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Articles and Additional Information on Natural Microdose DNA
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Index:
Natural Microdose DNA (Mucolyxir) Use In:
DNA-Nucleotide Immunotherapy & The Use of Microdose DNA: The New Frontier
Has Begun Research in this area has exploded in the last fifty years. DNA codifies, in its nucleotide sequences, the codes of life, which are at the core of our molecular origins of life and its progression. The Human Genome Project, which determined the exact sequence of the human genome, will have great impact for many decades and centuries to come in the areas of health, life span, politics and procreation. In many ways our genetics determine much of who we are and how we are. Synthetic Stimulatory DNA There is a newly discovered regulatory use of synthetic stimulatory DNA as a signaling molecule. We will start with a concise literature review of published literature which focuses on the use of a single sequence of synthetic DNA composed of guanine and cytosine, that has been shown to exert a profound effect on immunity, allergy, and inflammation. This synthetic DNA is being intensively studied for use as a vaccine, an immunotherapy and much more. It appears to be generally safe, fast-acting and dramatic. However, more research will be required for its full development as an FDA-approved DNA drug. Millions have already been spent and dozens of researchers are involved. Natural Microdose DNA (Mucolyxir) For more on natural microdose DNA (Mucolyxir), read the presentation from Dr. Allan Lieberman, M.D., as well as interviews with Dr. Ken Unice, D.O. and Dr. Jerry Dorsam, D.V.M..
The immunostimulatory effects of bacterial extracts, and its application to host defense have been studied for over 100 years. In the last 10 years, it has been determined that unmethylated nucleotides derived from bacterial DNA are responsible for the observed beneficial immune effects. Much of this research has been performed with a specific, patented sequence of nucleotides, CpG DNA. This form of synthetic DNA has been shown to stimulate the immune system, as well as being anti-inflammatory. A partial summary of findings below are taken from review of over thirty sophisticated research publications and associated with dozens of different researchers. Their work, through in vitro studies and animal and human research, shows the enormous therapeutic potential of synthetic stimulatory DNA. Based on this body of research with respect to immunological and inflammatory modulation, synthetic DNA sequences have been found to: * Balance and enhance the immune response via normalization of cytokine ratios.1 In ailments such as asthma and allergies that affect the respiratory tract, the ratio of type-1 and type-2 T-helper cells (Th1/Th2 ratio) is altered. Specifically, the Th2 immune response is enhanced, while the Th1 immune response may be suppressed, leading to unfavorable alterations in cytokine balances that favor the disease state. CpG DNA beneficially reduces the Th2 response and enhances the Th1 response to restore homeostasis.
Synthetic DNA-based vaccines (antigens prepared with DNA-specific sequences) have been created for treatment of allergic, infectious and other respiratory ailments.8 When tested in humans, these demonstrated great potential for a safe form of allergen-specific immunotherapy.9 These agents also may be used to create effective vaccines against infective pathogens.10 Antiviral actions have been attributed to the ability of synthetic DNA sequences to induce type 1 interferons.11 A DNA G vaccine significantly inhibited RSV (respiratory syncytial virus), viral replication, mucus expression, and importantly, was associated with inhibition of RSV-induced airways responsiveness.12 To provide just one recent, specific example regarding the use of synthetic DNA to treat respiratory ailments, consider the recent manuscript by Dr. Eyal Raz and his research team from the Respiratory Biology and Medicine Department of the University of California at Davis, and School of Medicine, University of California, San Diego. Dr. Raz was one of the original researchers to utilize synthetic DNA as an immune signaling molecule. The research team found that inhaled immunostimulatory oligonucleotides can attenuate the magnitude of airway hyperactivity and airway remodeling produced in primates with experimentally induced airway disease. The nucleotide sequence that was used, characteristic of bacterial DNA, was believed to be rapidly detected by vertebrate innate immune receptors, including those on dendritic cells, macrophages, monocytes and neutrophils. The sequence (delivered mucosally or systemically) had previously been shown to inhibit airway remodeling and airway hyper-responsiveness in rodents. The present study relied on a primate model of allergic asthma using aerosolized dust mite antigen. The model exhibited the hallmarks of allergic asthma. Airways from nucleotide-treated monkeys had thinner basement membranes, fewer mucus cells, fewer eosinophils and fewer mast cells than controls. The beneficial applications of synthetic DNA are by no means limited to respiratory diseases. For example, synthetic DNA can ameliorate experimental and spontaneous murine colitis.13 These findings suggest a physiologic anti-inflammatory role for synthetic DNA in the GI tract.14 In one related study, it was concluded that the protective effects of probiotics are mediated by their own DNA, rather than by either metabolites of the probiotics or by their ability to colonize in the colon.14 Natural Microdose DNA (Mucolyxir) as an Alternative to Synthetic DNA As an alternative to synthetic DNA, a number of clinical investigators have been studying the use of a proprietary formulation of natural microdose DNA (Mucolyxir) from mammalian or other eukaryotic sources for its use for patients with allergies and other respiratory conditions. The use of this natural microdose DNA (Mucolyxir) comes as a surprise in that the clinical effect is impressive, and yet the therapeutic agent is used in the LOW microgram level. This is reminiscent of both homeopathy, where very low dose agents are used, and low dose neutralization therapy, which is often used for allergies and hypersensitivities.
AAEM Allan Lieberman, M.D. on Natural Microdose DNA (Mucolyxir) About ten years ago one of my patients who had cystic fibrosis called and told me that the product which he was using every morning, in order to help clean out his lungs, Pulmozyme, cost $13,000 a year. I was so infuriated that I called a colleague of mine and complained to him and he said to me, “Well Lieberman, if they are using DNAse*, what should we use?” Then suddenly he said, “If they are using DNAse, why don’t we use DNA.” Now what you need to know is that the logic of using DNAse was that in cystic fibrosis, a lot of that phlegm and exudate, which is infiltrating the lungs in the airway of all of these patients, is made up of a massive amount of white blood cells and their debris, which is extremely high in DNA. So that’s why they use the DNAse. So that was their logic, but what I said to my colleague was, “How did you arrive at DNA?” and he said, “I don’t know, it just sounds right.” We went out and found two or three sources of DNA and we tried it. I was fortunate enough to have twins, in their mid-twenties who had cystic fibrosis that volunteered to try these DNA drops sublingually and by God, it really worked. It had incredible expectorant action, the mucus just kept coming up so incredibly thin that we had to learn very quickly to be careful that we don’t drown these patients. They improved their pulmonary function. They gained weight for the first time in years, so much so that they had to go out and buy new clothes to fit their new bodies, and they did not have to be hospitalized for the first time in years because of their disease. So based upon this initial study, we went out and looked for other cystic fibrosis patients. Over time, we accumulated enough cases for a pilot study to see that what we were doing was really working. After the successes with the microdose DNA (Mucolyxir) with cystic fibrosis, we wondered if it would also help patients with bronchitis, asthma, and COPD. We were amazed to find that in the few cases that we tried, that it too worked, and the most amazing thing was it didn’t have any side effects. Based upon these preliminary studies, we were ready for a Proof of Concept Trial for chronic bronchitis and COPD. We hired a clinical research organization who did a study on 100 patients with these diseases. In the bronchitis study, the summary was: In patients with wet cough, sputum production, and impaired pulmonary function, which was a measure of forced expiratory volume in one second of about 65%, the DNA demonstrated increased sputum production and ease of expectoration. There was a very definite improvement in the symptoms of chronic bronchitis including ease of breathing. People were able to sleep through the night without coughing. There was significant improvement with walking and working. Objectively, there was improved pulmonary function, most notably on small airway flow, the FEV 25/75 fraction and by improved overall quality of life. The more important thing about this was it’s excellent safety profile. There was no question that there was a very statistically significant difference between the active and placebo groups. We looked at the COPD patients characterized by dry cough, little or no sputum production, and severely impaired pulmonary function, where their forced expiratory volume was in the vicinity of about 25% and with evidence of non-reversible disease. The microdose DNA (Mucolyxir) demonstrated increased sputum production with improvement in COPD symptoms, especially shortness of breath. There was obvious improvement in forced expiratory volume, and also in the carbon monoxide co-efficient of diffusion. There was significant increase in distance traveled during 6 minute walks, and a corresponding increase in their oxygenation, and again, with an excellent safety profile. After over ten years of working with microdose DNA in hundreds of patients on thousands of doses, it became apparent that there were other indications for its use. It was especially valuable in acute and chronic sinusitis, and in acute and chronic otitis media. Obstruction is often the pre-requisite of infection, so it should have come as no surprise to us that microdose DNA would also excel in chronic sinusitis and otitis media. Patients with chronic sinusitis would refuse literally to come off the microdose DNA (Mucolyxir) once we had put them on it because they felt so much better. We could pause here for just a second and ask ourselves - what’s the mechanism of action of microdose DNA (Mucolyxir), and how does it do the things we are seeing? Unequivocally, it has terrific decongestive and liquefying properties for tenacious secretions from the upper and lower airway. It also seemed to have an anti-allergy effect. When we take infants and children that are impossible to test in the office because of their size and because of their rambunctiousness, we use the DNA. We use one drop sublingually four times a day, and we find for example, that a lot of their allergic signs and symptoms literally are controlled with DNA. It also seems to have an incredibly wonderful property of reducing swelling and obstruction. We call this treatment signal therapy. It represents a whole new concept in medicine using natural products to signal the body’s regulatory systems - the nervous system, the immune system, and the endocrine system. As regulatory systems, what they’re really doing is up-regulating and down-regulating to induce homeostasis. I tell my patients that the signal is like a conductor of a symphony who stands in front of a 120-piece orchestra, and when he raises his baton and it goes down, they all play at the same time. The question of course is how does the body know whether it should up-regulate or down-regulate something. And I honestly tell them that I haven’t the foggiest idea of how the body knows to do it. The only thing I know when using this for over ten years, is it always does it right. I’ve saved the best for last because I’d like to tell you a little bit about an experience with microdose DNA (Mucolyxir) with a patient with acute and chronic otitis media. One day I was evaluating a child for ADHD. There was a terrible smell in the room and it soon became apparent that he had parulent exudate pouring out of his ear. He had a chronic otitis media, which had been there for months. The mother couldn’t clear it up. So that night I put him on microdose DNA and by morning, the exudate had reduced dramatically, and this time I looked and saw that the perforation, which was quite large initially, looked to me to be about half the size in just twelve hours. The mom called back and told me that in two and a half to three weeks, the perforation was totally closed and the exudate was gone. In clinical trials with over 100 infants and children with acute otitis media, what we found is that 80-90% of these children respond on microdose DNA (Mucolyxir). What we do at the very first sign of a cold or an ear infection is start with a drop under their tongue every 10-15 minutes for 4 doses, and a drop every one to two hours thereafter until the crying and pain subsides, and then four times daily until the infection is over. The medical literature is pretty clear that in the treatment of otitis media there are really no benefits in the use of antibiotics. But I could tell you as a pediatrician, or as an ex-pediatrician, that it is difficult to not want to use an antibiotic. We now have an agent which is extremely valuable in helping these patients. I have used natural microdose DNA (Mucolyxir) for ten years with hundreds of patients and thousands of doses. Every patient or household should have a bottle on hand for respiratory support and other uses as indicated.
Interview - Ken Unice, D.O. on Natural Microdose DNA (Mucolyxir), October 12, 2004 What do you use it for in your patients? Dr. Unice: I've used natural microdose DNA (Mucolyxir) in acute otitis media, especially in children, acute sinusitis, and acute bronchitis. I have used it in chronic bronchitis, reactive airways disease, emphysema, and mucositis. What do you have the most experience with? Dr. Unice: Probably upper respiratory, including sinusitis and bronchitis. Does it work well? Dr. Unice: Yes, I've had good success with it. If they had an infection wouldn't they need an antibiotic? Dr. Unice: Well, first of all with acute sinusitis and acute bronchitis, many of these are viral and there is no effective treatment. The good thing about microdose DNA is that it works for both viral and non-viral, or bacterial infections. That's a big plus because as it is now, there's a tremendous overuse of antibiotics. So in the viral form does it just ease the stress until the body repairs itself? Dr. Unice: No, you see results within hours the first day. You are doing something acutely, more than just giving the body time to fight the infection. In the bacterial form, even without antibiotics, you see it to be effective? Dr. Unice: Yes, this is successful in both. It's difficult to prove because we don't often look at samples of the fluid. But I would say those that appear to be bacterial respond well. So, percentage-wise is there a sense of how well it works? Dr. Unice: I would probably say 70-80%. What about the efficacy regarding otitis media? Dr. Unice: Well, I think the important thing is the relatively quick pain relief in the first three hours. There’s improvement in fever, irritability, and activity level, and the response is very quick and as I said, on the first day. Many of these children especially, will sleep the first night without pain, without waking up. And it reduces analgesic medication substantially. The good thing about it also, is that otitis has many origins including viral and bacterial and it seems to be effective in both types. Any adverse effects with any of this? Dr. Unice: I've never really seen any side effects. I've used it since 1998. I think the other point that you can make though, is there's a big trend these days to move away from antibiotic therapy. In some countries, especially in Europe, these infections aren't treated necessarily with antibiotics. However, the children are still much impacted by the infection. Also, we can help improve these situations without increasing antibiotic resistance, which is very important these days. And that's a good point, so what do you think it's doing? How do you think it's working? Dr. Unice: I don't know. I'd like to think of it as improving the drainage and mucus movement of the sinuses, and bronchial tree, and the middle ear. The response is fairly quick though, and there may be other mechanisms that are active here, like a thinning of mucus. Another use is for mucositis, which is a complication after radiation treatment for oral pharyngal cancer. So what happens there? Dr. Unice: A thick mucus is produced in the throat. It doesn't cure it, but it does improve the mucus, causing significant thinning. Have you yourself had experience with COPD? Dr. Unice: Yes, I've used it on many occasions. And there was an improvement in breathing and shortness of breath as well. So I guess that's what the trials were on, the COPD? Dr. Unice: Yes. And one of the things that might be important here is the DNA seems to effect a wide percentage of the population, suggesting more of a universal application. It doesn't have to be as selective to the patient, the dose is uniform as well, which is a good thing. So, selective in the type of therapy given? Dr. Unice: Yes. With antibiotics, you may have to gear it for specific bacteria. But this seems to be effective across a wide range with the same material, the same molecule. And I think that's important. Also the duration of treatment is shorter. Usually it is 5-7 days or less.
Interview - Jerry Dorsam, D.V.M. on Natural Microdose DNA (Mucolyxir), October 14, 2004 Dr. Dorsam: In terms of applications, our clinical case load changed due to the local humane society - we were seeing a lot of their puppies and kittens that were trying to be adopted. They were coming in with really massive and severe respiratory diseases. Characterized by sneezing, runny eyes, runny nose, fevers, not eating, depression, and listlessness - the whole nine yards. And the conventional thought has always been to treat these guys with antibiotics just because there really isn't anything else out there. And of course, a significant majority of these cases are indeed NOT bacterial. But are indeed viral, therefore, in the perfect environment, the antibiotic is not going to be of any help. So I started using the natural microdose DNA (Mucolyxir). We saw probably a predominant number of kittens and we noted, they'd come in with fevers, and we noted that after the third dose or eighteen hours, after the onset of therapy, they were completely normal. And that was something that really surprised us because we saw such an early response so quickly, and that was the end of it. Has any other medicine you used at the clinic been effective for these types of conditions? Dr. Dorsam: No, not even close. I mean, you can see some improvement with antipyretics, bringing their temperatures down and making them feel better. But nothing stops the discharge or the sneezing or the clinical symptoms like the DNA. I mean these kittens were pretty much on their way. And no other therapy was given, no antibiotics, no things to control fever, so we started using the DNA and found that we could almost wipe out an infection in most of these kittens. Now there were those occasional ones that would drag on, but our opinion was, and still is, that for the DNA, probably the very best indication is to use it very early on in respiratory disease. If you wait until these guys are sick, three to ten days down the line, or even longer, the DNA is going to have moderate improvement. If you catch a kitten or puppy at the outset of very early symptoms, you'll often times have a very positive outcome. If you do catch it early, how many of the patients respond percentage wise? Dr. Dorsam: Oh, almost 100% of them. A statistically significant majority will respond almost within the first 36 to 48 hours. In very, very few of them, you won't see some improvement. Have you ever used it for a bacterial infection? Dr. Dorsam: Because we’re not a laboratory where we test the fluids, we don’t know. We were treating these guys so they could be adopted. We were purely using it compassionately to get them better. Probably, if you talk to people in the SPCA environment, and they've had a chance to culture many of these nasal membranes and conjunctival membranes, they'll tell you that a lot of these guys are suffering from bacterial infections. That it isn't a pure viral epidemic that you see. So it's very difficult without having actually done culture studies to figure out who's got what and what's the percentage of that virus versus that bacteria versus the combination, etc. So, I don't know. But it helps. If I'm presented with a case of respiratory disease in a young kitten or puppy and I catch it early I'm going to treat it with the DNA and know that I'm going to make that particular individual feel a lot better in a very short time. Have you noticed any adverse effects? Dr. Dorsam: No, none, absolutely none. In fact I have a client who runs a rescue agency. She's been part of the Humane Society here in Charleston for 25 years and she got fed up with the buraeucracy so she started her own feline and canine rescue and fostering. And she'll come and get 100 cc's of the DNA. She uses it and is very well pleased, in fact there are so many people down the chain that use it that know that it has these benefits so, it works very well. How would you speculate that it's working, what do you think it does? Dr. Dorsam: Well, it has been suggested that it may stimulate the dendritic cells in the mucosa and may serve as a number of different things stimulating DNA and what not. I don’t really know what it's actually doing in the mucosa because it's given orally and it's absorbed through the oral mucosa, so it's not really something that you're nebulizing. It's going sublingually into the animal. Is there anything you’d like to add about the DNA? Dr. Dorsam: No, I can only tell you what my experience is. I've used it primarily in that instance. I know third-hand that it was used as a coughing model or for treating coughing horses. But if you talk to people who have used it in terms of respiratory disease in the horse, again this is third-hand and I can't comment directly, is that it's helped them. Would you use the same dose for a kitty as a horse? Dr. Dorsam: Yes but that's only what I've been told. And, we just give 0.2 cc's 2-3x per day sublingually. Editor’s Note on Natural Microdose DNA (Mucolyxir) Dr. Allan Lieberman, a 25-year member of AAEM, refers to the DNA effect as a ‘signaling’ effect, and the use of natural microdose DNA here as a signaling molecule. Similar results were found in clinical use in horses and dogs suffering from respiratory disorders. The animals could breathe easier and exercise more as a result of using the microdose DNA. Dr. Jerry Dorsam, DVM also used this for puppies and kittens from his local SPCA that were ‘waiting for adoption’, but were suffering from massive and severe respiratory conditions including sneezing, runny eyes, runny nose, fever and depression. Dr. Kenneth Unice, DO, a physician in private practice says that his otitis media patients usually respond very quickly. In the first few days there is an improvement in fever and irritability. “Many of these children will sleep the first night without pain and without waking up, and their use of analgesic medicine diminishes substantially.” Dr. Albert Dahlberg, M.D., Ph.D., a professor at Brown University, says that natural microdose DNA is different than other DNA-based therapies. “This approach does not effect gene transfer; it relies on the physical molecule itself to place into motion a series of events at the cellular level”. Dr. Dahlberg has determined that the nucleotide sequence doesn’t matter. Different animal sources of DNA were tested and found to work the same. Dr. Dahlberg created synthetic DNA with only adenine and thymine and it also appeared to produce the same results. So in opposition to the stated supposition of the published work, DNA can provide a general signal which may be related to the component nucleotides, but not necessarily their sequence. This is not to detract from the impressive body of work published by many scientists in dozens of publications. And we do not suggest that nonspecific microdose DNA application is the same as the heavily researched bacterial sequence DNA. However, there appear to be striking similarities. The safety of this microdose DNA (Mucolyxir) and lack of side effects is noteworthy. In both the published animal and human studies and in the clinical studies with nonspecific DNA sequences, the safety and lack of side effects appears to be consistent. There is much less than a gene’s worth of DNA in each dose of microdose DNA and therefore does not have any coding potential. “It appears to rely on harmonizing the body’s own regulatory systems.” What is particularly surprising is that a single dose ‘fits all’, and not only in humans. From interviews of doctors using natural microdose DNA (Mucolyxir), the same general dosages a few times a day works for kittens, puppies and horses, as well as for infants, children, and adults. So there is apparently quite a large range of dosages from which these benefits may generate. Increasing the dosage does make a difference to some in terms of achieving greater benefit. For others, the process may be too fast and they reduce the number of drops accordingly. From the studies and clinical work cited here, we are just seeing the ‘tip of the iceberg’ with these signaling regulatory DNA. It is likely that the reports of therapeutic benefit from oral DNA supplements may be related to the mechanisms and observations discussed here. The microdose DNA appears to stimulate P2Y receptors on epithelial cells that line the respiratory tract and ear canal. P2Y stimulation then causes the cilia to beat faster and stronger, which in turn enhances mucus movement leading to drainage, expectoration, etc., and thus altering, or disrupting that habitat so favored by infectious agents. That is to say, DNA may likely have no direct anti-bacterial or anti-viral effect, but rather, have a direct action on mucus itself in that those agents no longer find the ear canal or respiratory tract to be favorable habitats. The observations presented here also suggest that there is a whole different population of molecules in the body that represent unique therapeutic targets for intervention with other innovative ‘nanotechnology’ approaches. These appear to represent very safe pathways to intersect with. (Personal communications with A. Leiberman and L. Kaplan). Presently I am aware of a number of other natural agents used in microdoses that are being explored for a variety of interesting benefits including COBAT (carbobenzoxy beta-alanyl taurine), a dipeptide used in nanogram levels for reversing fatigue in various fatigue-causing conditions. I am often both stunned and thrilled by the novelty and utility that I come across as I investigate issues in nutritional medicine. The modality of natural microdose DNA clearly reflects to me how living bodies seem to seek to establish health and homeostasis. In this case, the stimulant is just a tiny bit of DNA.
Cited References 1. Chu W, Gong X, Li Z, et al. DNA-PKcs is required for activation of innate immunity by immunostimulatory DNA. Cell. 2000 Dec 8;103(6):909-18. 2. Ikeda RK, Nayar J, Cho JY, et al. Resolution of airway inflammation following ovalbumin inhalation: comparison of ISS DNA and corticosteroids. Am J Respir Cell Mol Biol.2003 Jun;28(6):645-7. 3. Youn CJ, Miller M, Baek KJ, et al. Immunostimulatory DNA reverses established allergen-induced airway remodeling. J Immunol, 2004 Dec 15;173(12):7556-64. 4. Datta SK, Cho HJ, Takabayashi K, et al. Antigen-immunostimulatory oligonucleotide conjugates: mechanisms and applications. Immunol Rev. 2004 Jun;199:217-26. 5. Rhee CS, Libet L, Chisholm D, et al. Allergen-independent immunostimulatory sequence oligodeoxynucleotide therapy attenuates experimental allergic rhinitis. Springer Semin Immunopathol. 2004 Oct 14. 6. Michelle V. Fanucchi, Edward S. Schelegle, Gregory L. Baker, et al. Immunostimulatory Oligonucleotides Attenuate Airways Remodeling in Allergic Monkeys. American Journal of Respiratory and Critical Care Medicine, Vol 170:1153-1157. 7. Datta SK, Raz E. Induction of antigen cross-presentation by Toll-like receptors. Springer Semin Immunopathol. 2005 Jan;26(3):247-55. Epub 2004 Oct 14. 8. Datta SK, Cho HJ, Takabayashi K, et al. Antigen-immunostimulatory oligonucleotide conjugates: mechanisms and applications. Immunol Rev. 2004 Jun;199:217-26. 9. Spiegelberg HL, Horner AA, Takabayashi K, Raz E. Allergen-immunostimulatory oligodeoxynucleotide conjugate: a novel allergoid for immunotherapy. Curr Opin Allergy Clin Immunol. 2002 Dec;2(6):547-51. 10. Horner AA, Ronaghy A, Cheng PM, et al. Immunostimulatory DNA is a potent mucosal adjuvant. Cell Immunol. 1998 Nov 25;190(1):77-82. 11. Lee J, Chuang TH, Redecke V, et al. Molecular basis for the immunostimulatory activity of guanine nucleoside analogs: activation of Toll-like receptor 7. Proc Natl Acad Sci USA. 2003 May 27;100(11):6646-51. Epub 2003 May 08. 12. Miller M, Cho JY, Beak KJ, et al. Plasmid DNA encoding the respiratory syncytial virus G protein protects against RSV-induced airway hyperresponsiveness. Vaccine. 2002 Jul 26; 20(23-24):3023-33. 13. Rachmilewitz D., Karmeli F, Takabayashi K, et al. Immunostimulatory DNA ameliorates experimental and spontaneous murine colitis. Gastroenterology. 2002 May;122(5):1428-41. 14. Rachmilewitz D, Katakura K, Karmeli F, et al. Toll-like receptor 9 signaling mediates the anti-inflammatory effects of probiotics in murine experimental colitis. Gastroenterology. 2004 Feb;126(2):520-8.
Kobayashi H, Horner AA, Takabayashi K, Nguyen MD, Huang E, Cinman N, Raz E. Immunostimulatory DNA pre-priming: a novel approach for prolonged Th1-biased immunity. Cell Immunol. 1999 Nov 25;198(1):69-75. Van Uden J, Raz E. Immunostimulatory DNA and applications to allergic disease. J Allergy Clin Immunol. 1999 Nov;104(5):902-10. Spiegelberg HL, Raz E. DNA vaccines. Allergy. 1999;54 Suppl 56:47-8. Martin-Orozco E, Kobayashi H, Van Uden J, Nguyen MD, Kornbluth RS, Raz E. Enhancement of antigen-presenting cell surface molecules involved in cognate interactions by immunostimulatory DNA sequences.Int Immunol. 1999 Jul;11(7):1111-8. Broide D, Raz E. DNA-Based immunization for asthma. Int Arch Allergy Immunol. 1999 Feb-Apr;118(2-4):453-6. Spiegelberg HL, Broide D, Tighe H, Roman M, Raz E. Inhibition of allergic inflammation in the lung by plasmid DNA allergen immunization. Pediatr Pulmonol Suppl. 1999;18:118-21. Broide D, Schwarze J, Tighe H, Gifford T, Nguyen MD, Malek S, Van Uden J, Martin-Orozco E, Gelfand EW, Raz E. Immunostimulatory DNA sequences inhibit IL-5, eosinophilic inflammation, and airway hyperresponsiveness in mice. J Immunol. 1998 Dec 15;161(12):7054-62. Spiegelberg HL, Tighe H, Roman M, Broide D, Raz E. Inhibition of IgE formation and allergic inflammation by allergen gene immunization and by CpG motif immunostimulatory oligodeoxynucleotides. Allergy, 1998;53(45 Suppl):93-7. Goodman JS, Van Uden JH, Kobayashi H, Broide D, Raz E. DNA immunotherapeutics: new potential treatment modalities for allergic disease. Int Arch Allergy Immunol. 1998 Jul;116(3):177-87. Tighe H, Corr M, Roman M, Raz E. Gene vaccination: plasmid DNA is more than just a blueprint. Immunol Today. 1998 Feb;19(2):89-97. Carson DA, Raz E. Oligonucleotide adjuvants for T helper 1 (Th1)-specific vaccination. J Exp Med. 1997 Nov 17;186(10):1621-2. Roman M, Spiegelberg HL, Broide D, Raz E. Gene immunization for allergic disorders. Springer Semin Immunopathol. 1997;19(2):223-32. Spiegelberg HL, Orozco EM, Roman M, Raz E. DNA immunization: a novel approach to allergen-specific immunotherapy. Allergy. 1997 Oct;52(10):964-70. Goodman JS, Raz E. Circling back to gene vaccines. Gastroenterology. 1997 Nov;113(5):1812-4. Roman M, Martin-Orozco E, Goodman JS, Nguyen MD, Sato Y, Ronaghy A, Kornbluth RS, Richman DD, Carson DA, Raz E. Immunostimulatory DNA sequences function as T helper-1-promoting adjuvants. Nat Med. 1997 Aug;3(8):849-54. Lee DJ, Tighe H, Corr M, Roman M, Carson DA, Spiegelberg HL, Raz E. Inhibition of IgE antibody formation by plasmid DNA immunization is mediated by both CD4+ and CD8+ T cells. Int Arch Allergy Immunol. 1997 May-Jul;113(1-3):227-30. Sato Y, Roman M, Tighe H, Lee D, Corr M, Nguyen MD, Silverman GJ, Lotz M, Carson DA, Raz E. Immunostimulatory DNA sequences necessary for effective intradermal gene immunization. Science. 1996 Jul 19;273(5273):352-4. Raz E, Tighe H, Sato Y, Corr M, Dudler JA, Roman M, Swain SL, Spiegelberg HL, Carson DA. Preferential induction of a Th1 immune response and inhibition of specific IgE antibody formation by plasmid DNA immunization. Proc Natl Acad Sci U S A. 1996 May 14;93(10):5141-5. Raz E, Ben-Bassat H, Davidi T, Shlomai Z, Eilat D. Cross-reactions of anti-DNA autoantibodies with cell surface proteins. Eur J Immunol. 1993 Feb;23(2):383-90. Van Uden JH, Tran CH, Carson DA, Raz E. Type I interferon is required to mount an adaptive response to immunostimulatory DNA. Eur J Immunol. 2001 Nov;31(11):3281-90. Broide DH, Stachnick G, Castaneda D, Nayar J, Miller M, Cho J, Rodriquez M, Roman M, Raz E. Immunostimulatory DNA mediates inhibition of eosinophilic inflammation and airway hyperreactivity independent of natural killer cells in vivo. J Allergy Clin Immunol. 2001 Nov;108(5):759-63. Cho JY, Miller M, Baek KJ, Castaneda D, Nayar J, Roman M, Raz E, Broide DH. Immunostimulatory DNA sequences inhibit respiratory syncytial viral load, airway inflammation, and mucus secretion. J Allergy Clin Immunol. 2001 Nov;108(5):697-702. Hayashi T, Rao SP, Takabayashi K, Van Uden JH, Kornbluth RS, Baird SM, Taylor MW, Carson DA, Catanzaro A, Raz E. Enhancement of innate immunity against Mycobacterium avium infection by immunostimulatory DNA is mediated by indoleamine 2,3-dioxygenase. Infect Immun. 2001 Oct;69(10):6156-64. Horner AA, Widhopf GF, Burger JA, Takabayashi K, Cinman N, Ronaghy A, Spiegelberg HL, Raz E. Immunostimulatory DNA inhibits IL-4-dependent IgE synthesis by human B cells. J Allergy Clin Immunol. 2001 Sep;108(3):417-23. Uchijima M, Raz E, Carson DA, Nagata T, Koide Y. Identification of immunostimulatory DNA-induced genes by suppression subtractive hybridization. Biochem Biophys Res Commun. 2001 Aug 31;286(4):688-91. Spiegelberg HL, Raz E. DNA based immunotherapeutics for allergy. Arb Paul Ehrlich Inst Bundesamt Sera Impfstoffe Frankf A M. 1999;(93):283-90; discussion 291-2. Horner AA, Datta SK, Takabayashi K, Belyakov IM, Hayashi T, Cinman N, Nguyen MD, Van Uden JH, Berzofsky JA, Richman DD, Raz E. Immunostimulatory DNA-based vaccines elicit multifaceted immune responses against HIV at systemic and mucosal sites. J Immunol. 2001 Aug 1;167(3):1584-91. Broide DH, Stachnick G, Castaneda D, Nayar J, Miller M, Cho JY, Roman M, Zubeldia J, Hayashi T, Raz E. Systemic administration of immunostimulatory DNA sequences mediates reversible inhibition of Th2 responses in a mouse model of asthma. J Clin Immunol. 2001 May;21(3):175-82. Ayash-Rashkovsky M, Weisman Z, Zlotnikov S, Raz E, Bentwich Z, Borkow G. Induction of antigen-specific Th1-biased immune responses by plasmid DNA in schistosoma-infected mice with a preexistent dominant Th2 immune profile. Biochem Biophys Res Commun. 2001 Apr 20;282(5):1169-76. |
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