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Borrelia burgdorferi reduces VDR expression
 Moderated by: Prof Trevor Marshall Page:  First Page Previous Page  1  2  3  4  5  Next Page Last Page  
 

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Prof Trevor Marshall
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 Posted: Mon Jul 11th, 2011 03:31

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Russ,
The key thing to understand is that a pathogen living in a biofilm outside a cell (for example, a biofilm on a hip-joint) can evoke an immune reaction, while a pathogen living inside a nucleated cell can change the way the body works. In particular, an intra-phagocytic pathogen can change the way that the immune system works.

So a pathogen in tissue or the bloodstream has to survive by evading the immune system, while a pathogen inside a cell can modify the immune system itself to survive - eg by dysregulating the VDR.

It is the second function - changing the way the body works - which causes chronic illness.

I did write a paper in 2003 explaining the importance of pathogens getting inside a cell, but it is such an old paper now, with so many poorly developed ideas (heck, that was nearly a decade ago) that I don't cite it much :)
http://www.ncbi.nlm.nih.gov/pubmed/15246025

Proteomic interference, genomic interference, the actual chronic disease mechanisms, can only occur when a pathogen survives phagocytosis and persists within the nucleated cell.

I hope that helps,
Trevor
 

seanlane
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 Posted: Mon Jul 11th, 2011 04:36

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That is a nice, concise description of chronic disease and the fundamental differences between the effects of microbiota persisting inside a nucleated cell and those gathered in colonies outside.

Many times I read or hear about biofilms in general being the big issue in chronic disease,never much about intraphagocytic microbiota.

That being said....can we assume biofilms that exist in outside these nucleated cells are probably persisting because of the changes that the intracellular bacteria have made to the immune system?

I wish there was a better way to limit the exaggerated immune responses to extracellular bacteria and proteins while the innate immune system clears.



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minski2
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 Posted: Mon Jul 11th, 2011 04:47

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Hi Dr. Marshall......that was a great explanation!  Helped me a lot!  Graduated college without ever having to take a biology course so this is a hard learning experience for me,  but between you and Google I'm doing O.K.   Have decided to be an immunologist in my next life.  Never really knew in this life!!!!!!!!!!!!

Dian



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ChrisMavo
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 Posted: Wed Jul 13th, 2011 15:25

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Reading this thread about Borrelia burgdoferi is interesting.  Since I watched Lida Mattman's presentation from the 2005 Chicago Conference about ALS being basically a late-stage Lyme disease I have wondered if I have borrelia causing my ALS.  While I had tests two years ago from the recognized leader in Lyme testing, and those tests came back negative for borrelia, I wonder if that pathogen is what ultimately tips the scales to ALS as Dr Mattman surmised. 

If, as described on this thread, borrelia downregulates the VDR and does not BLOCK it .. and that olmesartan may not be effective for pathogens that work by down-regulating the VDR ... then I wonder how effective my current regimen of just Benicar is going to be?  I have been on the MP now for almost two years and have not seen any neurological improvement yet.  Also Scott K was on the MP for over two years with ALS and did not get much improvement.  Given these facts, I wonder if a Benicar only approach is the correct path for ALS that possible could have borrelia as a main component of the microbiota that ultimately causes ALS! 



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Prof Trevor Marshall
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 Posted: Wed Jul 13th, 2011 15:31

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Lida Mattman was using (her own) antibodies to determine if a species was Borrelia. The poor selectivity of antibodies probably explains why everything she saw identified itself to be Borrelia :) :)

As for the scare mongering about people being too-ill to recover on the MP there is NOTHING, nothing at all, which would indicate that is true. Stop worrying, stress will definitely make the disease worse...

It is important to recognize the way that the disease, and IP, can change the way you think..
 

ChrisMavo
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 Posted: Wed Jul 13th, 2011 15:44

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Thanks Dr Marshall.. it is always reassuring to hear your positive attitude!  I am TRYING very hard to stay positive and not get under too much stress ... trust me on that.  But I must admit it is difficult to remain stress free given how much motor function I am losing and how close to be totally bed ridden I am coming!   I want to believe all this is just IP and part of the healing process.  But it is hard not to wonder and worry about the terrible consequences if it is NOT IP but just the normal progression of ALS.  Hopefully the pure olmesartan study can get underway SOON as I think that may help me considerably. 

As always I do really appreciate your reassuring advice!! 



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Prof Trevor Marshall
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 Posted: Wed Jul 13th, 2011 15:51

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It is almost certainly not the normal progression of ALS. Mean survival is 18 months after diagnosis :X Your cardiac and pulmonary status has not deteriorated at that rate...

I know it is tough losing so much neurological function, and it is also tough waiting for the body to regenerate. I thought your chess had been improving recently?
 

ChrisMavo
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 Posted: Wed Jul 13th, 2011 16:04

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Well now that you mentioned my chess ... that remains the lone bright spot in my life!  I just won my 15th game in a row last night!  And this is from a group of expert chess players that in the past I would have been lucky to break even with!  That is another thing I wonder about.. how is it that I have avoided the "brain fog" that so many others report as part of the IP. 

But it is known that ALS does not really affect the logical thinking processes much if at all.  It for whatever reason goes after primarily the motor CNS of the brain and spinal column.  And while it is true the mean time for ALS to mortality is startlingly short.. for some it can take years and years.   The neurologist that was my doctor's predecessor as head of the UCSF ALS center, Dr Olney, has had ALS now for 8 years and is just now reaching the fatal end stages.

You are correct that my pulmonary and cardiac function remain strong and healthy at this point.. exactly two years to the day from my ALS diagnosis!  So that is very encouraging indeed and something my neurologist stresses when I meet with her. 

I guess the only way of knowing the outcome of this long difficult journey is ... one foot in front of the other ... step by step ... til the end!  But be assured I AM willing to take this ALL THE WAY though to the end.  You will NOT see me giving up on the MP as others have done!  I intend to either prove it works for ALS.. or vice versa.  At least I have that to reassure me that my efforts will not be in vain and will help others in the future no matter my ultimate outcome.




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seanlane
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 Posted: Thu Jul 14th, 2011 03:35

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What exactly is the difference between the VDR being blocked and being downregulated?



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 Posted: Thu Jul 14th, 2011 04:09

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Hi Chris,

I guess you are in good smart company with Stephen Hawking! I know it is hard to wait around for progress but I am seeing some good results too after almost 2 years. My lungs feel so clear this summer in the middle of allergy season, so I am hanging onto that. It sounds like you have some excellent signs from what the experts have said.

Deb



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Frans
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 Posted: Thu Jul 14th, 2011 05:08

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seanlane wrote: What exactly is the difference between the VDR being blocked and being downregulated?
Blocked: a ligand, like 25D,  binds to VDR itself and shuts it off (number of VDR's stays the same)

Downregulated: upstream of VDR, Estrogen Receptor transcribes VDR, if a microbe blocks the Estrogen receptor, VDR will not be transcribed, ergo: downregulated  (number of VDR's goes down)

Hope this helps,

Best Frans



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 Posted: Thu Jul 14th, 2011 12:02

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Frans wrote:

Downregulated: upstream of VDR, Estrogen Receptor transcribes VDR, if a microbe blocks the Estrogen receptor, VDR will not be transcribed, ergo:



And if the Estrogen Receptor is blocked, Osteoporosis may be the consequence, isnĀ“t it ?

Thus the correlation between chronic infections, blocked VDR and Osteoporosis could be explained via ER ?

Alex

Last edited on Thu Jul 14th, 2011 12:03 by Alejandro



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 Posted: Thu Jul 14th, 2011 12:55

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Thanks for the encouragement Deb ... I appreciate it!

And Frans, thanks for the nice example of how upstream from the VDR the estrogen receptor can affect the expression of the VDR.  This makes me wonder about some studies I read recently that show some benefit for traumatic brain injuries by giving massive doses of progesterone.  Could it be that this helps the immune system clean up not only infected cells.. but also damaged cells? 

I guess I can only hope that IF borrelia does play a key role in ALS, and Dr Marshall has said it probably does NOT ... and if borrelia does downregulate the VDR somehow, that olmesartan will impact the proper receptors enough to eventually turn the tide against this terrible disease.

But it is interesting to speculate and wonder if this difference of blockade of a receptor versus downregulation of a receptor might account for the different rates of recovery for different chronic illnesses that we see on the MP.  Maybe there are pathogens that can still evade olmesartan's reactivation of the VDR ... by downregulating the VDR so that there are not many VDR expressed in those infected cells. 



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Prof Trevor Marshall
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 Posted: Thu Jul 14th, 2011 13:10

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Maybe there are pathogens that can still evade olmesartan's reactivation of the VDR ... by downregulating the VDR so that there are not many VDR expressed in those infected cells
But Olmesartan hits many receptors, at least a half-dozen strong-hits that I know of :) It apparently has just the right profile to do the job :)

Progesterone reduces inflammation, because it is immunosuppressive. Hence, the patient would feel better, and there would be less swelling (in the short-term) :)
 
 

ChrisMavo
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 Posted: Thu Jul 14th, 2011 13:16

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Thanks Dr Marshall!  Good to have it reinforced that olmesartan hits those other receptors also. 

Could this difference of VDR blockade vs VDR down regulation be the reason why the recovery rate for some chronic illnesses, i.e. neurological, take longer than others on the MP?  It would seem like a plausible reason why the recovery takes a lot longer in some illnesses.



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 Posted: Thu Jul 14th, 2011 13:19

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Indeed, variation from patient to patient, from microbiota to microbiota, is what causes the variable length of recovery (IMO). But I have seen no evidence to date that recovery does not come incrementally for all those who manage to stick with the IP for long enough...
 

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 Posted: Thu Jul 14th, 2011 13:23

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Music to my ears Dr Marshall!!  :D:D:D



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 Posted: Thu Jul 14th, 2011 18:39

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Chris,
If it is any consolation to you, I did not have any neurological improvements until I was well into my 4th year of the MP. Many times I felt much worse than I had before starting the MP....I believe it is IP you are dealing with.

Even knowing this does not make it any easier to go through.

It certainly seems to me that with your chess game improving things are looking up.



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ChrisMavo
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 Posted: Thu Jul 14th, 2011 23:57

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Thanks Aunt Diana for your encouragement! 

I guess I just have to be patient and wait for that turning point where I realize some neurological improvement.  But I do know if I continue on this trajectory for another two years ... it is going to get VERY difficult on me and my loved ones!  I was hoping that due to being relatively healthy back when I started in Aug 2009, that I'd have a faster recovery time.  Now that does not look like it is the case.

But as I said in an earlier post on this thread... I am in this til the end! ... whatever the ultimate outcome!   I intend to help prove that the MP either works or doesn't work for ALS!  You will NOT see me giving up on the MP to try some other crazy cure out there.  I have spent two years now studying and learning the science behind the MP.  The science is too strong to give up on.  And I feel strongly the MP gives me the BEST chance at defeating this terrible disease called ALS!! 

If I am fortunate enough to defeat this normally terminal disease with the MP ... you'll see me working as hard as I can to assist Dr Marshall's efforts to spread that victory as far and wide as possible!  That is a goal that helps me keep my sanity and focus when I am feeling down and tempted to doubt things. 

Chris



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 Posted: Tue Aug 9th, 2011 05:08

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Now Armin Alaedini at Weill Cornell Medical College in New York and his colleagues have found that patients diagnosed with post-Lyme disease syndrome have antibodies that suggest they carried the infection for an unusually long time. The finding, published in Clinical Immunology1, might help the syndrome to be better understood, diagnosed and treated.
Alaedini's team looked at antibodies made in response to a protein called VlsE, which is found on the surface of Borrelia burgdorferi, the tick-borne bacterium that causes Lyme disease.
The antibodies recognize a snippet of the protein called an epitope, and recruit the immune system to attack the bacterium. The researchers found that post-Lyme sufferers have a greater variety of antibodies to this epitope than patients whose infection cleared up quickly.
This finding suggests that patients with chronic symptoms have experienced a prolonged infection, caused by microbes that have evaded the immune system by varying the epitopes they carry. As a result of these variations, the body makes new antibodies targeting the modified protein. The longer the microbe manages to keep changing, the more diverse its host's antibodies become.

http://www.nature.com/news/2011/110805/full/news.2011.463.html#B1



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