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MAYO CLINIC ON XMRV: March 04th Talk in Sacramento

parvofighter

Senior Member
Messages
440
Location
Canada
CALLING ALL SACRAMENTO MEMBERS! CAN YOU ATTEND TOMORROW?
Another big gun interested in XMRV: The Mayo Clinic. :D

From: http://www.ucdmc.ucdavis.edu/cancer/calendar_events/professionals.html and http://calendar.ucdavis.edu/event_detail.lasso?eventID=10991

Thursday, March 4, 2010, 9:00 a.m. 10:00 a.m.
Speaker: Dr. Yasuhiro Ikeda
Assistant Professor, Dept. of Biochemistry & Molecular Biology, Mayo Clinic
Title: Characterization of a novel human retrovirus XMRV: Prevalence, antiviral drug sensitivity, and small animal model development
Keywords: XMRV, Xenotropic murine leukemia virus, RNASEL, AZT, Env, pseudotyping, neutralizing antibodies
Where: UCDMC Cancer Center auditorium, 4501 "X" Street, Sacramento
Host: Dr. Yoshi Izumiya


Contact if questions about this event:

Contact name: Fran Richardson
Contact e-mail:
frances.richardson@ucdmc.ucdavis.edu
Contact phone:
916-734-3111

Ummm... after the Conference on Retroviruses and Opportunistic Infections, I think we can start putting the tiresome "Does XMRV exist?" mantra to rest. Can't wait to hear the latest on RNase-L and neutralizing antibodies. This is just Step 1 of many. Hang in there - as Dr Mikovits and Klimas emphasized, credible work on XMRV and ME/CFS is yet to come.
 

Doogle

Senior Member
Messages
200
I will call today. I might be able to go. That's about an 1-3/4 hours from me but worst of all very early. LOL Anybody from the East Bay SF area up for carpooling? I have a van that someone can lay down in.
 

hvs

Senior Member
Messages
292
And as many of us know, the Mayo Clinic is renowned for being completely uninterested, if not actively hostile, to CFS. So, they have no horse in the xmrv+CFS race. If they are working on xmrv, it is not because they have any interest in CFS.
But...you know...it's really cute how you can't find XMRV in the UK, Imperial College. Keep trying at your "research."
 

FernRhizome

Senior Member
Messages
412
Actually I got a CFS diagnosis at Mayo (MN) in 1996! I was the first anyone had ever heard of getting a CFS diagnosis there! It was from the neurologist Dr. Low. He's reknowned in the dysautonomia field.....but I am not sure he still gives that diagnosis. I think he has stopped doing so....but not sure. But otherwise they don't have a rep of being very interested. When XMRV Science paper came out I e-mailed Dr. Low & asked if he'd be involved in testing & at least at that point he wasn't. But now, everyone wants a piece of the pie and a vial of our blood! ~Fern
 

parvofighter

Senior Member
Messages
440
Location
Canada
Yes, I do!

parvo..so you really think XMRV is it?

Ladybugmandy, I really DO think XMRV is IT. Yes, this still has to be credibly validated.
But I have yet to see an iota of intelligent, robustly conducted research with Canadian-criteria patients and appropriately sensitive/specific tissue/blood investigation that proves otherwise.
If anything, the case just keeps getting stronger..


ME/CFS is entirely consistent with a retrovirus
And I completely agree that ME/CFS fits the picture of a retrovirus. The classic component being infection by opportunistic infections. And of course that link with lymphomas. It is no surprise that ME/CFS has so many different faces, when there are so many different opportunistic infections. That's what retroviruses DO - they potentiate opportunistic infections, and that's what causes key morbidity.

No CREDIBLE research debunks the XMRV/ME/CFS link
I'm simply following the science like a dutiful nerd (WOOF!), and so far there is nothing credible that is swaying me off the XMRV path. Does all this make me 100% right? No. But I think time, and the continuing relentless progression of good science WILL tip the balance. In fact, the weak "replication attempts", with their grandiose conclusions and shaky foundation serve as excellent reminder of how medicine has allowed itself to be completely sidetracked into the psychogenic model of ME/CFS. It will make a brilliant article for some investigative journalist, and the great thing is that these bellicose pronouncements and policy decisions based on spurious "research" are preserved for posterity on the internet.

The Cohort issue remains MASSIVE!
Even in the absence of George and Gerwyn's outstanding critiques of the lab science (thanks!!), the cohort issue alone negates these studies: the fact remains that the "replication attempts" so far have used patients that attended CBT/GET clinics. Ask yourself, what person in their right mind would allow themselves to be abused in this way if they have relentless and marked post-exertional malaise - the hallmark of Canadian-Criteria ME/CFS? Sure, I tried to exercise myself out of ME/CFS in the early years. But now that I have severe PEM- there is NO WAY in heaven that I would subject myself to that abuse. It is the essence of common sense to avoid illness-producing behaviors. Any rat behaviorist knows that rats stop pushing a button if they keep getting electric shocks! The physical price in terms of predictable PEM, cardiac, and neuro consequences is just far too high. And it is an entirely sane behavior for patients with serious ME/CFS and PEM to self-select out of these CBT/GET abuse-clinics. This from a physio/occupational therapist! This is what self-selection is all about, and the Dutch and UK studies have failed miserably in patient cohort selection - even if they are masters at manipulating the gullible media.

They. Are. Not. Canadian. Criteria!

Yes, theoretically the looser criteria could allow a Canadian criteria patient or two to slip in. But in practice, the Canadian criteria patients would very logically self-select out of this CBT/GET madness, simply because they have to have PEM! And that makes a world of difference - something which even Suzanne Vernon has missed in her frustration with defining the Science cohort.

The scientific corroboration of XMRV as a potential cause of ME/CFS just keeps pouring in.
Just a few more goodies - from the general XMRV research field - that add more fuel to this argument:

From the CROI Conference 2010:
Slide 5: Acute XMRV infection in the chronically infected animals: http://app2.capitalreach.com/esp1204/servlet/tc?c=10164&cn=retro&e=12373&m=1&s=20431&&espmt=2&mp3file=12373&m4bfile=12373&seektc=7169.6&br=80&audio=false

  • XMRV caused a transient viremia in a male macaque Viremia was below the limit of detection in the other 2 monkeys
  • However XMRV proviral DNA was detected in all 3 original monkey PBMCs demonstrating infection!.
  • Shows graph of XMRV Env RNA copies/ml vs Time of infection. Copies/ml go down to zero after 15 days.
Conclusions from Sharma presentation. Slides 27,28: http://app2.capitalreach.com/esp120...m4bfile=12373&seektc=7169.6&br=80&audio=false


  • XMRV induces a persistent chronic infection in rhesus macaques
  • Wide dissemination of replication virus even with undetectable plasma viral load
  • Isolated lymphoid cells and primarily CD4 + T cells found in lymphoid organs-spleen, lymph nodes and GI tract
  • Frequency of infected cells appeared to decrease in spleen while increasing in the GI tract from acute to chronic infection (think: Kenny de Meirleir's work)
  • XMRV infection not restricted to bone marrow derived cells; showed distinct target specificities in various organs
    • Lung-positive cells exhibited a macrophage morphology
    • Foci of infected cells epithelial in prostate, seminal vesicles and epididymis; and interstitial in testes
    • Prostate and testes appeared to harbor replicating virus in both acute and chronic infection
    • In the female monkey, XMRV positive epithelial and fibroblast like cells detected in vagina and cervix
  • NB: Length of infection studied: 6 days 289 days
Conclusions from John Hackett, Manager, Emerging Pathogens & Virus Discovery Programs, Abbott Diagnostics. Slide 19: http://app2.capitalreach.com/esp120...m4bfile=12373&seektc=7169.6&br=80&audio=false

  • 1st demonstration of antibodies to multiple XMRV proteins in humans (3/2851 blood donors)
  • Detection of antibodies elicited to XMRV in humans has proven challenging
    • Reflect virus life cycle?
    • Due to combination of viral properties and length of time between infection and disease?
    • Does infection with XMRV influence the immune response? (We already have a preliminary answer to that: The recent French findings (Schlecht-Louf, et al) would suggest XMRV does in fact have an immunosuppressive function) http://www.ncbi.nlm.nih.gov/pubmed/...med_ResultsPanel.Pubmed_RVDocSum&ordinalpos=5 )
Keep in mind what Drs Klimas and Mikovits encouraged us to do... tough it out over the next few months. There will be slipshod rush-jobs, and there will be meticulous research. Unfortunately much of the media is incapable of differentiating the two. But I have yet to have my confidence scientifically shaken, in XMRV as potential root cause of ME/CFS.

Here's the scoreboard so far:

  1. Is XMRV a real retrovirus? YES
  2. Is XMRV found in humans? YES
  3. Is XMRV found outside the US and Japan (i.e. in the UK)? YES
  4. Is XMRV behavior consistent with what we know about ME/CFS? YES
  5. Might XMRV cause some prostate cancers? INCREASING EVIDENCE for YES
  6. Might XMRV cause ME/CFS? DEFINITELY PLAUSIBLE, BUT WE NEED TO WAIT FOR MORE VALIDATION/REPLICATION OF THE SCIENCE WORK.
Look at our progress: 5 months after the publication of the Science paper, it is reasonable to say that science has answered the first 4 questions (just look at the CROI retroviral conference thread). And keep in mind that early shoddy replication attempts challenged these 4 tenets too. Doesn't say much for their "science", does it, eh?:Retro smile:

Just stay focused, and digest all the forthcoming science - including that from WPI - with a critical eye. The good science will stand the test of scrutiny of cohort AND lab methods.

Parvo:Retro smile:
 

jewel

Senior Member
Messages
195
Thanks for this summary. It has me convinced, at least for now, that this is the most hopeful lead. take care, J.
 

Doogle

Senior Member
Messages
200
I made it. My recorder batteries died at the end of the lecture so I have to get some to ck my write up. And rest.
 

parvofighter

Senior Member
Messages
440
Location
Canada
Thank you Doogle!

I made it.
Doogle, you are brilliant. Thank you so much for taking the time (1 3/4 hrs drive!?) to attend, the effort to record... Just rest up, and we'll hear from you when you're up to it.

Again, your efforts MOST appreciated!:Retro smile:
 

ukxmrv

Senior Member
Messages
4,413
Location
London
Thank you Doogle,

Please rest up and not type anything until you are feeling better. That was a wonderful thing to do!
 

Countrygirl

Senior Member
Messages
5,427
Location
UK
Doogle;53398]I made it. My recorder batteries died at the end of the lecture so I have to get some to ck my write up. And rest.


:Sign Good Job: Doogle. Many thanks for your your efforts and we all look forward to hearing from you.


Rest up well:In bed: and I hope that the journey won't make you feel too :headache:


:thumbsup:

BW,

C.G.
 
D

dirtyharry

Guest
You should read the Mayo Clinic experience with POTS . I asked Low where I could buy a .357 magnum and he just laughed. (An insidie joke).
 

Doogle

Senior Member
Messages
200
Dr. Yasuhiro Ikeda Assistant Professor, Dept. of Biochemistry & Molecular Biology, Mayo Clinic
Characterization of a novel human retrovirus Characterization of a novel human retrovirus XMRV: Prevalence, antiviral drug sensitivity, and small animal model development
UCDMC Cancer Center auditorium, 4501 "X" Street, Sacramento Thursday, March 4, 2010, 9:00 a.m. – 10:00 a.m.

Disclaimer, the information Dr. Ikeda presented is not formally published. After his talk, I asked him to e-mail me what he would of the research information available from his lecture or otherwise. He seemed agreeable. I sat in the first row but my audio recording turned out very poor, and he has an accent. I have to get a different cable to download the audio file to my computer. I have a science background, but it's not in virology. This is only my interpretation of what he presented from notes, recollection and my poor recording.

Dr. Ikeda was impressive, friendly, and seemed meticulous. He presented research involving XMRV detection by PCR and antibody, cancer, antivirals, and finding a mouse model to grow the XMRV virus. The lecture was an hour long so he moved fast.

He started with an overview of prostate and ME/CFS XMRV research, positive and negative associations. He presented the XMRV association with ME/CFS studies matter of factly as 1 for and 3 against with DeRisi skeptical.

There was a slide about an indirect association of XMRV with H pylori, and Hepatitis C. He didn't go into detail.

The cell receptor for XMRV is XPR1.

After testing many types of mice they infected Mus pahari (wild-derived) mice with XMRV and thought them suitable (but they like to play dead and bite). They discovered one California strain of mouse that harbored an endogenous retrovirus closely related to XMRV sequences. The XMRV they sequenced had very few mutations. They found the virus in their infected mice most often in the spleen, blood and brain, not prostate. They were curious about the leukemia connection because they found very few infected leukocytes.

A number of antiviral drugs were tested at different concentrations with XMRV infected cells. They thought AZT seemed to be the only one that worked well without excessive toxicity to the cells (with about 100X reduction in viral activity). He stated that after stopping AZT treatment of the cells the virus started to replicate at rates comparable to before treatment. They had a slide that showed a sequence where HIV and XMRV were similar, and that they thought the drug was interrupting the replication at those sequences.

They did a human prostate cancer study. 159 samples of prostate cancer tissue (grade 5-7), and 201 controls were tested for XMRV. 4.5% were XMRV positive in PC tissue. 2.5% were XMRV positive in prostate tissue controls .

There was some confusing data on XMRV detection. He reported PCR seemed to be much less sensitive and often didn't detect XMRV (and they used multiple PCR testing with some samples to find XMRV) than with other methods. They found real time PCR was more sensitive than nested PCR. They didn't find XMRV in some of their first pass testing using western blot. They said that the positive tests had weak signals.

They are looking at XMRV surface glycoproteins for targeting. I'm not sure if he was talking vaccines or other treatments.

I found this very interesting. They found some standard cell lines of LnCap and 22Rv1 (biosafety level 2 lines) were already infected with XMRV before they came to their lab. Not all, just from some of their sources so they think that labs should be screening received cell lines by real time PCR.

At the end there was about a 10 minute presentation about stem cell research in his lab. He talked about adult stem cells and differentiating them into specific cell functions; heart, nerve, and so forth. He didn't say if this was related to his XMRV research.

In our discussion after his presentation he stated he is only consulting with Silverman. They will probably not do ME/CFS research because Mayo isn't big into ME/CFS. The docs there think the patient population is too heterogenous. I said the Science study used the most restrictive patient criteria and others the least restrictive. My impression was that he didn't know the details of the different definitions.
 

gracenote

All shall be well . . .
Messages
1,537
Location
Santa Rosa, CA
Wow, Doogle. Thank you so much. You managed to get a lot of information. Thanks for sharing.

And you're still waiting for additional information from Dr. Ikeda?

They will probably not so ME/CFS research because Mayo isn't big into ME/CFS.

Isn't Mayo doing a study on Amygdala Retraining for CFS? I thought there was a post on that a while ago.
 

Doogle

Senior Member
Messages
200
His slides were crammed with graphs like the drug concentrations and the specific sequence AZT blocked. I hope he sends them. If I don't get them in a week or so I will drop him a reminder.

Wow, Doogle. Thank you so much. You managed to get a lot of information. Thanks for sharing.

And you're still waiting for additional information from Dr. Ikeda?



Isn't Mayo doing a study on Amygdala Retraining for CFS? I thought there was a post on that a while ago.
 

FernRhizome

Senior Member
Messages
412
Thank you! Just exciting that one more serious researcher is interested enough to be doing research! Also interesting he mentioned hepatitis and H. pylori......~Fern