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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1984-11-28
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pubmed:abstractText |
Human tissue-type plasminogen activator (t-PA), obtained by expression in mammalian cells of recombinant DNA coding for the entire sequence of t-PA (rt-PA), was compared with natural activator from melanoma cell culture (mt-PA). In an in vitro system, composed of [125I]fibrinogen-labeled plasma clot suspended in circulating human plasma, rt-PA and mt-PA caused a very similar dose-related degree of fibrinolysis without causing extensive fibrinolytic activation and fibrinogen breakdown in the surrounding plasma. Urokinase only induced fibrinolysis at a 5- to 10-fold higher concentration and in association with extensive fibrinogenolysis. Intravenous injection of mixtures of labeled (0.4 microCi/kg) and unlabeled (2000 I.U./kg) mt-PA or rt-PA resulted in a rapid but similar disappearance of activity from plasma (T1/2 of 3 min) and specific accumulation of tracer in the liver. In rabbits with experimental jugular vein thrombosis, rt-PA and mt-PA caused a very similar dose-dependent thrombolysis without causing substantial systemic activation of the fibrinolytic system and fibrinogenolysis. Urokinase induced significant thrombolysis only at a 10-fold higher dose and this was associated with systemic fibrinolytic activation. Infusion of 96,000 I.U./kg (approximately equal to 1 mg/kg) of mt-PA or rt-PA over 4 hr induced approximately 70% lysis, whereas a 10-fold higher dose of urokinase yielded 35 to 40% lysis. Two subfractions of rt-PA differing in the extent of glycosylation had very similar thrombolytic properties. It is concluded that the potentially more readily available rt-PA could constitute a specific, fibrin-selective thrombolytic agent.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0022-3565
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pubmed:author | |
pubmed:issnType |
Print
|
pubmed:volume |
231
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pubmed:owner |
NLM
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pubmed:authorsComplete |
N
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pubmed:pagination |
146-52
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:6541693-Animals,
pubmed-meshheading:6541693-DNA, Recombinant,
pubmed-meshheading:6541693-Fibrinolytic Agents,
pubmed-meshheading:6541693-Humans,
pubmed-meshheading:6541693-Jugular Veins,
pubmed-meshheading:6541693-Kinetics,
pubmed-meshheading:6541693-Plasminogen Activators,
pubmed-meshheading:6541693-Rabbits,
pubmed-meshheading:6541693-Thrombosis
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pubmed:year |
1984
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pubmed:articleTitle |
Biological properties of human tissue-type plasminogen activator obtained by expression of recombinant DNA in mammalian cells.
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pubmed:publicationType |
Journal Article,
In Vitro
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