Yesterday, it actually snowed in Bournemouth. Not only that, it settled. Today I had to shovel snow from the drive and put down salt to clear the ice. All sorts of records for cold spells are being broken. It's nice to have a warm house.
I remember 1947. It was a Labour government then as well. Churchill said something like "On an island built of coal and surrounded by fish, you have contrived to produce a shortage of both."
I remember 1979. It was a Labour government then as well. The dead went unburied in the frozen ground and rats were feasting on the rubbish piled up on the street.
Very unlucky with the weather, Labour.
Sorry to hear that you had such inclement weather. isn't global warming fun?
ReplyDeleteThis is off topic, but could you explain sometime exactly what purine analogs do to T cells and why the effect is so long-lived? Do they suppress and/or kill the progenitor cells of T cells or do they kill only T cells already present in the body? Could T cells be harvested prior to treatment and reinfused some time after therapy to minimize immune suppression?
Thanks for your time and efforts!!!
I don't think it is clear how purine analogs preferntially damage T cells. They inhibit function of many different enzymes including multiple DNA polymerases, DNA primase and DNA ligase I.
ReplyDeleteOne study analyzed the in vitro susceptibility of T cell subsets to FLU-induced apoptosis. Contrasting with observations in vivo, Their results showed that treatment of peripheral blood mononuclear cells with FLU induced a higher level of apoptosis in CD8+ than in CD4+ T lymphocytes. This increased sensitivity of CD8+ T cells to FLU was observed in samples from both, healthy donors and B cell chronic lymphocytic leukemia patients, and resulted in higher CD4:CD8 ratios in FLU-treated than in untreated cultures (P<0.01). Expression of factors involved in FLU transport and metabolism was then evaluated by quantitative real time-PCR in normal T cell subsets. It was found that mRNA levels of human equilibrative nucleoside transporter-1 nucleoside transporter were higher whereas deoxycytidine kinase and IMP/GMP selective 5′-nucleotidase mRNA levels were lower in CD4+ cells. However the dCK/cN-II ratio was 2-fold greater in CD8+ than in CD4+ T lymphocytes, which could account for the higher apoptosis levels observed in the CD8+ subset. These results favor the view that decreased CD4:CD8 ratios in FLU-treated patients should be attributed to differences in cell recovery and/or homing between T cell subsets.
See how complicated it is!
The explanation that you gave is "above my pay grade", but nothing that you said would preclude reinfusing harvested T cells after the Fludarabine has been metabolized and re-establishing T cell populations. Do you think that harvesting T cells prior to therapy and infusing them at some point after therapy is practical and worthwhile?
ReplyDeleteI'm not sure that it is physically possible to harvest T cells without contaminating CLL cells and I'm not sure which T cells you would need to harvest. I doesn't sound to me to be a practical proposition. However, there is a purine analog that spares T cells while killing CLL cells. It is called Acadesine and it currently undergoing clinical trials.
ReplyDeleteWell 1963 was pretty dreadful too with a Tory government imploding dramatically as I remember...
ReplyDeletePerhaps freak weather is associated with changes of government in England
In 1963 I was a student and desperately wanted a Labour victory. It's why the under-25s should be disenfrachised ;-)
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