2, 0, 0, 0, 0, 0, 0, 0, 7, 8, 0, 0 ]

[ "Activity", "of", "the", "CBF", "site", "is", "shown", "to", "be", "critically", "dependent", "on", "the", "adjacent", "activator", "site", "Act-1", "." ]

[ 0, 0, 0, 1, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 2, 0 ]

[ "Together", "the", "Act-1", "and", "CBF", "sites", "form", "a", "functional", "unit", "(", "AC", "unit", ")", "with", "dual", "activity", "." ]

[ 0, 0, 1, 0, 1, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "The", "AC", "unit", "is", "demonstrated", "to", "enhance", "basal", "activity", "of", "promoters", "both", "in", "fibroblasts", "and", "T", "cells", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 7, 0, 7, 8, 0 ]

[ "This", "activity", "is", "further", "inducible", "in", "activated", "T", "cells", ",", "but", "not", "in", "fibroblasts", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 7, 8, 0, 0, 0, 0, 7, 0 ]

[ "In", "addition", "to", "the", "already", "identified", "NIP", "repressor", "site", ",", "evidence", "is", "presented", "for", "a", "second", "repressor", "region", "that", "restricts", "promoter", "activity", "in", "fibroblasts", "." ]

[ 0, 0, 0, 0, 0, 0, 1, 2, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 7, 0 ]

[ "Finally", ",", "a", "novel", "positive", "regulatory", "element", "has", "been", "mapped", "in", "the", "IL-3", "promoter", "between", "nucleotide", "-180", "and", "-210", "that", "leads", "to", "increased", "expression", "in", "T", "cells", "." ]

[ 0, 0, 0, 0, 1, 2, 2, 0, 0, 0, 0, 0, 1, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 7, 8, 0 ]

[ "Together", "these", "results", "demonstrate", "that", "T", "cell", "expression", "of", "IL-3", "is", "not", "specified", "by", "the", "activity", "of", "a", "single", "tissue-specific", "element", ",", "but", "instead", "involves", "multiple", "interacting", "elements", "that", "provide", "both", "specific", "positive", "regulation", "in", "T", "cells", "and", "specific", "negative", "regulation", "in", "fibroblasts", "." ]

[ 0, 0, 0, 0, 0, 7, 8, 0, 0, 9, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 7, 8, 0, 0, 0, 0, 0, 7, 0 ]

[ "Modulation", "of", "the", "expression", "of", "the", "IFN-gamma", "receptor", "beta-chain", "controls", "responsiveness", "to", "IFN-gamma", "in", "human", "peripheral", "blood", "T", "cells", "." ]

[ 0, 0, 0, 0, 0, 0, 9, 10, 10, 0, 0, 0, 9, 0, 7, 8, 8, 8, 8, 0 ]

[ "IFN-gamma", "has", "potent", "antiproliferative", "and", "apoptotic", "effects", "in", "T", "cells", "that", "are", "important", "in", "determining", "T", "cell", "development", "and", "polarized", "differentiation", "." ]

[ 9, 0, 0, 0, 0, 0, 0, 0, 7, 8, 0, 0, 0, 0, 0, 7, 8, 0, 0, 0, 0, 0 ]

[ "Therefore", ",", "any", "event", "that", "enables", "T", "cells", "to", "become", "less", "responsive", "to", "IFN-", "gamma", "may", "potentially", "alter", "immune", "responsiveness", "to", "Ag", "." ]

[ 0, 0, 0, 0, 0, 0, 7, 8, 0, 0, 0, 0, 0, 9, 10, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "In", "this", "work", ",", "we", "show", "that", "human", "peripheral", "blood", "T", "cells", "that", "are", "stimulated", "through", "the", "TCR", "and", "expanded", "with", "IL-2", "are", "unresponsive", "to", "IFN-gamma", ",", "as", "determined", "by", "a", "lack", "of", "activation", "of", "jak", "kinases", "and", "the", "transcription", "factor", ",", "STAT1", "(", "alpha", ")", ",", "a", "signal", "transducer", "and", "activator", "of", "transcription", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 7, 8, 8, 8, 8, 0, 0, 0, 0, 0, 9, 0, 0, 0, 9, 0, 0, 0, 9, 0, 0, 0, 0, 0, 0, 0, 0, 0, 9, 10, 0, 0, 0, 0, 0, 9, 10, 10, 10, 0, 0, 9, 10, 10, 10, 10, 10, 0 ]

[ "This", "nonresponsiveness", "occurs", "because", "of", "a", "lack", "of", "expression", "of", "the", "beta-", "chain", "(", "accessory", "factor", ")", "of", "the", "IFN-gamma", "receptor", ",", "while", "at", "the", "same", "time", "maintaining", "IFN-gamma", "receptor", "alpha-chain", "expression", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 9, 10, 0, 0, 0, 0, 0, 0, 0, 9, 10, 10, 0, 0 ]

[ "Expression", "of", "the", "beta-chain", "can", "be", "restored", "by", "secondary", "TCR", "ligation", "or", "PMA", "treatment", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 9, 0, 0, 0, 0, 0 ]

[ "T", "cell", "blasts", "treated", "with", "PMA", "are", "now", "responsive", "to", "IFN-gamma", "." ]

[ 7, 8, 8, 0, 0, 0, 0, 0, 0, 0, 9, 0 ]

[ "When", "freshly", "isolated", ",", "highly", "enriched", "(", ">", "98", "%", ")", "T", "cells", "are", "examined", "for", "IFN-gamma", "responsiveness", ";", "these", "cells", "can", "respond", "to", "IFN-gamma", "and", "express", "beta-chain", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 7, 8, 0, 0, 0, 9, 0, 0, 0, 0, 0, 0, 0, 9, 0, 0, 0, 0 ]

[ "Therefore", ",", "as", "T", "cells", "progress", "from", "primary", "TCR", "activation", "through", "IL-2", "-dependent", "proliferation", ",", "followed", "by", "secondary", "TCR", "stimulation", ",", "their", "responsiveness", "to", "IFN-gamma", "varies", ",", "and", "this", "may", "affect", "their", "ability", "to", "participate", "in", "an", "ongoing", "immune", "response", "." ]

[ 0, 0, 0, 7, 8, 0, 0, 0, 9, 0, 0, 9, 0, 0, 0, 0, 0, 0, 9, 0, 0, 0, 0, 0, 9, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "Age-related", "decreases", "in", "IL-2", "production", "by", "human", "T", "cells", "are", "associated", "with", "impaired", "activation", "of", "nuclear", "transcriptional", "factors", "AP-1", "and", "NF-AT", "." ]

[ 0, 0, 0, 9, 0, 0, 7, 8, 8, 0, 0, 0, 0, 0, 0, 9, 10, 10, 10, 0, 9, 0 ]

[ "Although", "transcriptional", "factors", "AP-1", "and", "nuclear", "factor", "of", "activated", "T", "cells", "(", "NF-AT", ")", "are", "important", "for", "the", "normal", "induction", "of", "IL-2", ",", "it", "is", "unknown", "if", "the", "age-related", "decline", "in", "IL-2", "production", "by", "activated", "human", "T", "cells", "may", "be", "associated", "with", "aberrancies", "in", "transcriptional", "regulatory", "proteins", "." ]

[ 0, 9, 10, 10, 0, 9, 10, 10, 10, 10, 10, 0, 9, 0, 0, 0, 0, 0, 0, 0, 0, 9, 0, 0, 0, 0, 0, 0, 0, 0, 0, 9, 0, 0, 0, 7, 8, 8, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "In", "the", "current", "studies", ",", "IL-2", "production", "by", "T", "cells", "from", "elderly", "(", "mean", "78", "years", ")", "and", "young", "(", "mean", "37", "years", ")", "humans", "was", "measured", "in", "cultures", "stimulated", "with", "PHA", ",", "PHA", "plus", "PMA", ",", "crosslinked", "anti-CD3", "mAB", "OKT3", "plus", "PMA", ",", "or", "PMA", "plus", "ionomycin", "." ]

[ 0, 0, 0, 0, 0, 9, 0, 0, 7, 8, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 9, 0, 9, 0, 0, 0, 0, 9, 10, 10, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "Substantial", "decreases", "of", "IL-2", "production", "were", "observed", "for", "cell", "cultures", "from", "7", "of", "12", "elderly", "individuals", "in", "response", "to", "the", "different", "stimuli", ",", "whereas", "the", "levels", "of", "IL-2", "produced", "by", "stimulated", "T", "cells", "from", "other", "elderly", "individuals", "were", "equivalent", "to", "those", "observed", "for", "stimulated", "T", "cells", "of", "young", "subjects", "." ]

[ 0, 0, 0, 9, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 9, 0, 0, 0, 7, 8, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 7, 8, 0, 0, 0, 0 ]

[ "Analyses", "of", "nuclear", "extracts", "by", "electrophoretic", "DNA", "mobility", "shift", "assays", "showed", "that", "decreased", "IL-2", "production", "by", "stimulated", "T", "cells", "of", "elderly", "individuals", "was", "closely", "associated", "with", "impairments", "in", "the", "activation", "of", "both", "AP-1", "and", "NF-AT", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 9, 0, 0, 0, 7, 8, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 9, 0, 9, 0 ]

[ "By", "contrast", ",", "T", "cells", "from", "elderly", "subjects", "with", "normal", "levels", "of", "IL-2", "production", "exhibited", "normal", "activation", "of", "AP-1", "and", "NF-AT", "." ]

[ 0, 0, 0, 7, 8, 0, 0, 0, 0, 0, 0, 0, 9, 0, 0, 0, 0, 0, 9, 0, 9, 0 ]

[ "In", "addition", ",", "the", "results", "of", "competition", "experiments", "analyzing", "the", "normal", "components", "of", "NF-AT", "showed", "that", "the", "age-related", "reductions", "in", "stimulus-dependent", "NF-AT", "complexes", "corresponded", "to", "the", "slow", "migrating", "complexes", "that", "were", "composed", "of", "c-Fos/c-Jun", "AP-1", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 9, 0, 0, 0, 0, 0, 0, 0, 9, 10, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 9, 10, 0 ]

[ "The", "resting", "and", "stimulated", "levels", "of", "NF", "kappa", "B", "were", "reduced", "in", "T", "cells", "from", "certain", "elderly", "individuals", ";", "however", ",", "alterations", "of", "NF", "kappa", "B", "did", "not", "correlate", "with", "changes", "in", "IL-2", "expression", "." ]

[ 0, 0, 0, 0, 0, 0, 9, 10, 10, 0, 0, 0, 7, 8, 0, 0, 0, 0, 0, 0, 0, 0, 0, 9, 10, 10, 0, 0, 0, 0, 0, 0, 9, 0, 0 ]

[ "Thus", ",", "these", "results", "show", "that", "age-related", "impairments", "in", "the", "activation", "of", "AP-1", "and", "NF-AT", "are", "closely", "associated", "with", "decreased", "expression", "of", "IL-2", "and", "further", "suggest", "that", "aberrancies", "in", "the", "signaling", "pathways", "important", "for", "the", "induction", "of", "transcriptionally", "active", "c-Fos/c-Jun", "AP-1", "may", "contribute", "to", "the", "impaired", "activation", "of", "NF-AT", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 9, 0, 9, 0, 0, 0, 0, 0, 0, 0, 9, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 9, 10, 0, 0, 0, 0, 0, 0, 0, 9, 0 ]

[ "IL-13", "induces", "phosphorylation", "and", "activation", "of", "JAK2", "Janus", "kinase", "in", "human", "colon", "carcinoma", "cell", "lines", ":", "similarities", "between", "IL-4", "and", "IL-13", "signaling", "." ]

[ 9, 0, 0, 0, 0, 0, 9, 10, 10, 0, 5, 6, 6, 6, 6, 0, 0, 0, 9, 0, 9, 0, 0 ]

[ "We", "have", "recently", "reported", "that", "IL-13R", "may", "share", "a", "component", "with", "IL-4R", ".", "Here", "we", "report", "that", "both", "IL-4", "and", "IL-13", "share", "signaling", "events", "in", "human", "colon", "carcinoma", "cell", "lines", "(", "HT-29", "and", "WiDr", ")", "." ]

[ 0, 0, 0, 0, 0, 9, 0, 0, 0, 0, 0, 9, 0, 0, 0, 0, 0, 0, 9, 0, 9, 0, 0, 0, 0, 5, 6, 6, 6, 6, 0, 5, 0, 5, 0, 0 ]

[ "IL-13", "caused", "rapid", "phosphorylation", "of", "the", "three", "out", "of", "four", "members", "of", "the", "known", "Janus", "family", "of", "kinases", "(", "JAKs", ")", "." ]

[ 9, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 9, 10, 0, 0, 0, 9, 0, 0 ]

[ "We", "show", "that", "JAK2", "kinase", "is", "rapidly", "phosphorylated", "and", "activated", "in", "response", "to", "IL-13", "." ]

[ 0, 0, 0, 9, 10, 0, 0, 0, 0, 0, 0, 0, 0, 9, 0 ]

[ "Within", "1", "min", "of", "activation", ",", "JAK2", "was", "phosphorylated", ",", "and", "peaked", "in", "10", "min", "." ]

[ 0, 0, 0, 0, 0, 0, 9, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "In", "addition", ",", "IL-13", "phosphorylated", "insulin", "response", "substrate-1", ",", "IL-4R", "p140", ",", "JAK1", ",", "and", "Tyk2", ",", "but", "not", "JAK3", "kinase", "." ]

[ 0, 0, 0, 9, 0, 9, 10, 10, 0, 9, 10, 0, 9, 0, 0, 9, 0, 0, 0, 9, 10, 0 ]

[ "IL-4", "also", "stimulated", "all", "three", "kinases", "and", "substrates", ",", "but", "unlike", "in", "immune", "cells", ",", "IL-4", "did", "not", "involve", "JAK3", "activation", "for", "its", "signaling", "in", "colon", "cancer", "cell", "lines", "." ]

[ 9, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 9, 0, 0, 0, 9, 0, 0, 0, 0, 0, 5, 6, 6, 6, 0 ]

[ "Furthermore", ",", "JAK2", "associated", "with", "the", "IL-4R", "p140", "before", "and", "after", "stimulation", "with", "IL-13", "." ]

[ 0, 0, 9, 0, 0, 0, 9, 10, 0, 0, 0, 0, 0, 9, 0 ]

[ "Both", "IL-13", "and", "IL-4", "induced", "phosphorylation", "of", "IL-4", "STAT", "(", "STAT6", ")", "but", "not", "STAT1", ",", "STAT3", ",", "or", "STAT5", "." ]

[ 0, 9, 0, 9, 0, 0, 0, 9, 10, 0, 9, 0, 0, 0, 9, 0, 9, 0, 0, 9, 0 ]

[ "125I-IL-13", "did", "not", "bind", "to", "colon", "cancer", "cell", "lines", ",", "but", "unlabeled", "IL-13", "competed", "for", "the", "binding", "of", "125I-IL-4", "." ]

[ 9, 0, 0, 0, 0, 5, 6, 6, 6, 0, 0, 0, 9, 0, 0, 0, 0, 0, 9, 0 ]

[ "Our", "data", "suggest", "that", "IL-13", "utilizes", "IL-4R", "and", "its", "signaling", "pathway", ",", "and", "JAK2", "may", "play", "an", "important", "role", "in", "the", "function", "of", "IL-4R", "and", "IL-13R", "in", "colon", "cancer", "cells", "." ]

[ 0, 0, 0, 0, 9, 0, 9, 0, 0, 0, 0, 0, 0, 9, 0, 0, 0, 0, 0, 0, 0, 0, 0, 9, 0, 9, 0, 7, 8, 8, 0 ]

[ "Differential", "regulation", "of", "IL-6", "gene", "transcription", "and", "expression", "by", "IL-4", "and", "IL-10", "in", "human", "monocytic", "cell", "lines", "." ]

[ 0, 0, 0, 1, 2, 0, 0, 0, 0, 9, 0, 9, 0, 5, 6, 6, 6, 0 ]

[ "IL-4", "and", "IL-10", "inhibit", "the", "cytokine", "production", "and", "mRNA", "expression", "by", "monocytes/macrophages", "." ]

[ 9, 0, 9, 0, 0, 0, 0, 0, 0, 0, 0, 7, 0 ]

[ "To", "investigate", "the", "molecular", "mechanism", "of", "the", "inhibitory", "effect", "on", "transcriptional", "or", "post-transcriptional", "regulation", "of", "IL-6", "gene", "expression", "by", "IL-4", "and", "IL-10", ",", "we", "studied", "IL-6", "production", ",", "expression", "level", "of", "IL-6", "mRNA", ",", "IL-6", "promoter", "activity", ",", "transcriptional", "activity", "of", "NF-kappaB", "and", "NF-IL-6", ",", "and", "IL-6", "mRNA", "stability", "in", "human", "monocytic", "cell", "lines", ",", "THP-1", "and", "U937", ",", "stimulated", "by", "PMA", "and", "LPS", "in", "the", "absence", "or", "the", "presence", "of", "IL-4", "or", "IL-10", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 0, 0, 9, 0, 9, 0, 0, 0, 9, 0, 0, 0, 0, 0, 3, 4, 0, 1, 2, 0, 0, 0, 0, 0, 9, 0, 9, 0, 0, 3, 4, 0, 0, 5, 6, 6, 6, 0, 5, 0, 5, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 9, 0, 9, 0 ]

[ "Both", "IL-4", "and", "IL-10", "were", "seen", "to", "inhibit", "IL-6", "production", "and", "the", "expression", "of", "IL-6", "mRNA", "in", "both", "monocytic", "cell", "lines", "studied", "." ]

[ 0, 9, 0, 9, 0, 0, 0, 0, 9, 0, 0, 0, 0, 0, 3, 4, 0, 0, 5, 6, 6, 0, 0 ]

[ "In", "chloramphenicol", "acetyltransferase", "assays", ",", "utilizing", "the", "transient", "transfection", "of", "a", "chloramphenicol", "acetyltransferase", "reporter", "plasmid", "containing", "the", "IL-6", "gene", "promoter", ",", "IL-4", ",", "but", "not", "IL-10", ",", "suppressed", "the", "transcriptional", "activity", "of", "the", "IL-6", "gene", "promoter", "stimulated", "by", "PMA", "and", "LPS", "." ]

[ 0, 9, 10, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 2, 2, 0, 0, 1, 2, 2, 0, 9, 0, 0, 0, 9, 0, 0, 0, 0, 0, 0, 0, 1, 2, 2, 0, 0, 0, 0, 0, 0 ]

[ "Electrophoretic", "mobility", "shift", "assays", "showed", "that", "IL-4", ",", "but", "not", "IL-10", ",", "inhibited", "nuclear", "NF-kappaB", "activity", ",", "and", "that", "IL-4", "and", "IL-10", "did", "not", "affect", "NF-", "IL-6", "activity", "." ]

[ 0, 0, 0, 0, 0, 0, 9, 0, 0, 0, 9, 0, 0, 0, 9, 0, 0, 0, 0, 9, 0, 9, 0, 0, 0, 9, 10, 0, 0 ]

[ "On", "the", "other", "hand", ",", "IL-10", "enhanced", "the", "degradation", "of", "IL-6", "mRNA", "in", "a", "mRNA", "stability", "assay", "." ]

[ 0, 0, 0, 0, 0, 9, 0, 0, 0, 0, 3, 4, 0, 0, 0, 0, 0, 0 ]

[ "These", "results", "suggest", "that", "IL-4", "may", "inhibit", "the", "transcription", "of", "the", "IL-6", "gene", "by", "affecting", "NF-kappaB", "binding", "activity", ",", "while", "IL-10", "may", "inhibit", "the", "IL-6", "mRNA", "levels", "post-transcriptionally", ",", "without", "suppressing", "promoter", "activity", "." ]

[ 0, 0, 0, 0, 9, 0, 0, 0, 0, 0, 0, 1, 2, 0, 0, 9, 0, 0, 0, 0, 9, 0, 0, 0, 3, 4, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "Therefore", ",", "we", "conclude", "that", "IL-4", "and", "IL-10", "inhibit", "IL-6", "production", "by", "different", "mechanisms", "in", "human", "monocytic", "cell", "lines", "." ]

[ 0, 0, 0, 0, 0, 9, 0, 9, 0, 9, 0, 0, 0, 0, 0, 5, 6, 6, 6, 0 ]

[ "Activation", "of", "nuclear", "factor", "of", "activated", "T", "cells", "in", "a", "cyclosporin", "A-resistant", "pathway", "." ]

[ 0, 0, 9, 10, 10, 10, 10, 10, 0, 0, 0, 0, 0, 0 ]

[ "The", "mechanism", "of", "action", "of", "the", "immunosuppressive", "drug", "cyclosporin", "A", "(", "CsA", ")", "is", "the", "inactivation", "of", "the", "Ca2+/calmodulin-dependent", "serine-threonine", "phosphatase", "calcineurin", "by", "the", "drug-immunophilin", "complex", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 9, 10, 10, 10, 0, 0, 0, 0, 0 ]

[ "Inactive", "calcineurin", "is", "unable", "to", "activate", "the", "nuclear", "factor", "of", "activated", "T", "cells", "(", "NFAT", ")", ",", "a", "transcription", "factor", "required", "for", "expression", "of", "the", "interleukin", "2", "(", "IL-2", ")", "gene", "." ]

[ 0, 9, 0, 0, 0, 0, 0, 9, 10, 10, 10, 10, 10, 0, 9, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 2, 2, 2, 2, 0 ]

[ "IL-2", "production", "by", "CsA-treated", "cells", "is", "therefore", "dramatically", "reduced", "." ]

[ 9, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "We", "demonstrate", "here", ",", "however", ",", "that", "NFAT", "can", "be", "activated", ",", "and", "significant", "levels", "of", "IL-2", "can", "be", "produced", "by", "the", "CsA-resistant", "CD28", "-signaling", "pathway", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 9, 0, 0, 0, 0, 0, 0, 0, 0, 9, 0, 0, 0, 0, 0, 0, 9, 0, 0, 0 ]

[ "In", "transient", "transfection", "assays", ",", "both", "multicopy", "NFAT", "-and", "IL-2", "promoter-beta-galactosidase", "reporter", "gene", "constructs", "could", "be", "activated", "by", "phorbol", "12-myristate", "13-acetate", "(", "PMA", ")", "/alpha-", "CD28", "stimulation", ",", "and", "this", "activation", "was", "resistant", "to", "CsA", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 1, 0, 1, 2, 2, 2, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 9, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "Electrophoretic", "mobility", "shift", "assay", "showed", "the", "induction", "of", "a", "CsA-resistant", "NFAT", "complex", "in", "the", "nuclear", "extracts", "of", "peripheral", "blood", "T", "cells", "stimulated", "with", "PMA", "plus", "alphaCD28", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 9, 10, 0, 0, 0, 0, 0, 7, 8, 8, 8, 0, 0, 0, 0, 0, 0 ]

[ "Peripheral", "blood", "T", "cells", "stimulated", "with", "PMA", "/alphaCD28", "produced", "IL-2", "in", "the", "presence", "of", "CsA", "." ]

[ 7, 8, 8, 8, 0, 0, 0, 0, 0, 9, 0, 0, 0, 0, 0, 0 ]

[ "Collectively", ",", "these", "data", "suggest", "that", "NFAT", "can", "be", "activated", "and", "IL-2", "can", "be", "produced", "in", "a", "calcineurin", "independent", "manner", "." ]

[ 0, 0, 0, 0, 0, 0, 9, 0, 0, 0, 0, 9, 0, 0, 0, 0, 0, 9, 0, 0, 0 ]

[ "Effects", "of", "interleukin-10", "on", "human", "peripheral", "blood", "mononuclear", "cell", "responses", "to", "Cryptococcus", "neoformans", ",", "Candida", "albicans", ",", "and", "lipopolysaccharide", "." ]

[ 0, 0, 9, 0, 7, 8, 8, 8, 8, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "Deactivation", "of", "mononuclear", "phagocytes", "is", "critical", "to", "limit", "the", "inflammatory", "response", "but", "can", "be", "detrimental", "in", "the", "face", "of", "progressive", "infection", "." ]

[ 0, 0, 7, 8, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "We", "compared", "the", "effects", "of", "the", "deactivating", "cytokine", "interleukin", "10", "(", "IL-10", ")", "on", "human", "peripheral", "blood", "mononuclear", "cell", "(", "PBMC", ")", "responses", "to", "lipopolysaccharide", "(", "LPS", ")", ",", "Cryptococcus", "neoformans", ",", "and", "Candida", "albicans", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 9, 10, 10, 0, 9, 0, 0, 7, 8, 8, 8, 8, 0, 7, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "IL-10", "effected", "dose-dependent", "inhibition", "of", "tumor", "necrosis", "factor", "alpha", "(", "TNF-alpha", ")", "release", "in", "PBMC", "stimulated", "by", "LPS", "and", "C.", "neoformans", ",", "with", "significant", "inhibition", "seen", "with", "0.1", "U/ml", "and", "greater", "than", "90", "%", "inhibition", "noted", "with", "10", "U/ml", "." ]

[ 9, 0, 0, 0, 0, 9, 10, 10, 10, 0, 9, 0, 0, 0, 7, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "In", "contrast", ",", "even", "at", "doses", "as", "high", "as", "100", "U/ml", ",", "IL-10", "inhibited", "TNF-alpha", "release", "in", "response", "to", "C.", "albicans", "by", "only", "50", "%", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 9, 0, 9, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "IL-10", "profoundly", "inhibited", "release", "of", "IL-1beta", "from", "PBMC", "stimulated", "by", "all", "three", "stimuli", "." ]

[ 9, 0, 0, 0, 0, 9, 0, 7, 0, 0, 0, 0, 0, 0 ]

[ "TNF-alpha", "mRNA", "and", "release", "was", "inhibited", "even", "if", "IL-10", "was", "added", "up", "to", "8", "h", "after", "cryptococcal", "stimulation", "." ]

[ 3, 4, 0, 0, 0, 0, 0, 0, 9, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "In", "contrast", ",", "inhibition", "of", "IL-1", "beta", "mRNA", "was", "of", "lesser", "magnitude", "and", "occurred", "only", "when", "IL-10", "was", "added", "within", "2", "h", "of", "cryptococcal", "stimulation", "." ]

[ 0, 0, 0, 0, 0, 3, 4, 4, 0, 0, 0, 0, 0, 0, 0, 0, 9, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "IL-10", "inhibited", "translocation", "of", "NF-kappaB", "in", "response", "to", "LPS", "but", "not", "the", "fungal", "stimuli", "." ]

[ 9, 0, 0, 0, 9, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "All", "three", "stimuli", "induced", "IL-10", "production", "in", "PBMC", ",", "although", "over", "10-fold", "less", "IL-10", "was", "released", "in", "response", "to", "C.", "neoformans", "compared", "with", "LPS", "and", "C.", "albicans", "." ]

[ 0, 0, 0, 0, 9, 0, 0, 7, 0, 0, 0, 0, 0, 9, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "Thus", ",", "while", "IL-10", "has", "deactivating", "effects", "on", "PBMC", "responses", "to", "all", "three", "stimuli", ",", "disparate", "stimulus-", "and", "response-specific", "patterns", "of", "deactivation", "are", "seen", "." ]

[ 0, 0, 0, 9, 0, 0, 0, 0, 7, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]