462 research outputs found
Fragile X syndrome, the search for a targeted treatment
Fragile X syndrome (FXS), the most common monogenetic cause of intellectual disability and autism spectrum disorders, is characterized by behavioral and physical problems. There is currently no adequate treatment available. While animal model studies seemed extremely promising, no success has been achieved in the larger clinical trials with human FXS patients. This short review describes the steps that have been taken in the development of a targeted treatment for FXS. Possible reasons for the lack of translation between animal models and human FXS patients are being explored and solutions are being proposed. The FXS story illustrates pitfalls and possibilities in translational research, that might especially be applicable for other neurodevelopmental disorders as well.
De verwondering begrijpen
Rede In verkorte vorm uitgesproken ter gelegenheid van het aanvaarden van het ambt van bijzonder hoogleraar met als leeropdracht Functionele neurogenetica aan het Erasmus MC, faculteit van de Erasmus Universiteit Rotterdam op 23 mei 201
Hepatic lipase is localized at the parenchymal cell microvilli in rat liver
Hepatic lipase (HL) is thought to be located at the vascular endothelium
in the liver. However, it has also been implicated in the binding and
internalization of chylomicron remnants in the parenchymal cells. In view
of this apparent discrepancy between localization and function, we
re-investigated the localization of HL in rat liver using biochemical and
immunohistochemical techniques. The binding of HL to endothelial cells was
studied in primary cultures of rat liver endothelial cells. Endothelial
cells bound HL in a saturable manner with high affinity. However, the
binding capacity accounted for at most 1% of the total HL activity present
in the whole liver. These results contrasted with earlier studies, in
which non-parenchymal cell (NPC) preparations had been found to bind HL
with a high capacity. To study HL binding to the different components of
the NPC preparations, we separated endothelial cells, Kupffer cells and
blebs by counterflow elutriation. Kupffer cells and endothelial cells
showed a relatively low HL-binding capacity. In contrast, the blebs,
representing parenchymal-cell-derived material, had a high HL-binding
capacity (33 m-units/mg of protein) and accounted for more than 80% of the
total HL binding in the NPC preparation. In contrast with endothelial and
Kupffer cells, the HL-binding capacity of parenchymal cells could account
for almost all the HL activity found in the whole liver. These data
strongly suggest that HL binding occurs at parenchymal liver cells. To
confirm this conclusion in situ, we studied HL localization by
immunocytochemical techniques. Using immunofluorescence, we confirmed the
sinusoidal localization of HL. Immunoelectron microscopy demonstrated that
virtually all HL was located at the microvilli of parenchymal liver cells,
with a minor amount at the endothelium. We conclude that, in rat liver, HL
is localized at the microvilli of parenchymal cells
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