Datasets:

---

SotiriosKastanas

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trygroto

like 0

[ "BMC", "Evolutionary", "Biology", "Research", "article", "Sequence", "and", "organization", "of", "coelacanth", "neurohypophysial", "hormone", "genes:", "evolutionary", "history", "of", "the", "vertebrate", "neurohypophysial", "hormone", "gene", "locus", "Pai-Chung", "Gwee1,", "Chris", "T", "Amemiya2,", "Sydney", "Brenner1", "and", "Byrappa", "Venkatesh*1", "BioMed", "Central", "Open", "Access", "Address:", "1Institute", "of", "Molecular", "and", "Cell", "Biology,", "A*STAR", "(Agency", "for", "Science,", "Technology", "and", "Research),", "Biopolis,", "138673,", "Singapore", "and", "2Benaroya", "Research", "Institute", "at", "Virginia", "Mason,", "Seattle,", "Washington", "98101,", "USA", "Email:", "Pai-Chung", "Gwee", "-", "pcgwee@imcb.a-star.edu.sg;", "Chris", "T", "Amemiya", "-", "camemiya@benaroyaresearch.org;", "Sydney", "Brenner", "-", "sydney_brenner@a-star.edu.sg;", "Byrappa", "Venkatesh*", "-", "mcbbv@imcb.a-star.edu.sg", "*", "Corresponding", "author", "Published:", "26", "March", "2008", "BMC", "Evolutionary", "Biology", "2008,", "8:93", "doi:10.1186/1471-2148-8-93", "This", "article", "is", "available", "from:", "http://www.biomedcentral.com/1471-2148/8/93", "Received:", "11", "January", "2008", "Accepted:", "26", "March", "2008", "©", "2008", "Gwee", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "The", "mammalian", "neurohypophysial", "hormones,", "vasopressin", "and", "oxytocin", "are", "involved", "in", "osmoregulation", "and", "uterine", "smooth", "muscle", "contraction", "respectively.", "All", "jawed", "vertebrates", "contain", "at", "least", "one", "homolog", "each", "of", "vasopressin", "and", "oxytocin", "whereas", "jawless", "vertebrates", "contain", "a", "single", "neurohypophysial", "hormone", "called", "vasotocin.", "The", "vasopressin", "homolog", "in", "non-mammalian", "vertebrates", "is", "vasotocin;", "and", "the", "oxytocin", "homolog", "is", "mesotocin", "in", "non-eutherian", "tetrapods,", "mesotocin", "and", "[Phe2]mesotocin", "in", "lungfishes,", "and", "isotocin", "in", "ray-finned", "fishes.", "The", "genes", "encoding", "vasopressin", "and", "oxytocin", "genes", "are", "closely", "linked", "in", "the", "human", "and", "rodent", "genomes", "in", "a", "tail-to-tail", "orientation.", "In", "contrast,", "their", "pufferfish", "homologs", "(vasotocin", "and", "isotocin)", "are", "located", "on", "the", "same", "strand", "of", "DNA", "with", "isotocin", "gene", "located", "upstream", "of", "vasotocin", "gene", "separated", "by", "five", "genes,", "suggesting", "that", "this", "locus", "has", "experienced", "rearrangements", "in", "either", "mammalian", "or", "ray-finned", "fish", "lineage,", "or", "in", "both", "lineages.", "The", "coelacanths", "occupy", "a", "unique", "phylogenetic", "position", "close", "to", "the", "divergence", "of", "the", "mammalian", "and", "ray-finned", "fish", "lineages.", "Results:", "We", "have", "sequenced", "a", "coelacanth", "(Latimeria", "menadoensis)", "BAC", "clone", "encompassing", "the", "neurohypophysial", "hormone", "genes", "and", "investigated", "the", "evolutionary", "history", "of", "the", "vertebrate", "neurohypophysial", "hormone", "gene", "locus", "within", "a", "comparative", "genomics", "framework.", "The", "coelacanth", "contains", "vasotocin", "and", "mesotocin", "genes", "like", "non-mammalian", "tetrapods.", "The", "coelacanth", "genes", "are", "present", "on", "the", "same", "strand", "of", "DNA", "with", "no", "intervening", "genes,", "with", "the", "vasotocin", "gene", "located", "upstream", "of", "the", "mesotocin", "gene.", "Nucleotide", "sequences", "of", "the", "second", "exons", "of", "the", "two", "genes", "are", "under", "purifying", "selection", "implying", "a", "regulatory", "function.", "We", "have", "also", "analyzed", "the", "neurohypophysial", "hormone", "gene", "locus", "in", "the", "genomes", "of", "opossum,", "chicken", "and", "Xenopus", "tropicalis.", "The", "opossum", "contains", "two", "tandem", "copies", "of", "vasopressin", "and", "mesotocin", "genes.", "The", "vasotocin", "and", "mesotocin", "genes", "in", "chicken", "and", "Xenopus,", "and", "the", "vasopressin", "and", "mesotocin", "genes", "in", "opossum", "are", "linked", "tail-to-", "head", "similar", "to", "their", "orthologs", "in", "coelacanth", "and", "unlike", "their", "homologs", "in", "human", "and", "rodents.", "Conclusion:", "Our", "results", "indicate", "that", "the", "neurohypophysial", "hormone", "gene", "locus", "has", "experienced", "independent", "rearrangements", "in", "both", "placental", "mammals", "and", "teleost", "fishes.", "The", "coelacanth", "genome", "appears", "to", "be", "more", "stable", "than", "mammalian", "and", "teleost", "fish", "genomes.", "As", "such,", "it", "serves", "as", "a", "valuable", "outgroup", "for", "studying", "the", "evolution", "of", "mammalian", "and", "teleost", "fish", "genomes.", "Page", "1", "of", "12", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Law", "et", "al.", "BMC", "Health", "Services", "Research", "2010,", "10:313", "http://www.biomedcentral.com/1472-6963/10/313", "S", "T", "U", "D", "Y", "P", "R", "O", "T", "O", "C", "O", "L", "Open", "Access", "Effects", "of", "prescription", "adaptation", "by", "pharmacists", "Michael", "R", "Law1*,", "Steven", "G", "Morgan2,", "Sumit", "R", "Majumdar3,", "Larry", "D", "Lynd4,", "Carlo", "A", "Marra4", "Abstract", "Background:", "Granting", "dispensing", "pharmacists", "the", "authority", "to", "prescribe", "has", "significant", "implications", "for", "pharmaceutical", "and", "health", "human", "resources", "policy,", "and", "quality", "of", "care.", "Despite", "the", "growing", "number", "of", "jurisdictions", "that", "have", "given", "pharmacists", "such", "privileges,", "there", "are", "few", "rigorous", "evaluations", "of", "these", "policy", "changes.", "This", "study", "will", "examine", "a", "January", "2009", "policy", "change", "in", "British", "Columbia", "(BC),", "Canada", "that", "allowed", "pharmacists", "to", "independently", "adapt", "and", "renew", "prescriptions.", "We", "hypothesize", "this", "policy", "increased", "drug", "utilization", "and", "drug", "costs,", "increased", "patient", "adherence", "to", "medication,", "and", "reduced", "total", "healthcare", "resource", "use.", "Methods/Design:", "We", "will", "study", "a", "population-based", "cohort", "of", "approximately", "4", "million", "BC", "residents", "from", "2004", "through", "2010.", "We", "will", "use", "data", "from", "BC", "PharmaNet", "on", "all", "of", "the", "prescriptions", "obtained", "by", "this", "cohort", "during", "the", "study", "period,", "and", "link", "it", "to", "administrative", "billings", "from", "physicians", "and", "hospital", "discharges.", "Using", "interrupted", "time", "series", "analysis,", "we", "will", "study", "longitudinal", "changes", "in", "drug", "utilization", "and", "costs,", "medication", "adherence,", "and", "short-", "term", "health", "care", "use.", "Further,", "using", "hierarchical", "modelling,", "we", "will", "examine", "the", "factors", "at", "the", "regional,", "pharmacy,", "patient,", "and", "prescription", "levels", "that", "are", "associated", "with", "prescription", "adaptations", "and", "renewals.", "Discussion:", "In", "a", "recent", "survey", "of", "Canadian", "policymakers,", "many", "respondents", "ranked", "the", "issue", "of", "prescribing", "privileges", "as", "one", "of", "their", "most", "pressing", "policy", "questions.", "No", "matter", "the", "results", "of", "our", "study,", "they", "will", "be", "important", "for", "policymakers,", "as", "our", "data", "will", "make", "policy", "decisions", "surrounding", "pharmacist", "prescribing", "more", "evidence-based.", "Background", "Context", "Access", "to", "primary", "care", "is", "an", "important", "concern", "for", "patients", "in", "almost", "every", "jurisdiction", "examined.", "In", "Canada,", "nearly", "4", "million", "individuals", "report", "not", "having", "a", "regular", "physician", "and", "over", "2", "million", "report", "difficulties", "in", "accessing", "routine", "or", "ongoing", "care", "[1].", "For", "at", "least", "some", "of", "these", "individuals,", "and", "for", "certain", "components", "of", "pri-", "mary", "health", "care,", "non-physician", "health", "professionals", "may", "represent", "high-quality", "alternatives.", "There", "is", "some", "research", "evidence", "on", "the", "potential", "of", "deploying", "pharma-", "cists", "in", "primary", "care", "[2];", "that", "literature,", "and", "practical", "experience", "in", "other", "jurisdictions", "points", "to", "a", "considerable", "amount", "of", "untapped", "pharmacist", "human", "resources", "[3-7].", "Expanding", "the", "scope", "of", "pharmacy", "practice", "may", "be", "a", "cost-effective", "way", "to", "enhance", "patient", "access", "and", "adher-", "ence", "to", "medicines,", "and", "to", "reduce", "the", "clinical", "burden", "on", "primary", "care", "physicians.", "*", "Correspondence:", "mlaw@chspr.ubc.ca", "1Centre", "for", "Health", "Services", "and", "Policy", "Research,", "School", "of", "Population", "and", "Public", "Health,", "The", "University", "of", "British", "Columbia.", "201-2206", "East", "Mall,", "Vancouver,", "BC,", "V6T", "1Z3,", "Canada", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "Around", "53%", "of", "Canadians", "fill", "one", "or", "more", "prescrip-", "tions", "each", "year,", "and", "at", "least", "half", "of", "these", "represent", "chronic", "medications", "used", "to", "manage", "cardiovascular", "risk", "factors", "[8,9].", "However,", "rates", "of", "continuous", "use", "of", "medi-", "cines", "for", "chronic", "conditions", "are", "often", "sub-optimal", "[10].", "But", "with", "prescription", "lengths", "limited", "to", "approximately", "3", "months", "in", "most", "provinces", "(with", "up", "to", "4", "refills", "if", "they", "are", "provided),", "access", "to", "primary", "care", "doctors", "for", "the", "purpose", "of", "prescription", "renewal", "may", "be", "a", "barrier", "to", "continuous", "adherence", "to", "long-term", "drug", "therapies.", "Thus,", "granting", "pharmacists", "prescribing", "authority", "may", "increase", "Canadians’", "access", "to", "medications.", "Though", "pharmacists", "are", "highly", "trained", "in", "matters", "related", "to", "the", "effects,", "interactions,", "and", "appropriate", "use", "of", "medicines,", "their", "expertise", "is", "seldom", "called", "upon", "as", "a", "first-line", "pri-", "mary", "health", "care", "provider", "in", "community", "settings.", "Recently,", "numerous", "Canadian", "provinces", "have", "imple-", "mented", "programs", "designed", "to", "expand", "the", "scope", "of", "phar-", "macy", "practice.", "The", "first", "province", "to", "move", "in", "this", "direction", "was", "Alberta,", "which", "implemented", "a", "program", "in", "2007", "that", "allows", "pharmacists", "to", "prescribe", "medications", "and", "adapt", "existing", "prescriptions", "[3].", "One", "year", "later,", "three-quarters", "of", "pharmacists", "in", "the", "province", "reported", "©", "2010", "Law", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "CytoJournal", "Research", "Scope", "of", "FNAC", "in", "the", "diagnosis", "of", "soft", "tissue", "tumors-A", "study", "from", "a", "tertiary", "cancer", "referral", "center", "in", "India", "Bharat", "Rekhi*1,", "Biru", "D", "Gorad1,", "Anagha", "C", "Kakade2", "and", "RF", "Chinoy1", "BioMed", "Central", "Open", "Access", "Address:", "1Dept", "of", "Pathology,", "Tata", "Memorial", "Centre,", "Dr", "E.", "B.", "Road,", "Parel,", "Mumbai,", "400012,", "India", "and", "2Clinical", "Trials", "Coordinator,", "Epidemiology", "&", "Clinical", "Trials", "Unit", "(ECTU),", "Advanced", "Centre", "for", "Treatment,", "Research", "&", "Education", "in", "cancer", "(ACTREC),", "Tata", "Memorial", "Centre,", "Khargar,", "Navi", "Mumbai,", "India", "Email:", "Bharat", "Rekhi*", "-", "rekhi.bharat@gmail.com;", "Biru", "D", "Gorad", "-", "drbdev@yahoo.com;", "Anagha", "C", "Kakade", "-", "akakade@actrec.gov.in;", "RF", "Chinoy", "-", "roshchinoy@gmail.com", "*", "Corresponding", "author", "Published:", "31", "October", "2007", "CytoJournal", "2007,", "4:20", "doi:10.1186/1742-6413-4-20", "This", "article", "is", "available", "from:", "http://www.cytojournal.com/content/4/1/20", "Received:", "7", "August", "2007", "Accepted:", "31", "October", "2007", "©", "2007", "Rekhi", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "Fine", "needle", "aspiration", "cytology", "(FNAC)", "forms", "one", "of", "the", "first", "diagnostic", "tools", "in", "the", "evaluation", "of", "tumors.", "Its", "role", "in", "diagnosing", "soft", "tissue", "tumors", "(STT)", "has", "been", "fairly", "documented,", "as", "well", "as", "debated.", "Present", "study", "was", "aimed", "at", "evaluating", "its", "scope", "in", "diagnosing", "127", "cases", "of", "soft", "tissue", "tumors.", "Methods:", "Conventional", "Pap", "and", "MGG", "staining", "was", "available", "in", "all", "the", "cases.", "Immunocytochemistry", "(ICC)", "was", "performed", "in", "15", "cases.", "Histopathological", "details", "were", "available", "in", "115", "cases.", "Results:", "50%", "cases", "were", "referred", "for", "a", "primary", "diagnosis,", "while", "26.8%", "&", "22.8%", "cases", "were", "evaluated", "for", "recurrent", "and", "metastatic", "lesions,", "respectively.", "Extremities", "were", "the", "commonest", "sites.", "On", "FNAC,", "101", "cases", "(79.5%)", "were", "labeled", "as", "malignant,", "whereas", "10", "cases", "(7.9%)", "were", "labeled", "as", "benign.", "The", "remaining", "16", "cases", "(11%)", "were", "not", "categorized", "and", "were", "labeled", "as", "'unsure/not", "specified'.", "Histopathological", "confirmation", "in", "115", "cases,", "gave", "a", "diagnostic", "accuracy", "of", "98%,", "with", "a", "positive", "predictive", "value", "of", "98%", "in", "malignant", "cases", "and", "a", "negative", "predictive", "value", "of", "100%", "in", "benign", "cases.", "Two", "cases", "were", "false", "positive.", "Among", "the", "various", "cytological", "categories,", "60", "cases", "(47.2%)", "were", "of", "spindle", "cell", "type,", "followed", "by", "32", "(25.2%)", "of", "round", "cell", "type", "and", "14", "cases", "(11%)", "of", "lipomatous", "type.", "Other", "12", "cases", "(9.4%)", "were", "of", "pleomorphic", "type;", "7", "(5.5%)", "cases", "of", "epithelioid", "type", "and", "remaining", "2", "cases", "were", "of", "myxoid", "type.", "All", "the", "round", "cell,", "pleomorphic", "and", "myxoid", "type", "of", "tumors", "were", "sarcomas,", "whereas", "73.3%", "cases", "of", "spindle", "cell", "type", "were", "labeled", "as", "'malignant'.", "Exact", "cytological", "sub", "typing", "was", "offered", "in", "58", "cases,", "with", "rhabdomyosarcoma", "(RMS)", "as", "the", "most", "frequently", "sub", "typed", "tumor.", "The", "two", "false", "positive", "malignant", "cases", "were", "of", "fibromatosis", "and", "a", "pigmented", "schwannoma,", "on", "biopsy.", "Out", "of", "28", "metastatic", "lesions,", "lymph", "nodes", "were", "the", "commonest", "site", "for", "metastasis,", "with", "epithelioid", "tumors", "that", "formed", "highest", "percentage", "of", "metastatic", "cases.", "Conclusion:", "FNAC", "is", "fairly", "specific", "and", "sensitive", "in", "STT", "diagnoses", "for", "primary,", "recurrent", "and", "metastatic", "lesions.", "The", "cytological", "types,", "especially", "round", "cell", "and", "pleomorphic", "sarcomas,", "can", "be", "quickly", "identified.", "Clinicopathological", "correlation", "with", "ICC", "as", "an", "adjunct,", "are", "valuable", "in", "exact", "sub", "typing.", "Page", "1", "of", "10", "(page", "number", "not", "for", "citation", "purposes)" ]

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"are", "insulin-sensitizing", "antidiabetic", "agents", "which—as", "an", "untoward", "side", "effect", "in", "obese", "diabetic", "patients—increase", "SAT.", "Furthermore,", "troglitazone", "has", "improved", "lipoatrophy", "and", "glycemic", "control", "in", "non-HIV", "patients", "with", "various", "forms", "of", "lipodystrophy.", "These", "data", "have", "led", "to", "14", "clinical", "trials", "to", "examine", "whether", "thiazolidinediones", "could", "be", "useful", "in", "the", "treatment", "of", "HAART-associated", "metabolic", "complications.", "The", "results", "of", "these", "studies", "indicate", "very", "modest,", "if", "any,", "effect", "on", "lipoatrophic", "SAT,", "probably", "due", "to", "ongoing", "HAART", "negating", "the", "beneficial", "effect.", "The", "benefit", "might", "be", "more", "prominent", "in", "patients", "not", "taking", "thymidine", "analoges.", "Despite", "the", "poor", "effect", "on", "lipoatrophy,", "thiazolidin-", "ediones", "improved", "insulin", "sensitivity.", "However,", "especially", "rosiglitazone", "induced", "harmful", "effects", "on", "blood", "lipids.", "Current", "data", "do", "not", "provide", "evidence", "for", "the", "use", "of", "thiazolidinediones", "in", "the", "treatment", "of", "HAART-associated", "lipoatrophy,", "but", "treatment", "of", "lipoatrophy-associated", "diabetes", "may", "be", "warranted.", "The", "role", "of", "thiazolidinediones", "for", "novel", "indications,", "such", "as", "hepatosteatosis,", "should", "be", "studied", "in", "these", "patients.", "Copyright", "©", "2009", "Jussi", "Sutinen.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "1.", "Introduction", "The", "prognosis", "of", "HIV-infection", "has", "drastically", "changed", "after", "the", "introduction", "of", "combination", "antiretroviral", "therapy", "[1]", "often", "referred", "to", "as", "highly", "active", "antiretroviral", "therapy", "(HAART).", "Since", "the", "eradication", "of", "the", "virus", "is", "impossible", "with", "current", "medicines", "[2]", "and", "since", "periodic", "treatment", "with", "HAART", "can", "be", "harmful", "when", "compared", "to", "continuous", "ther-", "apy", "[3],", "patients", "need", "to", "continue", "therapy", "uninterruptedly", "and", "permanently.", "Lifelong", "exposure", "to", "HAART", "puts", "patients", "at", "a", "signif-", "icant", "risk", "for", "long-term", "metabolic", "adverse", "effects", "includ-", "ing", "lipodystrophy,", "insulin", "resistance,", "hyperlipidemia,", "and", "increased", "cardiovascular", "morbidity", "[4,", "5].", "The", "most", "char-", "acteristic", "component", "of", "HAART-associated", "lipodystrophy", "is", "the", "loss", "of", "subcutaneous", "adipose", "tissue", "[6]", "which", "has", "proven", "to", "be", "very", "difficult", "to", "treat", "(Figure", "1).", "Thiazolidinediones", "(glitazones)", "are", "oral", "insulin-sensiti-", "zing", "antidiabetic", "agents.", "As", "an", "untoward", "side", "effect,", "gli-", "tazones", "increase", "subcutaneous", "fat", "mass", "in", "patients", "with", "type", "2", "diabetes", "[7–9].", "Additionally,", "in", "non-HIV", "infected", "patients", "with", "various", "forms", "of", "lipodystrophy,", "troglitazone", "has", "improved", "metabolic", "control", "and", "subcutaneous", "lipoatro-", "phy", "[10].", "These", "insulin-sensitizing", "and", "fat-inducing", "effects", "of", "glitazones", "have", "lead", "to", "several", "clinical", "trials", "examining", "whether", "these", "drugs", "could", "reverse", "lipoatrophy", "and", "insulin", "resistance", "in", "patients", "with", "HAART-associated", "lipodystrophy.", "The", "ensuing", "review", "is", "focused", "on", "summarizing", "the", "currently", "available", "clinical", "data", "on", "the", "use", "of", "glitazones", "in", "patients", "with", "HAART-associated", "lipodystrophy", "2.", "Thiazolidinediones", "Thiazolidinediones", "are", "synthetic", "ligands", "for", "peroxisome", "proliferator-activated", "receptor", "gamma", "(PPARγ).", "PPARγ", "is", "a", "nuclear", "receptor", "which", "alters", "expression", "of", "multiple", "genes", "including", "those", "regulating", "lipid", "and", "glucose", "metabolism", "[11].", "PPARγ", "is", "expressed", "mainly", "in", "adipose", "tissue", "and", "is", "also", "found", "in", "pancreatic", "beta", "cells,", "vascular", "endothelium,", "and", "macrophages,", "and", "in", "low", "quantities", "in", "other", "tissues", "such" ]

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[ "Research", "Fish", "Consumption", "and", "Advisory", "Awareness", "in", "the", "Great", "Lakes", "Basin", "Pamela", "Imm,", "Lynda", "Knobeloch,", "Henry", "A.", "Anderson,", "and", "the", "Great", "Lakes", "Sport", "Fish", "Consortium", "Division", "of", "Public", "Health,", "Wisconsin", "Department", "of", "Health", "and", "Family", "Services,", "Madison,", "Wisconsin,", "USA", "More", "than", "61", "million", "adults", "live", "in", "the", "eight", "U.S.", "states", "bordering", "the", "Great", "Lakes.", "Between", "June", "2001", "and", "June", "2002,", "a", "population-based,", "random-digit-dial", "telephone", "survey", "of", "adults", "residing", "in", "Great", "Lakes", "(GL)", "states", "was", "conducted", "to", "assess", "consumption", "of", "commercial", "and", "sport-caught", "fish", "and", "awareness", "of", "state-issued", "consumption", "advisories", "for", "GL", "fish.", "On", "the", "basis", "of", "the", "weighted", "sur-", "vey", "data,", "approximately", "84%", "of", "the", "adults", "living", "in", "these", "states", "included", "fish", "in", "their", "diets.", "Seven", "percent", "(an", "estimated", "4.2", "million", "adults)", "consumed", "fish", "caught", "from", "the", "Great", "Lakes.", "The", "percent-", "age", "of", "residents", "who", "had", "consumed", "sport-caught", "fish", "(from", "any", "water", "source)", "varied", "regionally", "and", "was", "highest", "among", "those", "who", "lived", "in", "Minnesota", "(44%)", "and", "Wisconsin", "(39%).", "Consumption", "of", "GL", "sport", "fish", "was", "highest", "among", "residents", "of", "Michigan", "(16%)", "and", "Ohio", "(12%).", "Among", "residents", "who", "had", "eaten", "GL", "fish,", "awareness", "of", "consumption", "advisories", "varied", "by", "gender", "and", "race", "and", "was", "lowest", "among", "women", "(30%)", "and", "black", "residents", "(15%).", "However,", "70%", "of", "those", "who", "consumed", "GL", "sport-caught", "fish", "twice", "a", "month", "or", "more", "(an", "estimated", "509,000", "adults", "across", "all", "eight", "states)", "were", "aware", "of", "the", "advisories.", "Findings", "from", "this", "survey", "indicate", "that", "exposure", "to", "persistent", "contam-", "inants", "found", "in", "GL", "fish", "is", "likely", "limited", "to", "a", "relatively", "small", "subpopulation", "of", "avid", "sport-fish", "con-", "sumers.", "Results", "also", "underscore", "the", "public", "health", "importance", "of", "advisories", "for", "commercial", "fish", "because", "an", "estimated", "2.9", "million", "adults", "living", "in", "these", "states", "consume", "more", "than", "104", "fish", "meals", "per", "year", "and", "may", "be", "at", "risk", "of", "exceeding", "the", "reference", "doses", "for", "methylmercury,", "polychlorinated", "biphenyls,", "and", "other", "bioaccumulative", "contaminants.", "Key", "words:", "advisory,", "awareness,", "fish,", "Great", "Lakes,", "sport", "fish.", "Environ", "Health", "Perspect", "113:1325–1329", "(2005).", "doi:10.1289/ehp.7980", "available", "via", "http://dx.doi.org/", "[Online", "13", "June", "2005]", "Consumption", "advisories", "for", "sport-caught", "fish", "were", "first", "issued", "by", "Great", "Lakes", "(GL)", "states", "during", "the", "1970s.", "These", "advisories", "were", "based", "on", "findings", "from", "investigations", "of", "the", "methyl-", "mercury", "poisonings", "that", "had", "occurred", "in", "Minamata,", "Japan,", "and", "on", "fish", "tissue", "analysis.", "Since", "that", "time,", "researchers", "have", "discovered", "that", "a", "variety", "of", "other", "persistent", "environmental", "contaminants,", "including", "PCBs", "(polychlori-", "nated", "biphenyls),", "DDT", "(dichlorodiphenyl-", "trichloroethane),", "and", "polybrominated", "diphenyl", "ethers,", "had", "found", "their", "way", "into", "the", "aquatic", "food", "chain", "and", "might", "pose", "a", "risk", "to", "frequent", "consumers", "of", "large,", "predatory", "fish.", "Currently,", "health", "departments", "and/or", "state", "environmental", "agencies", "in", "48", "states", "issue", "consumption", "guide-", "lines", "for", "local", "sport-caught", "fish—fish", "that", "is", "caught", "and", "not", "purchased.", "The", "recent", "methylmercury", "reference", "dose", "revision", "from", "0.5", "gµ/kg/day", "to", "0.1", "gµ/kg/day", "triggered", "states", "to", "review", "their", "sport-fish", "advi-", "sories", "and", "federal", "agencies", "to", "assess", "the", "need", "for", "a", "commercial", "fish", "advisory.", "In", "2004", "the", "U.S.", "Environmental", "Protection", "Agency", "(EPA)", "and", "the", "U.S.", "Food", "and", "Drug", "Administration", "(FDA)", "jointly", "issued", "consumption", "advice", "for", "commercial", "fish", "that", "was", "intended", "to", "protect", "women", "of", "childbearing", "age", "and", "young", "chil-", "dren", "against", "the", "neurodevelopmental", "effects", "of", "methylmercury.", "It", "became", "apparent", "to", "some", "states", "that", "there", "was", "a", "need", "for", "a", "holistic", "methylmercury", "fish", "consumption", "advisory", "that", "combined", "advice", "forlocal", "sport-caught", "fish", "and", "commercial", "fish.", "Up", "until", "this", "time", "sport-caught", "fish", "advisories", "largely", "ignored", "exposures", "from", "commercial", "fish.", "Current", "advisories", "are", "intended", "to", "assist", "anglers", "and", "consumers", "of", "commercial", "fish", "in", "selecting", "fish", "low", "in", "chemical", "contaminants", "as", "part", "of", "a", "healthy,", "balanced", "diet.", "In", "2001", "an", "estimated", "1.85", "million", "fisher-", "men", "purchased", "licenses", "to", "fish", "on", "the", "Great", "Lakes", "(U.S.", "Department", "of", "the", "Interior", "2002).", "Although", "this", "figure", "reflects", "an", "almost", "30%", "decline", "from", "2.55", "million", "in", "1991,", "GL", "sport", "fishing", "continues", "to", "be", "a", "popular", "recreational", "activity", "for", "many", "families.", "Frequent", "ingestion", "of", "fish", "from", "these", "lakes", "has", "been", "associated", "with", "higher", "body", "burdens", "of", "PCBs,", "DDT,", "and", "DDE", "(dichlorodiphenyldichloroethylene)", "(Anderson", "et", "al.", "1998;", "Fiore", "et", "al.", "1989;", "Humphrey", "1983;", "Schwartz", "e", "al.", "1983;", "Sonzogni", "et", "al.", "1991;", "Tilden", "et", "al.", "1997).", "These", "persistent", "contaminants", "accumulate", "in", "the", "body", "over", "time", "and", "increase", "the", "risk", "of", "a", "variety", "of", "health", "problems", "such", "as", "liver", "disease", "(Yu", "et", "al.", "1997),", "reproductive", "(Dar", "et", "al.", "1992;", "Weisskopf", "et", "al.", "2003)", "and", "neurologic", "prob-", "lems", "(Rogan", "and", "Gladen", "1992),", "endocrine", "changes", "(Braathen", "et", "al.", "2004;", "Persky", "et", "al.", "2001),", "and", "developmental", "delays", "(Jacobson", "et", "al.", "1990;", "Jacobson", "et", "al.", "1986;", "Kimbrough", "and", "Krouskas", "2003;", "Longnecker", "et", "al.", "1997;", "Tilson", "and", "Kodavanti", "1998).", "PCBs,", "DDT,", "and", "DDE", "have", "been", "classified", "as", "probable", "human", "carcinogens", "by", "the", "U.S.", "EPA,", "and", "sport-fish", "consumption", "has", "recently", "been", "associated", "with", "an", "increased", "risk", "of", "breast", "can-", "cer", "among", "young,", "premenopausal", "women", "(McElroy", "et", "al.", "2004).", "Environmental", "Health", "Perspectives", "•", "VOLUME", "113", "|", "NUMBER", "10", "|", "October", "2005", "Prenatal", "exposure", "to", "methylmercury", "has", "been", "associated", "with", "subtle", "learning", "delays", "and", "blood", "pressure", "changes", "(Grandjean", "et", "al.", "1998;", "Sorenson", "et", "al.", "1999).", "Methylmercury", "exposure", "during", "adulthood", "has", "recently", "been", "linked", "to", "higher", "rates", "of", "cardiovascular", "disease", "and", "acute", "myocardial", "infarction", "(Guallar", "et", "al.", "2002;", "Salonen", "et", "al.", "1995).", "Until", "the", "early", "1990s", "sport-fish", "consump-", "tion", "advisories", "were", "developed", "independently", "by", "each", "state.", "Development", "of", "these", "advisories", "may", "have", "been", "based", "on", "policy", "considerations", "as", "well", "as", "science.", "This", "led", "to", "confusion", "because", "neighboring", "states", "often", "provided", "dif-", "ferent", "advice", "for", "the", "same,", "shared", "body", "of", "water.", "This", "situation", "was", "confusing", "for", "anglers", "and", "may", "have", "reduced", "confidence", "in", "the", "advi-", "sories.", "At", "the", "direction", "of", "the", "Council", "of", "Great", "Lakes", "Governors,", "the", "states", "that", "border", "the", "Great", "Lakes", "(Illinois,", "Indiana,", "Michigan,", "Minnesota,", "New", "York,", "Ohio,", "Pennsylvania,", "and", "Wisconsin)", "developed", "a", "protocol", "for", "a", "Uniform", "Great", "Lakes", "Sport", "Fish", "Consumption", "Advisory", "(Anderson", "et", "al.", "1993).", "That", "1993", "advisory", "protocol", "provides", "information", "on", "the", "health", "benefits", "of", "fish;", "adverse", "effects", "of", "conta-", "minants;", "recommended", "quantity,", "frequency,", "and", "types", "of", "fish", "to", "consume;", "recommended", "fishing", "locations;", "and", "preparation", "methods", "that", "can", "be", "used", "to", "reduce", "exposure", "to", "bioaccumu-", "lative", "contaminants", "such", "as", "PCBs", "and", "DDE", "(Anderson", "et", "al.", "1993).", "In", "1991", "the", "Great", "Lakes", "Sport", "Fish", "Consortium", "of", "health", "departments", "in", "six", "of", "the", "eight", "GL", "states", "(Michigan", "and", "Pennsylvania", "were", "not", "members", "of", "the", "original", "consortium)", "was", "formed", "and", "received", "competitive", "funding", "from", "the", "Agency", "for", "Toxic", "Substances", "and", "Disease", "Registries.", "In", "1993–1994", "the", "consor-", "tium", "conducted", "a", "random-digit-dial", "telephone", "survey", "of", "8,306", "residents", "of", "the", "eight", "GL", "states", "to", "evaluate", "their", "total", "fish", "and", "GL", "sport-fish", "consumption", "habits,", "define", "at-risk", "subpopula-", "tions,", "and", "assess", "the", "effectiveness", "of", "state-issued", "consumption", "advisories.", "Households", "were", "selected", "by", "a", "computerized", "random-digit-dial", "system,", "and", "an", "adult", "was", "then", "randomly", "Address", "correspondence", "to", "P.", "Imm,", "Department", "of", "Health", "and", "Family", "Services,", "1", "West", "Wilson", "St.,", "Room", "150,", "Madison,", "WI", "53703", "USA.", "Telephone:", "(608)", "267-3565.", "Fax:", "(608)", "267-4853.", "E-mail:", "immpb@dhfs.state.wi.us", "This", "work", "was", "funded", "by", "U.S.", "Public", "Health", "Service", "Agency", "for", "Toxic", "Substances", "and", "Diseases", "Registry", "grant", "75/ATH598322-03.", "The", "authors", "declare", "they", "have", "no", "competing", "finan-", "cial", "interests.", "Received", "31", "January", "2005;", "accepted", "13", "June", "2005.", "1325" ]

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[ "Sironen", "et", "al.", "BMC", "Genomics", "2010,", "11:699", "http://www.biomedcentral.com/1471-2164/11/699", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "Knobbed", "acrosome", "defect", "is", "associated", "with", "a", "region", "containing", "the", "genes", "STK17b", "and", "HECW2", "on", "porcine", "chromosome", "15", "Anu", "Sironen1*,", "Pekka", "Uimari1,", "Szabolcs", "Nagy2,", "Sándor", "Paku3,", "Magnus", "Andersson4,", "Johanna", "Vilkki1", "Abstract", "Background:", "Male", "infertility", "is", "an", "increasing", "problem", "in", "all", "domestic", "species", "including", "man.", "Localization", "and", "identification", "of", "genes", "involved", "in", "defects", "causing", "male", "infertility", "provide", "valuable", "information", "of", "specific", "events", "in", "sperm", "development.", "Correct", "condensation", "of", "the", "sperm", "head", "and", "development", "of", "the", "acrosome", "are", "required", "for", "fertile", "sperm.", "In", "the", "Finnish", "Yorkshire", "pig", "population", "a", "knobbed", "acrosome", "defect", "(KAD)", "has", "been", "reported", "which", "appears", "to", "be", "of", "genetic", "origin.", "In", "previous", "studies", "we", "have", "shown", "that", "a", "large", "number", "of", "affected", "spermatozoa", "have", "a", "cystic", "swelling", "anterior", "to", "the", "apical", "part", "of", "the", "acrosome.", "Results:", "Characterization", "of", "the", "knobbed", "acrosome", "affected", "sperm", "revealed", "that", "both", "the", "acrosomal", "granules", "and", "chromatin", "are", "affected.", "This", "type", "of", "KAD", "appears", "to", "be", "a", "previously", "unknown", "and", "serious", "form", "of", "the", "defect.", "A", "genome", "wide", "scan", "with", "PorcineSNP60", "Genotyping", "BeadChip", "defined", "the", "KAD", "associated", "region", "within", "0.7", "Mbp", "on", "porcine", "chromosome", "15.", "Two", "genes,", "STK17b", "and", "HECW2,", "located", "within", "this", "region", "were", "sequenced.", "The", "expression", "of", "these", "genes", "appeared", "comparable", "in", "KA-affected", "and", "control", "boars.", "The", "known", "function", "of", "HECW2", "in", "acrosome", "development", "highlighted", "this", "gene", "as", "a", "good", "candidate", "responsible", "for", "the", "KAD.", "One", "nonsynonymous", "SNP", "was", "identified", "within", "the", "HECW2", "gene.", "However,", "as", "this", "mutation", "was", "found", "in", "homozygous", "state", "in", "individuals", "with", "normal", "sperm,", "this", "is", "not", "likely", "to", "be", "the", "causal", "mutation.", "Conclusions:", "In", "this", "study", "we", "identified", "two", "candidate", "genes", "for", "a", "severe", "defect", "affecting", "both", "the", "sperm", "acrosome", "and", "chromatin", "that", "causes", "infertility.", "One", "of", "these", "genes,", "HECW2,", "plays", "an", "important", "role", "in", "ubiquitination,", "a", "prerequisite", "for", "chromatin", "remodelling", "and", "acrosome", "formation,", "highlighting", "the", "involvement", "of", "this", "gene", "in", "the", "knobbed", "acrosome", "defect", "and", "male", "infertility.", "Background", "Male", "infertility", "is", "becoming", "increasingly", "prevalent", "partly", "due", "to", "environmental", "factors,", "but", "many", "defects", "in", "sperm", "development", "arise", "from", "a", "genetic", "cause.", "Problems", "in", "the", "production", "and", "maturation", "of", "sperm", "are", "the", "most", "common", "causes", "of", "male", "infertility", "resulting", "in", "low", "sperm", "numbers,", "morphologically", "abnormal", "sperm", "or", "low", "sperm", "motility", "[1-3].", "Despite", "efforts", "to", "reveal", "the", "genes", "and", "their", "functions", "in", "spermatogenesis,", "little", "is", "known", "about", "the", "underlying", "causes", "of", "male", "infertility.", "Therefore,", "the", "localization", "and", "identification", "of", "muta-", "tions", "specifically", "affecting", "spermatogenesis", "provide", "*", "Correspondence:", "anu.sironen@mtt.fi", "1Agrifood", "Research", "Finland,", "MTT,", "Biotechnology", "and", "Food", "Research,", "Genomics,", "FI-36100", "Jokioinen,", "Finland", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "invaluable", "information", "for", "investigating", "the", "causes", "of", "male", "infertility.", "Mammalian", "spermatogenesis", "is", "a", "complex", "process,", "where", "diploid", "spermatogonia", "develop", "into", "haploid,", "highly", "specialized", "spermatozoa.", "Spermatogenesis", "includes", "many", "testis-specific", "processes", "that", "are", "controlled", "by", "complex", "regulatory", "mechanisms", "[4,5].", "During", "spermiogenesis,", "hap-", "loid", "round", "spermatids", "undergo", "dramatic", "biochemical", "and", "morphological", "changes", "that", "are", "governed", "by", "specialized", "gene", "expression", "and", "interactions", "between", "various", "genes", "and", "their", "protein", "products", "[6].", "Identification", "of", "genes", "involved", "in", "sperm", "development", "is", "a", "prerequisite", "to", "under-", "standing", "the", "molecular", "mechanisms", "of", "spermatogenesis.", "Sperm", "development", "is", "known", "to", "be", "disrupted", "during", "spermiogenesis", "in", "several", "acrosomal", "defects;", "e.g.", "globo-", "zoospermia", "in", "humans,", "where", "spermatozoa", "lack", "an", "©", "2010", "Sironen", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Technical", "Note", "Polyhexanide", "and", "hydrogen", "peroxide", "inhibit", "proteoglycan", "synthesis", "of", "human", "chondrocytes", "Eric", "Ro¨hner1,", "Paula", "Hoff2,", "Tobias", "Winkler1,", "Philipp", "von", "Roth", "1", ",", "Jo¨rn", "Bengt", "Seeger1,", "Carsten", "Perka", "1", ",", "Georg", "Matziolis1", "1Department", "of", "Traumatology", "and", "Orthopaedics,", "and", "2Department", "of", "Rheumatology", "and", "Clinical", "Immunology,", "Charite´", "-", "Universita¨tsmedizin,", "Berlin,", "Germany", "The", "use", "of", "local", "antiseptics", "is", "a", "common", "method", "in", "septic", "joint", "surgery.", "We", "tested", "polyhexanide", "and", "hydrogen", "peroxide,", "two", "of", "the", "most", "frequently", "used", "antiseptics", "with", "high", "efficacy", "and", "low", "toxicity.", "The", "purpose", "of", "this", "study", "was", "to", "evaluate", "the", "effects", "of", "both", "antiseptics", "on", "the", "extracellular", "cartilaginous", "matrix", "synthesis", "of", "human", "chondrocytes.", "Chondrocytes", "were", "isolated", "from", "donated", "human", "knee", "joints,", "embedded", "in", "alginate", "beads,", "and", "incubated", "for", "10", "and", "30", "minutes", "with", "polyhexanide", "(0.04%),", "hydrogen", "peroxide", "(3%),", "or", "phosphate-buffered", "saline", "(PBS)", "for", "control.", "Cartilaginous", "matrix", "production", "was", "quantified", "through", "light", "microscopic", "analysis", "of", "Alcian", "blue", "staining.", "Cell", "number", "and", "morphology", "were", "detected", "by", "histological", "analysis.", "Chondrocytes", "showed", "a", "decreased", "intensity", "of", "blue", "colouring", "after", "antiseptic", "treatment", "versus", "PBS.", "In", "contrast", "to", "that,", "neither", "the", "cell", "number", "per", "view", "field", "nor", "the", "cell", "morphology", "differed", "between", "the", "groups.", "Polyhexanide", "has", "more", "toxic", "potential", "than", "hydrogen", "peroxide.", "Based", "on", "the", "fact", "that", "the", "cell", "number", "and", "morphology", "was", "not", "altered", "by", "the", "substances", "at", "the", "examined", "concentrations,", "the", "lower", "intensity", "of", "Alcian", "blue", "staining", "of", "treated", "chondrocytes", "indicates", "a", "decreased", "cartilage-specific", "matrix", "synthesis", "by", "polyhexanide", "more", "than", "by", "hydrogen", "peroxide", "and", "control.", "Keywords:", "Antiseptics,", "Human", "chondrocytes,", "Hydrogen", "peroxide,", "Polyhexanide,", "Proteoglycans", "Introduction", "Different", "studies", "showed", "that", "shoulder", "and", "knee", "joint", "infections", "often", "result", "from", "infiltrations", "with", "local", "anaesthetics,", "glucocorticoids,", "or", "hyaluronic", "acid", "con-", "trary", "to", "hip", "joint", "infections", "which", "are", "rarely", "infiltrated", "for", "diagnostic", "or", "therapeutic", "reasons.1–3", "In", "addition", "to", "arthroscopic", "or", "open", "debridement,", "the", "application", "of", "local", "antiseptics", "is", "a", "standard", "procedure", "in", "the", "treatment", "of", "joint", "infections.", "The", "most", "frequently", "used", "antiseptics", "of", "local", "joint", "and", "wound", "infections", "are", "polyhexanide,", "and", "hydrogen", "peroxide.", "In", "contrast", "to", "antibiotic", "substances,", "they", "do", "not", "differ", "between", "procariontic", "and", "eukaryontic", "cells.", "Therefore,", "the", "tissue", "toxicity", "of", "antiseptic", "substances", "has", "to", "be", "determined", "for", "every", "tissue", "coming", "into", "contact.", "There", "is", "an", "ongoing", "discussion", "between", "elimination", "of", "bacteria", "and", "toxicity", "against", "chondrocytes.4,5", "It", "should", "be", "assumed", "that", "the", "time", "of", "chondrocytes", "Correspondence", "to:", "Eric", "Ro¨hner,", "Center", "for", "Musculoskeletal", "Surgery,", "Orthopaedic", "Department,", "Charite´", "University", "Hospital,", "Berlin,", "Charite´platz", "1,", "10117", "Berlin,", "Germany.", "Email:", "eric.roehner@charite.de", "contact", "with", "local", "antiseptics", "should", "be", "between", "10", "and", "30", "minutes", "to", "eliminate", "most", "colonies", "of", "bacteria", "and", "though", "to", "limit", "chondrocyte", "toxicity.", "The", "most", "frequent", "bacteria,", "which", "are", "responsible", "for", "wound", "and", "joint", "infections,", "are", "staphylococci,", "streptococci,", "and", "Gram-negative", "bacteria.1,6–8", "Be-", "sides", "inducing", "cell", "death,", "antiseptic", "substances", "may", "alter", "the", "cartilage-specific", "synthesis", "of", "proteoglycan", "in", "chondrocytes", "and", "thereby", "affect", "the", "cartilage", "tissue.", "The", "undisturbed", "interaction", "between", "the", "chondrocytes", "and", "extracellular", "matrix", "plays", "an", "im-", "portant", "role", "for", "the", "regulation", "of", "chondrocyte", "homeostasis,", "which", "is", "important", "for", "the", "mainte-", "nance,", "the", "development,", "and", "the", "stabilisation", "of", "chondrocyte", "phenotype.9–12", "Consequently,", "an", "inter-", "ruption", "of", "proteoglycan", "synthesis", "results", "in", "cartilage", "damage", "with", "the", "loss", "of", "chondrocytes.9,13", "Two", "of", "the", "most", "commonly", "used", "antiseptics", "in", "septic", "joint", "surgery", "are", "polyhexanide", "and", "hydrogen", "peroxide.", "Literature", "reviews", "show", "insufficient", "data", "about", "the", "effects", "of", "antiseptics", "on", "human", "cartilage.", "2011", "National", "Society", "for", "Histotechnology", "MORE", "OpenChoice", "articles", "are", "open", "access", "and", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "3.0", "DOI", "10.1179/014788811X12949268296121", "Journal", "of", "Histotechnology", "2011", "VOL", "34", "NO", "1", "35" ]

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[ "Available", "online", "http://arthritis-research.com/content/6/6/R557", "Research", "article", "Vol6No6", "Analysis", "of", "HLA", "DR,", "HLA", "DQ,", "C4A,", "FcγRIIa,", "FcγRIIIa,", "MBL,", "and", "IL-1Ra", "allelic", "variants", "in", "Caucasian", "systemic", "lupus", "erythematosus", "patients", "suggests", "an", "effect", "of", "the", "combined", "FcγRIIa", "R/R", "and", "IL-1Ra", "2/2", "genotypes", "on", "disease", "susceptibility", "Open", "Access", "Andreas", "Jönsen1,", "Anders", "A", "Bengtsson1,", "Gunnar", "Sturfelt1", "and", "Lennart", "Truedsson2", "1Department", "of", "Rheumatology,", "Lund", "University", "Hospital,", "Lund,", "Sweden", "2Department", "of", "Laboratory", "Medicine,", "Section", "of", "Microbiology,", "Immunology", "and", "Glycobiology,", "Lund", "University,", "Lund,", "Sweden", "Corresponding", "author:", "Lennart", "Truedsson,", "lennart.truedsson@skane.se", "Received:", "22", "Dec", "2003", "Revisions", "requested:", "12", "Jan", "2004", "Revisions", "received:", "16", "Jun", "2004", "Accepted:", "16", "Jul", "2004", "Published:", "23", "Sep", "2004", "Arthritis", "Res", "Ther", "2004,", "6:R557-R562", "(DOI", "10.1186/ar1224)htp:/arthrits-research.com/content/6/6/R557", "©", "2004", "Jönsen", "et", "al.;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/", "2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "cited.", "Keywords:", "Fcγ", "receptor,", "HLA,", "interleukin-1", "receptor", "antagonist,", "mannan-binding", "lectin,", "systemic", "lupus", "erythematosus", "Abstract", "Dysfunction", "in", "various", "parts", "of", "immune", "defence,", "such", "as", "immune", "response,", "immune", "complex", "clearance,", "and", "inflammation,", "has", "an", "impact", "on", "pathogenesis", "in", "systemic", "lupus", "erythematosus", "(SLE).", "We", "hypothesised", "that", "combinations", "of", "common", "variants", "of", "genes", "involved", "in", "these", "immune", "functions", "are", "associated", "with", "susceptibility", "to", "SLE.", "The", "following", "variants", "were", "analysed:", "HLA", "DR3,", "HLA", "DQ2,", "C4AQ0,", "Fcγ", "receptor", "IIa", "(FcγRIIa)", "genotype", "R/R,", "Fcγ", "receptor", "IIIa", "(FcRγIIIa)", "genotype", "F/", "F,", "mannan-binding", "lectin", "(MBL)", "genotype", "conferring", "a", "low", "serum", "concentration", "of", "MBL", "(MBL-low),", "and", "interleukin-1", "receptor", "antagonist", "(IL-1Ra)", "genotype", "2/2.", "Polymorphisms", "were", "analysed", "in", "143", "Caucasian", "patients", "with", "SLE", "and", "200", "healthy", "controls.", "HLA", "DR3", "in", "SLE", "patients", "was", "in", "90%", "part", "of", "Introduction", "The", "genetic", "contribution", "to", "the", "aetiology", "of", "systemic", "lupus", "erythematosus", "(SLE)", "is", "high,", "as", "is", "indicated", "by", "familial", "aggregation", "and", "a", "higher", "concordance", "rate", "in", "monozygotic", "than", "dizygotic", "twins", "[1].", "The", "major", "histocompatibility", "com-", "plex", "(MHC)", "haplotype", "HLA", "DR3-DQ2-C4AQ0", "is", "strongly", "associated", "with", "SLE", "in", "Caucasians", "[2,3].", "The", "IgG", "Fc", "receptors", "appear", "to", "be", "important", "in", "the", "pathogenesis", "of", "SLE,", "as", "recently", "reviewed", "by", "Salmon", "and", "Pricop", "[4].", "With", "the", "allelic", "variant", "of", "R", "(arginine)", "instead", "of", "H", "(histidine)", "on", "amino", "acid", "position", "131,", "the", "ability", "of", "Fcγ", "receptor", "IIa", "(FcγRIIa)", "to", "bind", "IgG2", "is", "diminished", "[5].", "Similarly,", "an", "amino", "acid", "substitution", "in", "position", "158", "(phenylalanine", "[F]", "instead", "of", "valine", "[V])", "in", "the", "Fcγ", "receptor", "IIIa", "(FcγRIIIa)", "reduces", "the", "the", "haplotype", "HLA", "DR3-DQ2-C4AQ0,", "which", "was", "strongly", "associated", "with", "SLE", "(odds", "ratio", "[OR]", "2.8,", "95%", "CI", "1.7–4.5).", "Analysis", "of", "combinations", "of", "gene", "variants", "revealed", "that", "the", "strong", "association", "with", "SLE", "for", "HLA", "DR3-DQ2-C4AQ0", "remained", "after", "combination", "with", "FcγRIIa", "R/R,", "FcγRIIIa", "F/F,", "and", "MBL-low", "(OR>2).", "Furthermore,", "the", "combination", "of", "the", "FcγRIIa", "R/R", "and", "IL-1Ra", "2/2", "genotypes", "yielded", "a", "strong", "correlation", "with", "SLE", "(OR", "11.8,", "95%", "CI", "1.5–95.4).", "This", "study", "demonstrates", "that", "certain", "combinations", "of", "gene", "variants", "may", "increase", "susceptibility", "to", "SLE,", "suggesting", "this", "approach", "for", "future", "studies.", "It", "also", "confirms", "earlier", "findings", "regarding", "the", "HLA", "DR3-", "DQ2-C4AQ0", "haplotype.", "IgG1-,", "IgG3-,", "and", "IgG4-binding", "capacity", "of", "the", "receptor", "[6].", "These", "variants", "can", "result", "in", "suboptimal", "clearance", "of", "immune", "complexes", "from", "the", "circulation,", "which", "might", "con-", "tribute", "to", "the", "pathogenesis", "of", "immune-complex-mediated", "manifestations", "[7].", "Mannan-binding", "lectin", "(MBL)", "is", "structurally", "similar", "to", "C1q", "and", "has", "the", "ability", "to", "activate", "the", "complement", "cascade", "through", "the", "lectin", "pathway.", "Point", "mutations", "are", "found", "in", "the", "structural", "gene", "that", "affect", "the", "MBL", "serum", "concentration", "and", "the", "stability", "of", "MBL", "complex", "formation", "required", "for", "effi-", "cient", "complement", "activation", "[8].", "In", "the", "promoter", "regions,", "there", "are", "two", "polymorphisms", "that", "influence", "serum", "concen-", "tration,", "with", "LX", 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