chimerism and scleroderma....must read

whoo..don't know where to really start...but here goes.....

I have been reading about the 'causes' of Scleroderma. One aspect is called Chimerism. An example given was that of a pregnant woman.absorbing fetal cells into her 'system'. These fetal cells are foreign to the mother's body, and an immune response to the foreign cells ensue. Now let's take this a little deeper....how many of you patient's have had a blood transfusion? I did 19 years ago, and my body rejected the foreign dna immediately, and I went into renal failure....I had multiple blood donors...hence multiple foreign dna entered my system. Ok...here is where my interest is really peeked......GMO foods. If you haven't enlightened your mind to the atrocities of our food supply...NOW IS THE TIME!!!!! Genetically Modified Foods...have spliced and diced, inserting and depleting, whole dna, rna and gna cells. Did you know that the product roundup has been spliced into seeds, and when the plant grows, it develops it's own pesticides...fast forward to human consumption of matured vegetable which produces roundup......you got it...you eat the food, and ingest the whole dna factors of the roundup gene...guess what...you now produce roundup, a toxic to humans..in your very own system. Corn, wheat, soy, rice, beet sugar, many other veggies and fruits have all been sliced and diced genetically..adding foreign dna, rna or gna into the mix. And we eat them. Studies show the adverse affects on animals from gmo feeds. Other countries have done the research...and have banned all GMO's in their countries. Also meat eaters...you are eating genetically modified animals, as they eat genetically modified feeds...not to mention the hormones and chemical agents given to the animals in their feed. Now add vaccines into the mix, and do a little research on the additives and dna, rna and gna factors involved. Those healthy vitamins many of us take to aid our immune systems, are produced in a process where they are cultivated in gmo'd fecal matter and inulin. Are you starting to get a picture of the various avenues by which we could have gotten this disease, and/or a plethora of other diseases that may affect us or our loved ones? I am newly diagnosed...less than 2 months......and am learning much. I could go on and on...but I am hoping this opens up the general idea that perhaps it is NOT our immune system just going rogue and attacking itself...I believe that our immune systems are searching for the genetic culprits we have been infested with...and in the war..our own cells become collateral damage, Would love to hear opinions from others on this ...albeit..overwhelming topic.

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The connection to a viral or bacterial infection can also be clearly explained by a lack of protease.

Parasites, fungal forms, and bacteria are proteins (protease digest proteins) that additionally disguise themselves in a protein shell that our bodies may view as normal. A virus is essentially a nucleic acid (DNA or RNA) enclosed in a protein shell.
Proteases work by removing this protein shell. With the protective barrier down, your immune system can then recognize and destroy the invading organism. Autoimmune patients often say their disease was preceded by a viral or bacterial infection. If you are bordering on a protease deficiency and you contract a viral or bacterial infection, this would further deplete your protease, as they would be needed to ‘disarm’ the invader.

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Since I got my official diagnosis, I have pretty much ditched all my 'social' time on the computer. Instead I have spent time looking thru archives of personal stories, triumph and tragedies of Sclero....in a lot of those threads you get to glean useful nuggets of info and wisdom, from those who have come before you, and have nuggets to share. I enjoyed your post.....I have a list, and every time I read a post that has information that is helpful, or is about something interesting that I know nothing about, I add to my list. I know nothing about protease and its interaction with parasites..although I knew the parasites had that impermeable casing, In my attempt to cleanse my body of parasites in the least toxic way possible, as I have read many articles that the majority of Americans have gut parasites, the toxins excreted wreak havoc on immune systems. I started taking food grade diatomaceous earth, which has a debilitating effect on parasites, as well as bacteria, fungus and viruses. There is much written about it. My rheum did their own research on it and gave me the go ahead. I don't have time to list the benefits, but if it interests you..you could look it up. I shall go look up protease..as from the quick search I did on it...looks like it could be of great assistance to my cleansing quest. Your post is appreciated...could be a nugget when I needed it. I would like to expedite the process..the diatomaceous earth is a slow gentle way to do it..but nothing wrong with getting to the same destination a little ahead of anticipated arrival...lol.

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Just to throw another wrench in the works, it may well turn out that scleroderma is not just one disease. It may well be different auto immune reactions all being thrown under one umbrella because of lack of understanding.

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Carona~I think what you are doing is smart. Knowledge really is power. As I mentioned earlier every symptom and valid scientific finding of lupus can be traced directly back to these enzymes. Now I will go one step further by saying-every symptom and every valid scientific finding of every autoimmune disease can be traced directly back to these enzymes. If you are trying to put a puzzle together, but you don't know what the total picture is, it would be very difficult to figure out where each piece belongs within the puzzle. However, if you know, for instance, that the puzzle is a picture of a "cat", when you find a whisker, you are much more likely to know where it belongs. We know that lupus originates with DNase1 and protease, so we just have to figure out the role that protease play in each part of the disease process of lupus and in other autoimmune diseases. In addition to the information I posted from ScienceDaily on a lack of DNase1 in lupus, here are some additional studies that confirm the lack of this single enzyme will lead to lupus. This means that a lack of this enzyme will cause every single symptom of lupus.


Mutation of DNASE1 in people with systemic lupus erythematosus.
Yasutomo, K., T. Horiuchi, S. Kagami, H. Tsukamoto, C. Hashimura, M. Urushihara, Y. Kuroda. 2001. Nat. Genet. 28(4):313-4.
“These data are consistent with the hypothesis that a direct connection exists between low activity of DNASE1 and progression of human SLE.”


Lupus and deoxyribonuclease.
Lachmann, P.J., 2003. Lupus 12(3):202-6.
“Mice whose DNase 1 gene is knocked out are known to develop lupus and to be otherwise normal.”

Scleroderma and RA are associated with lupus. Now we just have to find the common pathological denominators between the diseases and show how these denominators originate with a lack of protease.

Here is one.

Protease regulate a part of the immune system called tumor necrosis factor (TNF). TNF is a cytokine. Elevated levels of TNF will cause heat, redness and swelling in the joints. (In fact, TNF is what the arthritis drug Humira was designed to target.)

“Aberrant regulation of TNF is also involved in the
development of psoriasis and psoriatic arthritis" as the following study states. The researchers
concluded, “Tumor necrosis factor plays a major role in the pathogenesis of
psoriasis and psoriatic arthritis.”
Potential of Tumor Necrosis Factor Inhibitors in Psoriasis and |
Psoriatic Arthritis
Krueger, G., K. Callis. 2004. Arch Dermatol.140:218-225.
Data Synthesis: Aberrant regulation of TNF is involved in the development of psoriasis
and PsA...
Conclusion: Tumor necrosis factor plays a major role in the pathogenesis of psoriasis
and PsA, and TNF antagonists provide clinicians with a worthy alternative to traditional
therapies, which are associated with toxic effects and poor compliance.

This is one of the reasons lupus overlaps with RA. They both share elevated levels of TNF.

“TNF appears to play a major pro-inflammatory role in SLE also,” as is stated
in the research article “The role of tumor necrosis factor-alpha in systemic
lupus erythematosus” (Aringer, 2008).

And finally, here is a study that shows TNF is involved in scleroderma.

Klin Med (Mosk). 2003;81(12):4-7.
[Tumor necrosis factor alpha in systemic scleroderma].
[Article in Russian]
Alekperov RT, Timchenko AV, Nasonov EL.
Abstract
The authors present the review of the literature on the role of tumor necrosis factor alpha (TNF alpha) in scleroderma systematica (SS). It is shown that TNF alpha participates in activation of vascular endothelium, regulation of immune response and metabolism of the connective tissue by modulation of fibroblastic function. SS patients exhibit a systemic and local rise of TNF alpha content. This rise contributes to SS progression, development of fibrosing alveolitis and skin fibrous alterations in Raynaud's syndrome.

Here is a study that confirms protease regulate cytokines, such as TNF.

Neutrophil serine proteases fine-tune the inflammatory response.
Pham, C.T.N. 2008. Int J Biochem Cell Biol. 40(6-7):1317-1333.
“However, studies over the past several years indicate that neutrophil serine proteases may also be key regulators of the inflammatory response. Neutrophil serine proteases specifically process and release chemokines, cytokines, and growth factors, thus modulating their biological activity. In addition, neutrophil serine proteases activate and shed specific cell surface receptors, which can ultimately prolong or terminate cytokine-induced responses.”

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Yes, autoimmune disease DIAGNOSIS is on the rise. Of course it is; we have almost 3 times as many people as when I was born AND there are probably at least 4 times as many doctors as then, and they are much, much better educated with regard to autoimmune disease, which when I was born was poorly understood. Just consider that timeline above that Kzoo provided. No one even realized that scleroderma was systemic until 1945, and guess how long it took that information to become common knowledge without any internet back then. The current criteria for scleroderma weren't even written until 1980. How can you even expect to diagnose something without published diagnostic criteria? My father had all the same symptoms of scleroderma that I have, but he was never diagnosed. In fact never in his life did he get referred to a rheumatologist. Nor did his mother, who had the purse-string mouth, foot problems and vascular problems so common in limited scleroderma, and God only knows what else besides. Nor did his grandmother, who died of cirrhosis of the liver even though she did not drink - anticentromere antibodies can do that.

So just because more cases of scleroderma are being diagnosed does not mean that in proportion to the population that it is any more common than it ever was. For example, our neighbor died of renal failure. Back then it was called "Bright's Disease" and no one connected it with autoimmune disease, which is actually what probably caused it. The term "Bright's Disease" is now considered obsolete. http://en.wikipedia.org/wiki/Bright%27s_disease .

It's just like people saying that India has the lowest rate of celiac disease, so they must have a healthier diet. Well heck guys, that's because they aren't keeping good statistics there, because they have abysmal health care that rarely gets around to recognizing it - as proven by one of the very highest infant mortality rates in the world.

Back in the day, when all sorts of health problems (not just autoimmune disease) were poorly understood, things just didn't get diagnosed or were improperly diagnosed. That's my point. It's not just autoimmune disease that is more frequently diagnosed - it's everything! My hobby is genealogy. So I know that death certificates with "cause of death" didn't start being recorded in many U.S. jursidictions until after 1900. And if you read them, you'll see that TB was listed as "catarrh" or "consumption" and some even listed death as "old age." Either meningitis or encephalitis were listed as "brain fever". A stroke or cerebrovascular accident was listed as "apoplexy" while both hepatitis and gall bladder attacks were listed as "bilious attack," while any of these could alternatively be listed as "congestion of the liver": hepatitus, gallbladder disease, leptospirosis (bacterial), cirrhosis, alcoholic and other poisonings, and amebic infections. One forty-five year-old's cause of death was listed as "Change of life," while another recorded cause of death for the same woman was "poisoned face." (see http://www.progenealogists.com/19thdeathrecords.htm ) Another common one was "inflammation of the bowels." Another death certificate just said "cold." Anything with edema of the tissues could be listed as "Dropsy" whether it was from heart disease, kidney disease, or liver disease. "Paralysis of the bowels" could be obstruction from just about anything: tumor, a strangulation hernia, or a twisting of the intestine. I could go on and on. I hope I've made my point.

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P.S. I'm not saying that chimerism due to fetal cells isn't a trigger. It's high on my list of possibilities, because other suspected triggers (such as heavy metals, Silicon, pesticides, mycoplasma, and parvovirus) don't explain why this disease is so much more common in females than in males. Unless, of course our hormones make us females react differently to those triggers, which is of course possible.

MaggieMay, I think you're right. I recently found a very new piece of genetic expression research which supports scleroderma being an assortment of different diseases. I wish I could find it. It was a video presentation at one of the 2012 scleroderma symposiums. I wish I could find it - if I could, I'd post it.

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I think there is strong data to support that autoimmune diseases are increasing, not just diagnosis. Here are some quotes from this article on a recent study that confirms autoimmune diseases are increasing.

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Dr. Kirstin Bacani, a rheumatologist at McKay-Dee Hospital, said an increase in the incidence of rheumatoid arthritis among women has been recently shown. In 2005, 1.5 million adults in the U.S. were affected by the debilitating form of arthritis. That’s an increase over the last available report of 1.3 million adults.


The American Diabetes Association reported a 23 percent rise in type 1 diabetes over an eight-year period that ended in 2009.

Center for Disease Control researchers are unclear as to why autoimmune diseases are surging, according to the report.


Celiac disease, also shown to be on the rise, is an autoimmune disorder that causes the body’s immune system to attack the small intestine, according to the U.S. National Institutes of Health and the University of Chicago Celiac Disease Center.

Ladd said with the rapid increase in autoimmune diseases, it clearly suggests that environmental factors are at play due to the significant increase in these diseases. Genes do not change in such a short period of time, she said, adding the current state of autoimmune disease is an epidemic that should be of great concern to both the government and health officials.

http://www.standard.net/stories/2012/07/14/researchers-look-causes-autoimmu ne-diseases

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About Scleroderma being an umbrella encompassing multi auto immune disorders...my last visit with my rheum, I told her that I read that the SCL-70 blood test can exhibit a false positive...up to 50% of the time, as multi immune disorders may exist, and 'trip' the scl-70 as positive....Rhem laughed a little..and said yes that is true....but you have the symptoms to support the diagnosis....then I said...my symptoms cross over into a lot of auto immune symptoms, don't they?....Rheum said..well we can always hope in time, testing will become more sensitive, and we'll know for sure.

kinda goes along with some of the above comments, as to the 'syndrome' of diagnosing an auto immune disease in general.

You are right...in many respects...there seems to still be a lot of guesswork. with regard to Sclero and other immune disorders.

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I also wanted to share this information on silica dust and how it would relate to protease and tumor necrosis factor. As the following study states, tumor necrosis factor and protease activity were dose-dependently increased after silica exposure. This is why silica dust is associated with scleroderma.

Am J Respir Cell Mol Biol. 2007 January; 36(1): 43–52.
Published online 2006 August 10. doi: 10.1165/rcmb.2006-0197OCPMCID: PMC1899302Silica-Directed Mast Cell Activation Is Enhanced by Scavenger Receptors
Jared M. Brown, Emily J. Swindle, Nataliya M. Kushnir-Sukhov, Andrij Holian, and Dean D. Metcalfe
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; and Center for Environmental Health Sciences, Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MontanaCorrespondence and requests for reprints should be addressed to Jared M. Brown, Ph.D., Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10,

Abstract.Inhalation of crystalline silica results in pulmonary fibrosis and silicosis... However, TNF-α, IL-13, monocyte chemotactic protein-1, protease activity, and production of ROS were dose-dependently increased after silica exposure..."

Knowing that tumor necrosis factor is directly involved in the pathogenesis of scleroderma is powerful knowledge. You can lower TNF naturally without the risk of any side effects. You do not have to take a tumor necrosis factor blocker. Lowering TNF could have a profound effect on the course of the disease. There are other factors involved in scleroderma, but just like TNF, they can be explained.


Here is some information on turmeric and its ability to naturally block TNF.

“The active component of turmeric turns out to be the best blocker yet of a natural chemical called TNF, or tumor necrosis factor, which contributes to cancers and arthritis and is resistant to chemotherapy drugs,” stated Bharat B. Aggarwal, professor of cancer medicine in the Department of Experimental Therapeutics at the University of Texas M.D. Anderson Cancer Center, who has studied the spice for a decade. “You don't even need tens of thousands of dollars of TNF blockers," Aggarwal stated. "Turmeric does exactly the same thing."


Traditionally, turmeric has been consumed with some type of fat. In a typical curry, for example, turmeric root will be cooked in oil. Some of the ancient Ayurvedic texts recommend cooking turmeric in fatty buffalo milk. This ancient wisdom serves us well today. Turmeric is not absorbed well by the body unless it is consumed with some fat. Turmeric tea made with raw goat or cow’s milk will help your body properly absorb turmeric. The tea can be consumed daily.



TURMERIC TEA
Ingredients (all organic)
1 cup raw milk (goat’s or cow’s)
1/2 tsp turmeric
1 tsp cinnamon
1/4 tsp ginger
1 tsp raw honey or to taste
Directions:
Heat the milk on the stovetop until hot, stir in the spices and drizzle the honey on top. Stir and enjoy!

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Fabulous information! Thanks to all for sharing!

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Or you can just eat a lot of curry, too, since curry powder typically uses turmeric.

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As synchronicuty goes...I am weaning off initial course of methlpred, tho I started on regular prednisone, but could not refill it due to a National shortage of prednisone..seems that there has been a significant ncrease in it's use due to increasing diagnoses of auto immune diseases..per the GroupHealth Pharmacist in Tacoma, Any way more to my point....as the methylpred is decreased, my wrist pain and symptoms would increase...and in time wane, then we reduce dosage again. This last reduction left me , within one day, in a moderate amount of pain,and beginning that first night on last lowered dose, my hands, have began to fall asleep again, My hands falling asleep and waking me up repeatedly at night was my very first symptom, then the pain gradually increased until my wrist hurt so bad, I couldn't clean myself after using the bathroom, or even brush my teeth. Forget washing hair or body...I am talking totally hlpless for months .Rhuem says it's inflammation, So I decided to add an anti inflammatory, did some research on natural alternatives, and started Phenocane, which is cucurmin/(tumeric) and boswelia..and last night my hands didn't fall asleep. Hip hip hooray! As I had no reactions to the herb, I increased the dose today, and am pain free on top of it. i feel confident that removing the last 4 mg of methylpred will be doable, with this herb as a replacement. Today.. is a whoo hoo day! I am contemplating adding MSM, as I have read of it's succesful benefits in sclero forums, researched it, and my Rheum is on board with the MSM, says they have seen great results in some patient's and there are no harmful side effects.....sounds like a good thing to try, imo....but if anyone knows anything to the contrary..please give me a shout out!

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The turmeric doesn't contain a whole lot of the active ingredient which is the TNF blocker, curcumin. So when you combine it with other spices in a curry, you are getting even less of it. If you really want the active ingredient, what you want are the curcumin tablets. I tried taking them for a while along with my fish oil tablets. The problem was, it had piperine (pepper) in it to help absorption from the gut. And that aggravated my GERD. I would like to try it again, this time using a brand that doesn't have the piperine in it. However, I must acknowledge that the curcumin itself may aggravate GERD.

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tumeric can be added to foods as a food colouring and isn't just used in curries. I use it in all sorts of things such as potato dishes,
noodles, chili's and nacho stuff, rice noodles and the like. You'd be amazed at how much tumeric one can consume in the course of a week without ever having eaten a curry.

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There are many other choices available as well. Green tea, milk thistle, nettles, ginger, and rosemary for example are all good TNF blockers. Just be careful how you consume them. Just as the beneficial properties of turmeric as fat soluble, many of the beneficial compounds of herbs are water soluble. This means you should use whole organic herbs and steep them in hot water. (Make a tea) Here is a study on green tea and TNF.

http://www.ncbi.nlm.nih.gov/pubmed/11795518

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Wow, 10 cups of green tea a day was what that article was recommending! Think how much caffeine that includes! So I wonder if decaffeination also leaches out the TNF inhibitors.

Maybe I'll stick with curcumin. And yes, you can certainly use turmeric instead of a curry spice mixture. But even so Turmeric contains only 5% curcumin, so you'd have to eat an awful volume of turmeric-spiced food in order to get the equivalent of 1 tablet of Curcumin. And considering how poorly curcumin is absorbed by the stomach, you would need a significant amount to get any through to the blood stream.

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Educate yourself Carona. We are not eating aborted fetuses! One company in San Diego, Semonyx, patented a sweet taste flavor receptor derived from a cultured cell line from kidney cells taken from embryonic research in the Netherlands in 1970. This cell line is widely used in biotechnology and in no way can be construed as an "aborted fetus". Despite the ethical dilemmas that such biotech research and stem cell embryology brings forth, this is in no way a "natural flavor" derived from dead babies. At best, it is a cell receptor cultured and derived from embryonic kidney cells over 40 years ago that is used to TEST flavors.

Do your research before you go and assert such ridiculous claims.

ABC News confers (Jan. 2012) http://abcnews.go.com/blogs/health/2012/01/26/bill-would-ban-aborted-fetuse s-in-food/:

" Semonyx used proteins derived from human embryonic kidney cells to test artificial sweeteners. The cell line, known as HEK 293, was created from a human embryo in 1970 and has become a staple in biochemistry labs around the world."

NPR confers (Jan. 2012) http://www.npr.org/blogs/thetwo-way/2012/01/20/145539661/state-bill-outlaws -use-of-fetuses-in-food-industry-meets-visceral-reaction?sc=tw&cc=share:

"Based in San Diego, Senomyx has been accused of using proteins derived from human embryonic kidney cells in its research, which has been used by many large food companies. An article in the Miami New Times summarizes those claims, notes the company's denial of them — and also notes that in 2003, the company filed a patent for "recombinant methods for expressing a functional sweet taste receptor."

Agree or disagree about human cells used in biotechnology but WE ARE NOT EATING ABORTED FETUSES AS NATURAL FLAVOR!!

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A friendly response.......the embryo, as stated in your post, whose cells were used in the1970 discovery of HEK-293, was an embryo of approximate or greater than 8 weeks old. Aborted fetus is the technical term, although it is not clear whether is was the result of a 'spontaneous abortion' widely referred to as a miscarriage, or a 'selective' aborted fetus. Therefore, the statement 'aborted fetal cells', used within these 'natural flavor enhancers', is a true and correct statement, and in now way is meant to be misleading. The fact that these HEK-293 cells came from an embryo over 40 years ago, does not negate the fact that the reproduced, regenerated or cloned cells used, are any less, than from the origin of the original aborted human fetus

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC123709/.....below is a section within this link

We cloned human and rat T1Rs for functional expression experiments (Fig. ​(Fig.1).1). The G protein or G proteins that couple to the T1Rs in vivo are not known. Consequently, we transiently transfected the human T1Rs into a HEK-293-derived cell line that stably expresses Gα15, a promiscuous phospholipase C-linked G protein (15, 16). Sucrose elicited transient intracellular calcium increases in Gα15 cells cotransfected with human T1R2 and T1R3 but not in cells transfected with T1R2 or T1R3 alone. T1R2/T1R3 activity was inhibited by the sweet taste inhibitor lactisole (17); this inhibition likely reflects antagonism at the T1R2/T1R3 receptor, because lactisole did not inhibit the Gα15-dependent activity of endogenous β2-adrenergic receptor (Fig. ​(Fig.22A). In addition to sucrose, T1R2/T1R3 responded to all other sweet taste stimuli tested: the sugars fructose, galactose, glucose, lactose, and maltose; the amino acids glycine and d-tryptophan (but not its bitter enantiomer); the sweet proteins monellin and thaumatin; and the synthetic sweeteners acesulfame K, aspartame, cyclamate, dulcin, neotame, saccharin, and sucralose (Fig. ​(Fig.22B).

Senomyx has developed over 120 flavor lines, many via cloning of HEK-293....I have read 77 of their patents, 70 of them contain HEK-293.

In addition, just because it is used on a broad spectrum basis, and because it is accepted 'as business as usual', as stated by the Securities and Exchange Commision...doesn't change what it's origin is.

Now this is simply my opinion, this following portion, if the flavor enhancers are derived from a dead human, I don't care if it was grown in a petri dish, as a human...I would prefer not to unknowingly ingest, or knowingly for that matter. As a side note, because the amount of HEK-293, used as an additive is miniscule in overall use, so many parts per million, it does not require FDA approval, and because the cells are derived from an organic nature, meaning, an organic human, naturally developed, they are aloud to list the ingredient as a 'natural flavor'. Have you ever done any research on Graft vs Host disease? Some researchers believe it may be a causative factor in autoimmune diseases. That's another reason it bothers me...3 lousy months testing HEK-239 on rats...no FDA trials or tests, and in it is used in our mainstream food supply.

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I am tired, in a little pain and forgot to proof...please excuse my typos.

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