December Blood Prodcuts Advisory Committee Full Transcript

Otis

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From Judy:
In the assay that we used in the Lombardi study, shown in the top line here, we take plasma or activated -- this is dividing peripheral blood and mononuclear cells -- from the patients, and we co-culture them on the prostate cancer cell line, which was responsive to androgens and inflammatory cytokines. This is important because we know we have characterized the LTR, in Steve Goff's lab and Bob Silverman's lab, and we know that there are hormone-responsive elements there that would be an on switch to make the virus replicate more in the cells that were responsive to androgens.
Not sure how to interpret this but as I understand it the LTR contains the part of XMRV that responds to addrogens and cytokines. It sounds to me from the above quote that they might be using such cytokines and androgens to culture the virus (nor entirely sure here?).

This seems interesting as I am sure I saw somewhere along the line (I think from Sandra Ruscetti) that the hormone resonsive elements were not typical of MLV's but were on XMRV, though I dont know if that applied to the Lo/Alter strains. In a recent lecture MIkovits gave in Sweeden she said that the culture was expressing XMRV preferentially over MLV. I wonder if this is the reason why, though you think she would have said that in the talk?
In listening to the lecture Dr. Mikovits gave in Sweden, I understood her to be describing the attributes of the LNCaP cell line that led her to select it, not so much the LTR response. Her "guess" as to what cell line (LNCaP) to use as based, in part, on it's androgenic response but I can't recall why that was a criterion for a cell line so perhaps it's just my fuzzy memory. She was a bit modest in calling it a "guess". Darn good educated guess, I'd say. Too bad it won't grow the "poly" variants Lo/Alter found.
 

Otis

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Rhesus Macaques highlights

For me, this is where some interesting stuff really came out.

First off, perhaps a new hint for a cell line to use:

... where we tried to replicate the virus in a (monkey) primary fibroblast line that was developed in my lab. You can see that not only did the virus replicate, but we also got protein.
Perhaps a reason why serology tests are coming in negative:

But what I would like to draw your attention to is the fact that these antibody titers come back down significantly, suggesting that, similar to other infections that don't replicate a whole lot, there doesn't seem to be a lot of antigen available to the immune system to respond.
On to the prostate:

As aging males -- we have quite a few in this audience -- we're always interested in prostate.

The one thing that was really flabbergasting to us -- this is relatively low-power magnification of the prostate during the acute infection -- you can see that you have these foci of infection, which was mind-boggling, given the difficulty we had in finding the virus in the blood of these animals. There is no lack of virus elsewhere. Obviously, there was a fair amount of replication going on, or at least infection, and gag production in that organ. <...snip...>

Moving on to the chronic phase, though, to our surprise, the prostate was pretty much negative by in situ histochemistry. That was unexpected.

<...snip...> However, if you drill down, not looking for protein, but looking for the viral -- really, the FISH technique that we have detects XMRV RNA -- you can see that we find cells that are still positive there. So it's not like the virus was cleared out of the prostate, but it clearly is limited.
So perhaps when XMRV hits the prostate, it either kicks off those really aggressive forms of PC or it clears and if cancer occurs there later XMRV is in such low copy numbers that it isn't found.

The GI and lymphoid tissues seem also like good homes for XMRV and certainly areas where many of us have problems.

Finally, we're left with a hint about sexual transmission.
This is just a summary table of the detection by immunohistochemistry. These are the animals at different stages post-infection that were sacrificed. You can see that in the lymphoid organs, we find virus throughout. By that time, it was very difficult to find in the blood, except for the animal that was reactivated. The GI mucosa, of course, was fairly positive. Then we had a whole series of tissues where we couldn't find it, but then the reproductive organs, as you can see, were positive, both in male and female animals, which tends to suggest maybe some hint as to how that virus may be transmitted.
 

WillowJ

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sorry I didn't read the whole thread but wanted to make sure this was seen:

DR. COFFIN: My yes vote in the case of CFS was not based on the XMRV connection at all. On that basis alone, I would have voted no. But it was based on the evidence that I heard that matches my intuition and that of other people that there could well be an infectious agent here. It might be XMRV; it might be something else. For that reason, that kind of caution is warranted.
The vote they had just taken was to screen blood donors on medical history or diagnosis of CFS