http://www.ncbi.nlm.nih.gov/pubmed/19074813

PURPOSE: NOD1 plays an important role in host defense and recognizes the minimal component of bacterial cell walls, meso-diaminopimelic acid (iE-DAP). Polymorphisms in NOD1 are associated with autoinflammatory diseases characterized by uveitis such as Crohn’s disease and sarcoidosis. NOD1 is homologous to NOD2, which is responsible for an autosomal dominant form of uveitis. Nonetheless, the role of NOD1 in intraocular inflammation has not been explored. The induction of uveitis by iE-DAP in mice and the potential contribution of interleukin (IL)-1beta were investigated. METHODS: BALB/c mice or mice deficient in caspase-1 or IL-1R1 and their congenic controls were injected intravitreally with iE-DAP or saline. The time course, dose response, and contribution of IL-1beta to ocular inflammation were quantified by intravital video microscopy, histology, and immunohistochemistry. NOD1 and IL-1beta were measured in eye tissue by immunoblotting and ELISA. RESULTS: NOD1 protein is expressed in the eye and promotes ocular inflammation in a dose- and time-dependent fashion. The authors previously defined the role of IL-1beta in NOD2 uveitis and tested whether NOD1 and NOD2 used similar mechanisms. Treatment with iE-DAP significantly increased IL-1beta, which was caspase-1 dependent. However, in contrast to NOD2, caspase-1 and IL-1R1 were essential mediators of iE-DAP-induced uveitis, suggesting that NOD1 and NOD2 induce ocular inflammation by distinct mechanisms involving IL-1beta. CONCLUSIONS: These findings demonstrate that NOD1 is expressed within the eye and that its activation results in uveitis in an IL-1beta-dependent mechanism. Characterizing the differences between NOD1 and NOD2 responses may provide insight into the pathogenesis of uveitis.

This means that American consumers are being exposed to live bacteria that are known to cause Inflammatory Bowel Disease (Johne’s Disease) in a wide range of animals, including dairy and beef cattle, and is suspected of being a cause of human Crohn’s Disease.

The most important points are

1. From May 2002 through April 2003, milk was purchased from stores in California, Minnesota and Wisconsin – three of the USA’s top 5 milk-producing states. (The other two are New York and Pennsylvania.)

2. Milk was tested for presence of viable MAP, using methodologies created in the 1990′s by British researchers, to study the presence of MAP in retail milk in the UK. It has been known since 1998 that United Kingdom dairy products are contaminated with live MAP.

3. Of 702 US samples tested, 2.8 percent contained viable MAP – that is, MAP bacteria that was alive, capable of multiplying and establishing infection, and capable of causing Inflammatory Bowel Disease in susceptible species.

4. Rate of positives was similar among states, but there was a seasonal effect. More positive samples were found during July, August and September.

This study confirms what we in the Paratuberculosis Awareness and Research Association have long believed: that American consumers are eating and drinking food that contains a live and dangerous bacterium, through the medium of MAP-contaminated dairy products.

On average 2.8% of milk cartons were found to be contaminated. Assuming that the average milk consumer drinks from a single carton of milk per day, this means that the average milk consumer is exposed to live paratuberculosis on average ten times a year. Consuming from 2 different milk cartons per day, 20 times a year, etc. This applies particularly to children, who are encouraged to consume milk, for the calcium and protein content. An average American child living in Minnesota, California or Wisconsin, if they consume from one milk carton per day, will have been exposed to live paratuberculosis up to 100 times by their tenth birthday.

The published results apply only to milk. Although research has shown that the food treatment methodologies used to manufacture other dairy products, such as cheese, chocolate, whey, etc, are incapable of destroying MAP, no US research has sought to determine the percentage of these retail dairy products also contaminated with live MAP. The majority of Wisconsin milk is used for cheese manufacture. Recent scientific results have shown that the methods to manufacture cheddar cheese do not kill paratuberculosis.

To this date, the food safety regulators in the United States, the Food & Drug Admninistration (FDA), have taken no action on the presence of live paratuberculosis in milk, dairy and beef products. The time has now come for the FDA to revise its policy of inaction, and to act immediately to protect American consumers from this dangerous bacterium.

If you believe that the US Government should put the interests of the American public before the interests of American Dairy and Beef Industries, and act to eradicate MAP from human food, please visit the PARA web site for steps you can take to help.

1. Original datasheet from American retail milk study
http://www.johnes.org/newsfiles/109216471862392.html

2. Articles about live paratuberculosis contamination in human food
http://www.crohns.org/map_food

3. Articles about the relationship between Mycobacterium avium subspecies paratuberculosis and Crohn’s Disease.
http://www.crohns.org/articles
http://www.crohns.org/research
http://www.crohns.org/treatment

4. Government agencies with responsibility for regulating Food Safety.
http://www.crohns.org/governments

5. PARA’s work to get the US Congress to help address this problem.
http://www.crohns.org/congress

6. What you can do to help.
http://www.crohns.org/help

Since the National Institute of Allergy and Infectious Diseases (NIAID) hosted a workshop on possible infectious causes of Crohn’s Disease in 1998, attended by all of the PARA Board of Directors, including myself, PARA directors Cheryl Miller and Karen Meyer have worked tirelessly with both NIAID staff and with Crohn’s Disease researchers to obtain funding for those researchers who wish to investigate infectious causes of Crohn’s Disease.

The first spectacular success in this ongoing campaign to find a cure for Crohn’s Disease is the provision of US$1.8 million in funding for researchers who are investigating a infectious cause for Crohn’s Disease, with a strong emphasis on research into Mycobacterium avium subspecies paratuberculosis (MAP).

Further information from the PARA web site

http://www.crohns.org/

Among the researchers who have received research funding in this round are two members of PARA’s Scientific Advisory Council, Dr. Saleh Naser and Dr. Norman Pace.

http://www.crohns.org/council/naser.htm
http://www.crohns.org/council/pace.htm

The NIH funding involves not only the National Institute of Allergy and Infectious Diseases (NIAID), but also involves the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK), the National Institute of Health that has more traditionally been associated with Crohn’s Disease research.

Specifically, the NIDDK has funded another member of the PARA Scientific Advisory Council, Dr. Fouad El-Zaatari, to continue his long and detailed research program on the role of paratuberculosis in Crohn’s Disease. Dr. El-Zaatari has received funding to continue, among other research, his pioneering work on “In-Situ Hybridization”.

The latter is a technique whereby paratuberculosis bacteria which are present in gut tissue can be labelled and made detectable by attaching, for example, x-ray opaque metal atoms to them. This technique has potential for use as a clinical diagnostic technique, particularly because it can detect the cell-wall-deficient forms of MAP which are believed to be involved in the pathogenesis of Crohn’s Disease.

More details on Dr. El-Zaatari and his work from the following URLs

http://www.crohns.org/para/el-zaatari.htm
http://www.paratuberculosis.org/members/el-zaatari.htm

More information on In-Situ Hybridization from

http://www.paratuberculosis.org/proc6/abst5_2.htm
http://www.paratuberculosis.org/proc7/abst6_p7.htm

You can read more from the following links
NIAID: Crohn’s Disease: Is There a Microbial Etiology? Recommendations for a Research Agenda
NIAID: Recommendations for a Research Agenda
PARA’s efforts benefit Crohn’s sufferers – NIH allocates $1.8 million to study infectious cause of Crohn’s

Momentous developments are afoot!!

The investigators conducted a search for microbial antigens that pANCA binds to. The surprising result they found was that, in a percentage of Crohn’s patients, pANCA reacts strongly with a protein which is shared among several species of mycobacteria.

The importance of this is that the team doing the investigation were “mainstream” immunologists who started out looking at the immune responses of Crohn’s Disease and found mycobacteria, rather than starting out with mycobacteria and finding immune responses.

As the investigators themselves conclude: “The association of HupB- binding serum IgA with IBD provides new evidence for the association of a mycobacterial species with Crohn’s disease. ”

Abstract available from
http://www.ncbi.nlm.nih.gov/pubmed/10569769

Full abstract repeated at the bottom this post

================================================================

Journal: Infect Immun 1999 Dec;67(12):6510-7
Title: Identification of a novel mycobacterial histone H1 homologue (HupB) as an antigenic target of pANCA monoclonal antibody and serum immunoglobulin A from patients with Crohn’s disease.
Authors: Cohavy O, Harth G, Horwitz M, Eggena M, Landers C, Sutton C, Targan SR, Braun J
Address: Department of Pathology and Laboratory Medicine, Los Angeles,
California 90095, USA.

Abstract: pANCA is a marker antibody associated with inflammatory bowel disease (IBD), including most patients with ulcerative colitis and a subset with Crohn’s disease. This study addressed the hypothesis that pANCA reacts with an antigen(s) of microbial agents potentially relevant to IBD pathogenesis. Using a pANCA monoclonal antibody, we have previously identified the C-terminal basic random-coil domain of histone H1 as a pANCA autoantigen. BLAST analysis of the peptide databases revealed H1 epitope homologues in open reading frames of the Mycobacterium tuberculosis genome. Western analysis of extracts from six mycobacterial species directly demonstrated reactivity to a single, conserved approximately 32-kDa protein. Direct protein sequencing, followed by gene cloning, revealed a novel 214-amino-acid protein, an iron-regulated protein recently termed HupB. Sequence analysis demonstrated its homology with the mammalian histone H1 gene family, and recombinant protein expression confirmed its reactivity with the 5- 3 pANCA monoclonal antibody. Binding activity of patient serum immunoglobulin G (IgG) to HupB did not correlate with reactivity to histone H1 or pANCA, indicating the complex character of the pANCA antigen. However, anti-HupB IgA was strongly associated with Crohn’s disease (P < 0.001). These findings indicate that the 5-3 pANCA monoclonal antibody detects a structural domain recurrent among mycobacteria and cross-reactive with a DNA-binding domain of histone H1. The association of HupB-binding serum IgA with IBD provides new evidence for the association of a mycobacterial species with Crohn’s disease.

PMID: 10569769, UI: 20038316

The most important point made for sellers of cattle was that if they make a statement “This cow does not have Johne’s disease”, then they are legally liable if the cow does actually turn out to have JD, a strongly possible occurrence due to the inaccuracy of current testing methods for JD. The only statement they can make is that “This cow has tested negative for Johne’s disease, by methods X, Y, and Z”.

It is possible that this principle might be extended to “Mycobacterium paratuberculosis does not cause Crohn’s disease”, which is the current position of the dairy and beef industries around the world. If/when proof that paratuberculosis causes Crohn’s is revealed, then they might be liable, since evidence is becoming much stronger that live Mycobacterium paratuberculosis are present in cattle derived foods.

With 1.5 million people with clinical Crohn’s disease around the world, and at least 400,000 people with clinical Crohn’s disease in the USA, it could result in a class-action lawsuit on a Big Tobacco Scale.

If I were in the cattle industry, I would be moving to eradicate Johne’s disease from herds of food animals now. Instead, the US Animal Health Association advocates a “Voluntary Certification” program, whereby volunteer farmers test their herd for Johne’s disease, and there is no obligation if they test positive. Such animals currently go into the food chain to make hamburgers.

More info on the USAHA meeting available from

http://www.crohns.org/media/index.htm

Info on the finding of Mycobacterium paratuberculosis in British retail milk available from

http://www.crohns.org/governments/uk.htm

And of course, for a wealth of information about paratuberculosis and Crohn’s, visit

http://crohn.ie/archive/welcome.htm

__________________________________________________________________
Title
Identification of Mycobacterium avium complex in sarcoidosis.

Author
el-Zaatari FA; Naser SA; Markesich DC; Kalter DC; Engstand L; Graham DY
Address Inflammatory Bowel Disease Laboratory, Veterans Affairs Medical
Center, Houston, Texas 77030, USA.

Source
J Clin Microbiol, 34(9):2240-5 1996 Sep

Abstract
Cell wall-defective bacteria which later reverted to acid-fast bacilli have been isolated from sarcoid tissue. These have not been conclusively shown to be mycobacteria. Specific PCR assays were applied to identify mycobacterial nucleic acids in these cultured isolates and in fresh specimens obtained from patients with sarcoidosis. Positive amplification and hybridization were observed with Mycobacterium avium complex- and/or Mycobacterium paratuberculosis-specific probes in five of the six cultured isolates and two fresh skin biopsy samples and one cerebrospinal fluid specimen. There was no amplification or hybridization with Mycobacterium tuberculosis or M. avium subsp. silvaticum probes, respectively. Patients’ sera were also tested for antibody reactivities by immunoblotting with M. paratuberculosis recombinant clones expressing the 36,000-molecular-weight antigen (36K antigen) (p36) and the 65K heat shock protein (PTB65K). All seven sarcoidosis, four of six tuberculosis, and all six leprosy patient serum specimens showed strong reactivity with p36 antigen. In contrast, 13 of 38 controls showed only weak reactivity with p36 (P = 0.002 for controls versus sarcoidosis samples). Similarly, PTB65K reacted with high intensity with sera from 5 of 5 sarcoidosis, 5 of 6 tuberculosis, and 5 of 6 leprosy patients, compared with its low-intensity reaction with 5 of 22 controls (P = 0.001 for controls versus sarcoidosis samples). This study demonstrates the isolation and/or identification of M. paratuberculosis or a closely related M. avium complex strain from sarcoid skin lesions and cerebrospinal fluid. Furthermore, the reactivity of antibodies in sarcoid patient sera against p36 and PTB65K antigens was comparable to the reactivity of sera obtained from patients with known mycobacterial disease. Collectively, these data provide further support for the theory of the mycobacterial etiology of sarcoidosis.

____________________________________________________________________
Title
Serologic reactivity against Mycobacterium paratuberculosis antigens in patients with sarcoidosis.

Author
Reid JD; Chiodini RJ
Address
Robinson Memorial Hospital, Ravenna, Ohio.

Source
Sarcoidosis, 10(1):32-5 1993 Mar

Abstract
Although sarcoidosis has clinical and histopathologic similarities to some forms of tuberculosis and other mycobacterial infections, attempts to establish a mycobacterial etiology have not been successful. Using cytoplasmic antigens derived from a wild strain of Mycobacterium paratuberculosis in an enzyme-linked immunosorbent assay, patients with sarcoidosis were found to have immunoglobulin levels significantly higher than those found in a control population in the IgG, but not in IgA or IgM antibody classes. Results were comparable to those reported from patients with Crohn’s disease, where M. paratuberculosis has been intensively studied as a possible etiologic agent. To elucidate these relationships, examination of DNA from sarcoid tissues for possible homology with DNA from M. paratuberculosis and closely related organisms, as well as cultural attempts with techniques and media appropriate for M. paratuberculosis may be warranted.

__________________________________________________________________

A mother on the USA, Karen Meyer, has a son who has Crohns disease. She is very concerned that her son may have contracted Crohns from consumption of food contaminated with the bacterium M paratuberculosis, and is concerned that many other people in the USA may contract Crohns disease, again possibly as a result of consumption of contaminated food.

She has attempted to find out what actions the US government is taking to ensure that food purchased and consumed by the public at large is indeed safe. She has been in touch with several government agencies, including the FDA, the US Department of Agriculture and the US Animal Health Association.

She is very unhappy about the replies she has received, and has determined to raise awareness of this issue among members of government, so that answers can be found to the following important questions

o Is M paratuberculosis is involved in causing Crohns disease?
o Are consumers infected with M paratuberculosis through the food chain?
o If M paratuberculosis is involved with Crohns disease, then how can sufferers of Crohns disease be medically treated to eliminate the infection?

Mrs Meyer wants you to join her in her awareness-raising campaign, and has formed the “Paratuberculosis Awareness and Research Association” (PARA) to organize this campaign.

PARA has a web page. The URL for this page is

http://www.crohns.org/

The page contains details of correspondance that Karen has had with the various agencies of the US government, and minutes of meetings of some those same agencies.

I encourage all sufferers of Crohns in the USA, and elsewhere, to visit the PARA web site.

Mycobacterium paratuberculosis infects the milk supply. It is shed by infected cows in their milk, and it is not killed by standard pasteurization techniques. 2.9% of all dairy cattle in the USA are infected with Mycobacterium paratuberculosis.

Only the UHT (Ultra Heat Treatment) pasteurization process kills Mycobacterium paratuberculosis. Therefore, if you want to reduce your exposure to M paratuberculosis, you should switch to UHT milk. Also, you should only consume other dairy products (cream, cheese, etc) that have been made with UHT pasteurized milk.

Also, there are other pathogenic bacteria that are not killed by standard pasteurization. Some of these cause food poisoning, and would have an extremely adverse affect on people with active IBD (Inflammatory Bowel Disease) if they were infected with these bacteria. Again, only UHT pasteurization is capable of destroying these bacteria.

I have gathered together the relevant information and research about bacteria, milk and pasteurization onto a web page. The URL is

http://crohn.ie/archive/uhtmilk.htm

I strongly recommend that you visit this web page.

This is part of a larger site that contains all of the research relevant to whether or not Mycobacterium paratuberculosis causes Crohns disease. The URL is

http://crohn.ie/archive/welcome.htm

If you have Crohns disease, I recommend that you visit the site.

This organism causes a chronic intestinal disease, which is extremely similar to Crohn’s disease, in cattle, sheep, goats, chickens, monkeys, deer, dogs, horses, and rabbits, to name a few. Mycobacterium paratuberculosis is endemic to diary cattle in most countries of the western world, including most parts of the USA and Canada.

The organism is shed by infected cows in their milk, and is not killed by pasteurization. There is a high probability that Mycobacterium paratuberculosis infects the milk that you personally drink.

If you want to read about this further, see the URL

http://crohn.ie/archive/welcome.htm