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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. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    Hi Alex. Could you elaborate a little? Why actual damage and not reduced oxygenation/blood flow (which is what SPECT scans are picking up)?
     
  2. currer

    currer Senior Member

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    MY understanding of this is-

    If the macaques were infected with XMRV, as a retrovirus it would initially circulate in the bloodstream causing an immune reaction following injection and then integrate into DNA in tissue reservoirs thus becoming latent.

    I have always assumed this is why the antibody titres diminish initially.

    However, because the XMRV also integrates into DNA in the immune cells, particularly B cells, once the immune system is stimulated by any other virus coming along later, these immune cells rapidly divide (as part of the immune reaction) and in so doing multiply the XMRV they are infected with.

    Presumably at this stage virions are produced again and get into the bloodstream.

    XMRV is not like HIV and seems to divide only with the division of the host cell. So it is only when the B cells are rapidly dividing to respond to another immune challenge that XMRV would again become apparent in the blood.

    This is why any challenge to the immune system results in a rise in XMRV antibodies as the memory cells recognise XMRV as a past infection and respond to it by reactivating the immune response to XMRV. A reaction to a prior infection rapidly produces high antibody levels.

    I suppose having an infection in the immune system itself could damage the ability of the immune system to respond adequately over the long term, or at any rate modify its response.

    That is how have interpreted the information.

    The thing to remember is that according to JMs hypothesis, the immune system itself is the target of a pathological process. So you would expect immune dysfunction.

    (could this be how the rituximab fits into the picture?)

    (Now with regard to my own memory issues - I have noticed difficulty in remembering events from the recent past. Also locating in my memory bits of useful information and integrating it with other relevant bits - almost like a memory concentration issue.
    Having said that i've been ill over thirty years and of course when in a relapse cant concentrate at all. So this is my memory when "well".
    Maybe its not that abnormal for someone in their mid fifties?. I dont think there's a rapid neurological decline as I dont know anyone with long term ME who is noticeably gaga.

    Although a supporter of the retroviral hypothesis I am not convinced by the ideas as to why we have neurological issues. I just dont think there is progressive damage - I think we would see much more evident problems in PWME otherwise)
     
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  3. Jemal

    Jemal Senior Member

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    That's a nice writeup currer, it would make sense out of a lot of things.
    I also believe (and hope) the damage is low and could be reversed, as long as the cause for all our inflammation issues is treated or even resolved.
     
  4. currer

    currer Senior Member

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    Last May,in the IiME talk, Dr,Mikovits said she can find different antibody reactions in her patients.

    Some samples are positive for antibody to env proteins GP70 or the recombinant env protein
    .
    Some patients are not positive for those but are positive for gag P12 or P30.

    She emphasised that patient plasma is reactive to multiple XMRV proteins.

    To further characterise the findings Gel electrophoresis was used to specify antigen binding to an antibody.

    This shows that there is an XMRV there it is not a non - specific cross reactivity.

    (As you can see, im in the middle of listening to this talk, this is just a first response.)
     
  5. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    currer, although my impressions of what happens gels with what you said, I'm not sure this is 100%. In addition to cell mitosis, I think XMRV can and does to a limited extent also spread the normal way via reverse transcriptase, although this mechanism is blocked in most places by APOBEC3 (you may have known this and left it out because of context). It still occurs where APOBEC3 isn't present - can't remember which parts of the body that is (testicles?).

    PS And of course reverse transcriptase is the mechanism HGRVs use to get into cells in the first place, I imagine.:D
     
  6. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    This a positive HGRV study that has not been published. It makes a lie of claims that Mikovits hasn't followed up on her Science paper and underscores the point that she isn't being allowed to publish.
     
  7. currer

    currer Senior Member

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    Hi Rusty,

    The Ashford study did not go near the WPI or Vip Dx because JM was under a lot of pressure at the time and they wanted to prove that other labs could find the virus.

    She says on the DVD that the patients were seen by indipendent phlebotomists, the blood aliquoted and sent to three indpedent labs for testing (the labs want to remain anonymous for fear of being attacked) audience laughter.

    They looked for Direct RNA from plasma so the blood was delay processed to lyse the cells and tested with nested primers.

    The result was 65% positive with viral and antibody tests.

    I dont know what the status of this research is now, since the BWG.

    This is the problem when studies cannot find a publisher, we do not know whether to accept these findings as valid still, of whether some new information means there is a problem with the results.

    There is no published information to look back on to see exactly what was done so we will not know how to interpret these results with our current knowledge.
     
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  8. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    Thanks currer. Well I guess we'll have to take her at her word (gasp!).
     
  9. ukxmrv

    ukxmrv Senior Member

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    There is also a Norweign study but as it was intending to use the WPI I don't know what is happening to that now

    http://esme-eu.com/news/the-norwegi...irus-related-gene-sequences-article487-7.html

    The project manager of the research project is Dr. Mette Johnsgaard, general manager, physician and researcher at Lillestrm Health Clinic. She has a very strong project team with her:

    - Professor Ola Didrik Saugstad, Rikshospitalet University Hospital in Oslo. (Supervisor of the research study)

    Researcher Prof. Dr. Med Judy Mikovits, director of research Whittemore-Peterson Institute (WPI), Reno i USA.

    Researcher Dr. Med. Mauro Malnati, group manager for human virology at the San Raffaele Scientific Institute in Milano, Italia.

    Researcher and physician Dr. Ingrid Lund, Lillestrm Health Clinic

    Researcher and physician Dr. Sigrid Holterman Holmen, Lillestrm Health Clinic
     
  10. alex3619

    alex3619 Senior Member

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    Hi RustyJ, there is no way to say if its actual physical damage or not. It appears to be progressive in many of us, so is more typical of physical damage. However, this is an educated guess. Cumulative issues with cytokines, nutrion (including methylation etc) or oxidative stress could be more to blame. We simply don't know. IF its not physical damage thats great - and in short term patients I actually think it isnt or that there isnt much physical damage. However as the decades pass I suspect this is likely to cause more damage than aging itself. I hope I am wrong. I prefer to err on the side of caustion and treat it as an urgent matter, which physical damage certainly is. As for blood flow issues, I think this is a major reason for short and medium term problems. I do not think its progressive though, which is why I tentatively discount it for long term damage. Bye, Alex
     
  11. Bob

    Bob

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    My cognition, memory, and ability to visualise (e.g. visual imagination), all took a massive hit when I became ill.
    When I wasn't in the middle of a relapse, it was always my biggest regret with the illness.
    I always used to have an amazing ability to visualise and think clearly.
    As the ME has stabilised for me over the years, so these abilities have returned to a degree, but still impaired.
    If I'm feeling extra run down, or tired, or if I've got a cold then my memory fails.
    I've done so much reading and research over the past couple of years about XMRV and retrovirology, that I should be a walking encyclopedia, but even the most basic facts often fail me.
    As an example, I know I've read the recombination paper (by Switzer & co?) which succeeded the Coffin recombination paper, and I found it fascinating, but I just can't remember any of the details now. And there's plenty of other examples like that.


    My sleep pattern was a major problem for me. I was almost nocturnal at times, which was extremelly inconvenient and depressing. However hard I tried, I just couldn't shift it to a normal sleep pattern - and i tried every trick to do it.
    What fixed it in the end is that my endocrine system seemed to start fluctuating, starting with clinically low thyroid levels which unexpectedly fixed itself a few months later. Then I think my adrenaline and neurotransmitters went a bit high, and then I thought I had sub-clinical diabetes, and then my histamine levels when wild, with new allergies that I hadn't had before. I was all over the place.
    Anyway, when the adrenaline and neurotransmitters seemed to go high, it helped some long-term mood problems and it totally fixed my sleep issues, almost over-night. With the fluctuating adrenaline and neurotransmitter levels, I thought I might have bi-polar developing for a while, but it all settled down again in the end.

    I think something is going on with my hypothalamus or pituitary. Virus or autoimmune?
     
  12. VillageLife

    VillageLife Senior Member

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    I heard last week the UK Ash50 results are still 'solid'
     
  13. Bob

    Bob

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    That's very interesting currer...
    I haven't come across that theory before...

    As you suggest, retroviral integration into B cells could explain so much about ME.
    I don't know much about immunology, but if B cells replicate wildly when fighting an infection, then it could indeed be a perfect explanation for why (secondary) pathogens are trigger events for ME...

    JM says that the B cells are indeed a reservoir for XMRV, doesn't she?

    If B cells are a reservoir for the virus, then this could also explain why Rituximab works...
    If the bone marrow and stem cells, that create the fresh B cells, are uninfected, then the new B cells would be uninfected and so would function properly, until reinfected.
     
  14. free at last

    free at last Senior Member

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    Many would dismiss that idea Village life, Are you allowed to say where you heard this, I have a particular interest in the study as i was one of them who tested positive. But i really dont think xmrv seems to be holding up very well as a theory. I belived it 100% based on personal experiance and types of symptoms. Now i belive if Judy is right, it might be another retrovirus, i just dont know ?
     
  15. Sushi

    Sushi Moderator and Senior Member Albuquerque

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    Maybe this is part of the rationale for the combo of GcMAF and Nexavir. GcMAF activates macrophages that go after "marked" or infected B cells, and Nexavir is supposed to help heal the cell wall and prevent new cells from being infected.

    Just a layman talking and trying to figure this out.

    Sushi
     
  16. VillageLife

    VillageLife Senior Member

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    @freeatlast It's a Fact! :)
     
  17. free at last

    free at last Senior Member

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    Try persuading my doctor with that statement village life. Im assuming Judy might still stand by the result. which does seem a little odd, but then shes closer to more of the science and info, we can only see whats happening around other tests and studys. Unless the evidence becomes forthcoming. Making those statements, as i mentioned wont convince many. Especially my doctor. Im still open to the restrovirus idea. But xmrv seems shakey to say the least. Even if it is fact. without hard proof, It wont help any. My health is pretty good at the mo. But it changes so fast. Inflamation seems to come and go in ways that seem plain nuts. But i know its reall. Something affects our bones ( not just muscles ) as the years tick by. And im not talking old age here. But some kind of bone problem.inflamation or something else. If im ever up xxxx creek. I need evidence in the real world. Word of mouth wont cut it. however much i wish it did. But you certainly got my interest. As i really did belive i found out what actually happened to me. Now i dont know anything. pretty much back to square one. Apart from a realization or belef. that a retrovirus is possiblt to have caused these symptoms of immune dysfunction and other stuff. Ive pretty much give up on learning the truth. But hey you never know. Stranger things have happened i guess
     
  18. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    Hi Bob, this is not just a theory. Without spending a lot of time on it, there is a series of studies and findings to support this mechanism going back more than 12 mths which provides bits and pieces of evidence. Mikovits has been adamant it is being harboured in B cells for a long time. It has been well documented, perhaps not on this site. And yes it is a very strong reason, not just speculation as to why Rituximab works. So rather than diffusing the RV theory, it very much strengthens it. Off topic, I am curious as to how the oncologists got funding for such an obscure study with very expensive drugs. There must be some tie in to ME researchers somewhere.

    I am not sure why the Norwegians persisted in using VP-62 plasmid to look for HGRVs, but their claims that XMRV doesn't exist in their patients would not convince me at all.

    I do have a wiki that is slowly building up. If anyone has documentation of the B cell-Mikovits tie in, I would appreciate it. Currer? It all helps against those who think shooting goldfish in a bowl is fair sport.;)
     
  19. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    free at last. There is no evidence as yet that any of the WPI/VIPdx or the Ashford 50 positives are in doubt. Politically, HGRVs are very much in doubt. Science-wise, not by a long shot.
     
  20. VillageLife

    VillageLife Senior Member

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    @freeatlast Remember u can always log in to the uk study forum.
     

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