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Post XMRV - For those that think this is dead...

Discussion in 'XMRV Research and Replication Studies' started by JT1024, Oct 16, 2011.

  1. currer

    currer Senior Member

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    I find all this retroviral research really interesting.

    It has brought to light so many fresh and exciting new ideas which are not restricted to ME but could also apply to other diseases.

    Rather that trying to "close down" we need to encourage as much creative and innovative thought as we can.

    We ought to have the courage to pursue unpopular ideas and see where they lead and not be put off.
     
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  2. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    Not sure why anyone would rule out infectivity on evidence of serum inactivation, as another retrovirus, JSRV, does exactly the same thing. And guess what, JSRV is aerosolized as well. Who has done lots of work with JSRV? Arthur Dusty Miller. I just hope that with all his recombinant work on JSRV, nothing recombined with an XMLV (say a human cell line already infected with XMRV) and escaped the lab. Now that really would be more serious than misplacing a slide at a seminar, don't you think?

    http://patents.com/us-20030104357.html
     
    currer likes this.
  3. Mula

    Mula Senior Member

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    Blinding prevents investigators from knowing the subjects status. Use of 5-aza was therefore not limited to patients, but only gives the appearance of being limited to patients in that single western used for publication.

    Dr Coffin/Science/editors have always known 5-aza was used for the experiments as they requested the label switch.
     
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  4. Mya Symons

    Mya Symons Mya Symons

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    The Rhesus study-this is why 10% of me still believes that XMRV could exist in humans. No one has yet explained adequately why at least one of the monkies symptoms after being infected reslembled our symptoms so much. No one has explained the similarities regarding the lymph tissue resevoirs. Or have they. Have I missed something?
     
  5. Deatheye

    Deatheye Senior Member

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    What Sympthoms? As far as I remember they stated that no sympthoms could be seen?
    I agree this also still worries me, just can't remember anything about sympthoms discovered. Which a lot of people thhought could be cause of the short live span till they got killed after infection.
     
  6. Mya Symons

    Mya Symons Mya Symons

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    If I remember correctly, one of the monkeys experienced unusual fatigue while the others did not. I could be wrong. My memory sucks. Also, didn't they find the virus in reservoirs - wherever there was lymph tissue?

    Perhaps if they had kept at least some of the monkeys alive we would know more by now.
     
  7. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    To my knowledge Myra, there was evidence of HGRV in brain tissue, though not whole virus. No symptoms were recorded, though this does not deviate from the conjectured long-term progressive nature of the disease. The theory is that virus amplification, through mitosis in particular, by a number of possible triggers such as a secondary disease, progesterone, stress etc can cause symptoms to rapidly escalate. Thus the disease may seem to be sudden onset, but in most cases is not. It may be that Mikovits was looking at sudden onset as a way of increasing the odds of finding the virus in the blood, the theory being that during rapid or sudden onset the virus is in amplification and may be in higher titres in blood, and may also have an antibody response. I might add that none of these characteristics are unique in a retrovirus, as any retrovirologist would know.

    There could be some qualification to the resu sstudy. It is not known which particular HGRV strain causes which symptoms. They will have unique symptoms, depending on which member of the HGRV family the virus belongs to. So it is quite reasonable to argue that the strain Silverman used in the rhesus study may not have been pathological, but other strains could still be.

    I hope this helps.
     
  8. VillageLife

    VillageLife Senior Member

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    There has been a study not performed at WPI.
    Or vipdx.

    The Ashford 50 uk study.

    This study was presented at the FDA blood meeting last year and presented at the XMRV conference in September last year.

    This study did not go near WPI or vipdx it went to the NCI from Ashford hospital london.

    Antibody and culture ....remember the Dr Alter slide from the NCI conference.
    Harvey Alter said he found this study convincing.

    http://www.youtube.com/watch?v=hWN3rkbXCm4&feature=youtube_gdata_player



    A huge amount of the 50 were virus positive.Ok it's never been published but it's still more evidence outside of WPI and vipdx that there are Gamma retroviruses being picked up.


    [​IMG]
     

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  9. currer

    currer Senior Member

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    I think Judy Mikovits mentions this in her IiME talk, Villagelife. It is on the DVD.

    Yep, just checked.

    She says the blood was collected by indepndent phlebotomists, sent to NCI, aliquoted and sent to three separate laboratories (who prefer to remain nameless so they are not attacked) Audience laughter.

    65% positive by antibody or viral isolation.
     
  10. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    Thanks VillageLife. If you are referring to my response to Myra, I didn't mean to infer that Mikovits hadn't found an antibody response (as further evidence of HGRVs). In the main it appears that HGRVs don't provoke a antibody response. The rhesus study showed this, even though there was still provirus in reservoirs, such as the brain. It is a somewhat illusory marker. The problem with HGRV is that antibody production is not an adequate clinical indication of viral load, or location, by itself. With HGRVs it appears that this immune response is suppressed most of the time. So you have to test patients at the right time.

    And of course the naysayers have used this behavior as evidence of absence of HGRVs, when this is already a noted characteristic of other retroviruses, possibly including HIV. Just recently new strains were detected in patients being treated successfully with ARVs. They believe the news strains may explain the slowly progressing neurological problems of many AIDS patients, even though every other symptom was under control. I suspect there was no antibody production for these strains either, or they would have been discovered earlier. This finding also shows how ARVs need to be tailored for individual strains, not just individual diseases.
     
  11. Bob

    Bob

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    I think you've got this slightly wrong actually Rusty...
    There was an antibody response in the macaques.
    And Judy Mikovits seems to rely on serology tests quite heavily.

    "All three macaques developed XMRV-specific antibody responses during the second week post infection"
    http://www.retrovirology.com/content/7/1/68
     
  12. alex3619

    alex3619 Senior Member

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    On antibody responses, I think there are many open questions. Some with ME seem to lose the ability to produce antibodies to vaccines for example, and this is probably true of disease. It might indicate there is a problem with memory cells in the immune system. If B cells are dying, as suspected, then this could account for it.

    The macaques may or may not have shown this kind of problem if they had been kept alive long enough. It is an open question in my view. I have not read material relating to this recently so I am unsure of the details, but whether they did or did not show antibody responses does not say much about long term efffects. These animals were sacrificed to examine tissue load, not to monintor long term effects. A long term animal model would be required to learn more.

    Bye
    Alex
     
  13. Bob

    Bob

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    "Antibody titers increased to peak levels ... to... day 158 for RIl-10 and RYh-10. After the second XMRV inoculation (day 158), the antibody responses were boosted substantially; the titers gradually decreased to basal levels and were maintained through day 275 PI."
    http://www.retrovirology.com/content/7/1/68

    Graph of antibody titres in the macaques:
    http://www.retrovirology.com/content/7/1/68/figure/F3
     
  14. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    First time I have seen that graph. Thanks Bob. I was under the impression that antibody response eventually disappeared. However the graph showed decreased antibody response, but still evident. Not sure what basal level means. I was sure Mikovits has stated there is not a prolonged antibody response and that that is why nonone else was picking it up. Need these sort of things in a good wiki. Does anyone have a reference to what she has said? Damn my poor memory.
     
  15. Bob

    Bob

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    Actually Rusty, I think you are right. I think that "basal" means that the levels return to baseline levels - i.e. the levels before exposure to XMRV (or, looking at the graphs it means moving 'towards' baseline levels.) So it looks like you are correct about the antibodies not being long lasting, and that they eventually disappear to undetectable levels. Looks like they lasted for a number of months.

    I hadn't heard Judy say that about the antibodies, and I'm surprised because I thought she had had more success with antibodies than PCR.

    But like you, my memory is totally useless! If I had a memory, I'm sure I'd be an expert virologist by now! Well, maybe not quite an expert!
     
  16. alex3619

    alex3619 Senior Member

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    Hi Bob, thanks for the details, my memory is not what it used to be. It would still require a long term study with large numbers of macaques (something I doubt there will ever be funding for) to demonstrate that immune anergy (non-response) and hence lack of antibodies does not occur at least in macaques. Nobody doubts that antibodies should be produced at some point, especially early on. That is why I think it is still an open question. If funding could be found, which would require at least a positive result from the Lipkin XMRV study and probably some political will, then we could learn a lot from a very long term study (five to ten years).

    Bye
    Alex

    ps Fog and memory issues are why I don't do much science these days. Rich and I used to debate science and models all the time, but it was when my memory was much better and I had the resources to pursue etiological models.

    Reduction to basal levels does not mean that there were not antibody producing cells though. These are memory cells. They simply stop pumping out antibodies until they see it again. This is why antibody levels are restored fast when the infection is visible again, or the immune system is stimulated. The problem I am discussing seems to be that long term (and this is only an observation, still not understood) many of us lose the capacity to retain memory cells or respond at all. The macaque study did not show that I think because I recall the antibody response returned, or am I mis-recalling that too? I am too busy with other science at the moment (biomarkers) to give this the attention it deserves.
     
  17. Bob

    Bob

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    That's right alex...
    The antibodies returned swiftly to high levels when XMRV was re-administered to the macaques...
    On the first exposure to XMRV, it took a couple of weeks (I think) for a good antibody response.
     
  18. barbc56

    barbc56 Senior Member

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  19. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    I don't know about memory response of immune system, but my cognitive abilities seem to be slowly declining even though other symptoms are pretty much the same. This happens in HIV, even with successful ARVs. Does anyone else think this is happening to them?

    Again, for those that think a retarded or non-existent antibody response is not seen in other RVs, you are wrong.
     
  20. alex3619

    alex3619 Senior Member

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    Definitely RustyJ, my episodic memory is almost nonexistent, and my formerly fantastic semantic memory is in decline. Its not my reason that is going, but reason requires memory to be effective - if you can't remember stuff you have nothing to reason with. If you recall only some of the relevant facts, you draw erroneous conclusions. So this is not dementia, more like partial progressive amnesia. Other neurocognitive issues seem to be stable, and my energy levels fluctuate but appear to be on an upward tread - still bad but not as bad as two years ago. However, some of that could be circadian induced memory impairment. When I am done with my current project (biomarkers) I am thinking of writing up an hypothesis about circadian impairment and CFS. The trigger for this was my serendipitous discovery that the drug clonidine restored my circadian pattern after a decade either with severe non 24 hour syndrome or no circadian pattern at all. This drug is an adrenaline antagonist, sometimes used to treat adrenergic POTS, high blood pressure, neuropathy and sleep disorders, and I think this ties in to both the Light's research and some research from 2003 I found that showed that physical activity induced circadian dysfunction in CFS.

    The Komaroff spectral coherance EEG paper indicated we may have a problem reintegrating memory. Memory is stored in different parts of the brain. If this problem is the issue, it might indicate slowly progressive brain damage. For many of us a good treatment can't come soon enough.

    Bye
    Alex
     

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