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HGRVs - Constructive general discussion - for exploring HGRV research

Discussion in 'XMRV Research and Replication Studies' started by Bob, Oct 25, 2011.

  1. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    What's very interesting about the negative PCR study is that they didn't even look at the VP-62 issue. So this means a potential fail on at least 2 levels.

    Sensitivity = FAIL
    Optimization = FAIL

    These guys deserve a pat on the back. They seem to have blown a raspberry in the face of every 'eminent' researcher who worked on the negative studies. There should be a big blow back on this one. Will it happen? Probably not. The negatives studies were about public relations.

    You know what this reeks of: INCOMPETENCE or deliberate obfuscation.
  2. Bob

    Bob

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    Yes, there are aspects of Singh's study that cannot easily be explained by contamination...
    I'd have to read the paper again, but didn't Dr Singh also show an association between disease progression and levels of the virus in the tissue?
    Or something similar... I can't remember the details now... Does anyone remember? I'll think i'll have to read it again, because it would be a very significant part of the study if that was the case.
  3. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    Is this the study you are looking for Bob?

    XMRV is present in malignant prostatic epithelium and is associated with prostate cancer, especially high-grade tumors.

    Schlaberg R, Choe DJ, Brown KR, Thaker HM, Singh IR.

    Proc Natl Acad Sci U S A. 2009 Sep 22;106(38):16351-6. Epub 2009 Sep 8.

    PMID:
    19805305
    [PubMed - indexed for MEDLINE]

    Free PMC Article
  4. Ernie

    Ernie Senior Member

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    The research Director for VIPdx was and has always been Lombardi. Why do you think he didn't mention Judy's name. And just who is the Research Director for the institute is what patients should be asking. Just who is it that has always been making the decisions related to VIP. Look to the owners.

    And speaking of frauds how's that vitamin CFS cure all going Blacksheep?
  5. currer

    currer Senior Member

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    Lets look at some of the things Singh did, and see if this virus appears to be really infecting prostate cancer patients.

    She constructed an artificial molecular clone of XMRV and found that it efficiently replicated in LNCaP cells (a prostate cancer cell line)
    Viral release was first seen on day 7 and peaked on day 12, wheras no particles were released from similarly infected 293T cells until day 14.

    She used quantitative PCR which was specific for XMRV sequences and did not amplify murine or human endogenous retroviruses.

    (No amplification products were seen when testing C57BL/6 mouse genomic DNA or human placental DNA)

    233 prostate cancer specimens and 101 controls (transurethral prostate resection) were used.

    XMRV was detected in 6% of prostate cancers and 2% controls.

    The interesting thing here is that her PCR was designed to detect XMRV from tissue, not blood.
    The tissue was embedded in formalin fixed paraffin embedded TISSUES.
  6. currer

    currer Senior Member

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    I find her immunohistochemistry tests the most compelling.

    She developed an XMRV specific antisera from rabbits which was specific to a 75-kDa band on the surface unit of the envelope protein of XMRV. (This area is specific to XMRV only) This antiserum did not react to the envelope protein of Moloney murine leukemia virus which is a highly similar MLV retrovirus, so it was specific to XMRV only.http://www.stanford.edu/dept/EHS/prod/researchlab/bio/docs/Moloney_Murine_Leukemia_Virus.pdf

    This antisera did not stain when exposed to XMRV uninfected cells. Rabbit serum from an animal which had not developed immunity to XMRV also did not result in staining.
    Artificially XMRV infected cells stained in proportion to the known percentage of infected cells in the mixtures.
    The prostate cancer samples which had tested positive by PCR did show granular cytoplasmic staining.

    All 334 prostate cancer samples and controls were then tested.
    XMRV protein expression was found in 23% of prostate cancer samples as opposed to 4% controls.

    XMRV staining was predominantly in malignant epithelial cells.

    There was a correlation between higher grade of cancer and XMRV infection.
  7. currer

    currer Senior Member

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    Singh states that XMRV is very similar in morphology to moloney murine leukemia virus. However the XMRV-SU specific antisera did not cross react with MOMLV-SU and the two proteins only share a 54% similarity. The SU (surface unit) of the envelope protein determines host specificity and sets xenotropic viruses apart from other related murine leukemia viruses.

    Singhs immunohistochemistry results seem to me to be pretty unassailable.
    If it isnt XMRV in these cells it is impossible to guess what else could be there, as her antisera do not react with the controls or cross react with a highly similar MLV.

    One interesting point she raises is that not all the malignant cells expressed XMRV proteins. This could be because the XMRV proviral DNA may be lost over time. Apparently this is a phenomena seen in avian leukosis virus - it seems that the virus can turn on the oncogenic mechanism and this will be maintained even after the loss of the viral genes.
  8. currer

    currer Senior Member

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    So this paper of Singhs is a very convincing piece of research. We have forgotten how convincing it is. It seems to me that unless this work can be shown to be at fault somehow, HGRVs really do exist despite the announcement of the BWG. I cannot see the prostate cancer researchers giving up on their findings.
  9. Bob

    Bob

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    Thanks for that currer... You've answered my questions about Singh's study...

    It's this bit that I was thinking of when I said that her study was difficult to explain away with a contamination theory:

    But the other parts of the study look equally robust.

    I'm having a look over some old studies myself... If I come across anything worth highlighting, then i'll post it here.
  10. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    Thanks KFG.
  11. Jemal

    Jemal Senior Member

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    Yeah, very interesting, thanks! I hope there's still enough researchers interested in this.
  12. leela

    leela Slow But Hopeful

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    Yes, ignoring is a really good idea. DO NOT engage and thus distract from the purpose of this thread.

    However I must add that I completely disagree with Kurt's post. This is an open forum, and that ought to include threads in which people respectfully ask others to keep it completely ON TOPIC--which in this case means ONLY discussing the proposed topic, and not fomenting discourse as to its validity.

    People are welcome to start another thread all about why and how there is no such thing as HGRV; they are free to do that, and welcome to request that those with an opposing view refrain from participating within the confines of that thread.
    Someone could also open a Let's debate about HGRVs thread as well.

    This is not censorship! This is keeping a thread ON topic.
  13. kurt

    kurt Senior Member

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    The topic of this thread is ' HGRVs - Constructive general discussion - for exploring HGRV research'. I fail to see how staying 'on topic' means to restrict to pro-HGRV posts that you or others here agree with. If you want to discuss only one viewpoint of a topic, then I agree, you should start a thread that is restricted, not 'general discussion' as this thread is. In other words, the topic of this thread has not been restricted to just one viewpoint. You are welcome to start a thread on any topic, but I think it is unrealistic to expect no opposing views. For a one-sided discussion I think starting a group makes more sense.
  14. leela

    leela Slow But Hopeful

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    Maybe you "failed" to read the opening post #1 by Bob? Here it is, for clarification.

    ETA: And FYI I am neither pro nor anti HGRVs. I am interested in hearing about it the possibilities within the research but not interested in ugly arguments about it.
  15. Mark

    Mark Acting CEO

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    Bob's first post in this thread makes it clear what is on-topic for this thread. Posts that - as Bob puts it - "are not interested in XMRV or HGRVs, or who think that HGRV research is a waste of time, or that XMRV is purely a contaminant" are well-defined by Bob as off-topic for this thread, and if such posts are reported, they will be removed as 'off-topic'. Knowing the posters on this thread, I think they will be open to a degree of feedback on matters of fact, eg: regarding any inaccuracies or misunderstandings, but that's up to those posters to decide (especially Bob, since it's his thread).

    This general principle has been discussed behind the scenes recently, and (pending a more detailed confirmation) we seem to have agreement that members may post threads and define what is 'off-topic' to their thread, and of course members who disagree are free to then create a separate thread with an opposing view.

    For example: a member might post a thread "discussion of ways to support Dr X", and arguments about whether to support Dr X would be off-topic on that thread. Another member might (theoretically) post a thread "reasons not to support Dr X" and define that arguments defending Dr X would be off-topic on that thread (unpalatable, perhaps, but only fair). A third thread might be more open-ended - "discussion of the controversial Dr X" - where both viewpoints are permitted. Anyone may, of course, post their responses to posts from either of the 'closed topic' threads on another thread - so there is a "right of reply" in that sense, but not within the 'closed thread' itself.

    Kurt may be right that a group is more appropriate for 'closed' discussions like this, and indeed a private group facility will be provided shortly for HGRV discussion. In the meantime, I hope that circumstances where 'closed' thread topics are required will be rare, but I think it is quite reasonable for members to wish to create threads and define them as being only for positive discussion of a particular subject and to stipulate that arguments about the validity of that positive discussion must take place elsewhere.

    I hope that these guidelines will reduce friction on certain discussion topics, and provide the sort of 'safe havens' that some members are looking for. Open discussion is generally preferable, and actually I think that most of us here value input from opposing points of view, and the forum provides for that in general. However, some arguments continue endlessly and are unlikely to ever be resolved, and in those circumstances, separate sub-groups do sometimes want to have productive discussions on subjects of common interest, without being distracted. So: We will experiment with the above 'closed thread topic' guidelines and see how it goes...please report any off-topic posts and they will be moderated.
  16. currer

    currer Senior Member

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  17. Bevbh

    Bevbh

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    Thanks for starting this thread. I'm not up to trying to sort out all the details of the PRC and antibody studies but I appreciate that you are trying, especially the prostate cancer work. My question is that as far as I understand it, Dr. Mikovits said that she had isolated a GRV from a CFS patient. This virus was supposed to be sequenced by Dr. Silverman but he actually sequenced an XMRV contaminent. Which means that we still dont know what virus was really isolated. Do I understand that correctly?
  18. redo

    redo Senior Member

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    As for the general notion that retroviruses may be behind this disease, I think this theory sheds some interesting light on the possibility for retroviruses being latent in most people, and than getting activated by an infection. If it's not HGRV, I think it might very well be an endogenous retrovirus we're dealing with.
  19. justy

    justy Senior Member

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    thanks for the link Redo, absolutely facinating stuff. Where are the treatments based on this though for MS suffereres and scizophrenics? can an endogenous retrovirus even be treated?

    I guess this could explain why its so hard to find THE virus that causes M.E.
  20. Daffodil

    Daffodil Senior Member

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    redo.....if its an endogenous retrovirus, why would there have been cluster outbreaks of this disease?

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