Date: 24 Jun 1995 18:05:36 Reply-To: Conference "aidstreatment" From: FRSHAW@delphi.com Subject: Chinese herb formulas & HIV W. Fred Shaw, L.Ac., Dipl.Ac., M.S., M.T.O.M. Licensed Acupuncturist and Herbalist Technical Advisor, ACT UP San Francisco The following is a Letter by Misha Cohen, Designer of the Enhance herbal formula for HIV disease and Director of the Quan Yin Clinic of San Francisco. This letter appeared in the California Acupuncture Association (CAA)Bulletin, May/June 1995, p15-17. This is an uncopyrighted work. Comments preceded by ">" are those of Misha Cohen. The response following each statement of Cohen's are those of the above author. >I have debated whether or not to respond to the article printed >in the CAAOM Bulletin by Mr. Fred Shaw. I am disappointed that >the CAAOM chose to publish an article of such an inflammatory >and derogatory nature without so much as an editor's note. It >clearly deserves a response. Why doesn't the author explain what was inflammatory or derogatory? Is the concept of science inflammatory ? Is the challenge to the validity of Chinese herbal formulas for HIV disease derogatory? What is really bothering Ms. Cohen? >Those of us who have been at the forefront, working with people >with AIDS, have labored for over ten years seeing thousands of >people to determine the most efficacious treatment. Has this truly been "ten years" of "labor" or one year of labor ten times? It appears that nothing has changed in the Traditional Chinese Medicine (TCM) response to AIDS sine to mid- to-late 1980s. >We have done this while remaining true to the principles of >Chinese medicine. Why hasn't the author set forth the traditional precedent for the protocol she modified (Enhance) of nearly 40 herbs (Enhance plus Clear Heat) all day, every day, for the life of every HIV patient! Where is the precedent for this? >To undermine the efforts of Chinese medicine practitioners >along with their attempts to build bridges with Western medical >practitioners is, I believe, a mistake and grave disservice to >those committed to treating people with AIDS. Undermine efforts? How? By questioning the validity of the formulas designed by Misha Cohen and Subhuti Dharmananda? By developing an understanding of the true immunological effects of the individual herbs in the formulas according to the facts of science. Who is really committing a "grave disservice" here? >Mr. Shaw's criticism is based on a highly suspect and biased >look at the available "research". This is an insult to the cutting-edge scientific research in immunology. Where is Ms. Cohen's scientific rebuttal to the research she feels is suspect and biased? Why does Ms. Cohen demonize the research rather than provide a scientific rebuttal or explain why it is "highly suspect" or "biased"? >He made three points which I found inflammatory and counter to >the work that I feel needs to be done. The first and most basic >issue, that TCM treatments of HIV and AIDS are "not based on >any true historical precedent", overlooks the fact that there >is no precedent in recorded medical history for anything like >HIV and AIDS. This is inflammatory? Doesn't progress warrant an examination of the facts, assumptions and precedents of any therapy? Isn't every single symptom seen in AIDS also already known to Traditional Chinese Medicine (TCM)? Is the lack of precedent of a disease just like AIDS and HIV disease an excuse for "anything goes"? >Traditionally Chinese Medicine has developed through just this >type of challenge and has a great deal to offer in terms of >treatment and research. As for the new herbal formulas not >having historic precedence in Chinese medicine, I beg to >differ. The theory of Chinese medicine is quite diverse. Much >of its history documents epidemic disease and its treatment. Since Chinese Medicine has developed through "just this type of challenge", then why stop it from developing now - why not meet the challenge instead of demonizing the science? Are the commercial interests of Enhance, Composition-A and Resist so great that we cannot allow for an examination of what Chinese medicine has to offer? Epidemic disease treatment is associated with Fu Zheng Therapy. According to Subhuti Dharmananda (1988 Chinese Herbal Therapies for Immune Disorders, page 7) "Fuzheng Guben Therapy is administered in the form of a combination of tonic herbs, typically containing 10-18 medicinal materials". Further, Dharmananda admits that Fuzheng therapy has only "proven" itself in the past few decades. This is the "history" Ms. Cohen depends on to defend her formula protocol of nearly 40 herbs? There is a substantial amount of skepticism as to the effectiveness of even the large formulas of 18 herbs - much less the huge formulas of 40 herbs. Why not use 200 herbs in a formula - wouldn't the same precedent apply to even more and more herbs? >In epidemic disease, the disease process includes certain >syndromes and symptoms that show up in all individuals >regardless of constitution or individually acquired syndromes. >The epidemic disease is, therefore, often treated with a broad >formula. The founders of Chinese medicine would be appalled by this statement. Cohen suggests that all individuals manifest the same symptoms at all stages of this 10-15 year disease process "regardless of constitution or individually acquired syndromes"! Isn't this counterintuitive to the holistic practice of Chinese medicine? Isn't the strength of Chinese medicine based on individual therapy and finely crafted herbal formulas? This is the defense for the "broad formula" of nearly 40 herbs - the "shotgun" therapy that is advocated by Ms. Cohen? >The individual manifestations, however, must be approached >individually and this is the beauty of Chinese medicine. We can >alter our base formulas to suit the individual using additional >formulas or even abandoning the base formulas for periods of >time while we treat specific symptom-sign complexes. Using Enhance, a formula of 28 herbs, is the "beauty" of individual treatment? The alteration of this base formula is simply the replacement of Clear Heat! Is this how a treatment is individualized - by changing what is added to the basic "shotgun" formula? This is a one-size-fits-all therapy for HIV disease based purely on western symptoms - not TCM symptoms! >Not only is there a history of epidemic disease treatment with >large formulas, but there is a history of treatment of >debilitating chronic disease with large formulas. For chronic >disease these base formulas were used with the addition of >small variations of constituents and herbs to prevent the >person from becoming adapted to the formula. How are persons being prevented from becoming adapted to Enhance - since it is always to be used, every day, for life? Is Ms. Cohen suggesting that the periodic replacement of Clear Heat (when disease symptoms and infections arise) a method to prevent adaptation? What is the precedent - even in chronic disorders - for using any formula of nearly 40 herbs for the life of the patient? Isn't the beauty of Chinese herbal medicine in the finely crafted herbal formulas to address the exact signs and symptoms of each individual patient at the various times of the healing response to the chronic disease? How can these large formulas - abominations of this holistic medicine - even begin to approach the fine craftsmanship of traditional herbal medicine? >Secondly, to engage in the political polarization pitting ACT- >UP and what he referred to as "AIDS Inc." or the >"establishment" against one another only serves to make >collaborative work more difficult. Here's the smokescreen - a poor attempt to divert attention away from the subject of Chinese herbs and the lack of the scientific and traditional medical knowledge of the author. As to the "collaborative work" with the "establishment", is the author talking about the marketing of her formula? Building bridges with western medicine? If the latter is the case, the author better be ready to answer the questions presented in this response - and stop responding with smokescreens and the demonization of science! >His information about ACT-UP is also misleading. There is, to >my knowledge, only a very small splinter group within ACTUP >which supports the sole use of DNCB as a agent for the >treatment of HIV. Obviously, the author has no concept of the science or the traditional medicine and must resort to diversionary tactics. Ms. Cohen is repeating her smokescreen attack on DNCB Now! - an organization affiliated with ACT UP San Francisco. Her last attack was in the Bay Area Reporter (5/11/95 page 8), a weekly newspaper of the San Francisco gay and lesbian community. Ms. Cohen is repeating the mistaken "party line" of organizations opposed to ACT UP San Francisco. No one likes DNCB - it itches, it looks bad and it is inconvenient. Fortunately, DNCB is the only known way to safely boost cell-mediated immunity. >Most of ACT-UP is interested in a continuous and on-going >discussion of treatment protocols which have worked well both >symptomatically and to improve quality of life, as well as >having possible long-term positive effects in increasing >longevity. This includes the increased use of Chinese medicine >as the most popular and reproducible treatment for persons with >HIV. The organizations and "treatment protocols" Ms. Cohen refers to include those of the well-known "checkbook activists" of the HIV-positive community for the past ten years (ACT UP Golden Gate, Project Inform, etc.). These are the desperate and panicked "drugs into bodies" organizations that are mired in conflicts of interests - made up of organizations and individuals that are either supported by, or get frequent remuneration from drug companies to play an advocacy role on the drug company's behalf. These groups have poisoned the HIV community with misinformation, false "cures" (antivirals) and are directly responsible for the premature death of tens of thousands of HIV patients with drugs that have yet to show any survival benefits. With the ONLY exception of PCP prophylaxis, none of these "treatment protocols" Ms. Cohen supports have ever been shown to increase survival in this disease. On the other hand, many of these aggressive "treatment protocols" have greatly damaged the quality of life of AIDS patients, leaving them in wheelchairs, blind and suffering in untold ways from the many aggressive medical interventions that destroy their bodies. Why would a system of natural healing ever want to be associated with this crowd? Why is Ms. Cohen defending these drug pushers? Does Ms. Cohen also have a conflict of interest in this regard? What is Ms. Cohen's financial affiliation with Health Concerns - the company that manufactures and sells her formulas? On the other hand, only ACT UP San Francisco advocates the activation of the immune system by any means. DNCB is one of those means - it is a topical, nontoxic agent that, when used properly, safely induces the immune system to activate cellular immunity. This has been shown in studies in the U.S., Brazil and at the Institute for Traditional Medicine (S. Dharmananda's clinic) to boost cytotoxic T-lymphocyte activity, reduce HIV viral load - while stimulating the arm of the immune system that is required to defend the body against opportunistic infections. >Thirdly, the selective representation of "research" brought to >attention in the article must also be addressed. Unfortunately, >what is called "research" has also been affected by the biasing >of facts according to one's own opinion. This is a depraved "anti-science" position - one reason cited Subhuti Dharmananda for not attending the 1995 3rd Annual Conference on TCM and AIDS in New York! Why doesn't Ms. Cohen provide a scientific response? What "opinion" is Ms. Cohen referring to? How are facts "biased" if each fact is from a peer-reviewed journal? Why can't Cohen give specifics? Is this just another smokescreen to cover Ms. Cohen's lack of knowledge? >First, there is research that supports both the improvement of >humoral AND cell-mediated immunity, not just suppression of >cell-mediated immunity, using Chinese herbs and particularly >the polysaccharides (the latest research, March 1994, suggests >that the administration of APS may restore impaired CMI - see >reference). This "reference" is cited at the end! >Second, there is no way to appropriately separate the >stimulation of cell-mediated immunity from humoral immunity. >The science is just not sophisticated enough at this time. This statement reveals the depth of Ms. Cohen's knowledge of immunology. I thought she worked in this field for 10 years - or was it really 1 year of work 10 times? Naturally, Ms. Cohen needs to examine the various references regarding the Type IV allergic response - delayed-type hypersensitivity - the response induced by DNCB. (cited in the response following Cohen's letter) >Even if it were, Chinese medicine does not support this type of >separation, due to its view of the human body as a whole being. Doesn't Chinese medicine separate the whole being according to organ systems, meridians, syndromes and symptoms? Doesn't TCM separate the concepts of the body into internal, external, yin, yang, excess and deficiency? Wouldn't humoral immunity be yang and cell-mediated be yin? >Third, there is conflicting evidence that the immune system has >a T-1 /T-2 switch in HIV disease -there has been no >corroboration of this theory. It is an interesting theory, but >it's just that, a theory. I am in no position, therefore, to >say one way or another whether this theory is correct or >incorrect. Who cares about the switch theory? This is another irrelevant smokescreen. The switch theory is last year's old news - just a theory. However, it is a KNOWN SCIENTIFIC FACT that the non- starch polysaccharides in many of the Chinese herbs in these AIDS formulas activate humoral immunity - exactly what is needed for HIV replication and HIV disease progression. >I am in a position to say that our approach from the point of >view of Chinese theory is to regulate and tonify, as opposed to >only tonify. Tonify what? Obviously, by encouraging the environment needed for HIV disease progression, the only thing being tonified is the pathogen - the only thing being regulated is the upregulation of this disease process. >This brings me to the issue of polysaccharides, specifically >Astragalus and Ganoderma, from a Chinese medicine viewpoint. We >DO NOT use these herbs in isolation from the rest of the theory >of HIV disease. Who said anything about using these herbs individually? The problem is in the cumulative effect of the huge non-traditional formulas taken for the rest of each patient's lifetime! >In fact, I personally have been making this point for many >years that tonification alone would lead to severe trouble in >HIV disease. This is a basic and ancient paradigm of Chinese medicine - why does Ms. Cohen feel she is the inventor of this concept? >The herbal formulas that I have been developing have been >created with a balanced view of tonification and regulation >theory, as well as clearing formulas such as Enhance and >Tremella American Ginseng by Health Concerns, and Composition A >by ITM also meet these criteria. Based on a traditional precedent or based on commercialization and marketing? >In conclusion, attacking and blaming serves no purpose. Then why does Ms. Cohen attack the science and blame ACT UP San Francisco? Why all the smokescreens and political diatribe? Why doesn't Cohen just deal with the scientific facts? The science clearly shows that these formulas are immune suppressing. Where is the scientific basis for using these formulas in HIV disease? >I feel that we must continue on our current track of trying to >provide the highest quality of care for persons with HIV. How does the "highest quality of care" come about - by demonizing the science and raising political objections? >I would also like to acknowledge that many people with HIV have >greatly benefited from the treatment of Chinese medicine over >the many years of the epidemic. Where are the studies? Where is the scientific benefit that increases survival? Ms. Cohen presided over a study of Enhance and Clear heat that was completed in 1988 and then again three years ago. Why hasn't either study been published in a peer- reviewed journal? Why were the data cherry-picked for the single announced benefit of "well-being" - a benefit that is easily replicated using steroidal (saponin-containing) herbs? >We need to support research and the need for a cure. How do we support research - by attacking and demonizing the science? By characterizing these issues as "inflammatory and derogatory"? Why not publish the research that has already been completed on these HIV formulas? Is there a commercial conflict of interest that is obstructing the release of the data of the studies that have been completed since the late-1980's? >However, management of symptoms allows for a natural balance to >occur which often leads to increased quality of health and >increased longevity. How do these shotgun formulas help the body back to a "natural balance"? Where is the data? What traditional precedent justifies these huge formulas in long-term use? How is quality of health increased when many of the basic herbal substances being used are scientifically known to suppress cellular immunity - in a disease process that is characterized by suppressed cellular immunity? >Ask any of our long-term survivors -- they are the true test. The science suggests these survivors would have been even better off without the formulas and they are surviving despite them. What about the vast majority of patients who progress and die while taking these formulas? >Misha Cohen, OMD.L.Ac. >Clinical Director >Quan Yin Healing Arts Center 1748 Market Street San Francisco, CA 94102 (415) 861-4964 Fax (415) 861-0579 >1 Liang H; Zhang Y; Geng B. (1994) "The effect of astragalus >polysaccharides (APS) on cell mediated immunity (CMI) in burned >mice" Chinese Journal of Plastic Surgery and Burns, March >1994,10(2):138-41. This "reference" is actually a Medline database abstract. This abstract is often cited by Ms. Cohen as a "reference" - yet it is not. It simply is an abstract of a Chinese-language non-peer- review paper that only SUGGESTS that Astragalus polysaccharides MAY activate cell-mediated immunity. This suggestion is based on IL-2 production. The assumption that IL-2 production requires a cell-mediated response is no longer valid since B-cell activation can also produce IL-2. This is discussed and a reference is provided in the follow-up article following this discussion of Ms. Cohen's letter. Liang H; Zhang Y; Geng B. [The effect of astragalus polysaccharides (APS) on cell mediated immunity (CMI) in burned mice]. Chung-Hua Cheng Hsing Shao Shang Wai Ko Tsa Chih Chinese Journal of Plastic Surgery and Burns, 1994 Mar, 10(2):138-41. Language: Chinese. ABSTRACT: In this paper, the changes in CMI in mice were determined after burn injury, and the effects of APS on CMI of burned mice were investigated in vivo. The results showed that on day 6 postburn, spleen index and thymus index were reduced, T lymphocyte transformation and interleukin 2 (IL-2) production were suppressed. Furthermore, the serum and macrophages from burned mice showed significant suppressive activity upon T lymphocyte transformation in vitro, and suppressive index (SI) of suppressor T cell (Ts) was greater than that of normal controls. Intraperitoneal administration of APS (250mg/kg daily, from day 0 to 5 could restore spleen index and thymus index of burned mice, reverse the suppression of T lymphocyte transformation and IL-2 production, reduce remarkably the suppressive activity of serum, macrophages and Ts. It is SUGGESTED that (1) burn injury-induced suppression of CMI MAY be related to the augmented suppressive activity of serum, macrophages and Ts; (2) administration of APS MAY restore the impaired CMI after burn injury by reducing the suppressive activity of postburn serum, macrophages and Ts. Why can't Cohen provide any basic research demonstrating the ability of polysaccharides to stimulate cell-mediated immunity? Many foreign research articles must be CAREFULLY scrutinized for their methods and premises to determine the validity of any conclusions made. Abstracts must not be relied on as a sole source of scientific fact - they are only a guide to the entire research paper. If the research paper is not available or in a foreign language, how does one analyze the premises, assumptions, methods and materials used in the final outcome as stated in the article? Why is an article that is simply suggestive used to defend a failed and expensive therapy - and attack the statements by others that have been well-researched and properly referenced? =============================== RESPONSE TO MISHA COHEN'S LETTER TO THE EDITOR IN May/June 1995 CAA BULLETIN TO: CAA Bulletin June 23, 1995 Letters to the Editor Sirs, "Real gold does not fear the heat or even the hottest fire". This Chinese proverb appeared in an article in the May/June 1995 CAA Bulletin to validate the statement by Bill Moyers that "if it is truly effective, Chinese medicine will stand up to the most rigorous scrutiny". Ironically, several pages later in the same issue, the letter to the editor by Misha Cohen clearly failed the rigorous scrutiny advocated by Bill Moyers. Regarding the immune-suppressing effect of the "shotgun" herbal formulas advocated for HIV disease, Ms. Cohen stifles scientific debate and attempts to politicize her lack of scientific knowledge by focusing on subjects such as ACT UP San Francisco and the alternative treatment DNCB (dinitrochlorobenzene) which are not the discussion issues in this journal. Interestingly, since DNCB is applied topically and acts both systemically and indirectly, it fits in well with the concepts of Chinese medicine. Further, Ms. Cohen demonizes well-documented and current research as opinionated and "highly suspect and biased" - but fails to identify even one single valid peer-review English language scientific reference to support her defense of the Chinese herbal formulas for HIV disease. Clearly, the proverbial "gold" does fear the heat. The scientific facts are well understood - non-starch polysaccharides (as from herbs) are among the most important thymus-independent antigens "all of which induce specific antibody production (humoral activation)" (1). Such Polysaccharides cannot directly trigger T-cells - they simply do not bind to MHC class II molecules - ". . . thereby negating their possible interaction with T-cells" (2). But, continuous activation of non-T-cell antibody responses by polysaccharides, results in bystander effects thus systemically activating other antibody responses utilizing antibody-helper (Th2) CD4 T-cell help. This is exactly the environment required for HIV viral replication and HIV disease progression since the virus replicates preferentially in Th2 CD4 T-cells. Also, such activation of antibody responses suppress the protective cell- mediated immune response (Th1). (3-4). Once polysaccharides are internalized and retained in a macrophage, they can interfere with the cell's ability to couple pathogen peptides with class II MHC (5). In other words, polysaccharides also suppress the immune response by interfering with the macrophage's ability to present antigens. Interestingly, the vast majority of HIV/AIDS opportunistic infections reside in tissue macrophages, and any impairment of these critical antigen-presenting cells can result in "breakouts" of the infections that lead to morbidity and mortality. The use of humoral-activating herbs for prolonged periods of time, as advocated for the popular Chinese formulas for HIV disease, holds the potential for continuous polyclonal B-cell activation. It has been established that continual polyclonal B- cell activation - the key element in the pathogenesis of non- Hodgkins and Burkitt's Lymphoma - will result in ". . . the emergence of immortalized but not fully transformed B-cell clones"(6). An increasing incidence of lymphoma has been noted in AIDS since it became a CDC case definition for AIDS in 1985 (7). The role these herbal formulas may play in lymphopathogenesis needs to be evaluated. Not only is the cell-mediated immune response (Th1) suppressed by the antibody response (Th2), it is selectively suppressed by various steroidal (saponin-containing) herbs in the popular "shotgun" formulas for HIV disease, such as ginseng and peony (8-10). Since the immunopathogenesis of HIV/AIDS is defined by dysfunctional cell-mediated immune responses, further suppression by saponin-containing herbs is exacerbating an already deadly situation. Contrary to the scientific facts, a reference is cited to assert that Astragalus polysaccharides stimulate cell-mediated immunity. This "reference" is a Medline database abstract of the non-peer review Chinese language journal "Chinese Journal of Plastic Surgery and Burns", which merely suggests that Astragalus polysaccharides "MAY restore CMI" (cell-mediated immunity)" in the skin. The abstract's circumstantial evidence for this speculation was based on the production of interleukin- 2 (IL-2). While IL-2 can be produced by the cell-mediated arm of the immune system, recent research has shown that IL-2 is also produced by activated B-cells of the humoral arm (11). Basic research in immunology is progressing at such a fast pace that previous concepts and study results are no longer valid in the newly-derived paradigms. Ms. Cohen incorrectly states that "there is no way to appropriately separate the stimulation of cell-mediated immunity from humoral immunity". DNCB has been shown to specifically stimulate the cell-mediated immune response (12-13). The statement that "long-term" survivors are the "true test" of the success of a treatment is also flawed. Certainly, the science suggests that such anecdotal information without clinical data only demonstrates that these long-term survivors are alive despite (not because of) the herbal formulas. The Enhance/Clear Heat clinical trial completed three years ago was not followed by publication of a peer-reviewed study. It has been established that steroidal herbs, by causing immunosuppression of normal immune responses, will result in the subjective feeling of "well-being" - the single benefit cited by the Enhance study. Is the fact that AIDS is an unprecedented disease, a defense for using these huge herbal formulas of nearly 40 herbs (the Quan Yin protocol of Enhance plus Clear Heat) in HIV patients, every day, for the rest of the patient's life? Doesn't every symptom seen in AIDS have a TCM precedent? Have we lost our therapeutic focus with these formulas? If "shotgun" therapies are the way to go, then why not use formulas of 200 herbs or more? Where do we draw the line between the "real thing" and the commercial evisceration of our healing art? Unfortunately, these immunosuppressive and antibody-producing commercialized formulas, have been made available over-the- counter. In far too many cases, this has rendered the TCM practitioner irrelevant to the treatment of HIV. Desperate patients simply buy their Enhance, Composition-A or Resist at drug or herb stores and use it as if it were aspirin for AIDS. Isn't the strength of TCM in individual diagnosis and treatment? Isn't TCM herbal therapy based on the finely crafted herbal formulas and patent medicines to deal with every patient's unique and changing condition? Why has TCM been reduced to a one-size-fits-all therapy for AIDS? W. Fred Shaw, L.Ac., Dipl.Ac., M.S., M.T.O.M. 1. Abbas, et.al. 1994. Cellular and Molecular Immunology. W.B. Saunders Co. 202. 2 Paul, William E. 1993. Fundamental Immunology. 3rd ed. Raven Press. 128. 3. Romagnani, G. 1994. Role of Th1/Th2 Cytokines in HIV Infection. Immunological Reviews. No. 140:82. 4. Maggi, E. et.al. 1994. Ability of HIV to promote a Th1 to Th0 shift and to replicate preferentially in Th2 and Th0 cells. Science. Jul. 8, 265(5169):244-248. 5. Unanue, E.R. 1989. Macrophages, antigen-presenting cells, and the phenomena of antigen handling and presentation. In: Paul, W.E. ed. Fundamental Immunology, 2nd ed. New York: Raven Press, 108. 6. Berkow, B., ed. 1992. The Merck Manual of Diagnosis and Therapy. Rathway, NJ: Merck Research Laboratories, 1248. 7. Kristal, A.R. et.al. 1988. Changes in the epidemiology of non-Hodgkin's lymphoma associated with epidemic human immunodeficiency virus (HIV) infection. American Journal of Epidemiology. 128:711-718. 8. Harper, J.I.1990. Chinese Herbs for Eczema. The Lancet (letter). 336:177. 9. Galloway, J.H., et.al. 1991. Chinese herbs for eczema, the active compound? The Lancet. (letter) 337:566. 10. Yeung, H.W., et.al. 1982. Immunopharmacology of Chinese Medicine 1, Ginseng Induced Immunosuppression in Virus- Infected Mice. American Journal of Chinese Medicine, Vol. X, No.1-4, p44-54. 11. Kindler, V., et.al. 1995. Interleukin-2 secretion by human B lymphocytes occurs as a late event and requires additional stimulation after CD40 cross-linking. European Journal of Immunology., Jun., 25:1239-1243. 12. Dearman RJ; Kimber I. 1991. Differential stimulation of immune function by respiratory and contact chemical allergens. Immunology, Apr, 72(4):563-70. 13. Cumberbatch M; Gould SJ; Peters SW; Basketter DA; Dearman RJ; Kimber I. 1992. Langerhans cells, antigen presentation, and the diversity of responses to chemical allergens. Journal of Investigative Dermatology, Nov., 99(5):107S-108S.