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Klimas XMRV Lecture in Florida

Sing

Senior Member
Messages
1,782
Location
New England
Thanks and Immune System Question

I am so appreciative of your work, Kim. I am thrilled--and also amused--by the back and forth on this thread. I feel proud to be part of this forum!

Cecelia

Oh, and I still don't know about all the parts of the immune system. Different types of WBC? Their order in the immune process. If someone knows where I could go, or what to read to find out, please let me know--and it could be another thread--to educate those who need it about the immune system.
 

gracenote

All shall be well . . .
Messages
1,537
Location
Santa Rosa, CA
do "less" than

I'm going to transcribe section 6 - then I'm done. I already see Koan and gracenote and Marylib getting ready to whack me. (I'm having a good day - feeling okay except for the yucky Biaxin nausea and bad taste in my mouth - will not do more than I feel up to. I pinky swear)

Kim, the transcripts are amazing. I'm having transcription envy!

But you're right. Koan and Marylib and I are watching you. No whacks, though. Just a reminder to maybe, possibly, at least consider doing "less" than you feel up to. We want to keep you around!

So thank you for the transcripts. And I will thank you just as much for no transcripts. :):):)
 

blackbird

caged.
Messages
100
Location
UK
I'm over half way through segment 1, but I'm having to do it a minute (of video) at a time.

It's a while since I did any solid work at the computer. Reading and writing general forum stuff is so easy in comparison. Same for twitter, facebook et al.

Should be finished with it tomorrow.
 
K

_Kim_

Guest
Section 6: Virus life cycle, immune modulators

Nancy Klimas Lecture
Section 6: Virus Life Cycle, Immune Modulators

And heres the real compelling question: will antivirals work? This is a virus thats sort of coming in to a white blood cell and its hunting for its receptor. And then its going to attach to this cell. This is a retrovirus attaching to the cell. Now in this virus, we dont know what that receptor is yet in human. We actually sort of have an idea from the mouse work, but we dont know for sure. But theres an attachment step. And then the virus enters the cell. It fuses to the cell. In HIV theres these entry inhibitors and fusion inhibitors that prevent that so there are potential therapies if it were the same receptor. I kind of doubt it. I dont think well be using those particular HIV drugs.

Then it gets into the cell and when it gets into the cell, it dumps its RNA into the cell. It pokes a little hole and the virus comes in. And then that RNA comes out. And were DNA, not RNA. The nucleus of our cells is DNA, so it has to be turned into DNA. And to do that, it uses an enzyme called reverse transcriptase and that turns the (see I knew before that thing before it told me. I am smart). Anyway, it turns RNA into DNA and that is a wonderful target for this virusthe reverse transcriptase inhibitorsbecause then the DNA can integrate into the cell. Now we have integrase integration inhibitors alsoin HIVintegrase inhibitors. But they are fairly selective for HIV. I dont know that they would be effective in another retrovirus.

And then, when the cell is activated and its DNA starts making stuff like this, it has to beit makes these great big long proteins and those proteins have to be cleaved into little pieces (see Im sinking here). And thats the protease inhibitor line in HIV, the proteases that cleave are inhibited and that prevents that piece from being torn up. And then all these bits and pieces assemble themselves over on the cell wall and they bud off BOP and theres a virus. And thats how viruses are made.

So, we have entry inhibitors, we have reverse transcriptase inhibitors, we have integrase inhibitors, we have protease inhibitors. And then all those put together is the whole repertoire of drugs that have been developed over the last 20 years or so for HIV.

But, be it known that there are literally thousands of compounds in the pharmaceutical companies shelves that they developed for HIV that werent as good as things for HIV that approved that might be the very perfect thing for this virus. So, were not starting from scratch here with this virus at all! The other thing about this virus, and this is just from what Dr. Coffin said at the Chronic Fatigue meeting on Friday (Im not a retrovirologist as brilliant as these guys) but I can parrot them pretty well. Dr. Coffin said because this virus doesnt seem to mutate very much, its a great target for vaccine trials.

And when you ask - what about antibodies? if we vaccinated people to this virus that already had the virus, we could goose up their immune response to this particular virus. Thats what theyre doing in HIV trials, they vaccinate infected people. So you might suppress the virus with an antiviral and then goose up the immune system with vaccines, so it could really work hard on this virus and then reduce it. So you could start postulating. Isnt it fun to be able to postulate therapiesI mean, its great. Im loving this. Im lying awake at night thinking of all these things. Its like oooh,we could do this oooh, we could do that. Good stuff. I know, I know, Im an immunologist, what can I say?

Of course one of the things I think about is immunomodulators drugs that would either quiet immune activation or enhance cell function are very appropriate. Okay, so whats already out there? Well, Ampligen, Ampligens an interesting drug. And they actually showed they had 8 patients that had Ampligen data that they showed at the CFSAC meeting that Dan showed. And it had a mixed result. In some cases, Ampligen was very effective in suppressing this virus, and in some cases it was not in those 8 patients. Thats not very many. But Ampligen sounds kind of promising because its an antiviral thats an immunomodulator that enhances natural killer cells and cytotoxic T-cell function. Its even more intriguing than before in my mind, I think Ampligens got some real potential.
Immunovir (Isoprinosine) some of my patients are on this medication. Its only had phase 2 trials, it hasnt had phase 3 trials. But its more or less a nutraceutical, its an amino acid. But it is also an NK cell enhancer and a cytotoxic T-cell enhancer that may have some antiviral effect.

This cell therapy I referred to this ex-vivo cell therapy some of you were in this study It was in 1993 orit was 1993. Well we took a lymph node from a patient and we grew the cells in a laboratory and we made literally a transfusion of white blood cells. Max did that. He was busy, busy transfusing my patients with white blood cells their own white blood cells. But in the test, in the laboratory, we had grown them, fixed sort of what was broken about them, and then we got some very very nice clinical responses in that Phase 1, that study that never got to go to a Phase 2 study for lack of funding. And then finally, this makes cytokines that are either directly antiviral or immune enhancing more interesting.

The nutraceuticals, they have less work done. Omega-3s are anti-inflammatory, the mushroom extracts that the Japanese use to enhance natural killer cell function, but these arent studies that had placebo control data and looked promising. CoQ10 at roughly 100 twice a day that was really anti-fatiguing and enhanced cell functions. TNF inhibitors, we have a couple few patients on TNF inhibitors and Im seeing some nice responses if theyre cytokines are way wacked out and theyre super revved up.

Thats a natural killer cell, the little guy killing that target cell. Thats an Epstein Barr virus infected target. And theres that little white blood cell doing its job. Thats what were trying to do. So the white blood cells infected with virus and you want these cells to go in there and kill that cell. So, the other question with this is: okay youve got one virus, but what if youve got this virus plus a couple of other viruses? Whats the role of all these viruses all together? What about HHV-6, EBV, enteroviruses, and this virus. If we say that all these viruses are doing their work together, it might be necessary to treat more than one virus. It might be necessary to design a study that has the retrovirus piece and a Herpes virus piece because sometimes viruses lend each other machinery to make their infections more potent and damaging.
 

fds66

Senior Member
Messages
231
OK, given section 9 a go. Got slower and slower as I got more tired. I had trouble hearing some of it so it's my best guess. Feel free to correct me if you disagree. Hope it's helpful.



Segment 9:
Testing for XMRV
Q&A Antibodies

So, there are some issues here. That blood test only identified 67% so if I ordered a blood test on you right now and it was negative, what would happen to your soul? You know, and yet it might not really be negative, in fact its got a one chance in three of being wrong. The blood test that we dont have yet that we will have very shortly, those tests are going to be improved on.

When the first HIV blood test came out it wasnt any good either. You know, it went through stages and stages and stages before we got a really good one. Dont rush to get the test. Why, because youre not going to act on that test quite yet. The knowledge of being positive is not going to give you an anti viral prescription from anyone right now because we dont know which one to give and if its safe or if its toxic. The HIV drugs are not been gentle, OK, and you guys are really tender. So, if you knew your status today it really wouldnt change anything.

If they are right 99% of you are positive. And if they are wrong then 95% of you are positive.

So when? Soon, really soon. But you wouldnt be able to bear the false negative right now so be careful OK. There are kits already out there, they want cash and theres no reimbursement from your insurance provider yet. I was talking to this great scientist at the VA and he said, you know, my lab develops tests. Thats what we do. Whats wrong with the tests you got? Oh, I could fix that and he got all jazzed and Im thinking, damn, get another guy in the field and you know, and hes fixed your test, thats great. So these people, theyre already out there and they know how to do it and tests will improve.

If you dont have this virus what if you didnt. Well, you know, thats good news too because that puts you in a different group and we know not to do all that toxic stuff to you. So thats an important thing to do too. So dont be discouraged even if youre negative.

We talked about these other people that might also actually be infected. We dont know. These are just people we are going to be looking at. The Gulf War Illness group Im desperate to see right away because it could change the whole direction of that work and they have a fair amount of money to do that work.

So the conclusion, it really is a big thing. Its a big thing. You should be very excited. Its a very hopeful thing. Yeah, the research is already underway, more to come. The more we can get funded the more focused and intense we will be in getting this work done as quickly as possible. That work we were already doing plays right into this. All the genomics work and all the immunology work. That is all critical to the better understanding of this illness and how this virus plays into it.

Those of you that are in my good day bad day study, its nice because weve got your stuff already in the freezer and well be looking at this virus as quickly as we can get access to the assay. That study, thats a really important study. It looks at people in relatively better times and worse times and well know if viral load is causing that. If theres anything about this virus. Were already looking at all the immune parameters and endocrine parameters and everything under sun. But were trying to understand what mediates relapse.

There are people in this room that have been in my genomics study where we put people on a bike and made them sick on purpose and then watched why they got sick. That was a heroic thing to do, we appreciate it, weve learned a tremendous amount from that study. We want to continue doing that study. Were fundraising to do the last of the chronic fatigue group. Were going to run 15 more chronic fatigue patients and then we ran out of money. Im looking to finish that study. You can be sure well look at viral expression now that we know that we should be looking for viral expression.

So, all these thing are important. They all tie together,

You can make a difference. You can make a difference by volunteering for studies, you can make a difference by spreading this word. If any of you guys know someone thats too sick to get out of the house and so discouraged that they look like they are going to give up , make them feel optimistic. Thats your job. OK, this is not a good time to give up. And then finally be charitable and find charitable people to help you with that. Give, we need funds, we really do.

Im going to stop my official talk and take questions and answers.

Beth.

(Question from the audience) Over time as you discover and find the blood tests to test your patients and then you find that patients whove done better over time actually do have the virus. What does it mean for those types of patients?

(Answer) Patients who are recovering despite having the infection. Well, I can tell you what I would anticipate that their immune systems are recovering. I would anticipate that people who could control their viral infection will do better. So, what youll hear in peoples histories very frequently, that have had this illness for a long time and had long, long, long periods of recovery, is that they tend to only get ill again if they are recovering, during times when they have a massive infection of some sort or some big immune event.

Now Ive had it flip the other way. Ive had more than one patient who were just very ill and just cruising on very ill and they got something terrible like a pneumonia that put them in the hospital with a high fever and huge immune response and when they came out of it they were much better from their chronic fatigue. Its like getting their immune system so maybe it was the fever, maybe it was the immune system response, maybe with all the cytokines but sometimes youll see the flip of that.

But I think that people that are remit, relapse, remit, relapse - most of you guys know your pattern. Most of you guys relapse because you do too much and you crash. Youre all crashers. Because you dont know when you are feeling well to stop acting like you are 100% because when you are feeling well you are not 100%. But, thats a little different. Thats your body being out of balance and you dont have the reserves of a normal person, you literally use them up and you crash.

The best question is the flip. If people are getting better over time, why are they better. If you look at their immune systems, they are better because their immune system is better. And that has clinically been my experience. The natural killer cells are behaving better, their immune activation is less and activation drives the virus.
 

MEKoan

Senior Member
Messages
2,630
Ok, this is the first time I have looked at this thread and, Kim, I AM going to whack you!

Are you not the secret weapon?! Did I not warn you not to wear yourself out with eagerness re just that?! Did I have any idea you were going to do this?!

WHUMPH!

(I'm so sorry I had to do that but it was a nurf bat.)

And, I can't even read that much text so I do not have a complete appreciation of just what you did... but I am pretty darn sure you sh...

Ok, not my place to tell you what you should or should not be doing. You are a totally out of control helper which is a really lovely thing to be. However, I do feel the need to protect the secret weapon!!!

WHUMPH!

Please be a good girl now.

Please!
 
K

_Kim_

Guest
Ok, this is the first time I have looked at this thread and, Kim, I AM going to whack you!

Are you not the secret weapon?! Did I not warn you not to wear yourself out with eagerness re just that?! Did I have any idea you were going to do this?!

WHUMPH!

(I'm so sorry I had to do that but it was a nurf bat.)

And, I can't even read that much text so I do not have a complete appreciation of just what you did... but I am pretty darn sure you sh...

Ok, not my place to tell you what you should or should not be doing. You are a totally out of control helper which is a really lovely thing to be. However, I do feel the need to protect the secret weapon!!!

WHUMPH!

Please be a good girl now.

Please!

I would ask to be called SW, but some nefarious being already has claim to those initials.

I'm done with the Klimas transcriptions. Since I have a big crush on her, it actually was a delight to listen to these over again.

I promise that in other parts of my life, I have backed off. I really do rest, but get restless if I don't keep my mind amused. Better to be happily busy than to brood about how my life has changed.

I really appreciate all the caring and gentle (virtual switches and whacks and nerf WHUMPs) reminders to pace myself.
 

MEKoan

Senior Member
Messages
2,630
OMG! I have a big crush on her, too!

hahaha!

But now, rest!

My Whumpher is always at the ready.
 

Cort

Phoenix Rising Founder
You guys are great. This is a community in action!

Some highlights for me: the WPI researchers actually found XMRV in virtually every ME/CFS patient in their study; about 2/3rds of them had an active infection but 30/33 patients without an active infection were found to have a latent infection; that is, the virus was found in their cells. I had no idea that was true.

When she says they found antibodies though my impression the antibodies were to a mouse retrovirus - not XMRV in particular. Then again the possibility of having both retroviruses seems pretty low.

Dr. Klimas is also very clear that this virus is causing the natural killer (NK) cell and T-cell dysfunction found in this disease. The NK cell dysfunction is pretty significant since NK cell problems have been consistently found in ME/CFS and I'm not aware they are connected with other diseases. So XMRV provides a very nice tie-in with a particular abnormality in ME/CFS.
 

MEKoan

Senior Member
Messages
2,630
Yes, but do you have a crush on her?
:D

Sorry, that's totally OT and inappropriate and foolish.

Nancy Klimas... sigh
:p
 

CBS

Senior Member
Messages
1,522
Transcripts

Does anyone have a list of all the sections transcribed to this point?

I'll pitch in an do one if you promise not to tell my wife (she'd want to throttle me for making the effort).

Shane
 

Marylib

Senior Member
Messages
1,153
Bad mommy is back

Well, I guess you kids can do a little transcribing, as long as you tell auntie Gracenote and auntie Koan.

I will be away for awhile, attending a court mandated social services workshop called "Drop that Switch."
 

CBS

Senior Member
Messages
1,522
Spousal Support

I'm lucky enough (I think) to have a wife that won't hesitate to call me an idiot for doing something I know will make me crash (or for now, crash further).

Honestly, I have put her through so much. As my autonomic system has taken a beating over the last 18 months, she's been with me to the ER 14 times since in 12 months (I told her to just stay in bed at 2 am for my 15th trip which turned out to be for septic shock and a three day stay on the heart/lung ward (talk about a place to get great care!) - man, did she feel bad - but she did visit!).

That said - and that's probably all that I should say about that - is anyone working on section 7? If not, I'd be glad to take it on.

Shane
 

fds66

Senior Member
Messages
231
Transcripts so far:

1 Blackbird is doing
2
3 Kim
4 Kim
5 not up yet
6 Kim
7 ComeBackShane is doing
8
9 fds66
10
11
12 not up yet

Think that's the current list.
 
K

_Kim_

Guest
Yes, but do you have a crush on her?
:D

Sorry, that's totally OT and inappropriate and foolish.

Nancy Klimas... sigh
:p

Bwwahhhaaahhhaa!! Tears now flowing...so funny. Thank you very much Koan. I just showered and put on mascara to go to work. That was a big waste of time.
 

Lily

*Believe*
Messages
677
Shane...

It's a good thing that I don't know how to reach your wife. That would present quite a dilema. I'm all for a woman who tries to protect her man from himself:p;)
 

Eric Johnson from I&I

Senior Member
Messages
337
about 2/3rds of them had an active infection but 30/33 patients without an active infection were found to have a latent infection; that is, the virus was found in their cells

Being PCR- culture+ doesnt necessarily indicate latency.