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Meg Mangin R.N.
Research Team (on leave)
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Posted: Sun Apr 24th, 2005 18:36 |
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Cell Wall Deficient Bacteria and the Marshall Protocol
Varient bacteria cause inflammatory response
The Th1 (T-helper) inflammatory response occurs in reaction to the invasion of cells by extremely tiny varient bacteria. These parasitic bacteria are also called pleomorphic (many shapes) or L-form (named for the Lister Institute where they were discovered) or Cell Wall Deficient (CWD) or cell wall divergent or cell-wall defective or large bodies or cryptic or nanobacteria or spores. Coccoid (spherical) is a term that refers to these elemental forms. Cysts or colonies of these tiny L-forms can be enclosed within a protein shell.
Intracellular bacteria are extremely small
These bacteria are about 0.01 microns in diameter, smaller than any known viral or fungal particle. They are the smallest identified bacterial forms and are too small to be seen with normal optical microscopes.
There are many species of L-form bacteria
There are at least 53 identified species of L-form (little and large) bacteria. You can see the wide variety of these bacteria in Dr. Lida Mattman's slides Cell Wall Deficient Forms: Stealth Pathogens, Third Edition and see moving photos of them in Dr. Andy Wright's slides on the Chicago Conference DVDs.
Exposure to these bacteria comes from many sources
We are exposed to CWD pathogens in our food/milk (they are not killed by pasturization), water (they are not killed by chlorination), intimate contact (spouses are at higher risk), before birth (via sperm), at birth (mother to child transmission) and biologic (injectible) medicines (they are too small to be filtered during the 'purification' processes used in pharmaceutical manufacturing procedures). They have even been cultured from dry soil. L-forms of Bacillus anthracis (Anthrax) are known to survive in dry soil indefinitely.
Detecting L-form bacteria is difficult
A few researchers are using dark field microscopy to detect CWD bacteria in the blood stream. These intracellular (within the cell walls) bacteria will not necessarily show up in lab cultures because they are very difficult to grow. The will not show up in antibody testing because they are nestled inside the cells of the immune system which has been unable to detect them and kill them so antibodies have not formed. Polymerase Chain Reaction (PCR) tests may only show small (almost undetectable) quantities of the bacterial 16S RNA because the lifetime of the phagocytes is long (slowed apoptosis) so they don't die and expose their 'insides' to the bloodstream very often.
Biopsy testing doesn't usually work because the bacteria are destroyed when taken out of the body as their homeostasis is destroyed and the lysosomes in the immune system kill them. It is not possible to identify the bacterial species which are most successful (those that thrive without killing their host), because they are not being killed by the immune system. All that can be detected with routine testing are those bacteria which are being killed and those aren’t the ones that are causing problems.
Koch's postulates
One of the paradigm shifts we had to make was to realize that the Postulates of Koch are badly flawed, especially in so far that they have caused Medicine to rely almost totally on response to antibiotic in a petrie dish, in-vitro, rather than in-vivo.
Physicians have not been trained to contemplate the way antibiotics actually function, but to produce a diagnosis, which allows the "correct" antibiotics to be read from one of the many "cookbooks" containing list of diagnoses vs antibiotics. Typically, of course, the results from a lab susceptibility test are used by a Physician to select the antibiotic to be used.
Even though Medicine has known that some pathogens have to be grown on special substrates, such as Treponema (syphilis) and Helicobacter, they have continued to ignore the potential presence of pathogens which do not show up in standard lab cultures.
How the bacteria enter the cells
This paper provides a wonderful review of the complexities of how the bacteria can enter macrophages and infect them.
Co-infections do not cause chronic inflammation
There may be bacteria detectable by routine methods in the bloodstream (co-infections) but these are not the bacteria that usually make people chronically ill. The so-called ‘stealth’ bacteria have developed the ability to morph into a tiny form without cell walls in order to evade the immune system and survive the antibiotics that kill bacteria by inhibiting cell wall formation. These variant forms of the original parent bacteria have learned how to live within the cells, including the cells of the immune system (phagocytes) that are supposed to kill them.
Intracellular bacteria control the action of the immune system
The bacteria control the actions of the immune system by the proteins and toxins they release. They act directly on the proteins and/or kinases within the phagocytic cells to directly release the Th1 cytokines (small secreted proteins which mediate and regulate immunity). It is the proteins secreted by the bacteria themselves that uniquely and solely produce what we know as the "Th1 immune response." The resulting inflammation is what causes Th1 inflammatory symptoms.
Antibiotics alone are ineffective
The occult bacterial pathogens causing the chronic Th1 diseases have evolved mechanisms to defeat the action of antibiotics alone and multiply safely sequestered within the cells. The inflamed tissues produce an excess of the secosteroid hormone dihydroxyvitamin-D. High levels of 1,25-D allow the bacteria to colonize the phagocytes, avoiding the lysosomal phagocytosis.
Dysregulated vitamin D metabolism
Th1 inflammation always involves this dysregulation of Vitamin D metabolism because it is the clever tactic that intracellular bacteria have evolved to hide from the immune system. The Marshall Protocol (MP) uses Benicar to control 1,25-dihydroxyvitamin-D and angiotension II. Amongst other actions, this blocks the cytokine cascade, thus defeating this survival mechanism and helping the immune system to 'see' the intra-phagocytic bacteria. Then the correct antibiotic regime weakens these antibiotic-resistant bacteria so the immune system can more effectively kill them.
Beta-Latam antibiotics promote the formation of L-forms
The Beta-Lactam antibiotics (cephalosporins and penicillins) that attack cell walls are deadly to blood-borne bacteria but ineffective against Cell Wall Deficient bacteria. In fact, they actually promote the formation of the tiny L-forms which have been photographed living inside phagocytes. Because the beta-lactams protect the CWD bacteria they are even used in-vitro (in a test tube) when culturing and growing the tiny L-forms.
These studies show that beta-lactam antibiotics actually cause Cell Wall Deficient bacteria to form from blood-borne bacteria: http://tinyurl.com/572yt http://tinyurl.com/6b3lv
The MP uses bacteriostatic antibiotics
The sequencing of the human genome has enabled scientists to identify exactly how antibiotics work at the molecular level. The Marshall Protocol uses bacteriostatic antibiotics known as "Protein Synthesis Inhibitors" (PSI) to inhibit bacterial growth and assist the immune system in eliminating these CWD bacteria. The tetracyclines are all different at the molecular level and minocycline is the tetracycline of choice.
Minocycline
CWD bacteria have only one known resistance mechanism 30S ribosomal subunit, a single SNP, making minocycline a suitable first-line antibiotic. Minocycline (one of the widest spectrum antibiotics available), stops bacterial protein synthesis by binding to the 30S Ribosomal sub-unit in the region of the helix which advances to 'read' the mRNA. It reportedly also binds to the 16S RNA at five other positions in the 30S subunit, but its hindering of the helix advance is believed to result in its primary functional inhibition of protein synthesis. One molecule of minocycline inhibits one 70S bacterial Ribosome from manufacturing proteins.
This paper describes the extra features which make minocycline far superior to any other tetracycline. http://www.postgradmed.com/issues/1997/04_97/cunha_1.htm
Note the following particularly:
1. Better lipid solubility -> better CNS and cellular penetration
2. Effectiveness against Staph, which is one of the strains contributing to these chronic diseases
How antibiotics inhibit bacterial protein synthesis
A website put together by two scientists from the Max Planck Institute in Germany, collates together the knowledge about how antibiotics inhibit bacterial protein synthesis. The molecular models are taken from a variety of scientific papers, and provide a clear insight into exactly how each antibiotic works. The page for the 30S antibiotics is at URL http://www.riboworld.com/antib/30santib-eng.shtml
A paper by Burke Cunha, detailing the bacterial spectrum of minocycline is available at this url: http://www.postgradmed.com/issues/1997/04_97/cunha_1.htm
Minocycline can also inhibit mammalian protein synthesis to a small degree, which is undesirable because this can suppress the immune system and other important functions. The goal is to use just enough minocycline to block the bacterial pathogens ability to synthesize proteins without significantly inhibiting the body’s own ability to synthesize proteins. Therefore, minocycline is used in low, pulsed doses on the MP. It then has more of an effect on bacterial protein synthesis than on mammalian protein synthesis. Thus, the immune system enhancement by the Benicar blockade and the unique MP antibiotic regimen significantly tilts the advantage in favor of the immune system which is actually the most effective ‘antibiotic’.
This paper explains the interactions between antibacterial agents and phagocytes http://cmr.asm.org/cgi/content/full/13/4/615
Antibiotic combinations work synergistically
All bacteria need to manufacture a variety of proteins in order to survive and the MP is designed to make that task progressively harder. For that reason, the MP progresses from pulsed, low-dose minocycline monotherapy to a synergistic, dual-therapy with an azolide antibiotic that forms a unique double bond in the 23S RNA which none of the others of the macrolide class possess. This second phase MP antibiotic is a totally unique azolide that binds into the key pockets of the 50S bacterial ribosomal subunit where there are actually two molecules which obstruct each ribosome. None of the other 50S inhibitors do this. The key difference is that this unique antibiotic has superior tissue penetration resulting, for the first 5 days after administration, in a greater concentration of the drug in the tissue than circulates in the plasma compartment.
This webpage summarizes the 50S ribosome blockade: http://www.riboworld.com/antib/50santib-eng.shtml
There are likely to be many different species of bacteria involved in causing the Th1 disease in any individual. Killing the bacteria causing these chronic diseases is a very difficult task, and that is why the MP is not just a simple "take these pills for 5 days" treatment. The final phase of the MP involves various three-antibiotic combinations, one of which binds to a different region of the 50S Ribosomal subunit and is therefore able to kill even more resistant CWD species.
Antibiotic resistance
Antibiotic resistance mechanisms are becoming well known at the molecular level which will ensure effective alternate antibiotic choices if resistance evolves. Statistically, the chance that bacteria will evolve that cannot be killed by the MP is so close to zero it is inconsequential. The combination of an angiotensin receptor blockade to engage the immune system with the safe, wide-spectrum, symbiotic antibiotics of phase two and three seem to effectively eliminate all strains of antibiotic-resistant bacteria.
The MP will eliminate co-infections
When the body is weakened by these Th1 diseases co-infections are very common, as the immune system is 'busy' dealing with the pathogens which have parasitized the phagocytes and can't deal as effectively with the opportunistic infections. Co-infections that have been resistant to treatment, will likely be eliminated by the immune system as its proper function is restored with the Marshall Protocol.
Differences in antibiotic effectiveness
There is definitely a variation in the effectiveness of various antibiotics in patients. The factors seem to be:
1. Patient's prior exposure to the antibiotics
2. Strength (or weakness) of the patient's own immune system
3. Species of bacteria present
4. Concomitant health problems - eg kidney failure
5. Concomitant infections - eg fungal, viral
6. Medications being taken by the patient
White blood cells and phagocytosis
Phagocytes are a class of cells which include the monocytes, macrophages,lymphocytes, neutrophils, dendritic cells, and polymorphonuclear cells. They are loosely termed "white blood cells." Phagocytes have the ability to engulf and ingest, and therefore destroy, foreign matter or organisms. This process is called phagocytosis. Tutorial on Phagocytosis and Bacterial Pathogens.
The infected phagocytes circulate in blood and tissues. In the extreme case of sarcoidosis they clump together and form granuloma, clusters of phagocytes without the normal supporting structure. They are also capable of accumulating in regions of inflammation such as joints.
As distinct from normal red blood cells, these phagocytes have differentiated (formed) with a nucleus, mitochondria, and other structures useful in performing their function - to kill and digest old tissue and pathogens.
When a phagocyte becomes infected, intra-cellular bacteria can manufacture a lot more proteins, cytokines and toxins than they could if they had infected a red cell, as the cell nucleus and mitochondria allow them access to homo sapiens mRNA transcription, and homo sapiens nutrients.
Cytokines
The bacteria cause the phagocytes to emit Th1 cytokines, apparently giving the bacteria extra protection or nourishment (we just don't know why yet). Those cytokines are what cause long term damage to the tissue and to the well-being of the human host. For example, angiotensin II is known to accelerate the deposition of collagen into tissue and long-term deposition of collagen leads to fibrosis.
Cell life and apoptosis
Several studies have noted that the infectious agents (bacteria) do prolong the life of the cells by delaying maturity, but apoptosis (cell death) will eventually occur with all cells. However, a macrophage is one of the cells suffering the least apoptosis, typically accepted to have a 45 day life (plus or minus). By comparison, a neutrophil suffers apoptosis in 24 hours, and so they make very poor homes for chronic pathogens (by comparison with the macrophages).
Documentation of compromised white blood cells by intracellular pathogens
Compromised white blood cells in these diseases were reported by Dr Andrew Wright at our Chicago conference, who uses dark field imaging to see them in the blood from a pin-prick.
Alan Cantwell, MD was also able to image pathogens in the white cells and the Wirostko images of coccoids within a moncocyte are superb in this paper.
Microbiologist Lida H. Mattman, M.S.,Ph.D., former Director of the Nelson Medical Research Institute in Warren, Michigan, author of Cell Wall Deficient Forms-Stealth Pathogens, has isolated many L-forms in pure culture using blood samples.
See also:
What is the basic definition of Th1 inflammation?
Inside the Cell (a tutorial)
Do people with Th1 inflammatory disease have a genetic defect?
How the Immune System Works
Innate and Acquired Immunity
Immunology Syllabus
Inner Life of the Cell video
How Your Immune System Works
Understanding L-form Bacteria
Getting it right: How to correctly target L-form bacteria
A history of L-form bacteria: A selection of researchers who have worked with the L-form
Gerald Domingue: Pioneer of L-form bacteria
New molecular techniques shine light on the body's "zoo" of bacteria
New paper published in BioEssays and a review in the Journal of Bacteriology discuss important new research on L-form bacteria
Interview with evolutionary biologist Paul Ewald
Interview with Nadya Markova: L-form expert
Interview with Dr. Alan Cantwell
Last edited on Sat Jul 26th, 2008 04:37 by Meg Mangin R.N.
____________________
Nothing contained in this site is or should be considered, or used as a substitute for, medical advice, diagnosis or treatment by your physician.
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Meg Mangin R.N.
Research Team (on leave)
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Posted: Wed Oct 12th, 2005 02:10 |
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(filelink)
Common interpretation errors of bacterial cultures
I have to admit that I have grown weary of trying to point out the myriad of mistakes in the way the ID specialty thinks about bacterial disease, and about the pathogens themselves.
First, the assumption is that bacteria living in a person can be made to grow outside that body, in a petrie dish, or a broth. Yet ID has known for decades that neither Syphilis (Treponema pallidum) or Leprosy (Mycobacterium leprae) can be cultivated in this way. Why do they hold on to such a stupid pragma as assuming that everything must be reproducible in-vitro. That pragma makes their lives easier, but is just plain wrong.
So let's look at the observation that one of the cultures was susceptible to cephalosporins. This is almost certainly wrong. We know that the cephalosporins break down the cell wall, making the bacteria revert to much smaller SUB-MICROSCOPIC L-forms.
Sub-miscroscopic means they can't see them with their normal lab microscopes. So they assume the bacteria have gone away. Why do they assume this? Because they just haven't listened to the host of people over the last half-century, people like Virginia Livingstone, Alan Cantwell, Emil Wirostko, Thomas McPherson Brown and Lida Mattman. It is easier to shut their ears. So the patients suffer.
It is absolutely obvious (to me) why a tetracycline doesn't work against the organism in a broth in the same way it works in the body. They need to view my presentation on antibiotics at Chicago in order to go through the reasons, I am not going to cite them again.
The pathogens are acid-fast, gram-negative L-forms. They can look back in the papers from Livingstone or Brown in the 1940s and 1950s to find out more about this type of bacteria.
Propionibacterium Acnes is frequently assocciated with Sarcoidosis. I suspect it is only a coinfection, however, not the primary pathogen. Just look in any Pubmed search (eg this one) http://tinyurl.com/d9a84
Similarly, Borrelia, Rickettsia and Mycobacteria have all been closely associated with Sarcoidosis in the past.
..Trevor..
Randy Wymore's research
It looks like Randy Wymore's group is doing all the right things, and that they have observed the same pleomorphic bacterial forms as Emil Wirostko and Andy Wright observed. The lack of flagella seems characteristic of the pleomorphs behind Th1 disease. It is great that they are using blood-agar for their culturing, that is the first step towards the realization that these bacteria have a survival adaptation which can only persist in-vivo. It is also not new technology, as Treponema pallidum (syphilis) can only be cultured on fresh blood-agar, and I am amazed so few scientists have learn the lessons from Treponema and M.leprae.
We have recently been working with the genomes of a number of species, as Benicar is active against many of those which are known to form the Th1 pleomorphs. I will take a look at Stenotrophomonas maltophilia, but I suspect that this species is just a co-infection which one group acidentally noticed as being in the wrong place at the wrong time.
I think the big mistake is that pretty well everybody is still following the concept of Koch (mid-1800s)- that a single pathogen leads to a single disease. By working at the level of the bacterial genome I see much more similarity between the L-form species than one would expect, if Koch had been correct. Although it is still believed that one pathogen leads to, for example, leprosy, I am not so sure. The antibiotics used against these diseases are certainly wide-spectrum, and not species-specific[] With Th1 disease, there are certainly many active pathogens, none of which can be easily cultured from the pathogenic L-forms.
It will be interesting to see how things progress. Please let me know if anything new happens, and I will let you know if I find anything of special interest.
..Trevor..
P.S. Other abxs are probably not capable of killing the Th1 pleomorphs, so don't be surprised if others haven't seen the same responses as yourself. But please let Doc know what you have observed. Benicar is a key antibiotic in the mix we use, and the other MP abx are chosen specifically so as to go after the 70S bacterial ribosome. What we have discovered is totally unique. The more I unravel the underlying science, the more obvious that becomes.
Infectious diseases specialists
Researchers who are working on fundamentally revolutionary concepts are not generally welcomed by the specialty of Infectious Disease, which in most cases is still guided by the postulates of Koch, dating back to the 19th century.
There was a conference covered by CBC Radio in 1999 where many eminent professors described 'occult' forms of bacteria, yet nothing much has been done to follow this line of reasoning. Public health administrators seem to be looking for 'evidence' before they are prepared to use their imaginations. And evidence is hard to come by when you haven't thought very much about the underlying problem.
The CBC webpage is still online at
http://www.radio.cbc.ca/programs/ideas/shows/bacteria/bacteria.html
and the MP3 audio is at URLs
http://joimr.org/99-05-28-ideas.mp3
http://joimr.org/99-06-04-ideas.mp3
To find and culture CWD bacteria
What are the proper steps a doctor would need to take if he wanted to find or culture CWD bacteria?
The proper steps are these.
1. He would contact the scientist who has published papers describing the actions of the bacteria
2. He would contact the scientists who claim to have imaged the bacteria
3. He would contact scientists who claim to have cultured the bacteria
He might start, for example, by studying Lida Mattman's and Andy Wright's talks at the Chicago conference, or by picking up the phone and having a chat with me about our "Autoimmunity Reviews" paper.
Sitting back and twiddling your thumbs is not an acceptable substitute for any of the above actions.
..Trevor..
Viruses
Everybody is looking for something conventional, like a virus. Nobody in clinical medicine seems to understand how pathogenic the nasty species of bacteria are, particularly how mutagenic they are, and so they keep looking for viruses. Occasionally they find some bacterial species present which they can culture and it, too, is labelled as an "enfant terrible." But the real pathogenic mechanism remains un-noticed.
Additionally, it seems that those seeking it can't see the cause even when it stares them in the face. After all, we have been publishing our bacterial pathogenesis for several years now. Surely they have heard of it? None have called me to chat...
..Trevor..
Detection and Identification of Previously Unrecognized Microbial Pathogens
By David A. Relman, assistant professor of medicine and of microbiology and immunology at Stanford University, Stanford, California
Features of a number of important but poorly explained human clinical syndromes strongly indicate a microbial etiology.
Bacterial persistence and expression of disease.
http://tinyurl.com/644db
Domingue GJ Sr, Woody HB.
Note: This article is available for free downloading via the publisher's website.
"Growth of acid fast L forms from the blood of patients with sarcoidosis" Thorax. 1996 May;51(5):530-3
Almenoff PL, Johnson A, Lesser M, Mattman LH.
http://tinyurl.com/3mfcj
You can search for more of Lida Mattman's papers at
http://tinyurl.com/c9h7j
General Discussion of the Marshall Protocol-Using Microscopes to view the L-form Bacteria in your blood
Live Blood Analysis
LBA involves taking a pin prick of blood, smearing it on a slide and immediately viewing it under a high powered microscope with the image being projected onto a screen for viewing by the patient.
"In all science, in order to conduct a useful experiment, or perform a useful analysis, one has to understand what one is looking for.
As far as I know, none of the practitioners of LBA routinely look for the intraphagocytic pathogens, nor do they use techniques which would allow them to discover the Th1 pathogens.
It is technically possible for them to learn what to look for, but they do not seem to understand why they should. The LBA practitioners whom I have met, still cling to their old ideas and technologies, just like the practitioners of 'big M medicine'."
..Trevor..
Animal studies
Animal studies are useless to examine the effects of the Th1 pathogens. Please see may presentation to DMM2007 (Harvard).
http://autoimmunityresearch.org/dmm2007/dmm2007-handout.pdf
Last edited on Tue Mar 4th, 2008 22:49 by Meg Mangin R.N.
____________________
Nothing contained in this site is or should be considered, or used as a substitute for, medical advice, diagnosis or treatment by your physician.
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Meg Mangin R.N.
Research Team (on leave)
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Posted: Thu Oct 27th, 2005 02:40 |
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(filelink)
Photos and pictures of CWD bacteria
The most dangerous pathogens are the intra-cellular ones you can't see. They are not being killed, and so they don't create antibodies, and they slow apoptosis, so they are very weak on PCR as well. They are too small to see under the optical microscope (0.01-0.025 microns diameter) and hundreds live in a single white blood cell. Andy Wright dark-field images them as tiny filamental (chain of pearls) colonies. These are the pathogens the MP is killing.
Take a look at them in this photo:
http://autoimmunityresearch.org/wirostko-fig3.jpg
or in a short sequence from an Andy Wright movie:
http://autoimmunityresearch.org/budding1.wmv
The following papers explain Dr. Mattman's and Dr. Wrights' methodology.
Growth of acid fast L forms from the blood of patients with sarcoidosis.
Authors: Almenoff PL, Johnson A, Lesser M, Mattman LH
Thorax. 1996 May;51(5):530-3.
PMID: 8711683 [PubMed - indexed for MEDLINE]
Histologic observations of variably acid-fast pleomorphic bacteria in systemic sarcoidosis: a report of 3 cases.
Author: Cantwell, AR Jr
Growth. 1982 Summer;46(2):113-25.
PMID: 6184266 [PubMed - indexed for MEDLINE]
http://tinyurl.com/cjfx3
provides a wonderful review of the complexities of how the bacteria can enter macrophages and infect them. Although not really definitive as to the exact mechanism the CWD employ, it does cover most of the groundwork.
..Trevor..
Cysts are really colonies of these tiny L-forms enclosed within a protein shell. A good booklet to read on this (with pictures) is
http://tinyurl.com/3vnys
Using Microscopes to view the L-form Bacteria in your blood
Wirostko papers
(Soon to be available online)
If you look at the Wirostko photographs, and there are about 20 of them in the three papers, you will see the bacteria variously encased in tubules (what some seem to be referring to as 'biofilms') (and which seem similar to Dr Andy Wright's photographs) and exoskeletons, within which there is an homogenous medium..... The exoskeletons, however, should not be ignored, as the cytoplasm is a dynamic (moving) environment and I suspect protective proteins would be quickly eroded without some form of tubule or exoskeletal structure.
..Trevor..
____________________
Nothing contained in this site is or should be considered, or used as a substitute for, medical advice, diagnosis or treatment by your physician.
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Meg Mangin R.N.
Research Team (on leave)
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Posted: Thu Oct 27th, 2005 02:44 |
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(filelink)
Intracellular microbiota cause chronic, degenerative diseases
Microbiota
We have found that chronic inflammatory disease is caused by a hitherto poorly documented Microbiotia of intra-phagocytic biofilm-dwelling bacteria, a microbiota which was documented to exist in Stem Cells by the late Emil Wirostko (Columbia Uni, ca.1988).
I have fleshed out at least one molecular mechanism whereby this Microbiota can disable the Nuclear Receptor transcribing the 5 copies of the MTSS1 gene, and the 3 copies of the MTUS1 gene. ..Trevor..
The diversity of bacteria is hard to fathom
National Public Radio recently aired an interview explaining how the tools of molecular genomics have expanded our perspective of living things.
It used to be thought there were simply: "animals, vegetables and fungi." Now, since we can observe things on a molecular level, scientific classification has changed.
We know the animal kingdom is actually a very small branch in the tree of life, dwarfed by the vastness of microbes. If you listen to the following program (less than 10 minutes), it reviews how our perspective has developed but it also seems to point to how far we have to go in understanding microbiota.
National Public Radio, Science Out of the Box
'Animal, Vegetable, Fungi ' Lesson Revised by Angela Seabrook
aired on All Things Considered Dec. 1, 2007
http://tinyurl.com/36t5aw
This interview with Carl Zimmer includes such topics as the controversy caused in the late 1970's when Dr. Carl Woese at the University of Illinois redefined the "Tree of Life" classification by defining a new domain, Archaea.
A somewhat similar perspective, if a little more forcefully and controversially put forth, can be found at URL
http://rpvss.ucsd.edu:8080/ramgen/calit2/metagenomics/doolittle.rm
W.Ford Doolittle: Metagenomes and Metaspecies
"I will submit that there is no such thing as a microbial species"
Mechanism to avoid phagocytosis
The immune system destroys pathogens by a process of phagocytosis, where the macrophages engulf the pathogen and then digest it by breaking its DNA up into fragments. At that point it is no longer a viable organism.
The Th1 microbiota has developed a mechanism to avoid phagocytosis, and live inside the same cytoplasm that would normally digest the individual organisms. ..Trevor..
Biofilm species
The primary Th1 pathogens are biofilm-dwelling species. Lysobacter seems to pop up frequently in the studies, along with Staph, Eubacteria, Methylobacter, and others.
The L-forms of species which are not obligate biofilm dwellers, can contribute to the "pea-soup" by contributing their own survival genetics to the metagenomic community with horizontal transfer of their DNA, or by sharing the proteins and enzymes they produce.
L-forms are just a subset of the metagenomic community, and probably not the founding subset.
There are definitely multiple species within the biofilm-protected metagenomic communities in the phagocyte cytoplasm. All affect each other, and affect the host.
Take a look at this article on the subject, posted at Bacteriality.com.
..Trevor..
Last edited on Fri Jul 25th, 2008 21:58 by Meg Mangin R.N.
____________________
Nothing contained in this site is or should be considered, or used as a substitute for, medical advice, diagnosis or treatment by your physician.
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Meg Mangin R.N.
Research Team (on leave)
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Posted: Thu Oct 27th, 2005 03:23 |
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(filelink)
Understanding antibiotics action
This website was put together by two scientists from the Max Planck Institute in Germany, which collates together the knowledge about how antibiotics inhibit bacterial protein synthesis. The molecular models are taken from a variety of scientific papers, and provide a clear insight into exactly how each antibiotic works.
The page for the 30S antibiotics is at URL
http://www.riboworld.com/antib/30santib-eng.html
while the page summarizing the 50S ribosome blockade is at URL
http://www.riboworld.com/antib/50santib-eng.html
How Antibiotics Work
interactions between antibacterial agents and phagocytes
http://cmr.asm.org/cgi/content/full/13/4/615
Interference of Antibacterial Agents with Phagocyte Functions: Immunomodulation or "Immuno-Fairy Tales"?
____________________
Nothing contained in this site is or should be considered, or used as a substitute for, medical advice, diagnosis or treatment by your physician.
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Meg Mangin R.N.
Research Team (on leave)
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Posted: Thu Oct 27th, 2005 03:42 |
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How a scientist might be able to deduce how a microscopic bacterium worked, just by analyzing its genome
It is not complex, but I will use a lot of words to make sure I convey the concepts as succinctly a possible. Please bear with me 
I will discuss 2 examples of this, first our own paper "Putative Antibacterial Actions of Angiotensin Receptor Blockers" at URL http://tinyurl.com/249ks and secondly, "A study of the Protein Structures, Functions and Metabolic Pathways in Treponema pallidum and Borrelia burgdorferi" by a group at Yale led by Mark Gerstein. An abstract of their paper is at PubMed http://tinyurl.com/cbusy and a fulltext preprint at URL http://papers.gersteinlab.org/e-print/spirochete-jmmb/preprint.pdf
Let me take a different example first, a simple illustration of how we can use genomics to try and find what species of bacteria might be generating a particular toxin. The first job is to sequence the particular toxin, and determine its structure, particularly those sections of it which are pure protein, composed of amino acid sequences.
The National Library of Medicine maintains an online BLAST search containing the 387 bacterial genomes which have already been sequenced at URL http://www.ncbi.nlm.nih.gov/sutils/genom_table.cgi
A diagram showing the inter-relationships and subspecies of sequenced bacterial genomes is at URL http://www.ncbi.nlm.nih.gov/sutils/genom_tree.cgi
So, given our example of researching this toxin, we would take a small segment of its protein, maybe with 15-20 amino acids, and use BLAST (either online or downloaded to our workstations) to find candidate DNA in the 387 bacterial genomes which might be able to produce this toxin. Then, once we have a handful of prime candidates, we further narrow down the possibilities by using more and more knowledge of the decoded toxin structure.
Finally, we have to use our biochemistry to examine each of the structural anomalies, and try to identify enzymatic reactions which might be altering the toxin between its transcription from the organism's mRNA, and its final form in the bloodstream. In this step one has to model the molecular structure of the proteins, and use a lot of computer power to figure out instabilities in that structure where folds might occur, or where enzymes might interact to change its shape or structure.
Folds are very important in molecular biology, especially the transmembrane receptor proteins, where the folds are used to cleave and transport peptides and proteins from one side of the membrane to the other.
Broadly this is what Gerstein, et al, did. After matching up all the candidate proteins that they thought might be involved in the bacterial energy metabolism, they then identified folds and computer-generated the resulting final proteins.
At this point another set of computer programs are used to identify which molecules are likely to react with each other, and in particular, whether such reactions are likely to be involved in the energy metabolism.
Not easy work, and usually one involving many, many students (doing the grunt work).
In our own paper ("Putative..") we identified the section of the transmembrane G-protein called the "Angiotensin AT1 Receptor" when the ARB Benicar bound to the receptor, and looked for similar structures in the bacterial genomes, structures which might indicate how the bacteria were using the angiotensin they scrounge from the (human) host. We found no structures which correspond to that of the human, indicating that the angiotensin receptors in bacteria almost certainly have a different function from the angiotensin receptors in man. This conclusion is reinforced by Gerstein's work.
Clearly, the job of identifying single proteins which can be produced by a bacterial genome is very much easier than the Gerstein group work of identifying and mapping out an entire metabolic pathway. But I hope I have given you an overview of how Genomics can produce answers to dilemmas that are not readily solved by clinical medicine alone.
..Trevor.. (filelink)
The complexity of DNA to RNA to protein synthesis in the human body is beyond most scientist's comprehension. For example, there are micro-segments of RNA that never make it into proteins, due to interaction with enzymes, other proteins, and small molecules. . The complexity of the interaction between pathogens and the body defies complete description. If you can't deal with uncertainty, then please don't play with molecular medicine.
The number of antimicrobial peptides is large. The interactions between pathogenic proteins/RNA and human proteins/RNA is likely profound. In the healthy human body the immune system 'just works'. Until you understand the complexity of the body, at the molecular level, you can't develop an appreciation for the statistical improbability of such a hodge-podge system (as the immune system) 'just working.' The pragma of drug discovery have failed to produce a solution for chronic disease, and they will continue to fail because the concepts driving drug discovery represent a ridiculous over-simplification of the way the immune system really works.
..Trevor..
Last edited on Tue Mar 4th, 2008 22:48 by Meg Mangin R.N.
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Nothing contained in this site is or should be considered, or used as a substitute for, medical advice, diagnosis or treatment by your physician.
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Meg Mangin R.N.
Research Team (on leave)
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Posted: Wed Nov 30th, 2005 03:44 |
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The need for a Benicar blockade
(filelink)
The infected immune cells are phagocytes and they circulate in blood and tissues. Phagocytes are also capable of accumulating in regions of inflammation. In the extreme case of sarcoidosis they clump together and form granuloma; clusters of phagocytes without the normal supporting structure.
Th1 inflammation is due to the non-destruction of the phagocytes (reduced apoptosis) because the bacteria live within them in harmony. The bacteria are nicely nestled inside the phagocytes. The immune system is not killing them so no antibodies will be present. Although PCR does often give a weak signal, it is weak because the lifetime of the phagocytes is long (slowed apoptosis) and so they don't die and expose their 'insides' to the bloodstream very often.
The intracellular bacteria cause the phagocytes to emit the Th1 cytokines, apparently giving the bacteria extra protection or nourishment (we just don't know why yet). Those cytokines are what cause long term damage to the tissues and to the well-being of the human host.
The CWD bacteria are killed by blocking the synthesis of proteins by which they protect themselves from the phagocytic cells with antibiotics. When the CWD bacteria lose this protection, the cytokines in the cytoplasm of the phagocytes digest them. This will invariably lead to the destruction of phagocytic cells too.
The host phagocytic cells do regenerate due to apoptosis (programmed cell death) but there is now abundant evidence that the bacteria actually cause the phagocytes to live longer than the average 40 days (so as to not have to move-home so often, I guess).
Dieoff of the infected white cells is a problem. It is typical for the SED rate to increase and for the blood cell counts to move around from one extreme to the other as the MP progresses. Neither of these problems, both apparently due to phagocyte remnants, are negligible.
Additionally, antibodies will be formed when the phagocytes release their bacterial fragments. The antibodies cause malaise as well. How much malaise nobody knows just yet.
The Jarisch-Herxheimer reaction was first observed when mercury (a weak antibiotic) was used to treat the bacteria of syphilis (Treponema pallidum). Many bacterial infections cause Herxheimer. For example, in the recent Anthrax attacks people actually died because by the time they got to the hospital the Anthrax organisms had multiplied to the point where killing the organisms actually killed the patients.
Herxheimer itself is common; patients get Herx in Syphilis, Tuberculosis, and many other diseases. What is different in the Th1 diseases is, somewhat like the case with Anthrax, we are carrying a heavy load of pathogens by the time we become symptomatic. The degree of Herx experienced is because the Th1 infection has been growing, unhindered, for most of a patient's life. Sadly, many Tuberculosis patients do not kill off their TB bacteria, and end up with a condition which is just becoming recognized as "chronic TB." http://tinyurl.com/5hpmo
The actions of Benicar are extremely complex and I outlined some in our "Putative.." paper:
http://www.joimr.org/phorum/read.php?f=2&i=53&t=53
It is not helpful to look at Benicar in Th1 disease as an anti-inflammatory; this greatly simplifies the actions of the Angiotensin Receptor Blocker. The Benicar blockade weakens the bacterial defenses and Angiotensin II also participates in the complex signaling by the STAT receptors. All of which is far too complex to discuss in this forum. However, I will state that it is not helpful to look on Angiotensin blockade as being purely palliative (anti-inflammatory). It is much more complex than that and an effective angiotensin blockade is germane to ultimate recovery from these diseases.
The VDR Nuclear Receptor is key to the operation of the innate immune system, that part of the immune system which will attack intraphagocytic organisms. The VDR controls key elements of the body's innate immune response. The ARB Benicar dose-proportionally inhibits the runaway VDR in order to allow the innate immune system to operate again (the pathogens get it into an inoperable state by generating too much 1,25-D and possibly by generating cofactor-toxins as well).
Some other drugs, especially the azoles, also affect the operation of the D-metabolites, and/or the VDR. But they do it in a manner which is not dose-controllable, as Benicar does. Additionally, Benicar affects a number of other key receptors as well, and just happens to have a near-perfect mix of actions, from the point of view of making innate immunity function again, even in the continued presence of the pathogens."
Dr. Trevor Marshall, PhD
"Common Angiotensin Receptor Blockers may directly modulate the immune system via VDR, PPAR and CCR2b"
Theor Biol Med Model. 2006 Jan 10;3(1):1
PMID: 16403216 [PubMed - as supplied by publisher]
http://tinyurl.com/8wqk5
A copy of the PRELIMINARY PDF, which has the tables and figures arranged in a more easily readable format, can be downloaded from
http://AutoimmunityResearch.org/arb-tbiomed-paper.pdf
"Marshall TG: Molecular genomics offers new insight into the exact mechanism of action of common drugs - ARBs, Statins, and Corticosteroids. FDA CDER Visiting Professor presentation, FDA Biosciences Library, Accession QH447.M27 2006"
An online 'RealVideo 9' version of the DVD of Dr. Marshall's FDA CDER presentation is available online at url
http://autoimmunityresearch.org/fda-visiting-professor-7mar06.ram
____________________
Nothing contained in this site is or should be considered, or used as a substitute for, medical advice, diagnosis or treatment by your physician.
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Meg Mangin R.N.
Research Team (on leave)
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Posted: Sat Dec 10th, 2005 13:58 |
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Immunosupression and Anti-Inflammatory Activity of Antibacterial Agents
(filelink)
Two hypotheses have directed the use of antibacterial agents in inflammatory diseases: either the drug displays intrinsic anti-inflammatory activity (empirical observations or demonstrated in vitro or ex vivo effects) or it acts on a latent (unrecognized) pathogen (Chlamydia, Mycoplasma, etc.), causing chronic inflammation. Whatever the putative mechanism (direct or indirect), the modulation of detrimental phagocyte activity is recognized as the basis for antibiotic action.
The use of antibacterial agents as anti-inflammatory drugs falls into four categories: (i) agents which have been in use for a long time (sulfones, sulfonamides, and clofazimine); (ii) drugs which have recently triggered interest, particularly in rheumatoid arthritis (cyclines and ansamycins); (iii) drugs which are effective in specific diseases (for example, macrolides in diffuse panbronchiolitis) and show promise in other inflammatory settings; and (iv) drugs which could be developed in the near future but are at present only being studied in animal models.
Tetracycline is widely accepted as an effective drug in the treatment of inflammatory acne. One mechanism by which this drug exerts its effect is by inhibiting the proliferation of Propionibacterium acnes. However, the lack of correlation between the drug dose regimen and cutaneous bacterial counts has led to speculation that this drug also interferes with the inflammatory reaction .
Esterly, N. B., J. S. Koransky, N. L. Furey, and M. Trevisan. 1984. Neutrophil chemotaxis in patients with acne receiving oral tetracycline therapy. Arch. Dermatol. 120:1308-1313
http://tinyurl.com/8ep4q
Similarly, the theory that persistent Mycoplasma infections may cause rheumatoid arthritis has been suggested to explain the benefit of lengthy courses of tetracyclines in this disease.
Sanchez, I. 1968. Tetracycline treatment in rheumatoid arthritis and other rheumatic diseases. Bras. Med. 82:22-31.
Tetracyclines have been also used in reactive arthritis, i.e., nonpurulent inflammation of a joint following urogenital, gastrointestinal, or lower respiratory tract infections.
Lauhio, A., M. Leirisalo-Repo, J. Lähdevita, P. Saikku, and H. Repo. 1991. Double-blind, placebo-controlled study of three-month treatment with lymecycline in reactive arthritis with specific reference to Chlamydia arthritis. Arthritis Rheum. 34:6-14 http://tinyurl.com/anhha
Recently, a multicenter double-blind placebo-controlled trial concluded that minocycline was safe and effective in patients with mild to moderate rheumatoid arthritis, supporting the use of this drug (alone or as adjunctive therapy) in rheumatic diseases.
Tilley, B. C., G. S. Alarcon, S. P. Heyse, D. E. Trentham, R. Neuner, D. A. Kaplan, D. O. Clegg, J. C. C. Leisen, L. Buckley, S. M. Cooper, H. Duncan, S. R. Pillemer, M. Tuttleman, and S. E. Fowler. 1995. Minocycline in rheumatoid arthritis A 48-week, double-blind, placebo-controlled trial. Ann. Intern. Med. 122:81-89
http://tinyurl.com/exvam
A small trial performed in early diffuse scleroderma generated promise, since four of the six patients who completed the trial (minocycline at 50 mg × 2/day for 1 month, increasing to 100 mg × 2/day for the following 11 months) had complete resolution of their skin disease.
Le, C. H., A. Morales, and D. E. Trentham. 1998. Minocycline in early diffuse scleroderma. Lancet 352:1755-1756
http://tinyurl.com/7helz
The anti-inflammatory action of tetracyclines seems related to a nonantibacterial mechanism: impairment of phagocyte functions is widely acknowledged, as is the inhibitory effect of these drugs on collagenase and gelatinase activity. These latter effects have also been suggested to play a role in the tetracycline-induced improvement in periodontal disease.
Golub, L., S. Ciancio, N. Ramamurthy, M. Leung, and T. McNamara. 1990. Low-dose doxycline therapy. J. Periodontal Res. 25:321-330 http://tinyurl.com/duwhh
Further interesting hypotheses include the potential antitumor activity of doxycycline linked to its inhibitory effect on metalloproteases.
Fife, R. S., and G. W. Slede, Jr. 1995. Effects of doxycline on in vitro growth, migration, and gelatinase activity of breast carcinoma cells. J. Lab. Clin. Med. 125:407-411 http://tinyurl.com/c994b
In addition, the anti-inflammatory action of tetracycline has been proposed to be of benefit to prevent endotoxic shock by blockade of LPS-induced TNF- and IL-1 secretion.
Schapira, L., W. A. Soskolne, Y. Houri, V. Barak, A. Halabi, and A. Stabholz. 1996. Protection against endotoxin shock and lipopolysaccharide-induced local inflammation by tetracycline: correlation with inhibition of cytokine secretion. Antimicrob. Agents Chemother. 40:825-828 http://tinyurl.com/aqy8w
Excerpted from Interference of Antibacterial Agents with Phagocyte Functions: Immunomodulation or "Immuno-Fairy Tales"?
http://cmr.asm.org/cgi/content/full/13/4/615
........................................................................................
This paper states "Moreover, pre-exposure to agents that selectively inhibit protein synthesis (30 S or 50 S subunit inhibitors) or DNA metabolism (DNA gyrase) mitigated subsequent tPMP-1 induced killing of an otherwise susceptible S. aureus strain in vitro. "
In other words, the tPMP-1 antimicrobial peptide did not kill this intracelleular staph species if they had been pre-exposed to 30S or 50S inhibitors, such as mino, clindy or zith.
So it does look as though the immunosuppression from higher dose abx occurs because the immune system antimicrobial peptides don't work properly in the presence of the abx.
http://pharmrev.aspetjournals.org/cgi/content/full/55/1/27#SEC3_6_4
..Trevor..
Last edited on Thu Jun 21st, 2007 21:14 by Meg Mangin R.N.
____________________
Nothing contained in this site is or should be considered, or used as a substitute for, medical advice, diagnosis or treatment by your physician.
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Meg Mangin R.N.
Research Team (on leave)
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Posted: Sun Dec 18th, 2005 03:05 |
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(filelink)
Infection eyed as culprit in chronic disease
By Susan J. Landers Special to Hernando Today
Published: Sep 16, 2004
Imagine prescribing antibiotics for patients with atherosclerosis, or administering vaccines to prevent schizophrenia. Many researchers are thinking outside the box and are pursuing the infectious agents they believe might play a large role in causing chronic diseases.
''It is becoming increasingly acceptable and recognized that infections are probably an underappreciated cause of chronic disease," said Siobhan O'Connor, M.D., assistant to the director of the U.S. National Center for Infectious Diseases at the Centers for Disease Control and Prevention.
The list of chronic diseases known to be caused by infectious agents is growing. AIDS, cervical cancer, liver cancer and peptic ulcers all result from these bugs, and researchers are exploring links to heart disease, additional cancers and psychiatric disorders. About 70 percent of all deaths in the United States are caused by chronic diseases, making them a prime target for research attention.
There was a time when the very idea of an infectious agent causing a chronic disease brought heaps of scorn upon the scientists who proposed it. That's what happened in the 1980s, when it was suggested that ulcers were caused by the bacterium Helicobacter pylori rather than stress and spicy food. Since then, H. pylori has been linked to duodenal ulcers, gastric cancer and certain types of lymphomas.
The ulcer story caused a shift in thinking that went well beyond that one disease, said E. Fuller Torrey, M.D., associate director of laboratory research at the Stanley Medical Research Institute in Bethesda, Md. He has been examining the role of infectious agents in schizophrenia and bipolar disorder ''for more years than I care to remember." As for the current status of his research: ''I wouldn't say we were respectable, but we are no longer not respectable, either."
His work with Robert H. Yolken, M.D., a professor of pediatrics at Johns Hopkins University in Baltimore, has recently centered on the roles of the herpes viruses and a parasite, Toxoplasma gondii, as possible triggers for the psychiatric disorders.
But in general, even if an infection plays some role in chronic disease, it is hardly the sole cause, experts agree. Torrey and Yolken devised a working hypothesis, for instance, stating that most cases of schizophrenia are generated by infections and other environmental events occurring in genetically susceptible individuals.
The role of genes in many disorders has been recognized for about a century, Torrey noted, and the hope was that sequencing of the human genome would solve the riddle of chronic diseases and present a cure.
''If you asked someone in the mid- to late 1980s where we were going research-wise, they would say these are genetic diseases, and as soon as we get the human genome sorted out, we will identify the genes involved and we can all go home and play golf," Torrey said. ''That clearly has not been the case."
What is clear to him is that multiple genes are involved in many diseases, and evidence points to a link between predisposing genes and infectious agents. ''That made our research of greater interest."
The role of infection in cardiovascular disease is another area that, while not yet accepted, is attracting notice, particularly since heart disease is the No.
1 killer in the United States.
For example, recent studies have linked several common infections with a person's risk of developing atherosclerosis. It is possible that a bug causes the disease, said Michael Dunne, M.D., vice president of clinical development in infectious disease at the pharmaceutical giant Pfizer Inc. Chlamydia pneumoniae is his prime suspect at the moment. ''If you look at the arteries at autopsy of people with atherosclerosis, you find evidence of Chlamydia in 50 percent or 60 percent of patients."
''The next step is, can you do anything about it?" Dunne asked. That's where a series of antibiotic trials enter the picture. Although early results have not been positive, the findings from large trials could show whether a course of antibiotics is beneficial to heart patients.
Continuing search for MS trigger
The search for an infectious trigger for multiple sclerosis, or MS, also has been under way for decades, said Richard T. Johnson, M.D., distinguished professor of neurology, microbiology and neuroscience at Johns Hopkins School of Medicine.
When he first began researching the causes of MS in the 1960s, there was a firm conviction that the disease was due to an external agent, most likely a virus. But the early suspects turned out to result from mistakes, either misidentifications or lab contamination. That caused the idea to fall out of fashion.
Recently, however, interest peaked again. The targets are four rather ubiquitous agents: Chlamydia pneumoniae, herpes virus 6, Epstein-Barr virus and endogenous retroviruses. Since all are common, research is focusing on the quantity of the microbes and their location in the body. ''That's a very interesting but complicated argument," Johnson said.
New technologies should help with the recognition of novel agents or already established agents in chronic disease, O'Connor said. ''We also need to design epidemiologic studies in a more rigorous fashion so they are reproducible," she added.
Meanwhile, some of the confirmed relationships between infections and chronic diseases aren't receiving sufficient consideration in the clinical world, she said. Even the well-established link between H. pylori and peptic ulcers may be missed.
And other established links, such as that between Lyme disease and neurologic symptoms, also could go unrecognized, O'Connor said.
There are also prevention opportunities to be seized, she said. For example, physicians can tell patients that they have the power to prevent some liver cancers by avoiding exposure to the hepatitis B and C viruses.
MICROBES UNDER SUSPICION Some scientists contend that a substantial number of chronic diseases could be linked to infectious agents. The evidence trail is more pronounced for some than others, but the following were placed under the microscope at a recent Institute of Medicine Workshop:
Infectious agent: Chronic disease/condition
Chlamydia pneumoniae: atherosclerosis
Enteroviruses: diabetes mellitus type 1
Hepatitis B virus: liver cancer
Herpes simplex virus type 2: schizophrenia
Human papillomavirus: cervical cancer
Measles virus: developmental disabilities
Poliovirus: paralysis
Toxoplasma gondii: schizophrenia
Various viruses: multiple sclerosis
Source: The Institute of Medicine's The Infectious Etiology of Chronic Disease
This story can be found at:
http://www.hernandotoday.com/health/MGBQX5RE7ZD.html
Last edited on Thu Jul 26th, 2007 02:13 by Meg Mangin R.N.
____________________
Nothing contained in this site is or should be considered, or used as a substitute for, medical advice, diagnosis or treatment by your physician.
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Meg Mangin R.N.
Research Team (on leave)
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Posted: Sun Jan 15th, 2006 04:21 |
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The superiority of minocycline over other tetracyclines minosuperiorlink
Here is a paper describing the extra features of minocycline.
http://www.postgradmed.com/issues/1997/04_97/cunha_1.htm
Note the following particularly:
1. Better lipid solubility -> better CNS and cellular penetration
2. Effectiveness against Staph, which is one of the strains contributing to these chronic diseases
There is a HUGE difference. I have seen people die on doxycycline, while they recover on minocycline and demeclocycline. Please understand that the Marshall Protocol may seem simple, but it has a lifetime of my own research behind it. Anything you change will likely get you into trouble. That is why the website is here, and the moderators will help you understand issues like this.
Please understand that 99.9% of ID specialists do not fully understand the way that antibiotics work their magic on the pathogens' Genome, at the molecular level. Conversely, 99.9% of the material you will read about antibiotics is incomplete, and much is just guesswork.
Minocycline is a 30S bacterial ribosomal inhibitor,http://tinyurl.com/9r5hj so it preferentially inhibits protein synthesis of these bacterial pathogens. However, it can also inhibit mammalian protein synthesis to a degree, which we generally don't want to do...this can suppress the immune system and other important functions. So, we want just enough inhibition to block the pathogens ability to synthesize proteins without significantly inhibiting our own ability to synthesize proteins.
..Trevor..
Doxycycline
Doxycycline has some effect on the brain which can promote a feeling of 'euphoria.' Additionally, it does not kill all the L-form species (it is not nearly as wide-spectrum as Minocycline) these are both dangerous (IMO) characteristics because they can make people prematurely think they have 'conquered' their infection.
We have to remember that there are many species we are fighting against. Second, the immune system is so finely balanced between not killing them, and killing them, that small changes to our lifestyle, or to our food, or caused by other drugs we are taking, might stop the immune system from killing the bacteria. If there is no killing the patient will generally feel better.
I think it would be a miracle if anybody was able to clear their bodies of the bacteria in less than 12 months, and it seems to take 2-3 years (typically).
Long term therapy with any single antibiotic will cause the killing of bacteria susceptible to that antibiotic, and the repopulation of the tissues with bacteria resistant to that antibiotic. So your bacterial load may well be increasing while your original symptoms are feeling better. Chances are that the herx is being manifest as a totally different set of symptoms by the 'newer' species.
An MP abx holiday usually does not accelerate bug killing, but the same level of bug-killing can continue unabated. The exception to this is if you are using higher doses than the MP suggests, or taking the antibiotics more frequently, so that they have a suppressive effect on the immune system.
..Trevor..
____________________
Nothing contained in this site is or should be considered, or used as a substitute for, medical advice, diagnosis or treatment by your physician.
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Meg Mangin R.N.
Research Team (on leave)
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Posted: Tue Mar 7th, 2006 00:37 |
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Red cell versus white cell infection
The Red cells can still be infected, and Andy Wright's videos show that they are. But it is the infection in the phagocytes that feeds the cytokine release, and the disease process. The cell has to have a nucleus for the bacteria to work their magic on the DNA. Red cells don't have a nucleus, but they can still be infected. That would not normally lead to a Th1 chronic disease, as the immune system would be able to deal with the infection. Of course, your immune system is saturated with the Th1 attack, so you may not be generating antibodies, etc, from the red cell infection.
..Trevor..
____________________
Nothing contained in this site is or should be considered, or used as a substitute for, medical advice, diagnosis or treatment by your physician.
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Meg Mangin R.N.
Research Team (on leave)
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Posted: Tue Mar 7th, 2006 02:03 |
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[filelink]
Horizontal-DNA-transfer between intracellular bacteria
My own perspective is that the intra-phagocytic bacteria which cause chronic Th1 immune disease accumulate over a lifetime. We are not dealing with one species. Indeed, in Sarcoidosis many species have been identified, obviously using differing PCR primers.
We are almost certainly dealing with horizontal-DNA-transfer, the sharing of DNA between those bacterial species which have evaded phagocytosis. Sharing the aspects of their genomes which have produced the ability to persist inside phagocytes. The longer they have persisted in the human host, the more the opportunity for horizontal-DNA-transfer. That is why I call them "antibiotic resistant" species, trying to convey this concept with the most widely recognized terminology.
How do I know they are intra-phagocytic bacteria? It was predicted by the cellular biochemistry, and confirmed by the patients' Herxheimer response and white cell apoptosis (in their blood work). Confirmed also by microscopy (see below).
For example, Bacillus anthracis has two plasmids. One putatively contains the genes encoding its lethal toxicity, one putatively encodes genes allowing it to evade phagocytosis. In some regions this species is endemic in soil, and it is reasonable to expect that a human would have become exposed to low-levels, non-lethal levels, of this pathogen in the course of a lifetime.
Let's just suppose the plasmid containing the anti-apopotosis genes transfects into a host, or somehow persists through multiple cycles of phagocyte apoptosis. If that individual were to be exposed to Bacillus israelii, which lacks both plasmids, and is commonly used as an industrial insecticide, then what would result? Would the gene on the surviving anthracis plasmid(s) be trascribed by the israelii ribosome? In my opinion the answer is - "most probably." Would that horizontal-DNA-transfer produce a pathogen capable of evading phagocytosis - again, the answer is "most probably."
When you look at the Borrelia genome, with 17 to 21 plasmids, depending on which paper you rely upon, and then look at the other species known to be implicated in sarcoidosis, including Rickettsia, Mycobacteria, and Propionibacteria, it becomes obvious, to me at least, that the number of potential opportuinities for horizontal transfer of DNA becomes immense as the host grows older.
There is multiple experimental validation of the intraphagoctic infection hypothesis. Emil Wirostko, at Columbia in the late 1980s, imaged infected macrophages, lymphocytes, monocytes and neutrophils from patients with sarcoidosis, JRA, Crohn's and ulcerative colitis. He used TEM, and the images are stunning.
Dr Andrew Wright, from the UK, has developed a method using pinprick blood, allowed to degrade from 6-36 hours, a process which causes the bacteria to break out of cells, whence they can be seen on x8000 dark-field microscopy, using time-lapse video. Both nucleated cells and non-nucleated cells are shown to have been infected. Dr Bela Boszik recently developed a flourescent antibody to Borrelia, and stained the bacteria found using Andy's technique to show that at least some of the visible artifacts stain as Borrelia. But not all of them. There are multiple species present. And none take the traditional Borrelia spirochetal form until the blood gets very old, and then, only at the very edge of the sample. These are L-forms, and Andy has demonstrated some of them changing from intra-cellular to spirochetal forms.
..Trevor..
.......................................................................................
Resistance Genes In Our Food Supply
American Society for Microbiology
May 23, 2007
Science Daily — Could the food we eat be contributing to the continuing rise of antibiotic-resistant infections? Harmless and even beneficial bacteria that exist in our food supply may also be carrying genes that code for antibiotic resistance. Once in our bodies, could they transmit the resistance genes to disease-causing bacteria?
"The data indicate that food could be an important avenue for antibiotic-resistant bacterial evolution and dissemination. The role of commensals, especially food-borne microbes, in transmitting resistance genes are becoming a concern to the scientific community," says Hua Wang of the Ohio State University, presenting May 23, 2007 at the 107th General Meeting of the American Society for Microbiology (ASM) in Toronto.
The culprit is a process known as horizontal gene transfer, in which bacteria in close proximity to each other can share genetic information, including genes that code for antibiotic resistance. Horizontal gene transfer between disease-causing bacteria in the hospital setting has already been recognized as an important avenue for the exchange of antibiotic-resistance genes among pathogens.
Research has also already demonstrated that pathogenic bacteria have the ability to engage in horizontal gene transfer with various commensal bacteria and even beneficial bacteria, including those from the food chain. What concerns scientists is that the size and diversity of the gene pool represented by commensal bacteria increases the likelihood of gene transfer and some commensals possess high frequency gene transfer mechanisms.
"We have demonstrated not only that organisms carrying such intrinsic mechanisms have the potential to become an important reservoir for antibiotic resistance genes but, more importantly, that these intermediate organisms can disseminate antibiotic resistance genes in subsequent events much more effectively than the parental donor strain," says Hua.
"Once we no longer limit ourselves to foodborne pathogens and look at commensal bacteria, we will find that the magnitude of antibiotic-resistant bacterial contamination in the food chain is tremendous," says Hua.
In a study published last year, she and her colleagues tested a variety of ready-to-eat food samples including seafood, meats, dairy, deli items and fresh produce purchased from several grocery chain stores. With the exception of processed cheese and yogurt, antibiotic-resistance gene-carrying bacteria were found in many food samples examined.,
"Despite the fact that this study only screened for a limited number of resistance markers, it illustrated the prevalence of antibiotic-resistant commensals and antibiotic-resistance genes in retail foods," says Hua. "While further research is needed to establish the direct correlation between the antibiotic-resistant microbes from foods and the antibiotic-resistant population in host ecosystems, it is evident that a constant supply of antibiotic-resistant bacteria, partnered with occasional colonization and horizontal gene transfer, are at least partially responsible for the increased antibiotic resistance profiles seen in humans."
Antibiotic resistant infections are an increasing public health problem, says Marilyn Roberts of the University of Washington. Depending on the disease and the patient, an antibiotic-resistant infection could triple a hospital stay. A methicillin-resistant Staphylococcus aureus infection in a hospital patient can cost thousands of dollars more to treat. In some cases, such as the new extensively resistant tuberculosis, antibiotics are no longer effective, forcing doctors to take extreme measures like removing an infected lung.
The problem is not just confined to the food supply. Recent studies have shown antibiotic resistance genes in bacteria in the digestive tract of young infants. Since these children were still breast- or formula-feeding and had not eaten solid food yet, they must have acquired these genes somewhere other than the food supply. This suggests that resistance genes from the environment might have played an important role, says Hua.
"Antibiotics and the contamination of the environment is a medical problem, an agricultural problem and a human problem. Everybody plays a role in it. They also have a stake in it," says Roberts.
But there are things that can be done to minimize resistance genes in our food. Hua is currently working on characterizing the optimum conditions and processing parameters to minimize the emergence of these genes in fermented products. In time, and with a little help, she hopes to expand this research to other food industries as well.
"Given the proper investment of money, effort and time we can identify the steps that need to be taken at the processing level to minimize the emergence of antibiotic resistance genes in our food supply," says Hua.
Note: This story has been adapted from a news release issued by American Society for Microbiology
See also The Bacterial Boom...Implications of the Human Microbiome Project
Last edited on Wed Jul 30th, 2008 22:59 by Meg Mangin R.N.
____________________
Nothing contained in this site is or should be considered, or used as a substitute for, medical advice, diagnosis or treatment by your physician.
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Meg Mangin R.N.
Research Team (on leave)
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Posted: Thu Mar 9th, 2006 00:09 |
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Cytokines
Cytokines are proteins that are produced in response to an immune stimulus. They are released by cells for intracellular signalling and attacks on infections and altered cells. Cytokines stimulate immune cell growth and differentiation (what type of immune cell develops) and they can affect how cells behave.
Cytokines act by binding to specific membrane receptors which then signal the cell to alter its gene expression. Cytokines are often produced in a cascade, when one cytokine induces its target cell to make more cytokines and then that process is repeated over and over. There are a lot of different cytokines and they may work synergistically to increase the effects of each other (so their combined effect is greater than the sum) or antagonistically, causing opposing activities.
Cytokines can have an effect on the cells that secrete them (autocrine), on the cells nearby (paracrine) or even on distant cells (endocrine).
This information and more is included in this tutorial by Dr. Janet Decker at the University of Arizona.
Belinda
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Nothing contained in this site is or should be considered, or used as a substitute for, medical advice, diagnosis or treatment by your physician.
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Aussie Barb
Research Team
| Joined: | Thu Jul 22nd, 2004 |
| Location: | Australia |
| Posts: | 19446 |
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Posted: Mon Jun 5th, 2006 20:08 |
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Studies citing bacterial cause for chronic diseases (click here)
Even the CDC is starting to wonder about with chronic disease.
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Barb: Dx Inflammatory Disease Endocrine Imbalance 2003| 24+ years not Dx| ABCofMP
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Aussie Barb
Research Team
| Joined: | Thu Jul 22nd, 2004 |
| Location: | Australia |
| Posts: | 19446 |
| Status: |
Online
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Posted: Sun Jul 9th, 2006 04:31 |
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Antibiotics are not harmful
Dr Marshall wrote: Antibiotics are not harmful, per se, in fact, some are essential to maintenance of life.
There are many families of antibiotics, each different in their actions. One of my presentations at the recent LAX conference introduced some of them. I also spoke about them in Chicago, 2005. You can't make a wide-ranging statement about safety or efficacy. Each antibiotic is a little bit different in its actions and its properties.
The MP antibiotics are bacteriostatic, and there is no data that long term use of MP antibiotics leads to resistant species forming. In fact, Minocycline was introduced in 1968, and in those 40 years virtually no organisms have developed resistance. Minocycline is one of the few antibiotics still active against MRSA, yet it has been widely prescibed, for decades, to try and control teenage acne.
We use Minocycline as a base, and add other symbiotic bacteriostatic antibiotics, specifically to make sure that no species can escape. The molecular genomic science is clear and precise. I have presented the rationale consistently in all my presentations since about 2003. The MP is unique in its avoidance of the mechanisms leading to antibiotic resistance.
Your body produces its own endogenous antibiotics. Another of my presentations at the LAX conference, and my FDA presentation, reminded folks that the VDR is responsible for the expression of cathelicidin antimicrobial peptide (CAMP) part of the body's own response to pathogens expressing LPS. Antibiotics are not harmful, per se, in fact, some are essential to maintenance of life.
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Barb: Dx Inflammatory Disease Endocrine Imbalance 2003| 24+ years not Dx| ABCofMP
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Meg Mangin R.N.
Research Team (on leave)
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Posted: Fri Aug 11th, 2006 20:42 |
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Which cells are infected?
(whichcellsfilelink)
Th1 illness is caused by the cytokines created in the nucleus of cells. Nuclear receptors, such as the VDR, are key here (see my FDA presentation). Red cells do not have a nucleus. Forget the red cells, it is infection of the white cells which is making you really ill and perverting your immune system.
It was this breakthrough in understanding of the pathogenic process that allowed me to realize where the pathogens were, and how they drove disease. Even today, when I speak with an Infectious Diseases expert they always want to know the bacterial species. I tell them it doesn't matter - focus on what the bacteria do, and how they do it. The species are irrelevant.
Once you understand their biochemical fingerprint (Th1) then you can start looking for them physically, as Emil Wirostko did, and as Dr Andy Wright has recently done. We will be discussing Andy's microscopy at length during our soon-to-be-announced conference at LAX.
Phagocytes
Dendritic cells are just one type of phagocyte. Emil's TEM photographs shows that Neutrophils, Lymphocytes, Monocyctes and Macrophages are all infected in Th1 disease. In his day the dendritic cells had not been identified as a group seperate from macrophages. All these phagocytes contribute to the Th1 disease process.
In Babesia the phagocytes being infected with bacteria prevent them from mounting a Th2 response against the Baesia parasite. Basesia therefore remains in the bloodstream, and lives, and multiplies, in red blood cells. So it doesn't contribute much to the Th1 disease process or its severity.
Stem cells (mast cells)
Emil Wirostko was convinced that the stem cells were infected in folks with severe Th1 disease. Since all cells develop from the stem cells, under this scenario most cells in the body would harbor the pathogens. Although this is a concept foreign to medicine, it would explain why the pathogens spread to so many different body subsystems. And it certainly makes sense from a scientific point of view, since, if they can evade phagocytosis, there is no reason why the stem cells would not become infected during a life-long illness.
If there are not enough phagocytic cells to do the cleanup then one becomes ill. AIDS is of course a disease where exactly this occurs. The Lymphocyte count falls to zero, and the patient loses the ability to fight infection.
As an MP patient's body clears pathogenic DNA and dead cell fragments folks feel ill. We call it "herx."
..Trevor..
Take a look at Cutting edge: mast cell antimicrobial activity is mediated by expression of cathelicidin antimicrobial peptide.
There is the reason why mast cells become infected, and why the chronic diseases proliferate throughout all cell lines in the body, and why they are so tough to reverse...
..Trevor..
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I started a thread "all you need to know a | | |
