Epicutaneous Administration of Papain Induces IgE and IgG Responses in a Cysteine Protease Activity-Dependent Manner

ABSTRACTBackground: Epicutaneous sensitization to allergens is important in the pathogenesis of not only skin inflammation such as atopic dermatitis but also "atopic march" in allergic diseases such as asthma and food allergies. We here examined antibody production and skin barrier dysfunction in mice epicutaneously administered papain, a plant-derived occupational allergen belonging to the same family of cysteine proteases as mite major group 1 allergens.Methods: Papain and Staphylococcus aureus V8 protease were patched on the backs of hairless mice. Tran- sepidermal water loss was measured to evaluate the skin barrier dysfunction caused by the proteases. Papain or that treated with an irreversible inhibitor specific to cysteine proteases, E64, was painted onto the ear lobes of mice of an inbred strain C57BL/6. Serum total IgE levels and papain-specific IgE and IgG antibodies were measured by ELISA.Results: Papain and V8 protease patched on the backs of hairless mice caused skin barrier dysfunction and increased serum total IgE levels, and papain induced the production of papain-specific IgG1, IgG2a, and IgG2b. Papain painted onto the ear lobes of C57BL/6 mice induced papain-specific IgE, IgG1, IgG2c, and IgG2b, whereas papain treated with E64 did not. IgG1 was the most significantly induced papain-specific IgG subclass among those measured.Conclusions: We demonstrated that the epicutaneous administration of protease not only disrupted skin barrier function, but also induced IgE and IgG responses in a manner dependent on its protease activity. These results suggest that protease activity contained in environmental sources contributes to sensitization through an epicutaneous route

Intervention skills to facilitate productive occupational performance for persons with dementia : Interviews with expert occupational therapists

認知症者に対して小集団を形成し,生産的作業を実施する際に彼らに見られる作業上の問題および作業遂行を促進する支援技術を明らかにすることを目的に,熟練作業療法士5名に対して半構成的インタビューを行った.質的帰納的分析の結果,作業上の問題は19項目抽出され,支援技術は41項目抽出された.開始困難,作業中の停止など作業実行時にみられる問題だけでなく,仕上がりの悪さを卑下し,それが次の参加拒否に繋がるといった生産的作業特有の問題が抽出された.支援技術には,貢献欲を刺激するような目標設定や声かけによって動機づけすること,個人の性格特性だけでなく認知症タイプ特有の症状を考慮した小集団形成や作業選択をすることが含まれていた.黒子のように演じながら作業が淀みなく流れるように,言語的手がかりだけでなく視覚,触覚,聴覚,嗅覚といった様々な感覚モダリティーの手がかりをタイミング良く与えることが認知症者の作業遂行を促進するために重要である.The purpose was to identify problems in productive occupational performance of persons with dementia in small groups and to identify intervention skills. We interviewed five expert occupational therapists using a semi-structured interview. Using qualitative inductive analysis, we categorized the problems into 19 items and the skills into 41 items. As well as difficulties in initiating occupation steps, motion stop of occupation-in-action, problems in productive occupation whereby persons with dementia refuse participation in group activities when the quality of finished products is not good were also extracted. Setting up purpose and using phrases which enhanced clients' sense of contribution were included in the skills for inviting them to participate in activities. In addition, methods of selecting occupation and making groups with reference to personal character and dementia type were also included. It was found that experts give various sensory modality cues at appropriate timing, not only verbal cues but also visual, tactile, auditory and olfactory cues, acting as behind-the-scenes supporters

Presensitization to Ascaris antigens promotes induction of mite-specific IgE upon mite antigen inhalation in mice

Background: Patients with house dust mite (HDM) allergy or Ascariasis produce serum IgE specific to the antigens of HDM or nematode Ascaris, respectively. Although human IgE cross-reactivity has been reported between HDM and Ascaris antigens, it remains unclear whether it contributes to the pathogenesis of allergic diseases. We herein investigated the induction of cross-reactive antibodies and T cells in mice and effects of airway exposure to HDM antigens after preimmunization with Ascaris antigens. Methods: Mice were intraperitoneally immunized with HDM or Ascaris antigens with Alum, followed by the intranasal administration of HDM antigens. Serum antigen-specific IgE and IgG were measured by ELISA. Cytokine release in splenocytes from Ascaris-immunized mice upon in vitro restimulation with HDM antigens were measured by ELISA. Results: Immunization with Ascaris or HDM antigens induced cross-reactive IgG1. Splenocytes from Ascaris-immunized mice released IL-5 and IL-13 in response to the restimulation with HDM antigens. Subsequent airway exposure to HDM antigens promoted the induction of HDM-specific IgE and upregulation of HDM-specific IgG1 in Ascaris-immunized mice, whereas these responses were not detected or smaller without the Ascaris presensitization. Conclusions: We demonstrated that the immunization of naïve mice with Ascaris antigens induced production of antibodies and differentiation of Th2 cells, which were cross-reactive to HDM antigens, and accelerated induction of serum HDM-specific IgE upon subsequent airway exposure to HDM antigens in mice. These results suggest that sensitization to HDM towards IgE-mediated allergic diseases is faster in individuals with a previous history of Ascaris infection than in those without presensitization to Ascaris

Developmental Changes in RNA Synthesis in Nuclei Isolated from the Midgut of Bombyx mori

The rate of RNA synthesis in the midgut of Bombyx mori during the period of larvalpupal development was assayed in vitro with isolated nuclei. The synthesis was examined with or without ecdysterone added in the assay medium, and the products were analyzed by means of polyacrylamide gel electrophoresis. The rate of RNA synthesis in nuclei isolated at the gluttonous stage (day 3 of the 5th instar) was 2.5 times as high as that in nuclei from the mature larvae (day 7 of the 5th instar), and the RNA species synthesized in the two preparations of nuclei were different. Both syntheses were stimulated by ecdysterone added in the reaction mixture, but features of the hormonal effect were different between the two larval stages. In case of the gluttonous stage, new species of RNA xvere found to be synthesized in ecdysteronetreated nuclei. On the other hand, nuclei from the mature larvae showed only quantitative hut not qualitative stimulation by the hormone. Many of the ecdysterone-stimulated RNA species found in midgut cell nuclei from the gluttonous larvae were similar to those found in nuclei from the mature larvae

Developmental Changes in RNA Synthesis in Nuclei Isolated from the Midgut of Bombyx mori

The rate of RNA synthesis in the midgut of Bombyx mori during the period of larvalpupal development was assayed in vitro with isolated nuclei. The synthesis was examined with or without ecdysterone added in the assay medium, and the products were analyzed by means of polyacrylamide gel electrophoresis. The rate of RNA synthesis in nuclei isolated at the gluttonous stage (day 3 of the 5th instar) was 2.5 times as high as that in nuclei from the mature larvae (day 7 of the 5th instar), and the RNA species synthesized in the two preparations of nuclei were different. Both syntheses were stimulated by ecdysterone added in the reaction mixture, but features of the hormonal effect were different between the two larval stages. In case of the gluttonous stage, new species of RNA xvere found to be synthesized in ecdysteronetreated nuclei. On the other hand, nuclei from the mature larvae showed only quantitative hut not qualitative stimulation by the hormone. Many of the ecdysterone-stimulated RNA species found in midgut cell nuclei from the gluttonous larvae were similar to those found in nuclei from the mature larvae