Subject: Shiitake-Lentinan, Guerrilla Clinics (2 articles) Date: Dec 7 1986 (622 lines) &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& J O H N J A M E S writes on A I D S &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& posted 12/7/86; an additional article on Guerrilla Clinics posted 10/18/91 here, but it has been on display here since published in 1986, as #9 of this section. Sorry if this note is confusing. There seems to be no better way to handle this archival problem. These early articles are kept for historical interest and the material in them may or may not be valid today. SHIITAKE, LENTINAN, AND AIDS/ARC by John S. James for SF Sentinel Shiitake is a kind of edible mushroom traditionally cul- tivated in Japan, and now used as a delicacy in cooking throughout the world. Lentinan (pronounced len-tin'an), a sub- stance found in shiitake, has important effects on the immune system, and is now widely used in Japan for treating cancer. Re- cently there has been increasing interest in medicinal use of shiitake or the lentinan derived from shiitake, as well as other medicinal mushrooms that contain different active ingredients, as possible treatments for AIDS or ARC. Published medical studies, mostly from Japan, strongly sug- gest that lentinan may be valuable. But U. S. physicians cannot obtain the medicine, because of bureaucratic and commercial bar- riers -- a situation unlikely to change soon since apparently no formal research is being conducted on AIDS and lentinan in the U. S., in Japan, or anywhere else. Meanwhile, the mushrooms are available in grocery stores, and health food stores sell shiitake extracts. Researchers believe that lentinan could be effective orally if used properly. However, much of the commercial-product literature does not reflect information obtained from the scientific studies and med- ical trials. Anyone using lentinan should know what has been learned about how it should or should not be used. This article will discuss the Japanese use of lentinan with cancer and with a single case of ARC, and mention some of the many immune effects of this substance. Then we will look at the shiitake preparations available now in the United States, and what should be known about using them. In this article we can only touch on the very large subject of immune potentiators and antivirals from medicinal fungi. Lentinan and Cancer Japanese physicians have used highly purified lentinan as an immunotherapy in clinical trials with hundreds of patients with gastric and other cancers. Study after study found that lentinan combined with chemotherapy worked better than chemotherapy alone. For a review of the immune effects of lentinan, and its use in cancer treatment, see Aoki, 1984 (reference below). Tadao Aoki is the world's leading authority on the medical use of lentinan. Dr. Aoki has repeatedly urged that lentinan be tested for ARC or AIDS. Early animal studies of lentinan found no anticancer effect; later, scientists realized that the cause of this failure was that too large a dose had been used. With a correct dose, len- tinan caused complete regression of certain cancers in mice (see Aoki, 1984). The doses which failed were ten to 80 times too large, suggesting that the effective range may not be too cri- tical. Lentinan has many immune effects. Researchers are now most interested in its enhancement of "natural killer" (NK) cells, which, like T cells, are a subgroup of white blood cells. Len- tinan can also increase gamma interferon production. One study found that lentinan alone was not very effective in treating human cancer. For better results, doctors combine it with chemotherapy. The lentinan should be started first (Aoki, 1984). In both humans and animals, lentinan did not work if there was a protein deficiency (Akimoto, 1986). Physicians have found that to get the greatest effect, they should avoid giving lentinan every day. Aoki, 1984, suggested a dose of 1 mg twice a week. More recently, this dose has been given every other day. Doctors usually administer lentinan by injection, either intravenous or intramuscular. It can also be taken orally, but about five times the dose is required. We can find just one published case of lentinan used to treat KS. The patient, an 84 year old man who also had lung cancer, did not have AIDS. The KS lesions quickly improved, and disappeared in a couple months (Aoki and others, 1981). Lentinan and AIDS There is only one published case where doctors used lentinan for treating AIDS or ARC. But this case is crucial, because a person with ARC became antibody negative and remained that way even without the drug. She also improved clinically and is in good health today, two years later. The published report of this case appeared two years ago in THE LANCET (Aoki and others -- LANCET). The researchers also released a more detailed report (Aoki and others -- PROCEED- INGS). This writer learned of the current status through private communication. The patient, apparently exposed to AIDS by a transfusion, had grown progressively weaker, and repeatedly tested positive for AIDS antibodies. The T4 count was under 300, and other blood tests also suggested ARC. One mg per day of lentinan was given daily for five months; at that time the doctors did not know that giving it less often would be more effective. The patient's condition improved, and the blood counts went in the right direction. The T4 count reached about 500, although the T4/T8 ratio declined because the T8 count increased faster. After four months, the AIDS antibody test became negative and remained that way. Two years later, the patient is healthy. We do not know recent blood counts. Political Problems Obviously this case should be followed up, especially since lentinan has no serious side effects. But two years after publi- cation in one of the most widely circulated medical journals, we know of no other person with AIDS, ARC, or a positive test who has received lentinan, anywhere in the world. U. S. physicians cannot obtain the drug; Japanese physicians can use it, but they have few AIDS/ARC patients. At this time, the Bristol-Meyers corporation has an option to buy U. S. license rights to lentinan. We have heard that they have applied to the U. S. Food and Drug Administration for an IND -- permission to test an experimental drug -- but have not yet received it. We do not know whether Bristol-Meyers is interested in AIDS; the obvious commercial use for lentinan would be for treating cancer. Even if they are interested in trying it as an AIDS treatment, it could take years before it even gets tested on a handful of patients. The U. S. National Institutes of Health could obtain lentinan and test it, but so far has shown little interest. A colleague of Dr. Aoki sent a thousand doses to Dr. Anthony Fauci, director of the National Institute for Allergy and Infectious Diseases, but received no reply. Perhaps the package got lost in the mail. The U. S. National Cancer Institute has added lentinan to a list of over 80 drugs which people have suggested as possible treatments for AIDS. It's AIDS Drug Selection Committee plans to consider whether or not to follow up. What's Available Now? It may be possible to get lentinan treatment abroad. We have heard conflicting reports about whether persons known to have AIDS, ARC, or a positive antibody test can enter Japan for medical treatment, or for any other reason. The Japanese consulate was non-committal, which suggests that there may be a problem, and that we might not find out until someone tries to go. It may also be possible for clinics in Mexico or other coun- tries to buy lentinan from Japan. Another approach is to develop this treatment from available materials, outside of the official research system. The shi- itake mushrooms, which contain lentinan, and various extracts sold in health-food stores, are readily available. Researchers believe that lentinan can be effective when taken orally, if five times the injected dose is used. In November 1986, Dr. Aoki visited the U. S. National Institutes of Health and reported on the treatment of 59 patients for an immune deficiency called low natural killer cell condition; they received intravenous lentinan in the hospital, then took mainte- nance doses orally as outpatients. The natural killer cell activity improved greatly, an effect likely to be important for treating KS and other cancer. What we don`t know is how much lentinan is in the mushrooms or the commercial preparations. We don't yet know of any company which has tested its material and calibrated its pills or powder so that users know what they are getting. The chemical test is not available commercially, but could be done in a university lab. It is important that the products be tested, because too much lentinan can be not only ineffective, but harmful, because it can have the opposite of the intended effect. In one of the cancer studies, overdoses ten times too high markedly depressed the immune response (Aoki, 1984). But side effects of proper doses, which can include skin rashes and a feeling of heaviness in the chest, are rare and not serious when they do occur (Aoki, 1984). They clear up when the lentinan is stopped. Lentinan is "heat stable" (Aoki, 1984), which probably means it survives normal cooking. One paper reported 30 cases of skin rashes and itching, seen by dermatologists over nine years, caused by eating shiitake as an ingredient of oriental cooking (Nakamura and Kobayashi, 1985). The dermatologists believe that these effects were caused by lentinan, suggesting that it may be possible to get an effective dose through normal use of shiitake as food. Shiitake has long been a folk medicine for cancer in Japan and other Asian countries; and until U. S. physicians can get lentinan, traditional ways of using the mushroom may be the best available. Much of the commercial health-product literature for shi- itake preparations fails to inspire confidence. One flyer claims that its shiitake tablet "may be effective" for "allergy, hypertension, liver trouble, tumor, kidney trouble, post- operative discomfort, lymphnode, infectious hepatitis (B) (sic), collagen disease, rheumatism, gout, diabetes mellitus, gonorrhea, AIDS, common cold or flu, loss of energy". Another suggests what might be called the Godzilla theory of medicine: "It is believed that the mycelium in the earth had the strength to push its way through a thick layer of concrete. Obviously, if this tremendous power could be utilized for the good of the human body, amazing results could be expected." People facing death deserve better. We can let the public and professionals know the importance of this potential AIDS/ARC treatment, and the fact that it has been neglected for two years for no medical or scientific reason. A medicine known to be safe, easy to use, and outstandingly effective in the sin- gle case tried, at least deserves a second look. If more people were close enough to AIDS treatment research to know what is going on, they would insist that some way be found through the red tape and commercial obstacles which now block testing of some of the most promising treatment leads. ****** References Akimoto M, Nishihira T, and Kasai M.: Modulation of the Anti- Tumor Effects of BRM Under Various Nutritional or Endocrine Con- ditions. GAN TO KAGAKU RYOHO, Volume 13 Number 4 Part 2, pages 1270-1276, April 1986 (English summary). Aoki T. Lentinan. In Fenishel RL and Chirgis MA, editors, IMMUNE MODULATION AGENTS AND THEIR MECHANISMS, pages 63-77. Marcel Dekker, Inc., New York and Basel, 1984. Aoki T, Miyakoshi H, Horikawa Y, and Usuda Y. Staphage Lysate and Lentinan as Immunomodulators and/or Immunopotentiators in Clinical and Experimental Systems. In Hersh EM, Chirigos MA, and Mastrangelo M, editors, AUGMENTING AGENTS IN CANCER THERAPY, page 101-112, Raven Press, New York, 1981. Aoki T, Miyakoshi H, Usuda Y, Chermann JC, Barre-Sinoussi F, Ting RC, and Gallo RC. Antibodies to HTLV I and III In Sera From Two Japanese Patients, One With Possible Pre-AIDS. THE LANCET, page 936-937, October 20, 1984. Aoki T, Miyakoshi H, Usuda Y, Ting RC, and Gallo RC. Lentinan Treatment of Japanese Cases Infected With Human T-Lymphotropic Retroviruses (HTLV-I and -III). PROCEEDINGS OF THE SIXTH SYMPO- SIUM ON RATIONALE OF BIOLOGICAL RESPONSE MODIFIERS IN CANCER TREATMENT, Hakone, Japan, August 31-September 1, 1984. Nakamura T and Kobayashi A. Toxicoderma caused by the edible mushroom shiitake (lentinus edodes). HAUTARZT, pages 591-593, October 1985 (English summary). Wakui A and others. Randomized Study of Lentinan On Patients With Advanced Gastric and Colorectal Cancer. GAN TO KAGAKU RYOHO, April 1986 (English summary). For More Information: To find out more about lentinan, you can call Ivan John, (212) 288-2952. Call between 8 and 9 PM, New York time (5-6 PM in San Francisco). Ivan John is a medical student working with Nathaniel Pier, M. D., to get lentinan tested for AIDS or ARC. This article is the 16th in the author's series on experi- mental AIDS/ ARC treatments. Other treatments covered include DNCB, AL 721, naltrexone, BHT, glycyrrhizin, and AZT. ***** [There is no separate place for the following article on Guerrilla Clinics, so it has been appended here. It came in the flurry of articles in 1986 and was not included in the book. -- sysop] Subject: AIDS/ARC Guerrilla Clinics Spread Date Dec 1986 328 lines &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& J O H N J A M E S writes on A I D S &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& posted 12/14/86 AIDS/ARC GUERRILLA CLINICS SPREAD by John S. James Call (415) 647-8561 for location of guerrilla clinics. A network of guerrilla clinics, from San Francisco to New York, has sprung up to treat AIDS/ARC patients with a chemical compound called DNCB (dinitrochlorobenzene), a relatively common compound that has been used by a San Francisco physician, Dr. Bruce Mills, to treat AIDS patients since 1984. In 1980 Dr. Mills, while doing research at Stanford University, found that DNCB was successful in treating a form of warts. The guerrilla clinics do not charge for the compound or treatment and teach patients to administer it themselves and always advice that people consult with their regular physician before starting to use DNCB. But Jim Henry, the founder of the guerrilla clinic movement, warns that most doctors have not yet heard of the treatment and so frequently discourage its use. Henry has set up the DNCB Hotline (415/647-8561) to provide information on the location of the clinics and to provide the latest medical results and preferred method to administer DNCB. The first guerrilla clinic was started 14 months ago in San Diego by Henry who had heard about Dr. Mills work after it had been published in a medical journal. Since then the guerrilla clinics have been mushrooming. There are now 29 such clinics located across the country from coast to coast. First used on KS patients, DNCB is "painted" on the patient's skin. Since then it has been found to be effective with other forms of AIDS. When asked why much of the medical community is ignoring the treatment, Henry said there are two reasons. First, drug com- panies aren't interested in it because there is no profit for them and drug companies sponsor much of the medical research. Also much of the medical establishment is looking for anti-viral drug to attack the AIDS virus. DNCB appears to work differently. It strengthens and rebuilds the individuals immune system, let- ting the body's natural defenses deal with the disease. Recently the University of California at San Francisco has started a research program to augment the work of private phy- sicians like Dr. Mills. John James, in his regular column on AIDS research, pub- lished a report on DNCB in the SF Sentinel last September. Here are portions of his report. "...DNCB (dinitrochlorobenzene) is a chemical that affects the body much like poison oak. It penetrates the skin and binds onto protein there, rendering these proteins much more likely to stimulate an immune reaction. In a person who has normal immun- ity, DNCB causes a rash like poison oak. The pure chemical is so strong that it must be diluted almost a thousand times before use. "Immunologists have used DNCB extensively in their research. Several years ago, Dr. Bruce Mills -- then a Stanford research dermatologist studying the biochemistry of certain enzymes -- observed that DNCB successfully treated a kind of severe warts, in children, that could not be effectively treated convention- ally. Not only did the treated warts disappear, but all the other warts on the body, too. It turned out that the DNCB stimu- lated the development of T cells, correcting the immune defect which had allowed the warts to develop. The DNCB treatment -- for certain kinds of warts -- has become generally recognized as effective. "Next, Dr. Mills, now a physician in private practice in San Francisco, tried DNCB for treatment of KS lesions in persons with AIDS. Not surprisingly, it turned out that KS was more diffi- cult to treat than the warts. But there were dramatic improve- ments in many cases, and not only for KS. Recently, Dr. Mills has distinguished four groups of AIDS/ARC patients. Different treatments are appropriate to the different groups. THE AUTOIMMUNE THEORY OF AIDS/ARC "Before describing the four groups of patients, it is impor- tant to outline a new theory of AIDS now being developed by a number of researchers, including Dr. Mills. "In the conventional theory, the AIDS virus (formerly called HTLV-III, or LAV, now named Human Immunodeficiency Virus, or HIV) infects the T cells, especially the T4, or helper T cells, that control the immune system. The helper T cells normally recognize foreign proteins, and instruct the B cells (a different part of the immune system) to produce specific antibodies which attack the invading organisms. "In AIDS, the virus kills most of the helper T cells, so the immune system cannot identify the disease-causing organism. The B cells do generate lots of antibodies, but they are the wrong ones. Therefore, the body cannot resist certain opportunistic infections and cancers which, normally, it could easily control. "New T cells are being produced all the time, at least until the person is gravely ill. But, according to the conventional theory of AIDS, the virus keeps killing them. "The autoimmune theory accepts all of the conventional view outlined above. But it also says that a different mechanism can keep killing the T-cells, even if the virus is no longer a prob- lem in some patients. "This theory states that the high level of wrong antibodies produced by the B cells can begin attacking normal body cells, especially the T cells themselves. The result is a vicious circle -- with the T cells unable to control the B cells, and the B cells producing antibodies which in turn kill T cells. Many separate observations support the auto-immune theory: for exam- ple, the recent discovery of a new kind of anti-platelet antibody that is specific to AIDS/ARC patients. THE FOUR GROUPS OF PATIENTS "Dr. Mills' patients not only receive DNCB; they also receive extensive monthly laboratory blood tests, whenever finan- cially possible. The resulting data has led Dr. Mills to the following classification of patients: "The first question asked when he groups AIDS/ARC patients is whether the level of gamma globulin (immune globulins) is extremely high, close to 3000 or worse. If so, there is a prob- lem from too much antibodies. Dr. Mills calls these patients Group III (discussed below). "Group I patients get the most dramatic benefit from DNCB. Their immune globulin level is not too high, and these patients respond well to DNCB in three to six months -- in laboratory tests and by clinical improvement. These patients may not need any other treatment than DNCB. "Note that it does take time to get results, however. That is because DNCB works by stimulating the growth of new T cells, and it takes time for these cells to be produced and to mature. "Group II patients also have a reasonable immune globulin level, but they do not respond well to DNCB in three to six months. Dr. Mills believes these patients may also need an antiviral. "Group III, mentioned above, has the problem of too much antibodies. For these patients, many of the other lab results are unreliable. Dr. Mills hopes that about a year of treatment with DNCB can reduce the immune globulin level. "Group IV is end-stage AIDS. DNCB may raise the T cell counts a little, but it is too late to save the person's life. Note that Mills' classification is different from the normal dis- tinction of ARC vs. AIDS, and that many patients with pneumo- cystis or KS (for whom most doctors have all but given up) would not be in group IV, but in one of the other three groups. HOW IS DNCB USED? "Usually, a small amount of DNCB (2/15 of one percent) is dissolved in Vaseline Intensive-Care lotion. Sometimes other solutions are used. Once a week, the doctor paints a small patch on the arm, covers it with gauze, and tells the patient to remove the gauze and wash off the DNCB lotion in a certain number of hours. The DNCB should cause a rash to appear on the skin. Patients with a suppressed immune system will not react at first, but everyone tested so far has eventually achieved a reaction. "Sometimes the DNCB is painted directly on KS lesions, but usually only after a skin reaction has already been achieved elsewhere. "Dr. Mills also has patients take about a dozen blood tests. These include T cell subsets, immune globulins, lymphocytes, and platelets. Also included are blood lipids, liver function, and other tests to warn of any dangerous side effects of the DNCB; so far, none has been found. In addition, he runs standard tests for rheumatoid arthritis, lupus, and syphilis, even though the patients do not have these conditions, because positive results may indicate a malfunctioning immune system. A CASE HISTORY "We spoke with one patient -- not referred to us by Dr. Mills -- who is considered a star patient, because there are no complicating factors in his case. He started treatment early, while severely immune suppressed but not otherwise ill. He took no other treatments and had no opportunistic infections or other illnesses during the treatment. He received extensive lab work on several occasions, so there is much data available to study. And he continued the DNCB treatments without interrup- tion in the ten months he has been Dr. Mills' patient. "When he began treatment, his helper/suppressor ratio was that claimed that it was impossible to reconstitute the immune system if the helper number was less than about 245. "For the first five months, the number went up, but just a little: 118, 265, 295, 365. At that time he was discouraged and had no further tests done for four months, but he continued the DNCB. When retested, in June 1986, the helpers were 529, (within the normal range of 447-1284). This month (September 1986) they rose to 707. Total T cells went from 686 at the beginning, to 2259. The helper/suppressor ratio had climbed from .22 to .63 -- not yet normal, but a major improvement. "Meanwhile, all the other lab tests moved in the right direction (or stayed normal). Immune globulins decreased from 2600 to 1830 (normal range is 540-1480). Lymphocytes increased from 1400 to 2700 (normal is 800-3200). Hemoglobin improved from 12.7 to 15.3 (normal is 13.9-18). The lupus and rheumatoid arthritis tests went from positive to normal; the "syphilis" antibodies dropped. "The patient told us that Dr. Mills believes that it may eventually be possible to stop using the DNCB, but he isn't sure yet. "Despite these results, the patient is unsure how many oth- ers will have the persistence to follow the treatment con- sistently, even though the results are slight for the first several months. When he started DNCB, he was feeling well; he had only a positive antibody test. Fortunately, he then took the T-cell subset lab test, which showed that though he was feeling well, he was living on borrowed time; it is surprising that he had not already developed pneumocystis or other problems. He began the DNCB treatment immediately and stayed with it. "Since this patient was well throughout, there was no oppor- tunity to observe clinical improvement. Many others have shown major clinical improvement, including a resolution of nailbed fungal infections, KS lesions (even severe ones) that have almost disappeared, and generally feeling better and having more energy. WHAT'S NEEDED NOW? "The above case history, and the 26 others summarized by Dr. Mills in his letter published in the June 1986 JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY, are not scientifically con- clusive. The reason is that patients in a private practice are self selecting. Those who don't think the treatment is working usually leave, so that only the good results tend to be reported. We need well-designed, controlled clinical studies to prove the effectiveness of DNCB, and to provide further information on exactly how to use it most effectively. "We have heard reports that such studies are now beginning in New York and Los Angeles, but have not been able to investi- gate these reports by press time. "In San Francisco, Dr. William L. Epstein, Chairman Emeritus of the Department of Dermatology at U. C. Medical Center, wants to perform a study of DNCB (and also urushiol, the active ingredient of poison oak) for AIDS as well as other immune diseases. Dr. Epstein is President of the American Academy of Dermatology and the world's foremost expert on contact skin sen- sitization (such as caused by poison oak or DNCB). But, so far, the study has not been approved. The rumor we have heard -- not from Dr. Mills, nor from Dr. Epstein, who was not contacted for this story -- is that the study was first denied funding, and then also denied permission to use patients; and that the reason the study was prohibited was rooted in the politics of personal and professional rivalries, including the fact that cancer spe- cialists -- not immunologists -- have held political control of AIDS research. "Any physicians interested in studying or using DNCB for AIDS or ARC should note that, as far as we know, there have never been harmful effects from such use, except that with occasional patients the expected skin reaction can be severe. Dr. Mills does not know of any kind of AIDS/ARC patients who should NOT get DNCB, although clearly it will help some groups of patients more than others. DNCB is already used in medical practice, and a pharmacy can mix it for use. The cost is negligible. Applica- tion requires only a Q-tip, once a week, plus ordering standard laboratory tests. In short, there are no technical obstacles to wider use of DNCB, nor to conducting the kinds of studies needed to get definitive answers on its value for AIDS or ARC. " FOR MORE INFORMATION Published information can be found in the June 1986 JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY, pages 1089-1090. Also, see Michael Helquist's articles in COMING UP! (October 1985), and in THE ADVOCATE (November 12, 1985 and April 4, 1986), and Pat Christen's article in the BAY AREA REPORTER (June 19, 1986). Ann Guidici Fettner has a short article in the NEW YORK NATIVE (June 23, 1986). Also see "Autoimmune Drug Discovery Published", in UPDATE, June 11, 1986. Most physicians are not set up to handle large numbers of calls, and they can seldom return calls except from their patients or from other physicians. The best person to call for information about DNCB and the guerrilla clinics is Jim Henry, at (415) 647-8561. He can tell you whom to contact near your area about using DNCB. Another information source is the Project Inform hotline (800-334-7422 within California; 800-822-7422 from other states). Project Inform is primarily interested in ribavirin, but is also aware of DNCB, as the two treatments might complement each other. FOR OTHER ARTICLES This article is part of a continuing series by the author on experimental and alternative treatments for AIDS and ARC. Fif- teen articles have been published so far. The treatments covered include AL 721, BHT, analtrexone, and glycyrrhizin (found in licorice). You can reach the author at P. O. Box 411256, San Francisco, CA 94141, phone (415) XXX-XXXX. Copyright 1986 by John S. James; permission granted for non- commercial use. &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& End of display