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Discussion in 'Latest ME/CFS Research' started by Omar88, Nov 14, 2012.

  1. snowathlete

    snowathlete

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    I'm trying to understand this plosone paper.
    I think Alices post above from the Ohio State University source is very helpful. Thanks for that Alice.

    So, my understanding is that there are two forms of virual replication. lysogenic, where the virus's nucleic acid integrates with the human DNA in the cell, and then when the cell replicates as normal it also unwittingly replicates the viral nucleic acid as well. The virus then presumably kills the cell.

    At any rate, the plos paper is talking about the other type of viral replication - Lytic - in which the virus having invaded the human cell, uses the host cell's mechanics and energy to replicate itself until the host cell bursts. The cell is dead and there are loads more virons on the lose ready to infect the next cell.
    The lytic cycle is quicker.

    A thought - what is causeing the Lytic replication to abort in the first place?

    They only found antibodies to these EBV encoded dUTPase and DNA polymerase proteins in 6 people originally, I they were treated with Valtrex. Then they talk about larger numbers being positive to antibodies for dUTPase (23/52 - 44.2%) and to the EBV DNA encoded polymerase (41/52 - 78.8%). Is this when they looked back at older samples they had taken?

    This finding looks really important to me the more I look at it. But it's important to understand whether this subset is 6/142 or the higher figure (23/52 for the first antibody and 41/52 for the second)
    Big difference. Can anyone work out which it is we're talking about?
  2. snowathlete

    snowathlete

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    Reading it again, it is actually quite clear (man what I would do for a fully functioning brain) it is just six out of 142 that tested positive for these abortive related proteins. The 52 number is the number of blood tests they had between them over 13-16 months, which is consistent with Lernerscapproach to test them every 6 weeks or so.

    So, six is not many. Still, as the paper points out these are just the proteins we know about, have identified already. All of us could be reacting to another bit of the aborted virus replication for instance.
    At the moment though if this turns out to be correct then we are talking about being able to diagnose a very small subset here. Tat doesn't mean the same treatment won't work though, indeed this paper claims about 75% of those 142 patients improved significantly.
  3. alex3619

    alex3619 Senior Member

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    There were only six patients investigated in this study if you read the methods section, unless I am reading it wrong (I have had only a nights worth of sleep spread out over the last four days). However each patient had many samples taken. Only some of those samples showed positive results. This was a pilot study. My guess is there were very low antibody titres, or that the antibodies appear and disappear over time.

    The larger number of patients were the patient pool the six were taken from. The larger cohort is only mentioned in the background section, they have no part in this study.These six met minimum requirements for the study. It is hard to estimate what impact this would have had on the full patient cohort had they been studied, but only six patients were investigated in depth. It would have been nice to know more details about how and why the majority were not included, I am not sure the paper is clear on this. The paper kind of says this was to create homegeneity using the basic tests (elevated IgG to EBV plus optionally CMV or HHV6, versus the same but with additional coinfections, though it is not clear if this allowed for CMV or HHV6, although these are also herpes viruses - so maybe), but since the others were Group A or Group B I would think they would all be similar. So, again, how were these six patients chosen?.

    Maybe the stats would be similar for the whole cohort had it been used, or maybe this is a statistical anomaly. I think we have to wait and see.

    However Table 1 is confusing. How did they come up with 8 targets? Is this an error? Am I misinterpreting the meaning of target?
    merylg likes this.
  4. Sasha

    Sasha Fine, thank you

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    Would the current Lipkin study pick this up?
  5. alex3619

    alex3619 Senior Member

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  6. alex3619

    alex3619 Senior Member

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    A definite MAYBE. Doh, its not that simple. This is about non viremic virus particles - a failure in the normal virus lifecycle. I do not know enough about next generation sequencing to say if it can detect this. So, maybe.
    merylg likes this.
  7. Sasha

    Sasha Fine, thank you

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    Thanks, Alex! Good to know it's at least a possibility.
  8. snowathlete

    snowathlete

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    I think the paper said that 5 of the 6 had just EBV and were members of group A and that the other 1 was group B and had either CMV or HHV6. I read it over a week ago but im sure it said something like that.
  9. alex3619

    alex3619 Senior Member

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    Yes snowathlete, but is that enough information. I read that too. Why these five and one, and not any of the others?
  10. L'engle

    L'engle moderate ME

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    Where were you able to get this test, Sushi? (Sorry if you already posted this somewhere)
  11. Sushi

    Sushi Moderator and Senior Member Albuquerque

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    KDM tested me since he had seen earlier tests that suggested this--must have been RedLabs.

    Sushi
    L'engle likes this.

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