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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
1995-3-21
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pubmed:abstractText |
It was recently reported that the sequestration of virus by macrophages in reticuloendothelial system organs, such as lymph nodes, is possibly responsible for the clinical latency of disease in asymptomatic HIV-infected patients. Since macrophages may sequester HIV after phagocytosis, and because phagocytosis is a specialized function of any mammalian macrophage, a mouse-macrophage cell line (RAW 264.7) was used as a macrophage model to evaluate the uptake and binding of 2',3'-dideoxycytidine (ddC) encapsulated in liposomes of an average size of 300 nm containing 350 mumols of ddC per mmol of lipids. Liposomal ddC (L-ddC) was rapidly taken up by macrophages. In contrast, its free form (ddC) accumulated slowly in these cells. The accumulation of ddC from L-ddC into cells seemed to consist of two components: a saturable one, which fitted with the Michaelis-Menten model, and a nonsaturable one, which proceeded linearly in the presence of an excess amount of unlabeled liposomes. Under these conditions, we found an apparent Michaelis-Menten constant (Km) of 40 microM and an initial velocity of 0.12 nmol ddC/mg protein/min for the saturable component and a constant rate of accumulation (KN) of 0.017/min for the nonsaturable component. The inhibition of uptake of ddC from L-ddC in the presence of phagocytosis inhibitors (deoxyglucose plus sodium azide) and nucleoside transport inhibitors (dipyridamole or nitrobenzylthioinosine) also confirmed the existence of several mechanisms in the liposome-mediated accumulation process of ddC into macrophages. Furthermore, studies of efflux of ddC in drug-free medium from cells preloaded with L-ddC or ddC established longer retention of ddC in cells preloaded with L-ddC than with ddC.(ABSTRACT TRUNCATED AT 250 WORDS)
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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 |
Mar
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pubmed:issn |
1077-9450
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
8
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
227-35
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:7859133-Animals,
pubmed-meshheading:7859133-Binding, Competitive,
pubmed-meshheading:7859133-Cell Line,
pubmed-meshheading:7859133-Dose-Response Relationship, Drug,
pubmed-meshheading:7859133-Drug Carriers,
pubmed-meshheading:7859133-Kinetics,
pubmed-meshheading:7859133-Lipid Metabolism,
pubmed-meshheading:7859133-Liposomes,
pubmed-meshheading:7859133-Macrophages,
pubmed-meshheading:7859133-Mice,
pubmed-meshheading:7859133-Zalcitabine
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pubmed:year |
1995
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pubmed:articleTitle |
Uptake and binding of liposomal 2',3'-dideoxycytidine by RAW 264.7 cells: a three-step process.
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pubmed:affiliation |
Laboratoire et Service d'Infectiologie, Centre Hospitalier, Université Laval, Québec, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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