cdcvd/ejpfepj · Datasets at Hugging Face

tags sequencelengths 2 166	tokens sequencelengths 2 166
[ 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 ]	[ "Retinoic", "acid", "(", "RA", ")", ",", "a", "vitamin", "A", "derivative", ",", "exerts", "a", "wide", "range", "of", "biological", "effects", "related", "to", "cell", "proliferation", "and", "differentiation", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 0, 3, 0, 0 ]	[ "The", "pleiotropic", "effects", "of", "RA", "are", "thought", "to", "be", "mediated", "through", "specific", "nuclear", "RA", "receptors", "(", "RARs", ")", "." ]
[ 3, 0, 0, 0, 0, 3, 4, 4, 4, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 4, 4, 4, 4, 0 ]	[ "RARs", "are", "members", "of", "the", "steroid/thyroid", "hormone", "receptor", "superfamily", "and", "exhibit", "a", "molecular", "structure", "that", "possess", "discrete", "DNA-binding", "and", "RA", "(", "ligand", ")", "-binding", "domains", "." ]
[ 0, 0, 0, 0, 0, 0, 3, 0, 0, 3, 4, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 5, 6, 0 ]	[ "In", "hematopoietic", "system", ",", "RA", "and", "RARs", ",", "predominantly", "RAR", "alpha", "may", "play", "key", "roles", "for", "the", "proliferation", "and", "differentiation", "of", "hematopoietic", "progenitors", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0 ]	[ "However", ",", "it", "is", "currently", "unknown", "how", "RA", "and", "RARs", "are", "involved", "in", "regulating", "normal", "hematopoietic", "differentiation", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 4, 0, 3, 4, 0, 0, 5, 6, 6, 6, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 2, 0, 1, 2, 2, 2, 0, 0, 0, 0, 7, 8, 8, 0, 7, 0, 0, 0, 0, 0, 0, 0, 5, 6, 0 ]	[ "To", "make", "clear", "the", "roles", "of", "RA", "and", "RAR", "alpha", "in", "the", "normal", "hematopoiesis", ",", "I", "have", "introduced", "the", "construct", "of", "human", "RAR", "alpha", "(", "hRAR", "alpha", ")", "into", "murine", "bone", "marrow", "cells", "with", "retroviral", "vector", ",", "and", "selected", "infected", "cells", "with", "drug", "resistant", "marker", "(", "Neo", "(", "r", ")", ")", "cultured", "on", "the", "stroma", "cell", "line", "(", "PA6-neo", ")", ",", "and", "analyzed", "the", "behavior", "of", "infected", "cells", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 0 ]	[ "All", "of", "procedure", "were", "done", "in", "vitro", "." ]
[ 0, 0, 0, 0, 3, 4, 0, 5, 6, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	[ "Most", "cells", "infected", "with", "hRAR", "alpha", "exhibited", "promyelocytic", "morphology", "and", "were", "thought", "to", "be", "blocked", "at", "the", "promyelocytic", "stage", "in", "their", "myeloid", "differentiation", "." ]
[ 0, 0, 0, 5, 6, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	[ "Furthermore", ",", "these", "immature", "cells", "differentiated", "terminally", "into", "mature", "granulocytes", "by", "adding", "with", "RA", "(", "10", "(", "-6", ")", "M", ")", "." ]
[ 3, 4, 5, 6, 0, 0, 0, 0, 0, 0, 5, 6, 0, 0, 0, 0, 0, 0, 0, 0, 7, 8, 0 ]	[ "RAR", "alpha", "infected", "cells", "were", "also", "able", "to", "differentiate", "into", "mature", "macrophages", "in", "the", "both", "of", "long", "term", "culture", "and", "IL3", "colony", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 3, 4, 0, 0, 0, 0, 0, 5, 6, 0, 0, 3, 4, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	[ "These", "observations", "suggest", "that", "an", "overexpression", "of", "RAR", "alpha", "alone", "is", "effective", "to", "suppress", "myeloid", "cell", "differentiation", "and", "RAR", "alpha", "plays", "a", "crucial", "role", "in", "the", "terminal", "differentiation", "of", "myeloid", "precursors", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 0, 0, 0, 5, 6, 6, 6, 0 ]	[ "The", "system", "described", "here", "may", "serve", "as", "a", "model", "for", "studying", "the", "the", "essential", "genes", "for", "differentiation", "of", "normal", "bone", "marrow", "cells", "." ]
[ 0, 0, 0, 1, 2, 0, 0, 5, 6, 6, 0 ]	[ "Hypoxic", "induction", "of", "interleukin-8", "gene", "expression", "in", "human", "endothelial", "cells", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 5, 0, 0, 0, 0, 0, 0 ]	[ "Because", "leukocyte-mediated", "tissue", "damage", "is", "an", "important", "component", "of", "the", "pathologic", "picture", "in", "ischemia/reperfusion", ",", "we", "have", "sought", "mechanisms", "by", "which", "PMNs", "are", "directed", "into", "hypoxic", "tissue", "." ]
[ 0, 0, 5, 6, 6, 0, 5, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 5, 0, 0, 0, 0, 0, 3, 0 ]	[ "Incubation", "of", "human", "endothelial", "cells", "(", "ECs", ")", "in", "hypoxia", ",", "PO2", "approximately", "14-18", "Torr", ",", "led", "to", "time-dependent", "release", "of", "IL-8", "antigen", "into", "the", "conditioned", "medium", ";", "this", "was", "accompanied", "by", "increased", "chemotactic", "activity", "for", "PMNs", ",", "blocked", "by", "antibody", "to", "IL-8", "." ]
[ 0, 0, 3, 0, 0, 5, 0, 0, 0, 0, 0, 0, 0, 9, 10, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0 ]	[ "Production", "of", "IL-8", "by", "hypoxic", "ECs", "occurred", "concomitantly", "with", "both", "increased", "levels", "of", "IL-8", "mRNA", ",", "based", "on", "polymerase", "chain", "reaction", "analysis", ",", "and", "increased", "IL-8", "transcription", ",", "based", "on", "nuclear", "run-on", "assays", "." ]
[ 0, 0, 0, 0, 0, 0, 5, 0, 0, 0, 0, 0, 9, 0, 3, 4, 4, 0, 0, 0, 0, 0, 3, 4, 0, 3, 4, 0 ]	[ "Northern", "analysis", "of", "mRNA", "from", "hypoxic", "ECs", "also", "demonstrated", "increased", "levels", "of", "mRNA", "for", "macrophage", "chemotactic", "protein-1", ",", "another", "member", "of", "the", "chemokine", "superfamily", "of", "proinflammatory", "cytokines", "." ]
[ 1, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 5, 6, 0, 0, 0, 0, 0 ]	[ "IL-8", "gene", "induction", "was", "associated", "with", "the", "presence", "of", "increased", "binding", "activity", "in", "nuclear", "extracts", "from", "hypoxic", "ECs", "for", "the", "NF-kB", "site", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 0, 0, 0, 0, 0 ]	[ "Studies", "with", "human", "umbilical", "vein", "segments", "exposed", "to", "hypoxia", "also", "demonstrated", "increased", "elaboration", "of", "IL-8", "antigen", "compared", "with", "normoxic", "controls", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0 ]	[ "In", "mice", "exposed", "to", "hypoxia", "(", "PO2", "approximately", "30-40", "Torr", ")", ",", "there", "was", "increased", "pulmonary", "leukostasis", ",", "as", "evidenced", "by", "increased", "myeloperoxidase", "activity", "in", "tissue", "homogenates", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 3, 4, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0 ]	[ "In", "parallel", ",", "increased", "levels", "of", "transcripts", "for", "IP-10", ",", "a", "murine", "homologue", "in", "the", "chemokine", "family", "related", "to", "IL-8", ",", "were", "observed", "in", "hypoxic", "lung", "tissue", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	[ "Taken", "together", ",", "these", "data", "suggest", "that", "hypoxia", "constitutes", "a", "stimulus", "for", "leukocyte", "chemotaxis", "and", "tissue", "leukostasis", "." ]
[ 3, 0, 3, 4, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 0, 0, 3, 0, 0, 0, 0, 0, 0 ]	[ "Thrombin", "and", "thrombin", "receptor", "agonist", "peptide", "induce", "early", "events", "of", "T", "cell", "activation", "and", "synergize", "with", "TCR", "cross-linking", "for", "CD69", "expression", "and", "interleukin", "2", "production", "." ]
[ 3, 0, 0, 0, 7, 8, 8, 8, 8, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	[ "Thrombin", "stimulation", "of", "the", "T", "leukemic", "cell", "line", "Jurkat", "induced", "a", "transient", "increase", "in", "[", "Ca2+", "]", "i", "." ]
[ 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 3, 4, 0, 0, 0, 0, 0, 0, 0, 0 ]	[ "Proteolytic", "activity", "of", "the", "enzyme", "was", "required", "for", "this", "effect", "since", "diisopropyl", "fluorophosphate-thrombin", "failed", "to", "increase", "[", "Ca2+", "]", "i", "." ]
[ 0, 0, 0, 0, 3, 4, 0, 0, 0, 0, 0, 0, 0, 0, 0, 7, 8, 8, 0 ]	[ "Furthermore", ",", "hirudin", "and", "anti-thrombin", "III", "inhibited", "the", "thrombin-induced", "[", "Ca2+", "]", "i", "rise", "in", "Jurkat", "T", "cells", "." ]
[ 0, 0, 3, 4, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	[ "A", "synthetic", "thrombin", "receptor", "agonist", "peptide", "(", "TRP", ")", "of", "7", "residues", "(", "SFLLRNP", ")", "was", "found", "to", "be", "as", "effective", "as", "thrombin", "for", "[", "Ca2+", "]", "i", "mobilization", ",", "and", "both", "agonists", "induced", "Ca2+", "release", "exclusively", "from", "internal", "stores", "." ]
[ 3, 0, 0, 0, 0, 0, 0, 0, 3, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 0 ]	[ "Thrombin", "stimulated", "tyrosine", "phosphorylation", "of", "several", "proteins", "of", "molecular", "mass", "40", ",", "42", ",", "70", ",", "120", ",", "and", "130", "kDa", "." ]
[ 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	[ "There", "was", "a", "good", "correlation", "between", "thrombin", "-induced", "tyrosine", "phosphorylation", "of", "the", "latter", "three", "proteins", "and", "Ca2+", "mobilization", "." ]
[ 3, 0, 0, 0, 0, 0, 0, 3, 4, 4, 0, 0, 0, 0, 0, 0, 0, 0 ]	[ "Thrombin", "and", "TRP", "also", "caused", "translocation", "of", "protein", "kinase", "C", "from", "the", "cytosol", "to", "the", "plasma", "membrane", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 3, 0, 0, 3, 4, 4, 0 ]	[ "As", "a", "likely", "consequence", "of", "these", "events", ",", "thrombin", "activated", "the", "nuclear", "factor", "NF-kB", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 7, 8, 8, 8, 8, 0, 0, 7, 8, 8, 8, 0, 0, 0, 3, 0, 0, 0, 0, 0, 7, 0, 0, 7, 8, 8, 0, 0, 7, 8, 0, 7, 8, 0, 0, 0, 3, 0, 0, 0, 0 ]	[ "Several", "cell", "lines", "of", "hematopoietic", "origin", "including", "the", "leukemic", "T", "cell", "line", "HPB.ALL", "and", "the", "erythroleukemic", "cell", "line", "K562", "were", "responsive", "to", "thrombin", ",", "whereas", "others", "such", "as", "THP1", ",", "a", "myelomonocytic", "cell", "line", ",", "and", "BL2", ",", "a", "Burkitt", "lymphoma", "were", "refractory", "to", "thrombin", "or", "TRP", "stimulation", "." ]
[ 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 9, 10, 10, 0 ]	[ "The", "magnitude", "of", "the", "thrombin", "response", "in", "the", "different", "cell", "types", "paralleled", "the", "expression", "of", "the", "thrombin", "receptor", "mRNA", "." ]
[ 0, 0, 0, 0, 0, 7, 8, 8, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 9, 10, 10, 0, 0, 0, 0, 0, 0, 0, 0, 3, 0, 0 ]	[ "We", "found", "that", "activation", "of", "Jurkat", "T", "cells", "by", "a", "combination", "of", "phytohemagglutinin", "and", "phorbol", "12-myristate", "13-acetate", "led", "to", "a", "dramatic", "inhibition", "of", "thrombin", "receptor", "mRNA", "expression", "and", "to", "a", "concomitant", "loss", "of", "the", "thrombin", "response", "." ]
[ 0, 0, 0, 0, 0, 3, 0, 0, 0, 3, 0, 0, 3, 4, 0, 0, 0, 3, 4, 4, 0, 0, 0, 7, 8, 8, 0, 0, 0, 5, 0 ]	[ "Finally", ",", "we", "demonstrate", "that", "thrombin", "and", "TRP", "enhanced", "CD69", "expression", "and", "interleukin", "2", "production", "induced", "by", "T", "cell", "receptor", "cross-linking", "in", "both", "Jurkat", "T", "cells", "and", "peripheral", "blood", "lymphocytes", "." ]
[ 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 5, 6, 0, 0 ]	[ "These", "findings", "highlight", "the", "role", "of", "thrombin", "as", "a", "potential", "regulator", "of", "T", "lymphocyte", "activation", "." ]
[ 0, 0, 0, 5, 6, 6, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0 ]	[ "Stress", "response", "of", "senescent", "T", "lymphocytes", ":", "reduced", "hsp70", "is", "independent", "of", "the", "proliferative", "block", "." ]
[ 7, 8, 8, 8, 8, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 7, 8, 8, 0, 0, 0, 0, 0, 0, 0, 0 ]	[ "Senescent", "human", "T", "lymphocyte", "cultures", "are", "unable", "to", "undergo", "proliferation", ",", "but", "show", "no", "difference", "from", "early", "passage", "cells", "in", "cytotoxic", "function", "or", "surface", "antigenic", "profile", "." ]
[ 0, 0, 0, 0, 7, 8, 8, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0 ]	[ "A", "second", "feature", "of", "senescent", "T", "cells", "is", "the", "dramatic", "reduction", "in", "hsp70", "production", "in", "response", "to", "heat", "shock", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 2, 2, 0 ]	[ "This", "decline", "is", "associated", "with", "a", "decrease", "in", "binding", "of", "nuclear", "extracts", "to", "the", "consensus", "heat", "shock", "element", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 7, 8, 8, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	[ "Interestingly", ",", "the", "progressive", "decline", "in", "the", "heat", "shock", "response", "of", "cultured", "T", "cells", "correlates", "with", "the", "percent", "proliferative", "life", "span", "completed", "rather", "than", "with", "the", "actual", "proliferative", "activity", "at", "the", "time", "of", "heat", "shock", "." ]
[ 0, 0, 0, 0, 5, 6, 6, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 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, 0, 0, 0, 0 ]	[ "This", "suggests", "that", "for", "senescent", "T", "cells", "the", "reduced", "ability", "to", "respond", "to", "heat", "shock", "by", "producing", "hsp70", ",", "although", "possibly", "lying", "at", "the", "level", "of", "transcriptional", "control", ",", "may", "nevertheless", "be", "unrelated", "to", "the", "reduced", "DNA", "synthesis", "or", "the", "diminished", "proliferative", "activity", "also", "manifested", "by", "these", "cells", "." ]
[ 0, 0, 3, 4, 0, 0, 0, 0, 3, 4, 4, 0, 7, 8, 8, 8, 8, 0 ]	[ "Involvement", "of", "phospholipase", "D", "in", "the", "activation", "of", "transcription", "factor", "AP-1", "in", "human", "T", "lymphoid", "Jurkat", "cells", "." ]
[ 0, 0, 0, 0, 3, 3, 4, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	[ "The", "induction", "of", "the", "AP-1", "transcription", "factor", "has", "been", "ascribed", "to", "the", "early", "events", "leading", "to", "T", "lymphocyte", "activation", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 0, 3, 0, 0, 0, 0, 0, 3, 4, 4, 0, 0, 0, 0, 0, 0, 0, 7, 8, 8, 8, 0, 0, 0, 0, 0, 1, 2, 2, 0, 0, 1, 2, 2, 2, 0 ]	[ "We", "have", "examined", "the", "possibility", "that", "stimulation", "of", "phospholipase", "D", "(", "PLD", ")", "may", "regulate", "activation", "of", "transcription", "factor", "AP-1", "in", "human", "T", "cells", "by", "transfecting", "human", "T", "lymphocyte", "Jurkat", "cells", "with", "a", "plasmid", "containing", "an", "AP-1", "enhancer", "element", "and", "a", "chloramphenicol", "acetyltransferase", "reporter", "gene", "." ]
[ 0, 0, 0, 0, 3, 0, 7, 8, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 7, 8, 0, 0, 0, 0, 0, 3, 4, 4, 0 ]	[ "We", "have", "detected", "activatable", "PLD", "in", "Jurkat", "cells", ",", "and", "we", "have", "found", "that", "addition", "of", "phosphatidic", "acid", "(", "PA", ")", ",", "the", "physiologic", "product", "of", "PLD", "action", "on", "phospholipids", ",", "is", "rapidly", "incorporated", "into", "Jurkat", "cells", "and", "leads", "to", "activation", "of", "transcription", "factor", "AP-1", "." ]
[ 0, 0, 7, 8, 0, 3, 4, 0, 0, 3, 0, 3, 4, 4, 0 ]	[ "Treatment", "of", "Jurkat", "cells", "with", "anti-CD3", "mAb", "activated", "both", "PLD", "and", "transcription", "factor", "AP-1", "." ]
[ 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 3, 0, 0, 0, 0, 3, 0, 0, 1, 2, 0, 0 ]	[ "Wortmannin", ",", "an", "inhibitor", "of", "receptor-coupled", "PLD", "activation", ",", "blocked", "the", "anti-CD3", "-induced", "increases", "in", "both", "PLD", "activity", "and", "AP-1", "enhancer", "activity", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 7, 8, 0, 3, 0, 0, 0, 0, 1, 2, 0, 0, 0, 0, 0, 0 ]	[ "We", "found", "a", "good", "correlation", "in", "the", "transfected", "cells", "between", "PLD", "activation", "and", "induction", "of", "AP-1", "enhancer", "activity", "under", "different", "experimental", "conditions", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 1, 2, 0, 0 ]	[ "Furthermore", ",", "ethanol", ",", "an", "inhibitor", "of", "the", "PLD", "pathway", ",", "blocked", "the", "anti-CD3-stimulated", "AP-1", "enhancer", "activity", "." ]
[ 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	[ "However", ",", "this", "anti-CD3", "-mediated", "response", "was", "not", "inhibited", "by", "neomycin", ",", "an", "inhibitor", "of", "phosphoinositide", "hydrolysis", "." ]
[ 0, 0, 0, 1, 2, 0, 0, 0, 0, 0, 3, 4, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 0, 3, 4, 4, 0, 3, 0, 0 ]	[ "The", "increases", "in", "AP-1", "enhancer", "activity", "induced", "by", "PA", "or", "anti-CD3", "mAb", "were", "efficiently", "abrogated", "by", "the", "presence", "of", "propranolol", ",", "an", "inhibitor", "of", "PA", "phosphohydrolase", "and", "protein", "kinase", "C", "(", "PKC", ")", "." ]
[ 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 1, 2, 0, 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 3, 0, 0 ]	[ "Furthermore", ",", "the", "PA", "-and", "the", "anti-CD3", "-induced", "increases", "in", "AP-1", "enhancer", "activity", "were", "blocked", "by", "the", "presence", "of", "PKC", "inhibitors", "or", "by", "PKC", "down-regulation", "." ]
[ 0, 0, 0, 0, 3, 0, 0, 0, 0, 3, 4, 4, 0, 5, 6, 0, 0, 0, 0, 0, 0, 0, 1, 2, 0, 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	[ "These", "data", "indicate", "that", "PLD", "stimulation", "can", "activate", "the", "transcription", "factor", "AP-1", "in", "T", "lymphocytes", ",", "and", "suggest", "that", "the", "induction", "of", "AP-1", "enhancer", "factor", "activity", "by", "PA", "is", "mediated", "via", "PKC", "stimulation", ",", "either", "through", "a", "direct", "activating", "effect", "of", "PA", "or", "through", "PA-derived", "diacylglycerol", "formation", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 1, 2, 0, 0, 0, 0, 0, 0, 3, 4, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 5, 6, 0, 0 ]	[ "These", "data", "also", "provide", "evidence", "for", "a", "role", "of", "PLD", "-derived", "lipids", "in", "the", "induction", "of", "AP-1", "enhancer", "activity", "resulting", "from", "stimulation", "of", "the", "TCR/CD3", "complex", ",", "suggesting", "that", "increased", "PLD", "activity", "can", "play", "an", "important", "role", "in", "T", "lymphocyte", "activation", "." ]
[ 0, 0, 1, 0, 0, 3, 4, 4, 4, 4, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 0, 0, 0, 0, 0, 3, 4, 4, 0 ]	[ "Upregulation", "of", "bcl-2", "by", "the", "Epstein-Barr", "virus", "latent", "membrane", "protein", "LMP1", ":", "a", "B-cell-specific", "response", "that", "is", "delayed", "relative", "to", "NF-kappa", "B", "activation", "and", "to", "induction", "of", "cell", "surface", "markers", "." ]
[ 0, 0, 0, 0, 3, 4, 4, 4, 4, 3, 0, 0, 0, 0, 0, 5, 6, 6, 0, 0, 0, 0, 1, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 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, 0, 0 ]	[ "An", "ability", "of", "the", "Epstein-Barr", "virus", "latent", "membrane", "protein", "LMP1", "to", "enhance", "the", "survival", "of", "infected", "B", "cells", "through", "upregulation", "of", "the", "bcl-2", "oncogene", "was", "first", "suggested", "by", "experiments", "involving", "gene", "transfection", "and", "the", "selection", "of", "stable", "LMP1+", "clones", "(", "S.Henderson", ",", "M.", "Rowe", ",", "C.Gregory", ",", "F.Wang", ",", "E.Kieff", ",", "and", "A.Rickinson", ",", "Cell", "65", ":", "1107-1115", ",", "1991", ")", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 7, 8, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 0 ]	[ "However", ",", "it", "was", "not", "possible", "to", "ascertain", "whether", "Bcl-2", "upregulation", "was", "a", "specific", "consequence", "of", "LMP1", "expression", "or", "an", "artifact", "of", "the", "selection", "procedure", "whereby", "rare", "Bcl-2+", "cells", "already", "present", "in", "the", "starting", "population", "might", "best", "be", "able", "to", "tolerate", "the", "potentially", "toxic", "effects", "of", "LMP1", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 3, 4, 0, 0, 0, 0, 3, 4, 4, 3, 0, 0, 0, 0, 0, 0, 3, 0, 0 ]	[ "We", "therefore", "reexamined", "this", "issue", "by", "using", "two", "different", "experimental", "approaches", "that", "allowed", "LMP1", "-induced", "effects", "to", "be", "monitored", "immediately", "following", "expression", "of", "the", "viral", "protein", "and", "in", "the", "absence", "of", "selective", "pressures", ";", "activation", "of", "the", "NF-kappa", "B", "transcription", "factor", "and", "upregulation", "of", "the", "cell", "adhesion", "molecule", "ICAM-1", "were", "used", "as", "early", "indices", "of", "LMP1", "function", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 7, 8, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 1, 2, 0, 0, 0, 0, 3, 0, 0, 0, 0 ]	[ "In", "the", "first", "approach", ",", "stable", "clones", "of", "two", "B-cell", "lines", "carrying", "an", "LMP1", "gene", "under", "the", "control", "of", "an", "inducible", "metallothionein", "promoter", "were", "induced", "to", "express", "LMP1", "in", "all", "cells", "." ]
[ 0, 0, 3, 4, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 0 ]	[ "Activation", "of", "NK-kappa", "B", "and", "upregulation", "of", "ICAM-1", "occurred", "within", "24", "h", "and", "were", "followed", "at", "48", "to", "72", "h", "by", "upregulation", "of", "Bcl-2", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	[ "In", "the", "second", "approach", ",", "we", "tested", "the", "generality", "of", "this", "phenomenon", "by", "transiently", "expressing", "LMP1", "from", "a", "strong", "constitutively", "active", "promoter", "in", "a", "range", "of", "different", "cell", "types", "." ]
[ 0, 0, 7, 8, 0, 0, 3, 4, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 0, 3, 0 ]	[ "All", "six", "B-cell", "lines", "tested", "showed", "NF-kappa", "B", "activation", "in", "response", "to", "LMP1", "expression", ",", "and", "this", "was", "followed", "in", "five", "of", "six", "lines", "by", "expression", "of", "ICAM-1", "and", "Bcl-2", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 7, 8, 0, 3, 4, 0, 0, 3, 0, 0, 0, 0, 0, 0, 3, 0 ]	[ "In", "the", "same", "experiments", ",", "all", "three", "non-", "B-cell", "lines", "showed", "NF-kappa", "B", "activation", "and", "ICAM-1", "upregulation", "but", "never", "any", "effect", "upon", "Bcl-2", "." ]
[ 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	[ "We", "therefore", "conclude", "that", "Bcl-2", "upregulation", "is", "part", "of", "the", "panoply", "of", "cellular", "changes", "induced", "by", "LMP1", "but", "that", "the", "effect", "is", "cell", "type", "specific", "." ]
[ 0, 0, 0, 0, 0, 0, 3, 4, 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 3, 4, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 0 ]	[ "Our", "data", "also", "suggest", "that", "whilst", "NF-kappa", "B", "may", "be", "an", "essential", "component", "of", "LMP1", "signal", "transduction", ",", "other", "cell-specific", "factors", "may", "be", "required", "to", "effect", "some", "functions", "of", "the", "viral", "protein", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 3, 4, 0, 0, 0, 0, 3, 0, 0, 3, 0, 0, 7, 8, 8, 8, 8, 0 ]	[ "Long-term", "inositol", "phosphate", "release", ",", "but", "not", "tyrosine", "kinase", "activity", ",", "correlates", "with", "IL-2", "secretion", "and", "NF-AT", "induction", "in", "anti-CD3-activated", "peripheral", "human", "T", "lymphocytes", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 5, 6, 0, 0, 0, 0, 0, 0 ]	[ "The", "cascade", "of", "events", "within", "the", "first", "few", "minutes", "of", "T", "cell", "stimulation", "has", "been", "well", "characterized", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 5, 6, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 5, 6, 6, 0, 0, 0, 0, 0 ]	[ "Although", "many", "second", "messengers", "have", "been", "shown", "to", "be", "necessary", "and", "sufficient", "for", "T", "cell", "activation", "in", "a", "number", "of", "model", "systems", ",", "the", "rate-limiting", "step", "in", "peripheral", "T", "cells", "has", "not", "been", "demonstrated", "." ]
[ 0, 0, 0, 0, 0, 3, 0, 0, 0, 5, 6, 6, 0, 0, 0, 0, 3, 4, 0, 0, 0, 0, 0, 0, 0, 5, 6, 6, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 5, 6, 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 5, 6, 0, 0, 0, 0, 0 ]	[ "To", "model", "effective", "versus", "ineffective", "CD3", "-mediated", "stimulation", "in", "peripheral", "T", "cells", ",", "we", "used", "two", "anti-CD3", "mAbs", "that", "differ", "in", "their", "ability", "to", "stimulate", "purified", "T", "cells", ":", "OKT3", ",", "which", "causes", "early", "second", "messenger", "generation", "but", "is", "unable", "to", "activate", "T", "cells", "without", "a", "second", "signal", ",", "and", "64.1", ",", "which", "stimulates", "T", "cell", "proliferation", "on", "its", "own", "." ]
[ 0, 0, 0, 3, 4, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0 ]	[ "We", "found", "that", "tyrosine", "kinase", "activity", "was", "similar", "for", "both", "mAbs", "over", "a", "period", "of", "hours", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 0, 0, 3, 0 ]	[ "However", ",", "the", "inositol", "phosphate", "response", "was", "stronger", "for", "64.1", "than", "for", "OKT3", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 0, 3, 0, 0, 0, 0, 0, 3, 0, 0 ]	[ "To", "tie", "these", "events", "to", "gene", "activation", ",", "we", "measured", "NF-kappa", "B", "and", "NF-AT", "activity", "in", "the", "nucleus", "after", "anti-CD3", "stimulation", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 3, 4, 4, 0, 3, 0, 3, 0, 3, 0, 0, 0, 3, 0, 3, 4, 0, 0, 0, 3, 4, 0, 0, 0, 0, 0, 0, 0 ]	[ "Both", "stimuli", "induced", "the", "appearance", "of", "the", "NF-kappa", "B", "components", "(", "c-Rel", ",", "p65", "(", "RelA", ")", ",", "and", "p50", "(", "NF-kappa", "B1", ")", ")", "and", "NF-kappa", "B", "DNA", "binding", "activity", "in", "the", "nucleus", "." ]
[ 0, 0, 0, 3, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 5, 6, 0 ]	[ "However", ",", "only", "64.1", "induced", "NF-AT", "in", "the", "nucleus", ",", "correlating", "with", "its", "ability", "to", "activate", "T", "cells", "." ]
[ 0, 0, 3, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 0, 0, 0, 0, 0, 0, 0 ]	[ "Thus", ",", "NF-AT", "induction", "and", "IL-2", "secretion", "were", "correlated", "with", "the", "levels", "of", "inositol", "phosphate", "release", "but", "not", "with", "gross", "levels", "of", "tyrosine", "kinase", "activity", "induced", "late", "following", "the", "response", "." ]
[ 0, 0, 0, 0, 0, 3, 4, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 0 ]	[ "On", "the", "other", "hand", ",", "NF-kappa", "B", "induction", "and", "IL-2", "receptor", "expression", "occurred", "even", "with", "the", "smaller", "second", "messenger", "response", "generated", "by", "OKT3", "." ]
[ 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, 0, 0, 0, 0 ]	[ "HLA-DR-", ",", "CD33+", ",", "CD56+", ",", "CD16-", "myeloid/natural", "killer", "cell", "acute", "leukemia", ":", "a", "previously", "unrecognized", "form", "of", "acute", "leukemia", "potentially", "misdiagnosed", "as", "French-American-British", "acute", "myeloid", "leukemia-M3", "[", "see", "comments", "]" ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 5, 6, 6, 6, 6, 6, 6, 6, 0 ]	[ "We", "have", "identified", "and", "characterized", "a", "previously", "unrecognized", "form", "of", "acute", "leukemia", "that", "shares", "features", "of", "both", "myeloid", "and", "natural", "killer", "(", "NK", ")", "cells", "." ]
[ 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, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 0, 0, 3, 0, 0 ]	[ "From", "a", "consecutive", "series", "of", "350", "cases", "of", "adult", "de", "novo", "acute", "myeloid", "leukemia", "(", "AML", ")", ",", "we", "identified", "20", "cases", "(", "6", "%", ")", "with", "a", "unique", "immunophenotype", ":", "CD33+", ",", "CD56+", ",", "CD11a+", ",", "CD13lo", ",", "CD15lo", ",", "CD34+/-", ",", "HLA-DR", "-", ",", "CD16", "-", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 0, 3, 4, 4, 4, 0, 0, 5, 6, 0 ]	[ "Multicolor", "flow", "cytometric", "assays", "confirmed", "the", "coexpression", "of", "myeloid", "(", "CD33", ",", "CD13", ",", "CD15", ")", "and", "NK", "cell-associated", "(", "CD56", ")", "antigens", "in", "each", "case", ",", "whereas", "reverse", "transcription", "polymerase", "chain", "reaction", "(", "RT-PCR", ")", "assays", "confirmed", "the", "identity", "of", "CD56", "(", "neural", "cell", "adhesion", "molecule", ")", "in", "leukemic", "blasts", "." ]
[ 0, 0, 0, 0, 3, 0, 0, 0, 0, 3, 0, 3, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 0, 3, 4, 4, 4, 4, 4, 0, 0 ]	[ "Although", "two", "cases", "expressed", "CD4", ",", "no", "case", "expressed", "CD2", ",", "CD3", ",", "or", "CD8", "and", "no", "case", "showed", "clonal", "rearrangement", "of", "genes", "encoding", "the", "T-cell", "receptor", "(", "TCR", "beta", ",", "gamma", ",", "delta", ")", "." ]
[ 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, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 0, 3, 4, 0, 0 ]	[ "Leukemic", "blasts", "in", "the", "majority", "of", "cases", "shared", "unique", "morphologic", "features", "(", "deeply", "invaginated", "nuclear", "membranes", ",", "scant", "cytoplasm", "with", "fine", "azurophilic", "granularity", ",", "and", "finely", "granular", "Sudan", "black", "B", "and", "myeloperoxidase", "cytochemical", "reactivity", ")", "that", "were", "remarkably", "similar", "to", "those", "of", "acute", "promyelocytic", "leukemia", "(", "APL", ")", ";", "particularly", "the", "microgranular", "variant", "(", "FAB", "AML-M3v", ")", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 9, 10, 10, 10, 10, 10, 10, 10, 10, 10, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 0, 0, 0, 1, 2, 2, 2, 2, 2, 2, 0, 0, 0, 0, 1, 2, 2, 2, 2, 2, 2, 2, 2, 2, 2, 0, 0, 9, 10, 10, 10, 10, 10, 10, 0 ]	[ "However", ",", "all", "20", "cases", "lacked", "the", "t", "(", "15", ";", "17", ")", "and", "17", "cases", "tested", "lacked", "the", "promyelocytic/retinoic", "acid", "receptor", "alpha", "(", "RAR", "alpha", ")", "fusion", "transcript", "in", "RT-PCR", "assays", ";", "12", "cases", "had", "46", ",", "XX", "or", "46", ",", "XY", "karyotypes", ",", "whereas", "2", "cases", "had", "abnormalities", "of", "chromosome", "17q", ":", "1", "with", "del", "(", "17", ")", "(", "q25", ")", "and", "the", "other", "with", "t", "(", "11", ";", "17", ")", "(", "q23", ";", "q21", ")", "and", "the", "promyelocytic", "leukemia", "zinc", "finger/RAR", "alpha", "fusion", "transcript", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 2, 2, 2, 2, 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, 0, 0, 0, 0, 0, 0, 0, 0 ]	[ "All", "cases", "tested", "(", "6/20", ")", ",", "including", "the", "case", "with", "t", "(", "11", ";", "17", ")", ",", "failed", "to", "differentiate", "in", "vitro", "in", "response", "to", "all-trans", "retinoic", "acid", "(", "ATRA", ")", ",", "suggesting", "that", "these", "cases", "may", "account", "for", "some", "APLs", "that", "have", "not", "shown", "a", "clinical", "response", "to", "ATRA", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 5, 6, 6, 6, 6, 6, 6, 0 ]	[ "Four", "of", "6", "cases", "tested", "showed", "functional", "NK", "cell-mediated", "cytotoxicity", ",", "suggesting", "a", "relationship", "between", "these", "unique", "CD33+", ",", "CD56+", ",", "CD16", "-acute", "leukemias", "and", "normal", "CD56+", ",", "CD16-", "NK", "precursor", "cells", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 5, 6, 6, 6, 6, 6, 6, 6, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	[ "Using", "a", "combination", "of", "panning", "and", "multiparameter", "flow", "cytometric", "sorting", ",", "we", "identified", "a", "normal", "CD56+", ",", "CD33+", ",", "CD16-", "counterpart", "cell", "at", "a", "frequency", "of", "1", "%", "to", "2", "%", "in", "the", "peripheral", "blood", "of", "healthy", "individuals", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 5, 6, 6, 6, 6, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	[ "Our", "studies", "suggest", "that", "this", "form", "of", "acute", "leukemia", "may", "arise", "from", "transformation", "of", "a", "precursor", "cell", "common", "to", "both", "the", "myeloid", "and", "NK", "cell", "lineages", ";", "thus", "we", "propose", "the", "designation", "myeloid/NK", "acute", "leukemia", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	[ "Recognition", "of", "this", "new", "leukemic", "entity", "will", "be", "important", "in", "distinguishing", "these", "ATRA-nonresponsive", "cases", "from", "ATRA-responsive", "true", "APL", "." ]
[ 3, 0, 3, 0, 0, 3, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	[ "IL-4", "down-regulates", "IL-2", "-", ",", "IL-3", "-", ",", "and", "GM-CSF", "-induced", "cytokine", "gene", "expression", "in", "peripheral", "blood", "monocytes", "." ]
[ 3, 0, 0, 0, 0, 0, 5, 6, 6, 6, 6, 6, 6, 6, 6, 6, 6, 0, 0, 0, 0, 0, 0, 3, 4, 4, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 5, 0, 0, 0, 0, 0, 0, 0, 1, 2, 2, 2, 2, 2, 2, 0, 0 ]	[ "IL-4", ",", "a", "product", "of", "the", "T-helper", "0", "(", "Th0", ")", "and", "2", "(", "Th2", ")", "subset", ",", "was", "originally", "described", "as", "a", "B-cell", "stimulatory", "factor", "and", "has", "subsequently", "been", "found", "to", "suppress", "IL-1", "alpha", ",", "IL-1", "beta", ",", "IL-6", ",", "IL-8", ",", "and", "TNF-alpha", "gene", "expression", "in", "monocytes", "stimulated", "with", "LPS", ",", "and", "to", "upregulate", "IL-1", "receptor", "antagonist", "(", "IL1-RA", ")", "gene", "expression", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 1, 2, 0, 5, 0, 0, 0, 3, 4, 4, 0, 3, 0, 3, 0, 0, 3, 0 ]	[ "In", "this", "study", "we", "investigated", "the", "effect", "of", "IL-4", "on", "the", "expression", "of", "cytokine", "genes", "in", "monocytes", "evoked", "by", "other", "T-helper", "cell", "cytokines", ":", "IL-2", ",", "IL-3", ",", "and", "GM-CSF", "." ]
[ 3, 0, 0, 0, 0, 0, 3, 4, 3, 4, 0, 3, 0, 0, 3, 0, 5, 0, 0, 3, 0, 3, 0, 0, 3, 0 ]	[ "IL-4", "down-regulated", "mRNA", "accumulation", "of", "the", "proinflammatory", "cytokines", "IL-1", "beta", ",", "IL-8", ",", "and", "TNF-alpha", "in", "monocytes", "stimulated", "with", "IL-2", ",", "IL-3", ",", "and", "GM-CSF", "." ]
[ 3, 0, 0, 0, 3, 0, 3, 0, 0, 0 ]	[ "IL-4", "also", "suppressed", "the", "IL-2", "-induced", "IL-6", "mRNA", "expression", "." ]
[ 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 5, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0 ]	[ "Temporal", "analysis", "of", "the", "IL-4", "down-regulatory", "effect", "on", "the", "IL-2-", ",", "IL-3-", ",", "or", "GM-CSF-induced", "proinflammatory", "cytokine", "gene", "expression", "in", "monocytes", "provided", "evidence", "that", "IL-4", "acts", "predominantly", "on", "the", "post-transcriptional", "level", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	[ "This", "was", "supported", "by", "the", "observation", "that", "the", "down-regulatory", "capacity", "of", "IL-4", "appeared", "to", "be", "dependent", "on", "de", "novo", "protein", "synthesis", "." ]
[ 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 0, 0, 3, 0, 3, 0, 3, 0, 0, 3, 0 ]	[ "IL-4", "did", "not", "exert", "significant", "influence", "on", "the", "induction", "of", "expression", "of", "IL-1-RA", "or", "various", "CSFs", "by", "IL-2", ",", "IL-3", ",", "and", "GM-CSF", "." ]
[ 0, 0, 0, 0, 0, 0, 0 ]	[ "(", "ABSTRACT", "TRUNCATED", "AT", "250", "WORDS", ")" ]
[ 0, 0, 1, 0, 3, 0, 0, 0, 0, 0, 5, 0, 0, 7, 8, 8, 7, 0, 0, 0, 0, 0, 0, 0 ]	[ "Induction", "of", "proto-oncogene", "and", "cytokine", "expression", "in", "human", "peripheral", "blood", "monocytes", "and", "the", "monocytic", "cell", "line", "THP-1", "after", "stimulation", "with", "mycoplasma-derived", "material", "MDHM", "." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 5, 6, 0, 5, 6, 6, 0, 0, 3, 0, 0, 5, 6, 0 ]	[ "Mycoplasma", "fermentans-derived", "high-molecular-weight", "material", "(", "MDHM", ")", "was", "originally", "described", "to", "induce", "differentiation", "of", "murine", "thymocytes", "to", "cytolytic", "effector", "T-cells", "by", "stimulating", "IL-6", "release", "from", "adherent", "cells", "." ]

[ 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 ]

[ "Retinoic", "acid", "(", "RA", ")", ",", "a", "vitamin", "A", "derivative", ",", "exerts", "a", "wide", "range", "of", "biological", "effects", "related", "to", "cell", "proliferation", "and", "differentiation", "." ]

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

[ "The", "pleiotropic", "effects", "of", "RA", "are", "thought", "to", "be", "mediated", "through", "specific", "nuclear", "RA", "receptors", "(", "RARs", ")", "." ]

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

[ "RARs", "are", "members", "of", "the", "steroid/thyroid", "hormone", "receptor", "superfamily", "and", "exhibit", "a", "molecular", "structure", "that", "possess", "discrete", "DNA-binding", "and", "RA", "(", "ligand", ")", "-binding", "domains", "." ]

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

[ "In", "hematopoietic", "system", ",", "RA", "and", "RARs", ",", "predominantly", "RAR", "alpha", "may", "play", "key", "roles", "for", "the", "proliferation", "and", "differentiation", "of", "hematopoietic", "progenitors", "." ]

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

[ "However", ",", "it", "is", "currently", "unknown", "how", "RA", "and", "RARs", "are", "involved", "in", "regulating", "normal", "hematopoietic", "differentiation", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 4, 0, 3, 4, 0, 0, 5, 6, 6, 6, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 2, 0, 1, 2, 2, 2, 0, 0, 0, 0, 7, 8, 8, 0, 7, 0, 0, 0, 0, 0, 0, 0, 5, 6, 0 ]

[ "To", "make", "clear", "the", "roles", "of", "RA", "and", "RAR", "alpha", "in", "the", "normal", "hematopoiesis", ",", "I", "have", "introduced", "the", "construct", "of", "human", "RAR", "alpha", "(", "hRAR", "alpha", ")", "into", "murine", "bone", "marrow", "cells", "with", "retroviral", "vector", ",", "and", "selected", "infected", "cells", "with", "drug", "resistant", "marker", "(", "Neo", "(", "r", ")", ")", "cultured", "on", "the", "stroma", "cell", "line", "(", "PA6-neo", ")", ",", "and", "analyzed", "the", "behavior", "of", "infected", "cells", "." ]

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

[ "All", "of", "procedure", "were", "done", "in", "vitro", "." ]

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

[ "Most", "cells", "infected", "with", "hRAR", "alpha", "exhibited", "promyelocytic", "morphology", "and", "were", "thought", "to", "be", "blocked", "at", "the", "promyelocytic", "stage", "in", "their", "myeloid", "differentiation", "." ]

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

[ "Furthermore", ",", "these", "immature", "cells", "differentiated", "terminally", "into", "mature", "granulocytes", "by", "adding", "with", "RA", "(", "10", "(", "-6", ")", "M", ")", "." ]

[ 3, 4, 5, 6, 0, 0, 0, 0, 0, 0, 5, 6, 0, 0, 0, 0, 0, 0, 0, 0, 7, 8, 0 ]

[ "RAR", "alpha", "infected", "cells", "were", "also", "able", "to", "differentiate", "into", "mature", "macrophages", "in", "the", "both", "of", "long", "term", "culture", "and", "IL3", "colony", "." ]

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

[ "These", "observations", "suggest", "that", "an", "overexpression", "of", "RAR", "alpha", "alone", "is", "effective", "to", "suppress", "myeloid", "cell", "differentiation", "and", "RAR", "alpha", "plays", "a", "crucial", "role", "in", "the", "terminal", "differentiation", "of", "myeloid", "precursors", "." ]

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

[ "The", "system", "described", "here", "may", "serve", "as", "a", "model", "for", "studying", "the", "the", "essential", "genes", "for", "differentiation", "of", "normal", "bone", "marrow", "cells", "." ]

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

[ "Hypoxic", "induction", "of", "interleukin-8", "gene", "expression", "in", "human", "endothelial", "cells", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 5, 0, 0, 0, 0, 0, 0 ]

[ "Because", "leukocyte-mediated", "tissue", "damage", "is", "an", "important", "component", "of", "the", "pathologic", "picture", "in", "ischemia/reperfusion", ",", "we", "have", "sought", "mechanisms", "by", "which", "PMNs", "are", "directed", "into", "hypoxic", "tissue", "." ]

[ 0, 0, 5, 6, 6, 0, 5, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 5, 0, 0, 0, 0, 0, 3, 0 ]

[ "Incubation", "of", "human", "endothelial", "cells", "(", "ECs", ")", "in", "hypoxia", ",", "PO2", "approximately", "14-18", "Torr", ",", "led", "to", "time-dependent", "release", "of", "IL-8", "antigen", "into", "the", "conditioned", "medium", ";", "this", "was", "accompanied", "by", "increased", "chemotactic", "activity", "for", "PMNs", ",", "blocked", "by", "antibody", "to", "IL-8", "." ]

[ 0, 0, 3, 0, 0, 5, 0, 0, 0, 0, 0, 0, 0, 9, 10, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "Production", "of", "IL-8", "by", "hypoxic", "ECs", "occurred", "concomitantly", "with", "both", "increased", "levels", "of", "IL-8", "mRNA", ",", "based", "on", "polymerase", "chain", "reaction", "analysis", ",", "and", "increased", "IL-8", "transcription", ",", "based", "on", "nuclear", "run-on", "assays", "." ]

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

[ "Northern", "analysis", "of", "mRNA", "from", "hypoxic", "ECs", "also", "demonstrated", "increased", "levels", "of", "mRNA", "for", "macrophage", "chemotactic", "protein-1", ",", "another", "member", "of", "the", "chemokine", "superfamily", "of", "proinflammatory", "cytokines", "." ]

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

[ "IL-8", "gene", "induction", "was", "associated", "with", "the", "presence", "of", "increased", "binding", "activity", "in", "nuclear", "extracts", "from", "hypoxic", "ECs", "for", "the", "NF-kB", "site", "." ]

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

[ "Studies", "with", "human", "umbilical", "vein", "segments", "exposed", "to", "hypoxia", "also", "demonstrated", "increased", "elaboration", "of", "IL-8", "antigen", "compared", "with", "normoxic", "controls", "." ]

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

[ "In", "mice", "exposed", "to", "hypoxia", "(", "PO2", "approximately", "30-40", "Torr", ")", ",", "there", "was", "increased", "pulmonary", "leukostasis", ",", "as", "evidenced", "by", "increased", "myeloperoxidase", "activity", "in", "tissue", "homogenates", "." ]

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

[ "In", "parallel", ",", "increased", "levels", "of", "transcripts", "for", "IP-10", ",", "a", "murine", "homologue", "in", "the", "chemokine", "family", "related", "to", "IL-8", ",", "were", "observed", "in", "hypoxic", "lung", "tissue", "." ]

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

[ "Taken", "together", ",", "these", "data", "suggest", "that", "hypoxia", "constitutes", "a", "stimulus", "for", "leukocyte", "chemotaxis", "and", "tissue", "leukostasis", "." ]

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

[ "Thrombin", "and", "thrombin", "receptor", "agonist", "peptide", "induce", "early", "events", "of", "T", "cell", "activation", "and", "synergize", "with", "TCR", "cross-linking", "for", "CD69", "expression", "and", "interleukin", "2", "production", "." ]

[ 3, 0, 0, 0, 7, 8, 8, 8, 8, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "Thrombin", "stimulation", "of", "the", "T", "leukemic", "cell", "line", "Jurkat", "induced", "a", "transient", "increase", "in", "[", "Ca2+", "]", "i", "." ]

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

[ "Proteolytic", "activity", "of", "the", "enzyme", "was", "required", "for", "this", "effect", "since", "diisopropyl", "fluorophosphate-thrombin", "failed", "to", "increase", "[", "Ca2+", "]", "i", "." ]

[ 0, 0, 0, 0, 3, 4, 0, 0, 0, 0, 0, 0, 0, 0, 0, 7, 8, 8, 0 ]

[ "Furthermore", ",", "hirudin", "and", "anti-thrombin", "III", "inhibited", "the", "thrombin-induced", "[", "Ca2+", "]", "i", "rise", "in", "Jurkat", "T", "cells", "." ]

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

[ "A", "synthetic", "thrombin", "receptor", "agonist", "peptide", "(", "TRP", ")", "of", "7", "residues", "(", "SFLLRNP", ")", "was", "found", "to", "be", "as", "effective", "as", "thrombin", "for", "[", "Ca2+", "]", "i", "mobilization", ",", "and", "both", "agonists", "induced", "Ca2+", "release", "exclusively", "from", "internal", "stores", "." ]

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

[ "Thrombin", "stimulated", "tyrosine", "phosphorylation", "of", "several", "proteins", "of", "molecular", "mass", "40", ",", "42", ",", "70", ",", "120", ",", "and", "130", "kDa", "." ]

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

[ "There", "was", "a", "good", "correlation", "between", "thrombin", "-induced", "tyrosine", "phosphorylation", "of", "the", "latter", "three", "proteins", "and", "Ca2+", "mobilization", "." ]

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

[ "Thrombin", "and", "TRP", "also", "caused", "translocation", "of", "protein", "kinase", "C", "from", "the", "cytosol", "to", "the", "plasma", "membrane", "." ]

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

[ "As", "a", "likely", "consequence", "of", "these", "events", ",", "thrombin", "activated", "the", "nuclear", "factor", "NF-kB", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 7, 8, 8, 8, 8, 0, 0, 7, 8, 8, 8, 0, 0, 0, 3, 0, 0, 0, 0, 0, 7, 0, 0, 7, 8, 8, 0, 0, 7, 8, 0, 7, 8, 0, 0, 0, 3, 0, 0, 0, 0 ]

[ "Several", "cell", "lines", "of", "hematopoietic", "origin", "including", "the", "leukemic", "T", "cell", "line", "HPB.ALL", "and", "the", "erythroleukemic", "cell", "line", "K562", "were", "responsive", "to", "thrombin", ",", "whereas", "others", "such", "as", "THP1", ",", "a", "myelomonocytic", "cell", "line", ",", "and", "BL2", ",", "a", "Burkitt", "lymphoma", "were", "refractory", "to", "thrombin", "or", "TRP", "stimulation", "." ]

[ 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 9, 10, 10, 0 ]

[ "The", "magnitude", "of", "the", "thrombin", "response", "in", "the", "different", "cell", "types", "paralleled", "the", "expression", "of", "the", "thrombin", "receptor", "mRNA", "." ]

[ 0, 0, 0, 0, 0, 7, 8, 8, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 9, 10, 10, 0, 0, 0, 0, 0, 0, 0, 0, 3, 0, 0 ]

[ "We", "found", "that", "activation", "of", "Jurkat", "T", "cells", "by", "a", "combination", "of", "phytohemagglutinin", "and", "phorbol", "12-myristate", "13-acetate", "led", "to", "a", "dramatic", "inhibition", "of", "thrombin", "receptor", "mRNA", "expression", "and", "to", "a", "concomitant", "loss", "of", "the", "thrombin", "response", "." ]

[ 0, 0, 0, 0, 0, 3, 0, 0, 0, 3, 0, 0, 3, 4, 0, 0, 0, 3, 4, 4, 0, 0, 0, 7, 8, 8, 0, 0, 0, 5, 0 ]

[ "Finally", ",", "we", "demonstrate", "that", "thrombin", "and", "TRP", "enhanced", "CD69", "expression", "and", "interleukin", "2", "production", "induced", "by", "T", "cell", "receptor", "cross-linking", "in", "both", "Jurkat", "T", "cells", "and", "peripheral", "blood", "lymphocytes", "." ]

[ 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 5, 6, 0, 0 ]

[ "These", "findings", "highlight", "the", "role", "of", "thrombin", "as", "a", "potential", "regulator", "of", "T", "lymphocyte", "activation", "." ]

[ 0, 0, 0, 5, 6, 6, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0 ]

[ "Stress", "response", "of", "senescent", "T", "lymphocytes", ":", "reduced", "hsp70", "is", "independent", "of", "the", "proliferative", "block", "." ]

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

[ "Senescent", "human", "T", "lymphocyte", "cultures", "are", "unable", "to", "undergo", "proliferation", ",", "but", "show", "no", "difference", "from", "early", "passage", "cells", "in", "cytotoxic", "function", "or", "surface", "antigenic", "profile", "." ]

[ 0, 0, 0, 0, 7, 8, 8, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0 ]

[ "A", "second", "feature", "of", "senescent", "T", "cells", "is", "the", "dramatic", "reduction", "in", "hsp70", "production", "in", "response", "to", "heat", "shock", "." ]

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

[ "This", "decline", "is", "associated", "with", "a", "decrease", "in", "binding", "of", "nuclear", "extracts", "to", "the", "consensus", "heat", "shock", "element", "." ]

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

[ "Interestingly", ",", "the", "progressive", "decline", "in", "the", "heat", "shock", "response", "of", "cultured", "T", "cells", "correlates", "with", "the", "percent", "proliferative", "life", "span", "completed", "rather", "than", "with", "the", "actual", "proliferative", "activity", "at", "the", "time", "of", "heat", "shock", "." ]

[ 0, 0, 0, 0, 5, 6, 6, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 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, 0, 0, 0, 0 ]

[ "This", "suggests", "that", "for", "senescent", "T", "cells", "the", "reduced", "ability", "to", "respond", "to", "heat", "shock", "by", "producing", "hsp70", ",", "although", "possibly", "lying", "at", "the", "level", "of", "transcriptional", "control", ",", "may", "nevertheless", "be", "unrelated", "to", "the", "reduced", "DNA", "synthesis", "or", "the", "diminished", "proliferative", "activity", "also", "manifested", "by", "these", "cells", "." ]

[ 0, 0, 3, 4, 0, 0, 0, 0, 3, 4, 4, 0, 7, 8, 8, 8, 8, 0 ]

[ "Involvement", "of", "phospholipase", "D", "in", "the", "activation", "of", "transcription", "factor", "AP-1", "in", "human", "T", "lymphoid", "Jurkat", "cells", "." ]

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

[ "The", "induction", "of", "the", "AP-1", "transcription", "factor", "has", "been", "ascribed", "to", "the", "early", "events", "leading", "to", "T", "lymphocyte", "activation", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 0, 3, 0, 0, 0, 0, 0, 3, 4, 4, 0, 0, 0, 0, 0, 0, 0, 7, 8, 8, 8, 0, 0, 0, 0, 0, 1, 2, 2, 0, 0, 1, 2, 2, 2, 0 ]

[ "We", "have", "examined", "the", "possibility", "that", "stimulation", "of", "phospholipase", "D", "(", "PLD", ")", "may", "regulate", "activation", "of", "transcription", "factor", "AP-1", "in", "human", "T", "cells", "by", "transfecting", "human", "T", "lymphocyte", "Jurkat", "cells", "with", "a", "plasmid", "containing", "an", "AP-1", "enhancer", "element", "and", "a", "chloramphenicol", "acetyltransferase", "reporter", "gene", "." ]

[ 0, 0, 0, 0, 3, 0, 7, 8, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 7, 8, 0, 0, 0, 0, 0, 3, 4, 4, 0 ]

[ "We", "have", "detected", "activatable", "PLD", "in", "Jurkat", "cells", ",", "and", "we", "have", "found", "that", "addition", "of", "phosphatidic", "acid", "(", "PA", ")", ",", "the", "physiologic", "product", "of", "PLD", "action", "on", "phospholipids", ",", "is", "rapidly", "incorporated", "into", "Jurkat", "cells", "and", "leads", "to", "activation", "of", "transcription", "factor", "AP-1", "." ]

[ 0, 0, 7, 8, 0, 3, 4, 0, 0, 3, 0, 3, 4, 4, 0 ]

[ "Treatment", "of", "Jurkat", "cells", "with", "anti-CD3", "mAb", "activated", "both", "PLD", "and", "transcription", "factor", "AP-1", "." ]

[ 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 3, 0, 0, 0, 0, 3, 0, 0, 1, 2, 0, 0 ]

[ "Wortmannin", ",", "an", "inhibitor", "of", "receptor-coupled", "PLD", "activation", ",", "blocked", "the", "anti-CD3", "-induced", "increases", "in", "both", "PLD", "activity", "and", "AP-1", "enhancer", "activity", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 7, 8, 0, 3, 0, 0, 0, 0, 1, 2, 0, 0, 0, 0, 0, 0 ]

[ "We", "found", "a", "good", "correlation", "in", "the", "transfected", "cells", "between", "PLD", "activation", "and", "induction", "of", "AP-1", "enhancer", "activity", "under", "different", "experimental", "conditions", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 1, 2, 0, 0 ]

[ "Furthermore", ",", "ethanol", ",", "an", "inhibitor", "of", "the", "PLD", "pathway", ",", "blocked", "the", "anti-CD3-stimulated", "AP-1", "enhancer", "activity", "." ]

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

[ "However", ",", "this", "anti-CD3", "-mediated", "response", "was", "not", "inhibited", "by", "neomycin", ",", "an", "inhibitor", "of", "phosphoinositide", "hydrolysis", "." ]

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

[ "The", "increases", "in", "AP-1", "enhancer", "activity", "induced", "by", "PA", "or", "anti-CD3", "mAb", "were", "efficiently", "abrogated", "by", "the", "presence", "of", "propranolol", ",", "an", "inhibitor", "of", "PA", "phosphohydrolase", "and", "protein", "kinase", "C", "(", "PKC", ")", "." ]

[ 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 1, 2, 0, 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 3, 0, 0 ]

[ "Furthermore", ",", "the", "PA", "-and", "the", "anti-CD3", "-induced", "increases", "in", "AP-1", "enhancer", "activity", "were", "blocked", "by", "the", "presence", "of", "PKC", "inhibitors", "or", "by", "PKC", "down-regulation", "." ]

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

[ "These", "data", "indicate", "that", "PLD", "stimulation", "can", "activate", "the", "transcription", "factor", "AP-1", "in", "T", "lymphocytes", ",", "and", "suggest", "that", "the", "induction", "of", "AP-1", "enhancer", "factor", "activity", "by", "PA", "is", "mediated", "via", "PKC", "stimulation", ",", "either", "through", "a", "direct", "activating", "effect", "of", "PA", "or", "through", "PA-derived", "diacylglycerol", "formation", "." ]

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

[ "These", "data", "also", "provide", "evidence", "for", "a", "role", "of", "PLD", "-derived", "lipids", "in", "the", "induction", "of", "AP-1", "enhancer", "activity", "resulting", "from", "stimulation", "of", "the", "TCR/CD3", "complex", ",", "suggesting", "that", "increased", "PLD", "activity", "can", "play", "an", "important", "role", "in", "T", "lymphocyte", "activation", "." ]

[ 0, 0, 1, 0, 0, 3, 4, 4, 4, 4, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 0, 0, 0, 0, 0, 3, 4, 4, 0 ]

[ "Upregulation", "of", "bcl-2", "by", "the", "Epstein-Barr", "virus", "latent", "membrane", "protein", "LMP1", ":", "a", "B-cell-specific", "response", "that", "is", "delayed", "relative", "to", "NF-kappa", "B", "activation", "and", "to", "induction", "of", "cell", "surface", "markers", "." ]

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

[ "An", "ability", "of", "the", "Epstein-Barr", "virus", "latent", "membrane", "protein", "LMP1", "to", "enhance", "the", "survival", "of", "infected", "B", "cells", "through", "upregulation", "of", "the", "bcl-2", "oncogene", "was", "first", "suggested", "by", "experiments", "involving", "gene", "transfection", "and", "the", "selection", "of", "stable", "LMP1+", "clones", "(", "S.Henderson", ",", "M.", "Rowe", ",", "C.Gregory", ",", "F.Wang", ",", "E.Kieff", ",", "and", "A.Rickinson", ",", "Cell", "65", ":", "1107-1115", ",", "1991", ")", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 7, 8, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 0 ]

[ "However", ",", "it", "was", "not", "possible", "to", "ascertain", "whether", "Bcl-2", "upregulation", "was", "a", "specific", "consequence", "of", "LMP1", "expression", "or", "an", "artifact", "of", "the", "selection", "procedure", "whereby", "rare", "Bcl-2+", "cells", "already", "present", "in", "the", "starting", "population", "might", "best", "be", "able", "to", "tolerate", "the", "potentially", "toxic", "effects", "of", "LMP1", "." ]

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

[ "We", "therefore", "reexamined", "this", "issue", "by", "using", "two", "different", "experimental", "approaches", "that", "allowed", "LMP1", "-induced", "effects", "to", "be", "monitored", "immediately", "following", "expression", "of", "the", "viral", "protein", "and", "in", "the", "absence", "of", "selective", "pressures", ";", "activation", "of", "the", "NF-kappa", "B", "transcription", "factor", "and", "upregulation", "of", "the", "cell", "adhesion", "molecule", "ICAM-1", "were", "used", "as", "early", "indices", "of", "LMP1", "function", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 7, 8, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 1, 2, 0, 0, 0, 0, 3, 0, 0, 0, 0 ]

[ "In", "the", "first", "approach", ",", "stable", "clones", "of", "two", "B-cell", "lines", "carrying", "an", "LMP1", "gene", "under", "the", "control", "of", "an", "inducible", "metallothionein", "promoter", "were", "induced", "to", "express", "LMP1", "in", "all", "cells", "." ]

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

[ "Activation", "of", "NK-kappa", "B", "and", "upregulation", "of", "ICAM-1", "occurred", "within", "24", "h", "and", "were", "followed", "at", "48", "to", "72", "h", "by", "upregulation", "of", "Bcl-2", "." ]

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

[ "In", "the", "second", "approach", ",", "we", "tested", "the", "generality", "of", "this", "phenomenon", "by", "transiently", "expressing", "LMP1", "from", "a", "strong", "constitutively", "active", "promoter", "in", "a", "range", "of", "different", "cell", "types", "." ]

[ 0, 0, 7, 8, 0, 0, 3, 4, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 0, 3, 0 ]

[ "All", "six", "B-cell", "lines", "tested", "showed", "NF-kappa", "B", "activation", "in", "response", "to", "LMP1", "expression", ",", "and", "this", "was", "followed", "in", "five", "of", "six", "lines", "by", "expression", "of", "ICAM-1", "and", "Bcl-2", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 7, 8, 0, 3, 4, 0, 0, 3, 0, 0, 0, 0, 0, 0, 3, 0 ]

[ "In", "the", "same", "experiments", ",", "all", "three", "non-", "B-cell", "lines", "showed", "NF-kappa", "B", "activation", "and", "ICAM-1", "upregulation", "but", "never", "any", "effect", "upon", "Bcl-2", "." ]

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

[ "We", "therefore", "conclude", "that", "Bcl-2", "upregulation", "is", "part", "of", "the", "panoply", "of", "cellular", "changes", "induced", "by", "LMP1", "but", "that", "the", "effect", "is", "cell", "type", "specific", "." ]

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

[ "Our", "data", "also", "suggest", "that", "whilst", "NF-kappa", "B", "may", "be", "an", "essential", "component", "of", "LMP1", "signal", "transduction", ",", "other", "cell-specific", "factors", "may", "be", "required", "to", "effect", "some", "functions", "of", "the", "viral", "protein", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 3, 4, 0, 0, 0, 0, 3, 0, 0, 3, 0, 0, 7, 8, 8, 8, 8, 0 ]

[ "Long-term", "inositol", "phosphate", "release", ",", "but", "not", "tyrosine", "kinase", "activity", ",", "correlates", "with", "IL-2", "secretion", "and", "NF-AT", "induction", "in", "anti-CD3-activated", "peripheral", "human", "T", "lymphocytes", "." ]

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

[ "The", "cascade", "of", "events", "within", "the", "first", "few", "minutes", "of", "T", "cell", "stimulation", "has", "been", "well", "characterized", "." ]

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

[ "Although", "many", "second", "messengers", "have", "been", "shown", "to", "be", "necessary", "and", "sufficient", "for", "T", "cell", "activation", "in", "a", "number", "of", "model", "systems", ",", "the", "rate-limiting", "step", "in", "peripheral", "T", "cells", "has", "not", "been", "demonstrated", "." ]

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

[ "To", "model", "effective", "versus", "ineffective", "CD3", "-mediated", "stimulation", "in", "peripheral", "T", "cells", ",", "we", "used", "two", "anti-CD3", "mAbs", "that", "differ", "in", "their", "ability", "to", "stimulate", "purified", "T", "cells", ":", "OKT3", ",", "which", "causes", "early", "second", "messenger", "generation", "but", "is", "unable", "to", "activate", "T", "cells", "without", "a", "second", "signal", ",", "and", "64.1", ",", "which", "stimulates", "T", "cell", "proliferation", "on", "its", "own", "." ]

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

[ "We", "found", "that", "tyrosine", "kinase", "activity", "was", "similar", "for", "both", "mAbs", "over", "a", "period", "of", "hours", "." ]

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

[ "However", ",", "the", "inositol", "phosphate", "response", "was", "stronger", "for", "64.1", "than", "for", "OKT3", "." ]

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

[ "To", "tie", "these", "events", "to", "gene", "activation", ",", "we", "measured", "NF-kappa", "B", "and", "NF-AT", "activity", "in", "the", "nucleus", "after", "anti-CD3", "stimulation", "." ]

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

[ "Both", "stimuli", "induced", "the", "appearance", "of", "the", "NF-kappa", "B", "components", "(", "c-Rel", ",", "p65", "(", "RelA", ")", ",", "and", "p50", "(", "NF-kappa", "B1", ")", ")", "and", "NF-kappa", "B", "DNA", "binding", "activity", "in", "the", "nucleus", "." ]

[ 0, 0, 0, 3, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 5, 6, 0 ]

[ "However", ",", "only", "64.1", "induced", "NF-AT", "in", "the", "nucleus", ",", "correlating", "with", "its", "ability", "to", "activate", "T", "cells", "." ]

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

[ "Thus", ",", "NF-AT", "induction", "and", "IL-2", "secretion", "were", "correlated", "with", "the", "levels", "of", "inositol", "phosphate", "release", "but", "not", "with", "gross", "levels", "of", "tyrosine", "kinase", "activity", "induced", "late", "following", "the", "response", "." ]

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

[ "On", "the", "other", "hand", ",", "NF-kappa", "B", "induction", "and", "IL-2", "receptor", "expression", "occurred", "even", "with", "the", "smaller", "second", "messenger", "response", "generated", "by", "OKT3", "." ]

[ 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, 0, 0, 0, 0 ]

[ "HLA-DR-", ",", "CD33+", ",", "CD56+", ",", "CD16-", "myeloid/natural", "killer", "cell", "acute", "leukemia", ":", "a", "previously", "unrecognized", "form", "of", "acute", "leukemia", "potentially", "misdiagnosed", "as", "French-American-British", "acute", "myeloid", "leukemia-M3", "[", "see", "comments", "]" ]

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

[ "We", "have", "identified", "and", "characterized", "a", "previously", "unrecognized", "form", "of", "acute", "leukemia", "that", "shares", "features", "of", "both", "myeloid", "and", "natural", "killer", "(", "NK", ")", "cells", "." ]

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

[ "From", "a", "consecutive", "series", "of", "350", "cases", "of", "adult", "de", "novo", "acute", "myeloid", "leukemia", "(", "AML", ")", ",", "we", "identified", "20", "cases", "(", "6", "%", ")", "with", "a", "unique", "immunophenotype", ":", "CD33+", ",", "CD56+", ",", "CD11a+", ",", "CD13lo", ",", "CD15lo", ",", "CD34+/-", ",", "HLA-DR", "-", ",", "CD16", "-", "." ]

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

[ "Multicolor", "flow", "cytometric", "assays", "confirmed", "the", "coexpression", "of", "myeloid", "(", "CD33", ",", "CD13", ",", "CD15", ")", "and", "NK", "cell-associated", "(", "CD56", ")", "antigens", "in", "each", "case", ",", "whereas", "reverse", "transcription", "polymerase", "chain", "reaction", "(", "RT-PCR", ")", "assays", "confirmed", "the", "identity", "of", "CD56", "(", "neural", "cell", "adhesion", "molecule", ")", "in", "leukemic", "blasts", "." ]

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

[ "Although", "two", "cases", "expressed", "CD4", ",", "no", "case", "expressed", "CD2", ",", "CD3", ",", "or", "CD8", "and", "no", "case", "showed", "clonal", "rearrangement", "of", "genes", "encoding", "the", "T-cell", "receptor", "(", "TCR", "beta", ",", "gamma", ",", "delta", ")", "." ]

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

[ "Leukemic", "blasts", "in", "the", "majority", "of", "cases", "shared", "unique", "morphologic", "features", "(", "deeply", "invaginated", "nuclear", "membranes", ",", "scant", "cytoplasm", "with", "fine", "azurophilic", "granularity", ",", "and", "finely", "granular", "Sudan", "black", "B", "and", "myeloperoxidase", "cytochemical", "reactivity", ")", "that", "were", "remarkably", "similar", "to", "those", "of", "acute", "promyelocytic", "leukemia", "(", "APL", ")", ";", "particularly", "the", "microgranular", "variant", "(", "FAB", "AML-M3v", ")", "." ]

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

[ "However", ",", "all", "20", "cases", "lacked", "the", "t", "(", "15", ";", "17", ")", "and", "17", "cases", "tested", "lacked", "the", "promyelocytic/retinoic", "acid", "receptor", "alpha", "(", "RAR", "alpha", ")", "fusion", "transcript", "in", "RT-PCR", "assays", ";", "12", "cases", "had", "46", ",", "XX", "or", "46", ",", "XY", "karyotypes", ",", "whereas", "2", "cases", "had", "abnormalities", "of", "chromosome", "17q", ":", "1", "with", "del", "(", "17", ")", "(", "q25", ")", "and", "the", "other", "with", "t", "(", "11", ";", "17", ")", "(", "q23", ";", "q21", ")", "and", "the", "promyelocytic", "leukemia", "zinc", "finger/RAR", "alpha", "fusion", "transcript", "." ]

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

[ "All", "cases", "tested", "(", "6/20", ")", ",", "including", "the", "case", "with", "t", "(", "11", ";", "17", ")", ",", "failed", "to", "differentiate", "in", "vitro", "in", "response", "to", "all-trans", "retinoic", "acid", "(", "ATRA", ")", ",", "suggesting", "that", "these", "cases", "may", "account", "for", "some", "APLs", "that", "have", "not", "shown", "a", "clinical", "response", "to", "ATRA", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 5, 6, 6, 6, 6, 6, 6, 0 ]

[ "Four", "of", "6", "cases", "tested", "showed", "functional", "NK", "cell-mediated", "cytotoxicity", ",", "suggesting", "a", "relationship", "between", "these", "unique", "CD33+", ",", "CD56+", ",", "CD16", "-acute", "leukemias", "and", "normal", "CD56+", ",", "CD16-", "NK", "precursor", "cells", "." ]

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

[ "Using", "a", "combination", "of", "panning", "and", "multiparameter", "flow", "cytometric", "sorting", ",", "we", "identified", "a", "normal", "CD56+", ",", "CD33+", ",", "CD16-", "counterpart", "cell", "at", "a", "frequency", "of", "1", "%", "to", "2", "%", "in", "the", "peripheral", "blood", "of", "healthy", "individuals", "." ]

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

[ "Our", "studies", "suggest", "that", "this", "form", "of", "acute", "leukemia", "may", "arise", "from", "transformation", "of", "a", "precursor", "cell", "common", "to", "both", "the", "myeloid", "and", "NK", "cell", "lineages", ";", "thus", "we", "propose", "the", "designation", "myeloid/NK", "acute", "leukemia", "." ]

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

[ "Recognition", "of", "this", "new", "leukemic", "entity", "will", "be", "important", "in", "distinguishing", "these", "ATRA-nonresponsive", "cases", "from", "ATRA-responsive", "true", "APL", "." ]

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

[ "IL-4", "down-regulates", "IL-2", "-", ",", "IL-3", "-", ",", "and", "GM-CSF", "-induced", "cytokine", "gene", "expression", "in", "peripheral", "blood", "monocytes", "." ]

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

[ "IL-4", ",", "a", "product", "of", "the", "T-helper", "0", "(", "Th0", ")", "and", "2", "(", "Th2", ")", "subset", ",", "was", "originally", "described", "as", "a", "B-cell", "stimulatory", "factor", "and", "has", "subsequently", "been", "found", "to", "suppress", "IL-1", "alpha", ",", "IL-1", "beta", ",", "IL-6", ",", "IL-8", ",", "and", "TNF-alpha", "gene", "expression", "in", "monocytes", "stimulated", "with", "LPS", ",", "and", "to", "upregulate", "IL-1", "receptor", "antagonist", "(", "IL1-RA", ")", "gene", "expression", "." ]

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

[ "In", "this", "study", "we", "investigated", "the", "effect", "of", "IL-4", "on", "the", "expression", "of", "cytokine", "genes", "in", "monocytes", "evoked", "by", "other", "T-helper", "cell", "cytokines", ":", "IL-2", ",", "IL-3", ",", "and", "GM-CSF", "." ]

[ 3, 0, 0, 0, 0, 0, 3, 4, 3, 4, 0, 3, 0, 0, 3, 0, 5, 0, 0, 3, 0, 3, 0, 0, 3, 0 ]

[ "IL-4", "down-regulated", "mRNA", "accumulation", "of", "the", "proinflammatory", "cytokines", "IL-1", "beta", ",", "IL-8", ",", "and", "TNF-alpha", "in", "monocytes", "stimulated", "with", "IL-2", ",", "IL-3", ",", "and", "GM-CSF", "." ]

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

[ "IL-4", "also", "suppressed", "the", "IL-2", "-induced", "IL-6", "mRNA", "expression", "." ]

[ 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 5, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0 ]

[ "Temporal", "analysis", "of", "the", "IL-4", "down-regulatory", "effect", "on", "the", "IL-2-", ",", "IL-3-", ",", "or", "GM-CSF-induced", "proinflammatory", "cytokine", "gene", "expression", "in", "monocytes", "provided", "evidence", "that", "IL-4", "acts", "predominantly", "on", "the", "post-transcriptional", "level", "." ]

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

[ "This", "was", "supported", "by", "the", "observation", "that", "the", "down-regulatory", "capacity", "of", "IL-4", "appeared", "to", "be", "dependent", "on", "de", "novo", "protein", "synthesis", "." ]

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

[ "IL-4", "did", "not", "exert", "significant", "influence", "on", "the", "induction", "of", "expression", "of", "IL-1-RA", "or", "various", "CSFs", "by", "IL-2", ",", "IL-3", ",", "and", "GM-CSF", "." ]

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

[ "(", "ABSTRACT", "TRUNCATED", "AT", "250", "WORDS", ")" ]

[ 0, 0, 1, 0, 3, 0, 0, 0, 0, 0, 5, 0, 0, 7, 8, 8, 7, 0, 0, 0, 0, 0, 0, 0 ]

[ "Induction", "of", "proto-oncogene", "and", "cytokine", "expression", "in", "human", "peripheral", "blood", "monocytes", "and", "the", "monocytic", "cell", "line", "THP-1", "after", "stimulation", "with", "mycoplasma-derived", "material", "MDHM", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 5, 6, 0, 5, 6, 6, 0, 0, 3, 0, 0, 5, 6, 0 ]

[ "Mycoplasma", "fermentans-derived", "high-molecular-weight", "material", "(", "MDHM", ")", "was", "originally", "described", "to", "induce", "differentiation", "of", "murine", "thymocytes", "to", "cytolytic", "effector", "T-cells", "by", "stimulating", "IL-6", "release", "from", "adherent", "cells", "." ]