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Prof Trevor Marshall
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Interesting new paper explaining how the more aged or sick you are, the less it is going to help you to have an autologous stem cell transplant:

http://online.liebertpub.com/doi/full/10.1089/biores.2014.0042
"Aging and chronic diseases including CVD and diabetes substantially affect stem/progenitor cells of adult organism. Such conditions could restrict the effectiveness of autologous cell therapy in aged patients with CAD, lower limb ischemia, T2DM and other chronic pathologies, although these patients are some of the most obvious candidates for cell therapy. "
Nothing really new here, except that many companies (and University clinics) want to hype stem cell transplants as a panacea. I have spoken (at length) with those who perform the procedure, and they tell me that the really positive results you see on YouTube are few and far between, and frequently require yearly 'refresh' transplants. It is nice to have a detailed paper to help us discuss this issue when our friends and family are urging us to "have a stem cell transplant."

..Trevor..
 

leroybrown
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What they forget to tell you is that after the radiation and/or chemo treatments to kill off your immune system, the 1 year survival from HSCT is about 50%.

Prof Trevor Marshall
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Deb, not all autologous stem cell transplant practitioners require you to undergo severe immunosuppression. For example, when I met Shimon Slavin 2 years ago, he told me was not doing this. I note that his website now implies that they are doing immune interventions of some sort, however.

I recall he did say they were removing the lymphocytes from the transplant medium, which I guess is indicative of an intent to reduce immune activity... He also made it clear that "cures" were not the norm, but a state of "disease remission" was more often achieved, requiring maintenance repetition of the transplants. Seriously ill patients were a problem for him, as this article suggests.
 

leroybrown
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In the article I noticed they called it stem cell "treatments", so maybe it is something else. I know in horses you can have things like tendons injected with stem cells, so maybe it is something like that.

To me, what is the point of taking your stem cells and just putting them back - they were there in the first place, so why didn't they just do their thing while they were there the first time?

I know for transplants, they first give you neupogen to release excess stem cells from the marrow for harvest, then they kill - oh sorry - "condition" your marrow then they infuse the stem cells.

They are doing autologous stem cell transplants at my hospital for diseases like MS now. I read glowing reports and thought wow - but when I watched a video, they did say they were using heavy duty chemo. TGTBT (too good to be true).

leroybrown
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Interesting article in the paper today.

http://ottawacitizen.com/news/national/gordie-howe-stem-cell-tourist-experts-warn-of-worrisome-trend

Prof Trevor Marshall
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The article gets to the crux of the problem: "But it still will be years before the game-changing therapy is available as clinical treatment for patients, something that is hard for many members of the public to understand"

Why? If people are suffering and dying why is treatment being held back until it is generally regarded as 'safe'?  There is a huge gap between (desperate) patients' perception of "ready" and the industry's perception of "ready."
 

leroybrown
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I wonder if they're also talking about 2 different things? I watched videos presented by the local group (by Dr Harry Atkins) and they are talking about full body irradiation and/or high dose chemo and then an infusion of stem cells. Those types of treatments have around a 50% survival rate. Surely the treatment in Mexico is not the same thing? So the general public is hearing about some sort of stem cell 'treatment', the hospitals are talking about a different type of treatment - stem cell 'transplant', and because of the demand, they get govt funding.

I wouldn't call a 50% survival rate a very good treatment. I dunno.

Martha
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Northwestern University Medical Center's Dr. Burt is having very good success with autologous HSCT with MS achieving remission 10 years out and I believe no deaths in MS.

leroybrown
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Well, I am happy to say I stand corrected. The hospital here is ALSO doing a trial of stem cell treatments that DO NOT require chemo.

http://ottawacitizen.com/news/local-news/ottawa-patients-sought-for-testing-of-stem-cell-therapy-that-offers-hope-for-ms

Martha
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 I've noticed all kinds of places touting their successes with "stem cell therapy". I saw on TV the other day a chiropractor advertising it for pain. It probably does temporarily help symptoms. But the people who have successfully achieved remission that I've talked with say it's the chemo in the HCST that halts the AI disease (some diseases better than others) and the autologous stem cells help the immune system to recover quicker.
I believe the MP can work and am giving it my all. It is helping me so far with some symptoms....but there may come a time where I have to do something more drastic with scleroderma. My 9 y/o son whom I became pregnant with while on the MP is positive for SD antibodies and has a high sed rate and high ANA. I keep my eyes wide open for him and my other sons.

leroybrown
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I met with the transplant team at my hospital a couple years ago, but they use the chemo and / or full body irradiation method.

I did more reading about the mesenchymal stem cells and it seems they don't know if they can become any type of cell, they have a long way to go yet.

How long have you been on the MP Martha?

Deb

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Deb,

I've been back on MP since March of last year. I had started originally back in 2004 and was on it for 6 months for scleroderma and became pregnant at 45 years old and of course stopped the MP. After I gave birth to my son, at about 6 months post partem (after nursing him), I tried to go back on the MP. I was only able to hang in there on the MP for about a year because I couldn't drag my sorry bum out of bed to care for him. My BP was so low and I was so fatigued I just couldn't continue on the MP with a toddler. After d/c'ing MP, I did OK for a quite awhile with diet, etc and my disease slowly smoldered. Up until last March when my breathing and cough started getting bad again. I'm respiratory therapist by trade and so I recognized my SOB and heart palps as possibly symptoms of pulmonary hypertension. That's when I decided to get back on the MP last March. And once again my heart palps and cough and dyspnea went away. The difference this time was I also began the baking soda/salt water in 1.5 L of water/day. It has really helped me with the fatigue and maybe even palliated my symptoms.
After a year, I'm doing ok. I'm not any worse and feel I might be getting better in some ways.
I remember about 8 years ago, when I was doing some internet surfing, I came across a doctor at Johns Hopkins having  good success with aplastic anemia patients in high dose chemo without reinfusing stem cells. I remember his emphasis was in aplastic anemia. He said that the stem cells came back on their own after the chemo. Anyway, I'm not sure how long you've been plugging on MP...I could try to find that docs name if you'd like. I actually spoke with him on the phone-very nice man.
~ Martha



Last edited on Sun Feb 1st, 2015 12:07 by Martha

leroybrown
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Hi Martha,

This study with cyclophosphamide was stopped due to toxicity. I was offered that drug and refused. I also refused campath and prednisone and another whole pile of immune suppressing therapy. I tried cyclosporine, IVIG and an ATG-tacrolimus combination before giving up on conventional medicine.

http://www.bloodjournal.org/content/124/18/2758?etoc=&sso-checked=true

I'm glad the extra salt and baking soda are making the difference for you this time.

Deb

Joyful
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Wow Deb.
Your post led to a real "aha" moment for me...

I was curious about what Tacrolimus could possibly be.
Now I know, it is from a bacteria culture from soil. This quote leads to interesting thoughts...

Tacrolimus (also FK-506 or fujimycin, trade names Prograf, Advagraf, 'Protopic) is an immunosuppressive drug used mainly after allogeneic organ transplant to reduce the activity of the patient's immune system and to lower the risk of organ rejection. It is also used in a topical preparation in the treatment of atopic dermatitis (eczema), severe refractory uveitis after bone marrow transplants, exacerbations of minimal change disease, TH2-mediated diseases such as Kimura's disease, and the skin condition vitiligo.

It is a 23-membered macrolide lactone discovered in 1984 from the fermentation broth of a Japanese soil sample that contained the bacterium Streptomyces tsukubaensis. It reduces interleukin-2 (IL-2) production by T-cells.

... it was among the first macrolide immunosuppressants discovered ...
So, bacteria can be used to suppress production of cytokines (IL-2 in this case)?
Hmmmm...

Last edited on Sun Feb 1st, 2015 14:17 by Joyful

leroybrown
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Cyclosporine was found from bacteria or fungus in soil too.

lorenzo von matterhorn
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Human Embryonic Stem Cell-Derived Oligodendrocyte Progenitors Remyelinate the Brain and Rescue Behavioral Deficits following Radiation


https://www.sciencenews.org/article/shots-brain-cells-restore-learning-memory-rats



http://www.cell.com/cell-stem-cell/abstract/S1934-5909(15)00005-3

Here we tested whether human ESC-derived oligodendrocytes can functionally remyelinate the irradiated brain using a rat model.

Last edited on Tue Feb 10th, 2015 02:24 by lorenzo von matterhorn

Joyful
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Are they saying they un-mylenated the rat's brains using radiation? :shock:

Last edited on Tue Feb 10th, 2015 15:04 by Joyful

wirion
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Very interesting (to me at least).

I also didn't know that myelin was provided by oligodendrocytes in the brain, I thought it was Schwann cells everywhere. It's weird that two different types of cells provide almost the exact same function, but in different ways. The Schwann cell seems to sit on the nerve itself (with its nucleus) whereas the oligodendrocyte sits apart and casts up to 50 Schwann-like myelin wrappers onto multiple nerve segments. This is what I just read on the wikipedia, but I thought I'd share anyway. ;)

So for restoring the brain's sensitivity against EMF, and generally reducing brain fog I guess those oligodendrocytes are at least as important as Schwann cells. Please someone correct me if I got this wrong.

lorenzo von matterhorn
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For those with brain problems, more important, if you ask me!
I think Dr. Marshall's theory for myelin damage was bacteria in the
Schwann-cell and the cell sits on the myelin so it's easier to see that
myelin could be damaged too. But what happens in the brain? If the Oligodendrocyte doesn't sit on any cell what causes the myelin damage?
Or is the cell always connected to each and everyone of the myelin sites?


Without that cover, known as the myelin sheath, nerve cells can’t transmit information, leading to memory and other brain problems.


It's pretty amazing that they used human cells in the rats and it worked!
As I understand from the article that means it will be a shorter journey towards human trials.

leroybrown
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They used embryonic stem cells, so I don't know what the status of that type of research is. I was wondering if human cells worked in rats, would rat cells work in humans?

Prof Trevor Marshall
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Yes, I read that Wikipedia description too. But there are also papers describing Schwann cells associated with neurons. For example, "Microwave Mechanisms of the Mammalian Nervous System", Stocklin and Stocklin,  J.  Life  Sci., 1979, talks about "the formation of myelin sheath and the Nodes of Ranvier" on larger neurons."

So this is stored in my memory as "a question mark." Once again we have a great reliance on animal models in Neurology, and also a reliance on Pathology, coupled with a total lack of understanding as to how the signaling actually propagates (except for the above cited authors).

But in any case, it really doesn't hinder understanding of the demyelination mechanisms whichever pathology is present. We are still far from delving into specific pathways :)
 

lorenzo von matterhorn
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Article says:

Department of Neurosurgery and Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA

and

Credit: Dr. Denis Soulet/Laval Univ., Quebec


In assisted reproduction or what it's called, surplus embryos are just thrown in the garbage, so more and more countries are allowing them to be used for research. The right way to go if you ask me.

Markt9452
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Where is this country fellow you speak of?

I would like to have a word with him about the embryos.

Prof Trevor Marshall
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Lorenzo, I want to see the cells in a functioning human brain performing the operations they are reputed to do on Wikipedia. Such as CNS signalling by sending voltages down nerves using 'Calcium Efflux'. There are just too many holes in the whole patchwork of neurological 'knowledge' as far as I can see...

Notice that the IOM yesterday said there was no sign of inflammation in CFS/ME brains, and that is why they scrapped talk of the ME nomenclature. What were they using to look for it? A microscope and scalpel?

..Trevor..

lorenzo von matterhorn
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I have absolutely no idea about the science, I leave that to you:p
I'm in the wishful thinking business.

But it makes sense that one cell attends to several axioms when it's all clustered. It saves space. In the PNS the nerves are stretched out as far as I know and then the clustered approach just doesn't work.

Prof Trevor Marshall
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Well, is it clustered? I honestly don't know what the neuronal density is in the various regions of the brain. I saw a video of growing mouse neurons once, they didn't seem too clustered to me. Remember a neuron is a fairly large cell, and bigger than the typical Schwann. Maybe there are multiple nuclei with a common cytoplasm. I just don't know. Certainly a macrophage can be polymorphonuclear, so why not a dendrite? And then the differentiation signals might be different at different regions of the cell, not all producing myelin... Hmm...
 

lorenzo von matterhorn
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I did some "research":p

(Mouse brain)
http://www.ncbi.nlm.nih.gov/pubmed/2778101
The cortical volume occupied by cell bodies of neurons and glia cells amounted to 12%, that by blood vessels to 4%. The total average was 9.2 x 10(4) neurons/mm3 and 7.2 x 10(8) synapses/mm3.

So it's pretty spacious.



http://physicsworld.com/cws/article/news/2003/apr/24/physicists-investigate-brain-power
Researchers at the University of Tel-Aviv in Israel have now shown for the first time that neurons can self-organize themselves into electrically active clusters of cells in the laboratory. The clusters are linked together by bundles of axons

Oligodendrocytes are also holding the bundle together.

And from this article
http://www.nih.gov/news/health/aug2011/nichd-10.htm


Then the oligodentrocytes began depositing myelin on electrically active axons, but not on axons that were not electrically active.

Last edited on Wed Feb 11th, 2015 13:57 by lorenzo von matterhorn

wirion
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@Lorenzo:
For those with brain problems, more important, if you ask me!
Yes, of course. :) That was a little self-centered on my part.

When you say clustered, do you mean spatially distributed (possibly unformly) in 3 dimensions, as opposed to the PNS' linear arrangement of axons, or do you mean clustered as in regions of the brain with a higher density of neurons than others?

Even if you meant the first, yes I guess oligodendrocytes allow for some efficient ("hub and spokes") sharing of resources among their myelinating sites.

@Trevor
Thank you Trevor for sharing your current thinking on the issue. As to fine-grained brain anatomy I am unfortunately in the unknown unknowns camp, as I don't even know enough about it to know what is known and what isn't to "experts". Naïvely I would think that most of this should have been worked out years ago, but your current thinking on capacitive coupling as opposed to the widely accepted "electric cables" model of neuron communication has made me more careful about assuming what is known.

With animal models, shouldn't science at least have stumbled upon the capacitive coupling mechanism by now?

I read the abstract of the Stocklin and Stocklin paper, and it sounds super modern even though it was published more than 35 years ago... fascinating.

lorenzo von matterhorn
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I saw this article a while back.

http://www.nhs.uk/news/2015/04April/Pages/Athletes-foot-cream-could-also-treat-multiple-sclerosis.aspx

One of the chemicals they identified as promising in their screen was miconazole, which is the active ingredient in some types of antifungal creams used to treat athlete’s foot. They found that it increased the number of mature myelin-producing cells in the brains of baby mice. It also helped repair damaged myelin in a mouse model of MS, and this made the mice’s symptoms less severe.

Wasn't sure if it was even worth posting, but here it is. Fungus and brain are two things I don't want to hear in the same sentence:s

Joyful
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Often the measure of "success" is symptoms go away briefly. So, how long did they test in humans? Or did they only test in petri dishes?

Also, people with long term autoimmune diseases are often the target of many microbes. The fungus are an opportunistic infection that moves in when the body is struggling.

lorenzo von matterhorn
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New Stem Cell Treatment "Switches Off" Type 1 Diabetes
http://www.iflscience.com/health-and-medicine/remarkable-new-method-switches-diabetes-may-lead-future-without-insulin

..in both mice and nonhuman primates. Known as triazole-thiomorpholine dioxide (TMTD), this variant was shown to be able to hide from white blood cells within hyperglycemic mice with a very strong immune system. Following the transplant, these beta cells began to immediately produce insulin, and brought the blood sugar levels down to healthy levels for a remarkable 174 days, a significant length of time considering their lifespan.

Prof Trevor Marshall
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Well, I would be impressed except that Insulin is not what controls the blood-glucose level in humans. The brain uses Grehlin, and other metabolites, to keep control of BG. So this research will not translate to humans.
 

lorenzo von matterhorn
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But what are the beta cells and insulin good for then? Since we have it, it must serve a purpose. And why can diabetics regulate by taking insulin if it doesn't have any function in BG?

Prof Trevor Marshall
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Medicine has seized on insulin as being a  means to control diabetes, and failed to study the way the body really works. There has been lengthy discussion on this topic here in the past

for example:
https://www.marshallprotocol.com/view_topic.php?id=15998&forum_id=39

https://www.marshallprotocol.com/view_topic.php?id=16004&forum_id=39

Yes, the microbes do preferentially destroy mast cells, and that does affect body's insulin production. Whether this is an association with Diabetes, or a cause of the disease, is being re-examined.

lorenzo von matterhorn
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A Controversial Stem Cell Treatment Reversed Blindness, but We Don't Know Why

https://www.inverse.com/article/12177-a-controversial-stem-cell-treatment-reversed-blindness-but-we-don-t-know-why

This is basically what you have been talking about, Dr. Marshall.
Instead of going through all the hurdles and bureaucracy in those cases when there's really no need for it, and just go ahead if it makes scientifically sense.

I hope we will see a lot more of this type of direct approach.



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