The Marshall Protocol Study Site > PROF. MARSHALL'S PERSPECTIVE > Prof. Marshall's Perspective > Host Defences - UCSD 2006
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The Marshall Protocol Study Site > PROF. MARSHALL'S PERSPECTIVE > Prof. Marshall's Perspective > Host Defences - UCSD 2006 |
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| Moderated by: Dr Trevor Marshall | ||
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Dr Trevor Marshall Research Team 
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University of California-San Diego Frontiers of Clinical Investigation Conference Host Defense 2006: From Bench to Bedside Oct5-7 La Jolla, CA ................................................ Quotable quotes that stuck in my mind: "Everybody knows Inflammation induces Cancer"- Francesco Marincola MD, Senior Investigator, NIH "Vitamin D is Immunosuppressive" - Hans-Dieter Volk MD, PhD, Head of the Institute for Medical Immunology, Charite-University Medicine Berlin. --------------- Wow! What an amazing conference. Over 100 top researchers who were actually interested in what we have been doing, and who didn't recoil in horror whenever I mentioned "Vitamin D"  For anybody that is interested, the detailed schedule can be found here: http://cfdev.ucsd.edu:89/b2b2006/program.html I took a video aide-memoire for my own use on a small pocket camera, the quality is atrocious, and many of the slides are washed out. Nevertheless, one of the presentations was so compelling I have taken the effort to put it online. It explains how the antimicrobial peptides (the body's own antibiotics) are employed against the pathogens which cause Crohn's disease. Many of you have heard me talk about how important it is to get the VDR Nuclear Receptor working properly (one of the things Benicar does) because the VDR is responsible for the Cathelicin Anti-Microbial Peptides. It is also responsible for transcribing the genes of the Beta Defensins. This presentation explains how those, and the other Defensins, are important, and I think that those of you who track the science will find it very interesting indeed. The 24 Mbyte RealVideo 9 presentation runs for 30 minutes. You can stream it from URL http://autoimmunityresearch.org/crohns.ram and the more technically astute can download the whole presentation by right-clicking on this link. As my mind starts to relax I am sure I will think of more "interesting stuff," and your questions (on the molecular biology topic, please) will also help fuel the discussion. |
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paulalbert Board Staff 
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Nice video. Here's my favorite quote. Here's an inexact transcription. It comes at minute 20:Why are these data important? I think these data provide a rationale for alternative therapies. Right now, almost all of the therapies target inflammatory cells; they try to suppress the inflammatory response. Paul Last edited on Sun Oct 8th, 2006 22:56 by paulalbert |
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Freddie Ash Member in Phase 3 
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HI ALL This is Fred in WV. Here is some infomation I just read in my Oct issue of Prevention magazine. This was found in the article,"Take Your Vitamins." Under the vitamin D, it said: "There's no doubt about it: vitamin D is required to get calcium into the bones. Yet in the WHI study, volunteers given D plus calcium were as likely as other women to suffer fractures. Same thing with colon cancer: Although a 2005 review at the Naval Health Reach Center in San Diego concluded that people who took extra vitamin D halved their risk of the cancer, the WHI reported last year that D supplements did nothing to ward it off." WHI is Women's Health Initiaive. Remember, we are all in this together and I am pulling for us. Your friend in sarcoidosis Freddie |
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Dr Trevor Marshall Research Team
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Freddie, What you are seeing is a clash of cultures. Clinicians have come to rely upon observations of disease, of studies of people who are sick. Molecular Biologists have focused on an understanding of the complexities of the disease process itself. It is not possible for either group to fully understand the overview unless they listen to all inputs. An excellent example of this is my Letter to the Editor which was just published in The Lancet. The editors of The Lancet, the premiere British clinical journal, had no idea what I was talking about. They could not understand the depth of my knowledge about Statins and Vitamin D, or even that such knowledge was possible. Consequently they were promoting the views of Dr Grimes, who has some pea-brained concept that Statins improve health because they are "like Vitamin D." The Editors changed around the words I had written into a form which greatly diluted my message. Sigh... I am sure they had the best of intentions, but not the ability to comprehend ..Trevor.. ps: the Citation to my Lancet correspondence is: Marshall TG: Are statins analogs of vitamin D?. Correspondence to Grimes, DS. The Lancet 2006; 368:1234 doi:10.1016/S0140-6736(06)69509-3 and a copy is at URL http://tinyurl.com/r2gtl (I think you will have to register to get access) |
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UshiAad Member in Phase 3 
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Very interesting indeed and agree with Paul's remark. PD Although i don't have crohn's disease (as far as i am aware) before the unset of my ME/CFS in 1993 i had bowel problems and breakdown for years ....... |
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Frans Member in Phase 2 
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Trevor, wow ! How did you get this published in the Lancet, of all magazines? This is fantastic ! I can't wait to read any comments to your comment  If everyone is paying attention, it will blow a lot of people away !! I haven't seen anyone contesting that D3/25oh D act as ANTAgonist for the VDR. Let's see what happens with this information. |
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Frans Member in Phase 2
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Trevor, I have a question. I understand you applied for a CME certification. (For the ones who don't know: CME stands for Continuous Medical Education) Can we assume that the status of a CME certification is as much as a peer review? I ask since my company doc. last said: I will follow the literature... Does a CME-certification equal ... the literature... ? Did you also get a CME-certification for this conference in particular? And Karolinska? Sincerely, Frans |
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Dr Trevor Marshall Research Team
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Frans, The CME presentation is at the AAEM conference in Hilton Head later this month. I will be speaking to several hundred physicians, who will get CME points (they need a certain number each year to keep their licence) for listening to my presentation, and answering some simple 'exam-type' questions. This means that not only was the AAEM presentation invited, the abstract went through their Peer Review committee, objectives were set for what the audience is expected to learn, and then my final slides were also submitted for the Peer Review committee to approve. So the presentation has been made to jump through the hoops. I will be trying to get a video version of this presentation which we can put online for you all. It will be about 1 hour 15 minutes in length, and cover the MP science from end to end. ..Trevor.. |
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tickbite Member in Phase 2/3 
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Hi Trevor, By the sounds of this presentation, most probiotics don't really do a darn thing, unless you are using a Nissle strain. And even this is just another palliative approach. Would this be correct in your opinion? No doubt this presentation is very compelling. Did I hear the presenter say "Chromosomal DNA" being the true cuplrit to Crohn's and not the initial bacterial infection? Thanks so much for putting up the video for us. I for one, love to absorb as much as possible! |
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Dr Trevor Marshall Research Team
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The slide showing that 30% of Crohn's patients have a defect in the NOD gene was discussed a little, as well as the fact the Crohn's patients generally had fewer gene replications in the region of the Defensin genes. But the presenter understood that these were merely interesting associations, and did not present them to be causal. When I was speaking with him during the coffee breaks he semed to have a very good overview of the disease process, and he certainly took a copy of my Karolinska paper when I offered it |
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Ival Moderator 
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I find this video very interesting. The mutation in the intestines in crohn’s disease somehow are similar to my version of rheumatoid arthritis. One of my worst herxs in my intestines is right where the small intestine and the colon are connected right were 40 to 50% of the crohn’s disease cases occur. Whenever that part of my intestine would herxs my arthritis would double or triple for weeks at the beginning of the protocol. I know that’s the area where the herxs is because I had an Appendectomy in my early twenties and it hurts in the exact same spot. I’m sure I have other mutations like in my joints that affect my disease but the GI tract is definitely involved in RA at least in my version. That observation leaves me with a lot of questions. The first one being the barrier of the intestine is being compromised because of the mutations in the genes. Since we’re getting rid of the infections will those cells that are mutated eventually be replaced with healthy cells or will they always be a problem. My experience so far is they must be getting replaced or somehow repairing their self because when I herxs in that area now I very rarely have the arthritis symptoms follow and the herxs is only about half of what it used to be. The stem cells that he’s talking about in the video are located where. The intestinal tract or are they in other parts of the body. When is the mutations happening in those cells right when the stem cells makes them or is the mutation happening after the new cell becomes infected again with the infection in the area. Watching the video gives you one possibility of what the appendix does in the first place. That is a transition area between very little bacteria to a lot of bacteria. One of the possibilities is it delivers a special kind of peptides or at least just more of them in the area to make the transition easier. |
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Dr Trevor Marshall Research Team
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Ival, I wish I could describe the mechanism of DNA mutation to you. But I am not convinced by anything I have read. Which is sorta crazy - we have known for decades that radiation induces the DNA to mutate - but we don't yet seem to know how. Once I understand the exact mechanism, and whether the host DNA is changed by bacteria early in life, or whether it never changes, and whether it is reversible, only then I will be able to give you an answer. Maybe I will find out at the upcoming conference (at the start of November) "Nuclear Receptors - Bed to Bedside" as that seems to have some pretty smart people on the list of attendees, and we will have plenty of time to mix and chat... ps: here is a recent suggestion on mechanisms Last edited on Tue Oct 10th, 2006 23:17 by Dr Trevor Marshall |
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RobertTownsend Health Professional
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Trevor Not sure where to post this but there is a really interesting piece in this week's New Scientist "Researchers have cured viral meningitis in mice by blocking the action of an anti-inflammatory immune molecule" Researchers at the La Jolla Institute for Allergy and Immunology in California have found that an anti-inflammatory response ( in this case IL-10) was preventing the immune system from attacking the virus The piece is at http://www.newscientist.com/article.ns?id=dn10264&feedId=online-news_rss20 Seems to add much to your immmune-enabling proposals. I have not tracked back to the original research paper - but if you cannot get it from your own sources, I expect my Uni Online subscriptions should be able to turn it up for you. Regards RobertTownsend |
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RobertTownsend Health Professional
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Trevor PS The headline writer for the New Scientist got it wrong - it should read " Inflammation turned OFF " RobertTownsend |
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Dr Trevor Marshall Research Team
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Robert, Now that you mention it, there was a lot of talk about blocking IL-10 at the conference. I have to admit I thought it was such a stupid idea that I usually left the lecture hall and spent the time mixing/talking in the corridors during that type of presentation Also left during the ones examining the minutia of T-cell activation in mice... (those folk can't see the forest for the trees) |
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RobertTownsend Health Professional
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Trevor I think this is wholly consistent with your work, and indeed corrobates it becuase it is a different "entrenched pathogen" albeit a viral one. If you assume for the moment the simplified model that TH1 responses are to bacteria and TH2 responses are to viruses, then the dominant pro-inflammatory responses are Bacterial : TH1 elevated IL12 and IFNgamma ( I think these are the right ILs, though IL1 and IL6 will also be elevated) Viral : TH2 elevated IL10 Then this work of von Herrath on the immune systems elevated inflammatory response ( in this case elevated IL10 to a viral pathogen) blocking innate immunity is exactly equivalent to your observations that elevated Th1 inflammatory cytokines in bacterial infections are blocking innate immunity RobertTownsend PS incidentally we don't here subscribe to the full text of the source document Last edited on Wed Oct 11th, 2006 23:55 by RobertTownsend |
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tickbite Member in Phase 2/3
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I'm a little confused here on Robert's evaluation of LCMV creating an elevated inflammatory response. From the news article it sounds to me like the IL-10 creates an decreased immune response. Not that these cytokine reactions don't have any relavance to each other, they abosultely do. I love the article. It sounds like the two states of Th1 and this particular Th2 response are exact opposite in as far as inflammatory response. Is this a wrong observation? Thank you for the post Robert. |
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Dr Trevor Marshall Research Team
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I haven't had time to look at the paper, but many think that the best way to treat disease is just to suppress the inflammation. There is no thought of long-term prognosis. For example, the TNF-alpha blockers work in this way. I haven't had time to look into the IL-10 papers, but what little I did listen to, sounded as though the IL-10 blockade was a similar concept - stop the immune system creating inflammation - this was the stated goal. Very few scientists understand the concept of persistent bacteria. I was looking at this paper earlier today, for example, which found bacterial ribosomal DNA in the blood of supposedly healthy individuals, and did not know what conclusions to draw from this http://jcm.asm.org/cgi/content/full/39/5/1956?view=long |
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RobertTownsend Health Professional
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Trevor The abstract is at http://www.jem.org/cgi/content/abstract/jem.20061462v1 We don't have access to the full article RobertT |
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tickbite Member in Phase 2/3
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This may or may not be of any relevance, but IL-10R blockade is pro-inflammatory. I'm not sure what the researchers were saying at the conference but elevated IL-10 is anti-inflammatory from these references: http://www.eurekah.com/abstract.php?chapid=1690&bookid=118&catid=19 http://en.wikipedia.org/wiki/Interleukin_10 So, perhaps the headline writer for the New Scientist article got it right... "Inflammation 'turned on' to fight killer viruses" Sometimes not enough pro-inflammatory cytokines is bad? i.e. HIV? However, I realize that the whole concept of only looking at cytokines is lacking and the truth is an infectious etiology. By the way, i'm only an amateur. If i'm totally wrong about this please harass me. |
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Dr Trevor Marshall Research Team
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Greg, I won't be doing any 'harassing' until I get the 2006 DVDs shipped, and that will be a few days yet No time to read anything till then |
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tickbite Member in Phase 2/3
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Here is an abstract associating E. coli nissle probiotics with an increase in IL-10 anti-inflammatory cytokines. Lactobacilli, bifidobacteria and E. coli nissle induce pro- and anti-inflammatory cytokines in peripheral blood mononuclear cells. I've spent a while reading over abstracts involving IL-10. I really find the work confusing. In some viral models, IL-10 blockade helps rid the infection (Robert's post). In other models it gets too complicated. Some people inject IL-10 genes into models to reduce inflammation.....Personally, I think a lot of this research is just mad scientist style jabbing in the wind. However, it's all still note worthy. I think there's too much "autoimmune" belief, etc running around for there to be any clear cut truth to shine through yet. Unless I haven't found it. Fun to look at though. This next abstract I find very interesting (besides the researchers unaware of CWD) in the way of them describing borrelia eliciting suppressors of cytokine signaling proteins. Part of an IL-10 mediated inhibition of inflammatory cytokines....strange. Interleukin-10 anti-inflammatory response to Borrelia burgdorferi, the agent of Lyme disease: a possible role for suppressors of cytokine signaling 1 and 3. Forgive me if this is an unthoughtfull post. I just like discussion on these scientific subjects... ~Greg |
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Frans Member in Phase 2
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Trevor, I want to get back to the Letter to the Editor you got published in The Lancet. I am planning to get this message out to the general public via as many channels as I can reach, ie newspapers, serious medical scientific tv-programs, etc. The proble is that at this point my energy is lacking to write a piece that covers all the basics, but sitll gets a powerfulk message across. The Lancet has almost been proclaimed holy, so I think we should get the most out of this. Maybe someone can give some pointers as to how to approach this subject, to get me started on this. The subject being the fact that vitamin D is immunosuppressive, acts a lot like prednisolon etc. Trevor, have you perhaps got a .jpg that shows the likeness between the two as you showed at your presentation at FDA CDER ? I know that I for one was blown away when you showed how much the two molecules look alike. One picture says more than a thousand words, we say over here. Shall we milk this opportunity dry? Sincerely, Frans |
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kenc Member in Phase 3 
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The video on Crohn's disease suggests to me that a genetic defect leads to an underproduction of defensins. 1) Does this genetic mutation always lead to an underproduction of defensins or are there other mitigating factors? 2) What role, if any, do cell wall deficient bacteria have in the production of defensins? |
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Frans Member in Phase 2
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Hi all, I have been working on a document I want to send to newspapers, tv etc. I think we should make the most of the fact that Trevor has been published in The Lancet with the fact that vitamin D is not as fantastic as a lot of people think or want some experts want you to think and is really posing a threat to the general public's health. I will post the translated text here and I am open for suggestions for better or worse  I am also open for translational errors, so don't spare me Dear Madam, Sir, Hereby I want to draw your attention to a piece in The Lancet of (date, or number of article) from Trevor. G. Marshall phD. In this piece, Marshall explains at a molecular level that Viatmin D SHUTS DOWN / DISABLES the Vitamin D receptor (VDR). It is an ANTAgonist of the VDR. (Vitamin D: D3, 25ohD3, ergocalciferol) Recent research has shown that the VDR is responsible for the transcription of eg TLR2 and TLR4. (PMID ?????? Anyone know this/these??) These receptors are at the heart of Innate Immunity. If the transcription of these receptors is hindered (???), our innate immunity DOES NOT WORK !! Vitamin D is therefore immunosuppressive !! Just like prednisone… I have included a picture where dr Marshall shows the molecules of prednisone and Vitamin D next to each other. The similarities are obvious…. (I want to enclose a still from the presentation at FDA CDER which shows D and Prednison next to one another) Vitamin D has also been proven not to be a vitamin, but is, in actuality, a steroid ! Another similarity to prednisone… So why is dr Marshall's discovery so important ? Newborn children, whose adaptive immunity has not yet kicked in !, are totally dependant on a correct functioning innate immune system. BUT WE ARE KNOCKING THIS OUT WITH VITAMIN D !!!!!!! How come ?? Vitamin D is being supplemented in baby formula, in our daily foods, etc. Furhtermore doctors are telling young parents to supplement their children with vitamin D in the wrongful understanding that vitamin D is 'good' for you… dr Marshall has found that levels of 20NG/ML seriously impair innate immunity. These levels are however now called deficient !! A terrible mistake! Research has shown that only 1,25 Dihydroxyvitamin D (=1,25D), a successor of 25D, turns the VDR ON. This has to do with a necessary hydroxyl-group that is only present on the 1,25D molecule. All the other forms of vitamin D lack this necessary component, therefore lacking the ability to turn the VDR ON !! (here should be a link to KAROLINSKA) This hydroxyl Group is added to1,25D in the mitochondria of macrophages, as wel as in the kidneys, under influence of 1 alpha Hydroxylase (1a-OHase). This is regulated strictly. Too high 1,25D leads to calcium being resorbed into the bloodstream from the bones, leading to calcium being deposited in soft tissues. Vitamin D (25OHD) s being measured in NANOgrams. HOWEVER: 1,25D is being measured in PICO-grams !! So there is a factor 1.000 difference between 25OHD and 1,25D !! This makes it clear that the most part of the 25OHD we ingest, or acquire via light on our skin, floats around our bloodstream for an indefinite time, before it is picked up by DBP (Vitamin D binding protein) to be stored in our bodyfat. This free-floating 25OHD is present in such abundance that the molecules 25OHD will bind the VDR at the cost of the molecules 1,25D leading to a serious suppression of our innate immune system !!!! Sincerely, …. This is a first draft. TIA, Frans |
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Dr Trevor Marshall Research Team
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Ken, Beta Defensins are transcribed by the VDR. Folk with a dysfunctional Vitamin D system can't produce them. Although the author talks about a genetic defect, he points out it is not the cause of the disease, as only a minority of patients have it. I told the speaker about Vit D being immunosuppressive, and hopefully he will start looking in that direction now, instead of being distracted by mutations. |
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Brad Member in Phase 2/3
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Frans, At the risk of sounding stupid, I have never understood what each type of immune system is. Innate and Adaptive ? Also are you saying that 1,25D is the only thing that kicks in innate immunity, I thought too much 1,25D suppressed innate immunity. I thought benicar brought down 1,25D. The more I read the more confused I get. I wish there was a really simple chart or something to help us poor laymen understand . Thanks, Paulette |
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tickbite Member in Phase 2/3
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Brad/Paulette, A Brief Overview of Innate and Adaptive Immunity in Relation to the Marshall Protocol Innate and Acquired Immunity Unfortunately, coming across a simple layman's chart of everything at the moment might be a bit difficult. This chart shows what 1,25D affects: Hormonal Diagram Yes, 1,25D is the only thing which turns on the VDR. The problem is Th1 inflammatory disease patients have way too much of it. We only need a small amount. Excess 1,25D begins to affect other systems in very bad way indeed (that's why we're here): Hypervitaminosis-D Supplemented vitamin D (25D) begins to shut down innate immunity. I believe it is also wise to completely restrict natural sources of vitamin D also while recovering from Th1 disease. Frans, Good work. You did a good job. If you need help gathering other finer points of things I would be more than happy to help. Otherwise, continue on! perhaps showing a more finalized version would be another good idea. ~Greg |
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jrfoutin Research Team 
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Frans, I sent you a PM that may be of use. Also, the LAX Conference DVDs contain an excellent set of details. KAROLINISKA Do be sure to print out (on good paper at better resolutions) Dr Marshall's Karolinska poster, which is really a fantastic piece of efficient evidence, with charts and graphics that get to the point in a big hurry. FDA/CDER & AAEM Dr Marshall's Spring 2006 FDA CDER visiting professor presentation and the Fall 2006 AAEM continuing ed presentation for doctors, he describes exactly why Molecular Genomics is so important, and then goes on to show exactly what has been discovered. Those of us on the MP have catapulted beyond today's research processes into the future of medicine. VON ESCHENBACH/NORD Confirming that concept, the NORD presentation on Sept 29, 2006 "Does the FDA Critical Path Tie into the NIH Road Map?," Dr von Eschenbach, acting director of the FDA, used the term "typhoon of change" to describe how Molecular Genomics will exponentially change medicine as we know it today. Belinda quickly approache him after his presentation and asked him directly if he realized how true what he had said was, and he confirmed --with tone-- that he knew exactly what he was talking about! (You have to hand it to Belinda, she made it in front of a CNN reporter for that important discussion.) Once journalists begin to understand the definitive nature of Molecular Genomics science, then they can start to grasp just what one researcher has been able to do with it. ............... Research side notes:.................. An educated populace that is willing to take action is all that stands between corruption and correction.--Janet |
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ShrnHml Member in Phase 2/3 
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Frans.........I never cease to be amazed at your grasp of the science and especially your ability to put it into readable format. All of this while operating in a "foreign" language. Thank you for your posts. .................Sharon |
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Brad Member in Phase 2/3
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Greg, Thanks so much for the links, I missed reading that post by Joyce, now when I read the words innate and adaptive I will be able to somewhat follow along. Paulette |
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