Following the transfer into fertilized mouse eggs of recombinant genes composed of the upstream region of the rat insulin II gene linked to sequences coding for the large-T antigen of simian virus 40, large-T antigen is detected exclusively in the beta-cells of the endocrine pancreas of transgenic mice. The alpha- and delta-cells normally found in the islets of Langerhans are rare and disordered. Well-vascularized beta-cell tumours arise in mice harbouring and inheriting these hybrid oncogenes.

Heritable formation of pancreatic β -cell tumours in transgenic mice expressing recombinant insulin/simian virus 40 oncogenes

Transgenic mice harboring SV40 t-antigen genes develop characteristic brain tumors

The only real argument for establishing a specific diagnosis in allergic diseases is the institution of a specific treatment. Allergen avoidance and immunotherapy represent the only specific treatments we are able to offer allergic patients. The capacity of drug treatment is limited to the elimination or diminishing of symptoms, and no studies have been able to show that pharmacologic treatment of allergic diseases, not even corticosteroids, modifies the spontaneous, long-term course of the disease. Costbenefit studies of immunotherapy present problems, and we recommend that immunotherapy be an integrated part of the treatment of allergic disorders, thus reducing the disease severity, improving the quality of life of allergics, and diminishing the risk and cost of pharmacotherapy. The first EAACI Immunotherapy Position Paper was published in 1988. New insights into the pathogenesis of allergic diseases and recent publications on immunotherapy have called for a revision of the Immunotherapy Position Paper. However, allergenspecific immunotherapy is a controversial treatment, and drafting this 1992 revised Position Paper is difficult since: 1) We intend to recommend that immunotherapy be performed in the most scientific way, but supportive data are not always sufficient. 2) Although clinical experience is encouraging, particularly with recent high-quality extracts, a further reduction in the number of patients treated by immunotherapy, while we wait for further scientific data, will make improvements more difficult, and eventually lead to a halt in the production of allergen extracts. Our Position Paper, therefore, aims at reaching a consensus, balancing science, theory, and current practice in most European countries, at the same time intending to improve the scientific value of the 1992 revised EAACI Immunotherapy Position Paper . The outlines of the 1992 revised EAACI Immunotherapy Position Paper were debated at a one-day meetingin February 1991, in Copenhagen, Denmark, sponsored by ALK, Denmark. The first edition was drafted at a three-day meeting in May 1991, in Madrid, Spain, organized by Dr Emilio AlvarezCuesta and kindly sponsored by Abell6, Spain. The final revised edition of the Position Paper represents the opinion of the members of the EAACI Immunotherapy Subcommittee and includes comments from the EAACI associate European national societies of allergology. Hans-Jrargen Malling Bent Weeke

Position Paper: Immunotherapy

Publisher Summary This chapter reviews some of the experimental and clinical findings linking immunodepression with malignant development. This material has accumulated for the past two decades and sufficient information, whether contradictory or not, is now available to permit an appraisal of the role of immune functions as the regulators of tumor development in animals and man. The idea that immunodepression enhances malignant development has become an integral part of the experimental support of the immune surveillance theory. In its more formal presentations, the theory of immunological surveillance against neoplasia included some basic points, with variations in terminology, but which have appeared with regularity as an integral part of the theory. The degree of immunodepression obtained in many experiments is quite profound and is clearly of a different magnitude than the immune defects occasionally observed in tumor-bearing humans. If immune mechanisms are important in host resistance to antigenic malignancies, any interference with the normal expression of host immunity should facilitate malignant development. Thus, both clinical and experimental evidence indicates that the diseases or procedures that lower the immune functions in mammals are associated with a higher incidence of malignancies.

Immunodepression and malignancy.

Concerning the nature of intolerance to aspirin

Acth and cortisone in allergic manifestations: Therapeutic results and studies on immunological and tissue reactivity

Anaphylactic shock in the pertussis-vaccinated mouse☆

Summary 1.Bovine serum and crystalline egg albumin (Ea) when mixed with Hemophilus pertussis phase I organisms and inoculated intraperitoneally proved to be strong antigens in that a high percentage of female albino mice thus injected were fatally shocked by challenge with the homologous antigen. 2.Bovine plasma albumin and diphtheria toxoid were also effective in enhancing sensitization, although the manifestations thereof were to a lesser degree. 3.Neither precipitating nor non-precipitating or univalent antibodies were detected in mouse anti-Ea serum. It is suggested that tissue or sessile antibodies may be responsible for the heightened sensitivity. 4.Passive transfer could not be effected with homologous “antisera” in either control or pertussis inoculated mice. Some degree of transfer was found possible with rabbit antiserum in pertussis inoculated mice. 5.The enhancement of antigenicity is probably not mediated by virtue of the adjuvant or “schlepper” effect of the pertussis cells. Pertussis admixture was found to be much more effective than Freund9s adjuvant. Admixture is not necessarily a requirement but both the antigen and the pertussis organisms seem to be administered necessarily on the same day. 6.Various fractions of the pertussis organisms were found to possess this capacity, i.e. sonically disintegrated supernatant, alcohol precipitate, saline extract, etc. The acetic acid-insoluble (nucleoprotein?) fraction of the latter is also markedly effective. 7.No explanation is offered at the moment to explain this phenomenon.

Anaphylactic shock in the mouse vaccinated with Hemophilus pertussis. III. Antigens. antibody and passive transfer studies.

1.1. It has been confirmed that H. pertussis vaccination of white mice produces a fiftyfold increase in histamine sensitivity. 2.2. Brucella abortus vaccine enhanced histamine sensitivity to a much less but significant degree. 3.3. Mice immunized by an intraperitoneal injection of a mixture of H. pertussis vaccine and horse serum become markedly anaphylactically sensitive to the serum. Brucella abortus vaccine has a somewhat similar effect on anaphylaxis. 4.4. The results of further experimentation seem to substantiate the impression that histamine plays a minor role in anaphylaxis in the mouse even when the mouse has been made markedly histamine sensitive. 5.5. The possible relationship between the enhancement of experimental anaphylaxis by H. pertussis vaccine and the questionable observation of the production of the clinical syndrome of paralysis following vaccination is discussed.

Anaphylactic shock in the pertussis vaccinated mouse.

B. pertussis phase I vaccine is an effective adjuvant in the production of experimental aspermatogenesis in that profound testicular damage is produced in most of the animals. Pertussis organisms thereby are found to enhance hypersensitivity of the delayed as well as of the immediate type. The mechanism of action of pertussis vaccine is probably different from that of oily adjuvants.

Saul Malkiel

Papers

Acth and cortisone in allergic manifestations: Therapeutic results and studies on immunological and tissue reactivity

Anaphylactic shock in the pertussis-vaccinated mouse☆

Anaphylactic shock in the mouse vaccinated with Hemophilus pertussis. III. Antigens. antibody and passive transfer studies.

Anaphylactic shock in the pertussis vaccinated mouse.

Immunologically Induced Aspermatogenesis in the White Mouse