The retinoblastoma susceptibility (RB1) gene contains an unmethylated CpG-rich island at its 5' end. Using methylation-sensitive restriction enzymes, we have investigated the methylation status of this island in 21 sporadic unilateral retinoblastomas and 30 hereditary retinoblastomas. Three sporadic unilateral tumors were found to have hypermethylated RB1 alleles. In two tumors, the paternal allele was methylated, whereas the maternal allele had been lost. Cultured cells from one of these tumors were studied by the reverse transcription polymerase chain reaction and found to have a reduced level of RB1 mRNA. The third tumor had retained constitutional heterozygosity, and the paternal allele was specifically methylated. The combined data from previously published reports and from this study show that hypermethylation of the RB1 gene occurs in 13% of sporadic unilateral tumors and may reduce gene activity.
The major aim of this study was to prove or disprove the theories concerning the correlation between physicochemical properties of superparamagnetic iron oxide (SPIO) particles and their accumulation in the lymph nodes. New SPIO particles were produced using starch as stabilising polymer shell. The synthesis was done in a two-step procedure using conventional wet-chemical precipitation technique and subsequent coating of the iron oxide cores. The particles were physicochemically characterised and their lymphotrophy studied in rats using well described lymphotropic dextran-coated SPIO particles as reference. Despite the short blood half-lives of approximately 13 min and the relatively large sizes (approximately 60-90 nm), the starch SPIO particles proved at least as efficient in lymph node accumulation as the small 25 nm dextran SPIO particles having a half-life of 90 min. The currently accepted theories concerning the connection between particle properties and their uptake into lymph nodes are not generally valid, or have at least to be limited for dextran-coated SPIO particles. Lymph node targeting could be achieved despite the present theories consider small size (<30 nm) and long circulation times in the blood as prerequisites. Histological examination showed, that SPIO particles could only be found in lymph node areas where macrophages could be marked which enclosed the particles. Localisation in marginal areas of the lymph nodes indicates endothelial transcytosis as the major accumulation pathway.
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