Have a wonderful 2012! Thanks for all the great work you do to promote MS understanding and treatment.Judy
Happy New Year! to you and Prof G and everybody in Team G and all your families and all commentors and readers
Happy New Year!I think we should campaign for this year's X FACTOR charity single to raise money and awareness for MS research.
Yes, a really good idea - I have logged on today to add a comment that is unrelated to any threads, and is a question: do you think MSers inherit a predisposition to an inability to 'deal' effectively with the changes wrought by EBV, therefore leading to MS? Apologies if you can't understand my ramblings - gaps in my knowledge means that I am not able to express my idea entirely coherently (if you see what I mean!). Thanks for all the work you are doing, and the hope that accompanies it - and very best wishes for 2012
I had wondered about all the mouse outfits and imagined they were home made - my dreams have been shattered!
Re: "Do you think MSers inherit a predisposition to an inability to 'deal' effectively with the changes wrought by EBV, therefore leading to MS?"This is one of the theories; but how to investigate this is another question. I think we would need to focus on infectious mono and see if the immune dysregulation that occurs at this stage leaves behind a fingerprint that can be linked to MS later in life.
Re Mouse outfits. Yes home made but not by me.Sorry to burst the bubble
Re: "Do you think MSers inherit a predisposition to an inability to 'deal' effectively with the changes wrought by EBV, therefore leading to MS? - This is one of the theories; but how to investigate this is another question. I think we would need to focus on infectious mono and see if the immune dysregulation that occurs at this stage leaves behind a fingerprint that can be linked to MS later in life."I had a series of neurological symptoms as a teenager that were investigated (at Barts) but no conclusion was drawn. Two years later I got Infectious Mono and a further two decades on was diagnosed with MS. So in me the MS chicken seems to have come before the EBV egg...
Re: "So in me the MS chicken seems to have come before the EBV egg..."Interesting; I may be changing my position on EBV being the only trigger for MS. I beginning to suspect that other viruses can do it as well. Ram in our group has some new data that weakens the EBV-MS causation theory. "A dirty little fact slays the beautiful hyppothesis ... again?" Wait and see.
Re EBV: Oh no, it's very bad the facts don't fit. I thought the EBV link was the simplest route to prevention and perhaps treatment and cure.
So vascular abnormalities (CCSVI) can occur in anyone...healthy or not. How does this mean that MRV does not really add to CCSVI validity? Why do the changes seen need to be specific to MS? The confusing part is why researchers are fixated on this.There are many possible factors that can trigger MS - genetic, environment, bacteria, virus, venous insufficiency and more...or even various exposure levels of the above. Probably why MS symptoms and progression is unique to each and every MSer.
Re: "There are many possible factors that can trigger MS - genetic, environment, bacteria, virus, venous insufficiency and more...or even various exposure levels of the above."There is no evidence that venous insufficiency can trigger MS.
Re: "The confusing part is why researchers are fixated on this."They are not; the CCSVI lobby have demanded the research to be done. I personally disagree with all the money that has been spent on CCSVI research; it could have been better used studying progressive MS.
From your team! www.news-medical.net/news/20120106/Study-shows-how-Epstein-Barr-virus-triggers-MS.aspxCame up in a google alert
Thanks for the info. Dr.M and Prof Gwere not available to comment on my posthttp://multiple-sclerosis-research.blogspot.com/2011/12/researchebv-activating-immune-response.htmlToo busy enjoying foreign climes.
The reports are all calling this 'exciting new research'. Shows that despite all your teaching some of us have a lot of catching up to do. I had read the Dec post and never realised it's that important
Everything in the media is exciting.Maybe Prof G. will blow the trumpetif he has time and repost or perhaps Dr M will do do it as she is a better muscian than me.
Dear Dr.Meier, that was a vivid analogy, though possible explanations span a great deal. I have a question:What was the error margin in your detection of the EBV? Did you use a method that overcomes the reservations posed by the following, as far as confident detection of EBV in brain tissue is concerned?"Epstein–Barr virus in the multiple sclerosis brain: a controversial issue"http://brain.oxfordjournals.org/content/134/9/2772.abstractThank you.
Re: ‘…the CCSVI lobby have demanded the research to be done.’I’d just like to add that this is not the only reason for the CCSVI research that is currently taking place. The scientists who advised the Canadian federal government to go ahead with clinical trials have said it was new evidence - not public pressure - which changed their minds.Also, I imagine that NICE’s encouragement for CCSVI research in their provisional recommendations would not be influenced by a ‘CCSVI lobby’.Best wishes and a Happy New Year to all.
Dear Vasilis Vasilopoulos, please find technical details to the in situ hybridisation we used in the following papers:Khan G, Coates PJ, Gupta RK, Kangro HO, Slavin G. Presence ofEpstein-Barr virus in Hodgkin’s disease is not exclusive toReed-Sternberg cells. Am J Pathol 1992; 140: 757–62.Khan G, Coates PJ, Kangro HO, Slavin G. Epstein Barr virus (EBV)encoded small RNAs: targets for detection by in situ hybridisationwith oligonucleotide probes. J Clin Pathol 1992; 45: 616–20.
Typos changedUteChristianeMeier said...Imagine the brain as a forest. What we did is to look for dangerous forest fires (lesions) more closely. It took a lot of work to find out how long the fire had been around and to determine whether it was still burning or just simmering at the edge.How did we do this? We looked at a cytokine (messenger) IFN-alpha, which is known to drive inflammation. We then chose forest fires, which had started recently and looked for EBV infected cells.Now lets try to do this in mouse doctor style: If one takes the car to get closer to the forest fire along the narrow path (vessel) and approaches the crime scene (active lesion) what did we see? We found many cars parked next to the path. More surprisingly, we found several white vans (EBV infected cells) - more than you would usually find on a motorway. What’s strange about this- VW just issued a safety warning that these white vans had a problem with their fuel pump. It was known that oil could leak out.Now we have to consider the following scenarios:1) All cars drove there to have a close look (not sure they wanted to help or just look)2) One car came had a look and called the other cars to come over and check this out3) The vans leaked oil, which kept the fire going that had started previously4) The vans were parked there, oil leak out and started the fireAs you can see we need to do more work to solve the mystery of the white van …Conflict of interest: We did not receive funding from VW
Dear Dr.Meier,I am afraid i cannot evaluate the methods used, since i am unaware of the technical details of the reservations raised. However, could you tell me what is the problem with the following study?"Absence of Epstein-Barr virus in the brain and CSF of patients with multiple sclerosis"http://www.neurology.org/content/74/14/1127
For those wanting to follow the debate of EBV, is it there or not? should readBrain. 2011 Sep;1342772-86. Epstein-Barr virus in the multiple sclerosis brain: a controversial issue--report on a focused workshop held in the Centre for Brain Research of the Medical University of Vienna, Austria.Lassmann H, Niedobitek G, Aloisi F, Middeldorp JM; NeuroproMiSe EBV Working Group.http://www.ncbi.nlm.nih.gov/pubmed/21846731This I believe is open access
Dear Vasilisperhaps you find this helpful- from the discussion of our recent Neurology paper (Tzartos et al.(2012),Neurology, 3;78(1):15-23):Though the possible roles of viruses in the pathogenesisof MS have been discussed for many years, there are conflicting recent reports on EBV infection in the MS brain. Our findings are in line with previous reports, which describe the presence of EBER- cells in the MS lesions and the observation that active EBV infection is not a characteristic feature of the MS brain. However, our study included a novel preselection strategy and focused only on white matter MS lesions rather than meningeal areas. We believe that there are 2 primary reasons for the discrepancies in previous reports: the sensitivity and specificity of the methodology and the clinical material used. Techniques such as PCR, albeit very sensitive, are dependent on the quality of the extracted DNA, which is generally very poor from formalinfixed tissues and amplification of larger fragments of EBV (300 bp) is not consistently possible. In this context, using EBER-ISH is highly favored. However, during the establishment of the EBER-ISH methodology, we have identified that factors such as tissue digestion, probe design, labeling of EBER probes, amount of probe used, microwave heating prior to overnight hybridization, and the stringency washes posthybridization influenced its sensitivity and specificity. Our probe targets EBER1 and EBER2 in contrast to all the other studies. With our optimized protocol, we have consistently been able to detect as little as a few EBV-infected lymphocytes in entire sections.
Understood. But how did you get away with this (from the MouseDoc's link)?"Recent studies have, however, shown a function for EBERs in the cytoplasm, and secretion of EBERs via cytoplasmic vesicles or as La-EBER protein–RNA complexes may be physiological, thus weakening this strict diagnostic criterion"Sorry, for my poor understanding of your field, but what makes you sure that what you detected were really some EBV products?
The detection of small non-coding RNAs of EBV (EBERs) by in-situ hybridisation is the gold standard for EBV detection in the cancer field. We can learn a lot from this field and have been working closely with cancer/EBV labs, which I think is paramount to get the technology right. In the cancer field, EBER signal in the nucleus of an infected cell is considered specific."However (and that is what you cited and now makes sense) recent studies have, however, shown a function for EBERs in the cytoplasm, and secretion of EBERs via cytoplasmic vesicles or as La-EBER protein–RNA complexes may be physiological, thus weakening this strict diagnostic criterion"
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