Friday, 13 January 2017

Rumble in the Jungle

The Rumble in the Jungle was a historic boxing event in KinshasaZaire (now Democratic Republic of the Congo) on October 30, 1974 it pitted the undefeated world heavyweight champion George Foreman (of grease-proof grilling fame) against challenger Muhammad Ali, a former heavyweight champion who was stripped of the title and banned for 3 years because he was a consientious objector against the war in Vietnam.

Don King arranged this fight with the music businessman Jerry Masucci, who took his famed musicians, Fania All Stars, to play at the venue. King managed to get Ali and Foreman to sign separate contracts saying they would fight for him if he could get a $5 million purse. However, as King did not have the money, he began seeking an outside country to sponsor the event. Zaire's dictator Mobutu Sese Seko, eager for the publicity such a high-profile event would bring, asked for the fight to be held in his country.

It was the 25 year old Foreman against the 32 year old Ali.
                         
                   MrT said not that Black Swan Crap
       
         ProfG challenged MrT to say where is the evidence 
                               that MS is a T cell Disease

                                   MrT bellied-up    
                  (Can you help him with some ideas?)

                      So the idea for a Heavy Weight Fight           
The rumble (fight), hopefully will be be in a concrete Jungle (Paris) for ECTRIMS, and the we hope to get some heavy weights to do the "Burning Debate" debate
In the blue corner: Mr T
MS is a "T cell mediated disease" and in the 

Red corner is Mr B
MS is a "B cell-mediated disease" with little T cell involvement

What do you think? 

A slam dumk for the A team or "Rope a Dope"

9 comments:

  1. I'll take the easy route: natalizumab is an highly effective therapy that works by blocking VLA-4 ag expressed on t lymphocytes thus preventing egress into the CNS. The subsequent reduction in neuroinflammation significantly reduces lesion load and relapses. I pity the fool who disagrees that ms is not T cell centric ( I couldn't resist) :-)

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    Replies
    1. However in addition to T cells natalizumab binds to B cells and monocytes
      If you check you will see papers showing these cells are blocked by VLA-4 inhibition, so is it the monocyte or B cell?

      If we inhibit monocyte function in EAE we can inhibit EAE that looks like inhibition with T cell inhibition.

      The levels of CD4 in MS in the blood in MS aren't increased under natalizumab treatment, others are...which you would expected if they were the important cell types being blocked from entering the CNS

      There is plenty of data showing that VLA-4 inhibition in rodents, which is T cell mediated isn't that great...in fact look at the original Yednock study in Nature they only show data for a few days as EAE is developing in the treated group.

      Delete
    2. A study out of Finland has shown that certain B-cell populations, CD20+, rise in the peripheral blood following natalizumab treatment while CXCR3+,CD8+ T cells are depleted. Since both B and T-cells can express VLA-4 is the rise in B cells simply due to this blockade, subsequent release of B cells from bone marrow and lymph tissue and accumulation in peripheral blood or is there something else happening?

      Delete
    3. Nice one. I can't answer that as you say are the being kicked out of their niches or are they being stopped from entering the brain but now question comes does this make a time bomb. Stop tysabri and and is something lined up ready to rebound.

      Delete
  2. You have got to be joking! Everyone knows that MS in a T-cell mediated disease; more likely a Th17 disease. Are you trying to make a controversy out of a non-controversy?

    ReplyDelete
    Replies
    1. Ah, welcome back MrT. As you can see things have moved on since you first posted. Read the comments, then give us your definitive evidence for your assertion.

      Delete
    2. Where is the definative evidence that it is the T cell that is important
      in MS?. MS is not EAE.

      The evidence is circumstantial...like the autoimmune hypothesis..doesn't mean to say it is wrong, but circumstantial all the same.

      Treat MS with antigen-specific therapy and you may have evidence?
      These approaches have all failed to deliver so far,

      T cell specific..I mean specific approaches have also generally fallen by the way side, read the papers by Weindl

      Are companies putting their money into T or B cells as a treatment for MS?

      Why not reserect CD4 or CD8

      EAE is a T cell disease, not everyone working on rodents even agree that Th17 is the problem, what about the Th1 disease? Sweeping dogmatic statement?

      Blocking IL-17, which should block Th17 function is pretty rubbish in EAE, e.g the knockouts have a slight diminution of disease but still get disease, the antibodies don't do much better.

      In humans the influence of IL-17 blockade on MRI lesions was in the same ball part as teriflunomide...not exactly a MS stopper. You may say with a better antibody we will get better results...problem is we will never know unless someone is willing to take the risk as I dont think this is indevelopment in MS.

      The devils adovocate makes you think

      Delete
    3. Post comment and run away again, it appears.

      Delete
    4. Everyone knows.... it's not an infection.....isn't that what they said about stomach ulcers...until it was shown to be an infection

      Delete

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