id
string 29.1k
3.5M
| tokens
sequence | bboxes
sequence | ner_tags
sequence | image
image |
---|---|---|---|---|
2315648 | [
"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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"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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2164954 | [
"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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3211996 | [
"Abreu",
"et",
"al.",
"Nanoscale",
"Research",
"Letters",
"2011,",
"6:482",
"http://www.nanoscalereslett.com/content/6/1/482",
"N",
"A",
"N",
"O",
"E",
"X",
"P",
"R",
"E",
"S",
"S",
"Open",
"Access",
"Nanoliposomes",
"for",
"encapsulation",
"and",
"delivery",
"of",
"the",
"potential",
"antitumoral",
"methyl",
"6-methoxy-3-(4-",
"methoxyphenyl)-1H-indole-2-carboxylate",
"Ana",
"S",
"Abreu1,2*,",
"Elisabete",
"MS",
"Castanheira1,",
"Maria-João",
"RP",
"Queiroz2,",
"Paula",
"MT",
"Ferreira2,",
"Luís",
"A",
"Vale-Silva3",
"and",
"Eugénia",
"Pinto3",
"Abstract",
"A",
"potential",
"antitumoral",
"fluorescent",
"indole",
"derivative,",
"methyl",
"6-methoxy-3-(4-methoxyphenyl)-1H-indole-2-",
"carboxylate,",
"was",
"evaluated",
"for",
"the",
"in",
"vitro",
"cell",
"growth",
"inhibition",
"on",
"three",
"human",
"tumor",
"cell",
"lines,",
"MCF-7",
"(breast",
"adenocarcinoma),",
"A375-C5",
"(melanoma),",
"and",
"NCI-H460",
"(non-small",
"cell",
"lung",
"cancer),",
"after",
"a",
"continuous",
"exposure",
"of",
"48",
"h,",
"exhibiting",
"very",
"low",
"GI50",
"values",
"for",
"all",
"the",
"cell",
"lines",
"tested",
"(0.25",
"to",
"0.33",
"μM).",
"This",
"compound",
"was",
"encapsulated",
"in",
"different",
"nanosized",
"liposome",
"formulations,",
"containing",
"egg",
"lecithin",
"(Egg-PC),",
"dipalmitoyl",
"phosphatidylcholine",
"(DPPC),",
"dipalmitoyl",
"phosphatidylglycerol",
"(DPPG),",
"DSPC,",
"cholesterol,",
"dihexadecyl",
"phosphate,",
"and",
"DSPE-PEG.",
"Dynamic",
"light",
"scattering",
"measurements",
"showed",
"that",
"nanoliposomes",
"with",
"the",
"encapsulated",
"compound",
"are",
"generally",
"monodisperse",
"and",
"with",
"hydrodynamic",
"diameters",
"lower",
"than",
"120",
"nm,",
"good",
"stability",
"and",
"zeta",
"potential",
"values",
"lower",
"than",
"-18",
"mV.",
"Dialysis",
"experiments",
"allowed",
"to",
"monitor",
"compound",
"diffusion",
"through",
"the",
"lipid",
"membrane,",
"from",
"DPPC/DPPG",
"donor",
"liposomes",
"to",
"NBD-labelled",
"lipid/DPPC/DPPG",
"acceptor",
"liposomes.",
"Introduction",
"Anticancer",
"drugs",
"are",
"crucial",
"agents",
"in",
"the",
"global",
"approach",
"to",
"fight",
"cancer.",
"Drug-loaded",
"nanoparticles",
"provide",
"a",
"per-",
"fect",
"solution",
"to",
"afford",
"higher",
"therapeutic",
"efficacy",
"and/or",
"reducing",
"toxicity",
"and",
"the",
"possibility",
"of",
"targeting",
"cancer",
"tis-",
"sues.",
"Nanoliposomes",
"are",
"one",
"of",
"the",
"best",
"drug",
"delivery",
"sys-",
"tems",
"for",
"low",
"molecular",
"weight",
"drugs,",
"imaging",
"agents,",
"peptides,",
"proteins,",
"and",
"nucleic",
"acids.",
"Nanoliposomes",
"are",
"able",
"to",
"enhance",
"the",
"performance",
"of",
"bioactive",
"agents",
"by",
"improving",
"their",
"bioavailability,",
"in",
"vitro",
"and",
"in",
"vivo",
"stability,",
"as",
"well",
"as",
"preventing",
"their",
"unwanted",
"interactions",
"with",
"other",
"molecules",
"[1-3].",
"It",
"is",
"believed",
"that",
"the",
"efficient",
"anti-",
"tumor",
"activity",
"can",
"be",
"attributed",
"to",
"the",
"selective",
"delivery",
"and",
"the",
"preferential",
"accumulation",
"of",
"the",
"liposome",
"nano-",
"carrier",
"in",
"the",
"tumor",
"tissue",
"via",
"the",
"enhanced",
"permeability",
"and",
"retention",
"effect",
"[4-6].",
"Nanoliposomes",
"may",
"contain,",
"in",
"addition",
"to",
"phospholi-",
"pids,",
"other",
"molecules",
"such",
"as",
"cholesterol",
"(Ch)",
"which",
"is",
"an",
"important",
"component",
"of",
"most",
"natural",
"membranes.",
"*",
"Correspondence:",
"anabreu@quimica.uminho.pt",
"1Centre",
"of",
"Physics",
"(CFUM),",
"University",
"of",
"Minho,",
"Campus",
"de",
"Gualtar,",
"4710-",
"057",
"Braga,",
"Portugal",
"Full",
"list",
"of",
"author",
"information",
"is",
"available",
"at",
"the",
"end",
"of",
"the",
"article",
"The",
"incorporation",
"of",
"Ch",
"can",
"increase",
"stability",
"by",
"modu-",
"lating",
"the",
"fluidity",
"of",
"the",
"lipid",
"bilayer",
"preventing",
"crystalli-",
"zation",
"of",
"the",
"phospholipid",
"acyl",
"chains",
"and",
"providing",
"steric",
"hindrance",
"to",
"their",
"movement.",
"Further",
"advances",
"in",
"liposome",
"research",
"found",
"that",
"surface",
"modification",
"with",
"polyethylene",
"glycol",
"(PEG),",
"which",
"is",
"inert",
"in",
"the",
"body,",
"generally",
"reduces",
"the",
"clearance",
"of",
"liposome",
"by",
"RES,",
"and",
"therefore",
"allows",
"longer",
"circulatory",
"life",
"of",
"the",
"drug",
"deliv-",
"ery",
"system",
"in",
"the",
"blood",
"[3].",
"Pegylated",
"liposomal",
"doxoru-",
"bicin",
"has",
"shown",
"great",
"prolonged",
"circulation",
"and",
"substantial",
"efficacy",
"in",
"breast",
"cancer",
"treatment",
"[7].",
"The",
"net",
"charge",
"of",
"nanoliposomes",
"is",
"also",
"an",
"important",
"factor",
"and",
"generally",
"anionic",
"and",
"neutral",
"liposomes",
"survive",
"longer",
"than",
"cationic",
"liposomes",
"in",
"the",
"blood",
"circulation",
"after",
"intravenous",
"injection",
"[8,9].",
"In",
"the",
"present",
"study,",
"the",
"antitumoral",
"activity",
"of",
"the",
"fluorescent",
"indole",
"derivative",
"1,",
"methyl",
"6-methoxy-3-(4-",
"methoxyphenyl)-1H-indole-2-carboxylate",
"(Figure",
"1),",
"pre-",
"viously",
"synthesized",
"by",
"us",
"[10],",
"was",
"tested",
"for",
"the",
"in",
"vitro",
"growth",
"of",
"three",
"human",
"tumor",
"cell",
"lines,",
"showing",
"very",
"low",
"GI50",
"values.",
"Considering",
"its",
"promising",
"utility",
"as",
"an",
"antitumoral",
"drug,",
"compound",
"1",
"was",
"encapsulated",
"in",
"dif-",
"ferent",
"nanoliposome",
"formulations",
"and",
"the",
"mean",
"size,",
"size",
"©",
"2011",
"Abreu",
"et",
"al;",
"licensee",
"Springer.",
"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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2593088 | [
"Hindawi",
"Publishing",
"Corporation",
"PPAR",
"Research",
"Volume",
"2009,",
"Article",
"ID",
"373524,",
"15",
"pages",
"doi:10.1155/2009/373524",
"Review",
"Article",
"The",
"Effects",
"of",
"Thiazolidinediones",
"on",
"Metabolic",
"Complications",
"and",
"Lipodystrophy",
"in",
"HIV-Infected",
"Patients",
"Jussi",
"Sutinen",
"Division",
"of",
"Infectious",
"Diseases",
"and",
"Division",
"of",
"Diabetes,",
"Department",
"of",
"Medicine,",
"Helsinki",
"University",
"Central",
"Hospital,",
"00029",
"HUS,",
"Helsinki,",
"Finland",
"Correspondence",
"should",
"be",
"addressed",
"to",
"Jussi",
"Sutinen,",
"jussi.sutinen@hus.fi",
"Received",
"18",
"March",
"2008;",
"Accepted",
"25",
"August",
"2008",
"Recommended",
"by",
"Jacqueline",
"Capeau",
"Highly",
"active",
"antiretroviral",
"therapy",
"(HAART)-associated",
"metabolic",
"complications",
"include",
"lipoatrophy",
"(loss",
"of",
"subcutaneous",
"adipose",
"tissue",
"(SAT))",
"and",
"insulin",
"resistance.",
"Thiazolidinediones",
"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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3339391 | [
"Korkontzelos",
"et",
"al.",
"BMC",
"Medical",
"Informatics",
"and",
"Decision",
"Making",
"2012,",
"12(Suppl",
"1):S3",
"http://www.biomedcentral.com/1472-6947/12/S1/S3",
"P",
"R",
"O",
"C",
"E",
"E",
"D",
"I",
"N",
"G",
"S",
"Open",
"Access",
"ASCOT:",
"a",
"text",
"mining-based",
"web-service",
"for",
"efficient",
"search",
"and",
"assisted",
"creation",
"of",
"clinical",
"trials",
"Ioannis",
"Korkontzelos*,",
"Tingting",
"Mu,",
"Sophia",
"Ananiadou",
"From",
"ACM",
"Fifth",
"International",
"Workshop",
"on",
"Data",
"and",
"Text",
"Mining",
"in",
"Biomedical",
"Informatics",
"(DTMBio",
"2011)",
"Glasgow,",
"UK.",
"24",
"October",
"2011",
"Abstract",
"Clinical",
"trials",
"are",
"mandatory",
"protocols",
"describing",
"medical",
"research",
"on",
"humans",
"and",
"among",
"the",
"most",
"valuable",
"sources",
"of",
"medical",
"practice",
"evidence.",
"Searching",
"for",
"trials",
"relevant",
"to",
"some",
"query",
"is",
"laborious",
"due",
"to",
"the",
"immense",
"number",
"of",
"existing",
"protocols.",
"Apart",
"from",
"search,",
"writing",
"new",
"trials",
"includes",
"composing",
"detailed",
"eligibility",
"criteria,",
"which",
"might",
"be",
"time-consuming,",
"especially",
"for",
"new",
"researchers.",
"In",
"this",
"paper",
"we",
"present",
"ASCOT,",
"an",
"efficient",
"search",
"application",
"customised",
"for",
"clinical",
"trials.",
"ASCOT",
"uses",
"text",
"mining",
"and",
"data",
"mining",
"methods",
"to",
"enrich",
"clinical",
"trials",
"with",
"metadata,",
"that",
"in",
"turn",
"serve",
"as",
"effective",
"tools",
"to",
"narrow",
"down",
"search.",
"In",
"addition,",
"ASCOT",
"integrates",
"a",
"component",
"for",
"recommending",
"eligibility",
"criteria",
"based",
"on",
"a",
"set",
"of",
"selected",
"protocols.",
"Introduction",
"Clinical",
"trials",
"are",
"health-related",
"research",
"studies",
"on",
"humans.",
"A",
"description",
"of",
"a",
"clinical",
"trial",
"follows",
"a",
"pre-",
"defined",
"protocol",
"and",
"contains",
"various",
"information",
"about",
"the",
"study:",
"its",
"title,",
"the",
"condition",
"under",
"inspection,",
"the",
"target,",
"the",
"characteristics",
"of",
"patients",
"that",
"can",
"participate,",
"details",
"about",
"the",
"institutions",
"that",
"accomplished",
"the",
"study,",
"etc.",
"Clinical",
"trials",
"are",
"among",
"the",
"most",
"valuable",
"sources",
"for",
"guiding",
"evidence-based",
"medical",
"practice",
"and",
"designing",
"new",
"trials.",
"However,",
"the",
"vast",
"and",
"rapidly",
"growing",
"number",
"of",
"existing",
"trails",
"hinders",
"the",
"effective",
"use",
"of",
"this",
"information.",
"Significant",
"effort",
"has",
"been",
"devoted",
"to",
"efficient",
"search",
"applications",
"for",
"clinical",
"trials,",
"mainly",
"by",
"various",
"registries,",
"e.g.",
"the",
"UK",
"Clinical",
"Trials",
"Gateway",
"http://www.ukctg.nihr.ac.uk,",
"Free",
"International",
"Standard",
"Randomised",
"Controlled",
"Trials",
"(http://isrctn.",
"org)",
"and",
"http://controlled-trials.com.",
"However,",
"none",
"has",
"attempted",
"to",
"enrich",
"the",
"free",
"text",
"descriptions",
"with",
"structured",
"metadata",
"able",
"to",
"provide",
"search",
"with",
"extra",
"discriminative",
"powers",
"needed",
"for",
"customised",
"search.",
"One",
"of",
"the",
"most",
"difficult",
"parts",
"of",
"creating",
"a",
"new",
"clinical",
"trial",
"is",
"listing",
"the",
"eligibility",
"criteria,",
"i.e.",
"the",
"characteristics",
"*",
"Correspondence:",
"Ioannis.Korkontzelos@manchester.ac.uk",
"National",
"Centre",
"for",
"Text",
"Mining",
"&",
"School",
"of",
"Computer",
"Science,",
"The",
"University",
"of",
"Manchester,",
"Manchester,",
"M1",
"7DN,",
"UK",
"of",
"participants.",
"At",
"the",
"same",
"time,",
"eligibility",
"criteria",
"can",
"directly",
"affect",
"the",
"quality",
"of",
"the",
"experiment",
"and",
"its",
"out-",
"come.",
"Although",
"for",
"experienced",
"researchers",
"composing",
"the",
"eligibility",
"section",
"of",
"a",
"trial",
"might",
"be",
"straightforward,",
"for",
"inexperienced",
"ones",
"it",
"would",
"be",
"time-consuming.",
"It",
"would",
"imply",
"searching",
"for",
"relevant",
"trials",
"and",
"literature",
"and",
"then",
"processing",
"them.",
"In",
"this",
"paper",
"we",
"present",
"ASCOT",
"(Assisting",
"Search",
"and",
"Creation",
"Of",
"clinical",
"Trials),",
"an",
"efficient",
"search",
"applica-",
"tion",
"customised",
"to",
"clinical",
"trials",
"that",
"aims",
"to",
"address",
"the",
"information",
"overload",
"problem",
"and",
"to",
"assist",
"the",
"creation",
"of",
"new",
"protocols.",
"ASCOT",
"employs",
"state-of-the-art",
"text",
"mining",
"technologies,",
"clustering",
"and",
"term",
"extraction",
"algo-",
"rithms",
"applied",
"on",
"large",
"clinical",
"trial",
"collections.",
"It",
"is",
"available",
"at:",
"http://www.nactem.ac.uk/clinical_trials.",
"In",
"more",
"detail,",
"search",
"begins",
"with",
"a",
"textual",
"query.",
"Then,",
"it",
"can",
"be",
"narrowed",
"down",
"in",
"a",
"multitude",
"of",
"ways:",
"-",
"by",
"selecting",
"values",
"for",
"properties",
"that",
"correspond",
"to",
"XML",
"fields",
"of",
"the",
"clinical",
"trial",
"protocols.",
"-",
"by",
"selecting",
"one",
"of",
"the",
"automatically",
"induced",
"and",
"labelled",
"clusters",
"of",
"clinical",
"trial",
"protocols.",
"-",
"by",
"selecting",
"a",
"UMLS",
"or",
"SNOMED",
"CT",
"concept",
"to",
"occur",
"in",
"the",
"(inclusion",
"or",
"exclusion)",
"eligibility",
"cri-",
"teria",
"of",
"the",
"clinical",
"trial",
"protocols.",
"©",
"2012",
"Korkontzelos",
"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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1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
3,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
1,
9,
9,
9,
9,
9,
9,
9,
9,
9,
9,
9,
9,
9,
9,
9,
9,
9,
9,
9,
9,
9,
9,
9,
9,
9,
9,
9,
9,
9,
9,
9,
9,
9,
9,
9,
9,
9,
9,
9,
9,
9,
9,
9
] | |
1281274 | [
"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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35,
783,
60
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104,
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109,
88,
235,
108
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[
240,
88,
275,
108
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[
280,
88,
363,
108
],
[
368,
88,
471,
108
],
[
476,
88,
494,
108
],
[
498,
88,
529,
108
],
[
534,
88,
586,
108
],
[
591,
88,
644,
108
],
[
650,
88,
701,
108
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[
66,
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113,
130
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[
115,
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148,
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[
151,
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190,
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[
193,
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264,
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[
267,
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305,
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[
308,
116,
322,
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[
325,
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390,
130
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[
393,
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417,
130
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[
420,
116,
441,
130
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[
444,
116,
480,
130
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[
483,
116,
519,
130
],
[
523,
116,
559,
130
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[
562,
116,
588,
130
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[
591,
116,
666,
130
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[
66,
139,
109,
151
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[
112,
139,
123,
151
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1,
1,
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4
] | |
3016419 | [
"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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2596294 | [
"Mol",
"Genet",
"Genomics",
"(2008)",
"280:427–436",
"DOI",
"10.1007/s00438-008-0376-8",
"O",
"R",
"I",
"G",
"I",
"N",
"A",
"L",
"P",
"A",
"P",
"E",
"R",
"Experimental",
"evidence",
"for",
"splicing",
"of",
"intron-containing",
"transcripts",
"of",
"plant",
"LTR",
"retrotransposon",
"Ogre",
"Veronika",
"Steinbauerová",
"·",
"Pavel",
"Neumann",
"·",
"Jilí",
"Macas",
"Received:",
"8",
"July",
"2008",
"/",
"Accepted:",
"19",
"August",
"2008",
"/",
"Published",
"online:",
"2",
"September",
"2008",
"©",
"Springer-Verlag",
"2008",
"Abstract",
"Ogre",
"elements",
"are",
"a",
"distinct",
"group",
"of",
"plant",
"Ty3/",
"gypsy-like",
"retrotransposons",
"characterized",
"by",
"several",
"spe-",
"ciWc",
"features,",
"one",
"of",
"which",
"is",
"a",
"separation",
"of",
"the",
"gag-pol",
"region",
"into",
"two",
"non-overlapping",
"open",
"reading",
"frames:",
"ORF2",
"coding",
"for",
"Gag-Pro,",
"and",
"ORF3",
"coding",
"for",
"RT/RH-",
"INT",
"proteins.",
"Previous",
"characterization",
"of",
"Ogre",
"elements",
"from",
"several",
"plant",
"species",
"revealed",
"that",
"part",
"of",
"their",
"tran-",
"scripts",
"lacks",
"the",
"region",
"between",
"ORF2",
"and",
"ORF3,",
"carrying",
"one",
"uninterrupted",
"ORF",
"instead.",
"In",
"this",
"work,",
"we",
"investi-",
"gated",
"a",
"hypothesis",
"that",
"this",
"region",
"represents",
"an",
"intron",
"that",
"is",
"spliced",
"out",
"from",
"part",
"of",
"the",
"Ogre",
"transcripts",
"as",
"a",
"means",
"for",
"preferential",
"production",
"of",
"ORF2-encoded",
"proteins",
"over",
"those",
"encoded",
"by",
"the",
"complete",
"ORF2–ORF3",
"region.",
"The",
"experiments",
"involved",
"analysis",
"of",
"transcription",
"patterns",
"of",
"well-deWned",
"Ogre",
"populations",
"in",
"a",
"model",
"plant",
"Medicago",
"truncatula",
"and",
"examination",
"of",
"transcripts",
"carrying",
"dis-",
"sected",
"pea",
"Ogre",
"intron",
"expressed",
"within",
"a",
"coding",
"sequence",
"of",
"chimeric",
"reporter",
"gene.",
"Both",
"experimental",
"approaches",
"proved",
"that",
"the",
"region",
"between",
"ORF2",
"and",
"ORF3",
"is",
"spliced",
"from",
"Ogre",
"transcripts",
"and",
"showed",
"that",
"this",
"process",
"is",
"only",
"Communicated",
"by",
"M.-A.",
"Grandbastien.",
"Electronic",
"supplementary",
"material",
"The",
"online",
"version",
"of",
"this",
"article",
"(doi:10.1007/s00438-008-0376-8)",
"contains",
"supplementary",
"material,",
"which",
"is",
"available",
"to",
"authorized",
"users.",
"V.",
"Steinbauerová",
"·",
"P.",
"Neumann",
"·",
"J.",
"Macas",
"(&)",
"Institute",
"of",
"Plant",
"Molecular",
"Biology,",
"Biology",
"Centre",
"ASCR,",
"Braninovská",
"31,",
"37005",
"Beské",
"Bud5jovice,",
"Czech",
"Republic",
"e-mail:",
"macas@umbr.cas.cz",
"URL:",
"http://w3lamc.umbr.cas.cz/lamc/",
"V.",
"Steinbauerová",
"Faculty",
"of",
"Science,",
"University",
"of",
"South",
"Bohemia,",
"Beské",
"Bud5jovice,",
"Czech",
"Republic",
"partial,",
"probably",
"due",
"to",
"weak",
"splice",
"signals.",
"This",
"is",
"one",
"of",
"very",
"few",
"known",
"cases",
"of",
"spliced",
"LTR",
"retrotransposons",
"and",
"the",
"only",
"one",
"where",
"splicing",
"does",
"not",
"involve",
"parts",
"of",
"the",
"element’s",
"coding",
"sequences,",
"thus",
"resembling",
"intron",
"splic-",
"ing",
"found",
"in",
"most",
"cellular",
"genes.",
"Keywords",
"Retroelements",
"·",
"Transcription",
"·",
"Splicing",
"·",
"Medicago",
"truncatula",
"·",
"Pisum",
"sativum",
"Introduction",
"Long",
"terminal",
"repeat",
"(LTR)",
"retrotransposons",
"represent",
"a",
"group",
"of",
"mobile",
"genetic",
"elements",
"characterized",
"by",
"a",
"replica-",
"tive",
"(copy-and-paste)",
"mode",
"of",
"transposition",
"involving",
"tran-",
"scription",
"of",
"the",
"parental",
"element,",
"reverse",
"transcription",
"of",
"the",
"resulting",
"RNA",
"into",
"DNA,",
"and",
"subsequent",
"integration",
"of",
"a",
"new",
"element",
"into",
"the",
"genome.",
"The",
"LTRs,",
"which",
"contain",
"regulatory",
"sequences",
"for",
"transcription,",
"Xank",
"the",
"internal",
"region",
"(gag-pol)",
"encoding",
"proteins",
"with",
"structural",
"or",
"enzy-",
"matic",
"functions.",
"The",
"gag",
"gene",
"codes",
"for",
"proteins",
"needed",
"for",
"an",
"assembly",
"of",
"virus-like",
"particles",
"and",
"RNA",
"packaging.",
"The",
"pol",
"gene",
"encodes",
"enzymes",
"protease",
"(Pro),",
"reverse",
"transcrip-",
"tase/RNaseH",
"(RT/RH)",
"and",
"integrase",
"(INT).",
"RT/RH",
"and",
"INT",
"convert",
"the",
"retrotransposon",
"RNA",
"into",
"DNA",
"and",
"integrate",
"it",
"into",
"the",
"genome,",
"respectively.",
"Translation",
"of",
"the",
"gag-pol",
"region",
"is",
"initiated",
"from",
"a",
"single",
"site",
"on",
"full-length",
"RNA",
"and",
"individual",
"functional",
"proteins",
"are",
"released",
"from",
"a",
"precursor",
"polyprotein",
"by",
"the",
"action",
"of",
"protease",
"(Kumar",
"and",
"Bennetzen",
"1999;",
"Havecker",
"et",
"al.",
"2004).",
"While",
"the",
"gag-pol",
"genes",
"are",
"common",
"to",
"all",
"autonomous",
"LTR",
"retrotransposons,",
"there",
"are",
"diVerences",
"in",
"the",
"structure",
"of",
"their",
"coding",
"regions,",
"which",
"are",
"arranged",
"in",
"single",
"or",
"multiple",
"(overlapping",
"or",
"adjacent)",
"reading",
"frames.",
"Since",
"the",
"structural",
"proteins",
"encoded",
"in",
"the",
"gag",
"region",
"are",
"123"
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3093610 | [
"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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0,
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0,
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4
] |
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