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Biomedical subjects

Michiko Aihara

Publications and source records attributed to Michiko Aihara.

15 recordsLinked to original sources

Effects of tributyltin on the development of atopic dermatitis-like eruptions in DS-Nh mice.

BACKGROUND: In the last few decades, numerous chemical compounds have been produced as a result of industrial development. At the same time, the number of atopic dermatitis (AD) patients has been increasing. It has been reported that tributyltin (TBT) compounds have effects not only on the reproductive system but also on the immune system. OBJECTIVE: To investigate whether TBT has an effect on AD, we fed a diet containing TBT to DS-Nh mice, which spontaneously developed dermatitis under conventional conditions. METHODS: DS-Nh mice fed TBT or a control diet were examined for skin changes, number of Staphylococcus aureus on the skin and serum IgE levels. To determine Th1/Th2 cytokine production by lymphocytes, lymphocytes of DS-Nh mice fed TBT and of controls were cultured with staphylococcal enterotoxin B and cytokine levels in the supernatants were measured by ELISA. We observed not only spontaneous dermatitis but also dermatitis induced by sensitization with 2,4,6-trinitrochlorobenzene (TNCB). RESULTS AND CONCLUSION: The AD-like lesions induced by TNCB sensitization were more severe in the mice fed TBT than in those fed the control diet. A greater increase in S. aureus on the skin was observed in the mice fed TBT than in the mice fed the control diet. A decrease in IFN-gamma production and an increase in IL-5 and IL-13 production were observed in the mice fed the TBT diet and treated with TNCB. These findings suggest that the increase in S. aureus and the enhancement of Th2 response induced by TBT exacerbate the AD-like lesions in mice treated with TNCB.

Animals↗

Effects of photocatalytic agent on DS-Nh mice, developing atopic dermatitis-like eruption with an increase of Staphylococcus aureus.

BACKGROUND: Staphylococcus aureus(S. aureus) is thought to play a significant role in the exacerbation of atopic dermatitis (AD). DS-Nh mice, a non-hair-bearing mouse model of AD, spontaneously develop dermatitis under conventional conditions. A remarkable increase in S. aureus is considered to strongly relate to the induction and aggravation of this dermatitis. A topical use of anatase-type titanium dioxide (TiO2) followed by UV irradiation, acting as photocatalyst, is believed to have antibacterial activity. We investigated the bactericidal effect of TiO2 with UV irradiation on DS-Nh mice to prevent the aggravation of the dermatitis. METHODS: Ten-week-old DS-Nh mice were treated with TiO2 in petrolatum on the back, followed by UVA irradiation, for 11 weeks. The severity of dermatitis was assessed by evaluating individual lesions using a 4-grade scale and expressed as the total skin score. S. aureus colonizing the mouse skin was counted after isolation and incubation with agar medium. The skin barrier dysfunction was evaluated by measuring transepidermal water loss (TEWL). RESULTS: The mice treated with TiO2 and UV irradiation showed a significant increase in total skin scores, the number of S. aureus and TEWL values, compared with non-treated mice. In contrast, these parameters were significantly lower in the mice treated with petrolatum and UV irradiation. CONCLUSIONS: A significant increase in S. aureus was recognized on the skin together with the aggravation of AD-like dermatitis in our mice model. Skin barrier dysfunction induced by TiO2 and UV irradiation seems to facilitate the increase in S. aureus.

Animals↗

A case of cutaneous T cell pseudolymphoma in a patient with Helicobacter pylori infection.

Cutaneous pseudolymphomas (CPL) are benign cutaneous lymphoproliferative infiltrations of various origin, including among others bacterial infections, viral infections and drugs . Helicobacter pylori has been frequently founded in the stomach of patients with MALT lymphoma. In January 2001, a 43-year-old man was referred to our department because of a 1-month history of itchy erythematous patches, plaques and flat tumors on his body. Histological examination revealed nodular infiltrations composed of lymphocytes, plasma cells and histiocytes with exocytosis of lymphocytes within the epidermis. Molecular analysis of rearrangement of T cell receptor and immunoglobulin heavy-chain genes did not reveal monoclonality. Based on these clinical, laboratory and histopathological data, a diagnosis of cutaneous T cell pseudolymphoma (CTPL) was made. The patient was anti-H. pylori antibody-positive, and was treated with anti-H. pylori combination with the result that all of the tumors had disappeared by January 2002. The patient has maintained complete response up to the last follow-up visit in December 2005.

Adult↗

A pediatric case of anaphylaxis caused by matsutake mushroom (Tricholoma matsutake) ingestion.

BACKGROUND: Anaphylaxis is one of the severest forms of allergic diseases. Some kinds of mushroom are known as causative allergens in food anaphylaxis. Matsutake mushroom (Tricholoma matsutake) is a typical edible mushroom available in autumn in Japan. We encountered an 8-year-old Japanese girl who developed anaphylaxis after ingesting matsutake mushrooms. METHODS: We studied the case in detail, by measuring specific IgE antibodies and conducting skin tests, to confirm the diagnosis. We also detected seven cytokines and chemical mediators in the blood in order to study the pathophysiology of the anaphylaxis. RESULTS: We diagnosed anaphylaxis caused by ingestion of matsutake mushrooms based on the following. A skin prick test showed a positive reaction to matsutake mushroom, and specific IgE antibody for matsutake mushroom extract was detected in the patient's serum by fluorometric ELISA. Blood levels of chemical mediators including histamine, ECP, tryptase and cytokines such as IL-6, IL-5 and IL-10 but not IFN-gamma also increased significantly during the allergic episode. CONCLUSIONS: We demonstrated that chemical mediators including histamine, tryptase and ECP as well as several cytokines were involved significantly during the episode of anaphylaxis. In addition, eosinophils as well as mast cells played significant roles in the anaphylaxis. Furthermore, CD4+CD25+ T regulatory cells that released IL-10 were likely activated during the anaphylaxis. Matsutake mushroom should be considered as a causative allergen in food anaphylaxis.

Adrenergic Agonists↗

[Immedeate and delayed-type reactivity to fungi and effects of antifungal drugs on atopic dermatitis].

OBJECTIVE: To investigate immediate and delayed-type reactivity for fungi in atopic dermatitis (AD) patients and the effect of antifungal therapy. METHODS: We examined immediate and delayed-type reactivity in AD patients for Candida albicans and Malassezia furfur by skin prick test (SPT), and estimated the effect of amphotericin B (AMPH) and itraconazole (ITCZ). RESULTS: Twenty eight of 40 patients showed positive immediate-type reaction and 10 of 27 patients did delayed-type reaction for Candida albicans. As for Malassezia furfur, positive immediate-type reaction was shown in 30 of 40 patients and positive delayed-type reaction did in 4 of 27 patients. The RAST score of specific IgE to Candida albicans was low in the patients with positive delayed-type skin reaction for Candida albicans, while the score was high in the patients with the negative delayed-type skin reaction. Both of AMPH and ITCZ were effective to the patients with positive immediate-type reaction for Candida albicans in SPT. The skin reaction for Malassezia furfur was stronger in the patients treated with ITCZ effectively than in the patients treated not effectively. In addition, ITCZ was effective in all patients except one, who showed positive reaction for Malassezia furfur accompanied with negative reaction for Candida albicans in SPT. CONCLUSION: Fungal allergy is one of the aggravation factors of AD, and SPT is useful to evaluate fungal allergy and to choose effective antifungal therapy.

Adult↗

Effects of TNCB sensitization in DS-Nh mice, serving as a model of atopic dermatitis, in comparison with NC/Nga mice.

BACKGROUND: It has been predicted that a type-1 and type-2 helper T cell (Th1/Th2) imbalance exists in atopic dermatitis (AD). In DS-Nh mice, an AD mouse model, Staphylococcus aureus increases on the skin surface. OBJECTIVE: To investigate whether the Th1-dominant response has an influence on the development of AD, we induced chronic allergic hypersensitivity with 2,4,6-trinitrochlorobenzene (TNCB ) in two AD mouse models: NC/Nga mice and DS-Nh mice. Th1 and Th2 cytokine production of splenocytes was assessed under stimulation with staphylococcal enterotoxin B (SEB) which induces a Th1 response in DS-Nh mice with or without TNCB sensitization. METHODS: We examined clinical skin changes, transepidermal water loss (TEWL), the number of S. aureus on the skin and the serum IgE levels in these mice treated repeatedly with TNCB under conventional conditions (free of fur mites). The splenocytes of DS-Nh mice were cultured with SEB and the cytokine levels in the supernatants were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Significant skin changes were observed on the skin even where TNCB was not applied in both mice treated with TNCB. Increases in S. aureus on the skin and serum IgE levels were detected in DS-Nh mice, but not in NC/Nga mice. In DS-Nh mice, IFN-gamma and IL-13 production of splenocytes increased in the mice treated with TNCB. CONCLUSION: These results suggest that there might be a different mechanism of dermatitis induction between NC/Nga and DS-Nh mice. Th1 responses might play an important role in the development of dermatitis and increase in serum IgE levels in DS-Nh mice through an increase in IL-13 production.

Animals↗

Drug-induced hypersensitivity syndrome due to cyanamide associated with multiple reactivation of human herpesviruses.

Drug-induced hypersensitivity syndrome (DIHS), characterized by serious adverse systemic reactions in addition to skin rash, has unknown pathogenesis. Its association with human herpesvirus (HHV), mainly HHV-6, has been reported recently. A 46-year-old Japanese man is described in whom a generalized eruption developed about 1 month after taking cyanamide, a drug for alcoholism. This was associated with the following manifestations: high fever, lymphadenopathy, facial edema, marked leukocytosis with eosinophilia and atypical lymphocytes, lymphocytopenia, liver and renal dysfunction, and low IgG level. He was treated with 8 mg betamethasone daily and his condition improved, but he needed low-dose corticosteroid for almost 1 year because of several episodes of recurrence. HHV-6, HHV-7, herpes simplex virus (HSV), and cytomegalovirus (CMV) specific IgG titers showed more than a four-fold rise sequentially. Significant numbers of copies of HHV-6 and HHV-7 DNA were detected in the peripheral white blood cells by real-time polymerase chain reaction (PCR). HHV-6 and CMV DNA were detected in the serum by nested PCR. A patch test for cyanamide was positive. The diagnosis of DIHS due to cyanamide, which has never been reported as a causal drug of DIHS, accompanied by reactivation of not only HHV-6, but also HHV-7, CMV, and HSV, was made. Disturbance of the immune system was suggested by the persistent low level of IgG, and consecutive viral reactivation may have participated in the prolonged course in this case.

Agammaglobulinemia↗

Hyperproduction of IFN-gamma by CpG oligodeoxynucleotide-induced exacerbation of atopic dermatitis-like skin lesion in some NC/Nga mice.

Under conventional conditions, NC/Nga mice spontaneously develop an atopic dermatitis (AD)-like skin lesion accompanied by immunoglobulin E (IgE) hyperproduction and the expression of T helper 2 (Th2) cytokines. CpG DNA activates a strong interferon-gamma (IFN-gamma)-dominated T helper 1 (Th1) response, while inhibiting Th2-dependent allergies. In this study, we examined whether CpG oligodeoxynucleotide (ODN) could prevent the development of the skin lesions in NC/Nga mice. Sixteen of 26 NC/Nga mice did not exhibit dermatitis after CpG ODN was administered intraperitoneally every 2 wk for a total of five times. CpG ODN administration induced IFN-gamma production, which inhibited the production of Th2 cytokines (interleukin (IL)-4, IL-5, and IL-13) in both spleen and lymph node cells and culminated in a decrease in the serum IgE level. These data suggest that the CpG ODN has a therapeutic effect against AD; however, some mice (10 of 26) treated with CpG ODN exhibited an exacerbation of dermatitis accompanied by the hyperproduction of IFN-gamma, although Th2 cytokines were suppressed. These results suggest that the suppression of Th2 cytokines may not completely prevent dermatitis and that IFN-gamma may play a role in developing dermatitis in some NC/Nga mice.

Animals↗

Different patterns of cytokines, ECP and immunoglobulin profiles at two adverse drug reactions in a patient.

OBJECTIVES: Drug-induced hypersensitivity syndrome (HS) is a rare but life-threatening disease. We experienced carbamazepine-induced HS in a 14-year-old boy, who had cefaclor-induced cutaneous eruptions 15 months later. To clarify the mechanisms of HS and the differences between two diseases we studied this case in detail. METHODS: We investigated the associated viral agents by polymerase chain reaction and the specific antibodies. We also studied the mechanism of diseases by measuring chemical mediators including cytokines, ECP and immunoglobulins. RESULTS: The patient was diagnosed as having carbamazepine-induced HS associated with reactivation of human herpesvirus 6 based on the clinical course and laboratory data including drug-induced lymphocyte stimulation tests. Similarly, the diagnosis of cefaclor-induced eruption without any viral reactivation was made. Serum levels of IFN-gamma, IL-6, TNF-alpha, IL-5 and ECP were increased significantly at HS but mildly at cefaclor-induced eruptions. Furthermore, we detected transient hypogammaglobulinemia only at HS. CONCLUSIONS: This is the first report of anticonvulsant-induced HS followed by antibiotic-induced eruptions in a patient. In addition, we demonstrated difference in serum levels of inflammatory cytokines, immunoglobulins, activated eosinophils and viral reactivation between these diseases. This case would contribute to the understanding of the pathophysiology of adverse drug reactions including HS.

Adolescent↗

Neuropeptides concentrations in the skin of a murine (NC/Nga mice) model of atopic dermatitis.

BACKGROUND: It has been reported that the expression of neuropeptides (NPs), and the density and structure of peripheral nerves in atopic dermatitis (AD) are different from those in normal skin. OBJECTIVE: We investigated the role of NPs, in the development of AD with quantitative study of substance P (SP) and calcitonin gene-related peptide (CGRP) in the skin of AD-model mice. METHODS: We measured the NPs in the skin of mice (NC/Nga as AD-model mice, BALB/c and C57BL/6 as control) by enzyme-linked immunosorbentassay (ELISA). Peripheral nerve fibers and SP in the skin were stained by immunohistochemical staining, using anti-PGP9.5 antibody and anti-SP antibody. RESULTS: Under conventional condition, SP concentration in AD-like skin lesions of NC/Nga mice was higher than that in non-affected skin of the same mice. Under specific pathogen-free condition, SP concentration in the skin of NC/Nga mice was higher than that in the skin of BALB/c and C57BL/6 mice. In contrast, CGRP concentration in the skin lesions was lower than that in non-affected skin of NC/Nga mice. SP was detected not only in the nerve fibers in the dermis but also in mast cells in the inflammatory areas. CONCLUSIONS: The skin of NC/Nga mice contains more SP congenitally, and environmental factors may aggravate this abnormal condition. We hypothesize that increase of SP accompanied with a decrease of CGRP in the skin may play important roles in the pathogenesis and development of AD.

Animals↗

[Natural killer cell activity among patients with atopic dermatitis].

We examined natural killer (NK) activity in 128 patients with atopic dermatitis (AD) to investigate the relationships between NK activity and severity of dermatitis, duration of disease, and mental states. The results showed the following: 1) No relationship was shown between severity of dermatitis and NK activity, neither between NK activity nor eosinophilic counts nor serum IgE. 2) Patients with longer duration of AD lesions showed significantly lower NK activity (P=0.036). The significant relationship was recognized between severity of dermatitis and the duration of disease (P=0.014). 3) No relationships were recognized between NK activity and mental states evaluated using the Profile Of Mood States (POMS) questionnaire, as tension-anxiety, depression-dejection, anger-hostility, vigor, fatigue and confusion. From a psychoneuroimmunological viewpoint, chronic stress as having AD might influence the lower NK activity of patients with longer duration of AD.

Adolescent↗

[Effects of sedative odorant inhalation on patients with atopic dermatitis].

Atopic dermatitis (AD) has been clinically well-known to be frequently exacerbated by psychological and physiological stress. In this study, we examined effects of sedative odorant (modified valerian oil) inhalation on patients with AD. We investigated clinical scores, skin physiological parameters and psychological questionnaire (POMS) every 2 weeks. For first 2 weeks, we arranged non-inhalation period. Results for non-inhalation period were compared with these of 2- or 4-week inhalation. As results, sum of skin clinical scores significantly improved after odorant inhalation. Some patients improved for non-inhalation period, too. However, patients that had not improved for non-inhalation period significantly improved after odorant inhalation. Skin conductance and skin dryness/scaling score also improved after odorant inhalation without improving for non-inhalation period. Psychological parameter (POMS) also tended to improve after odorant inhalation. These results suggest that sedative odorants may be useful as a complementary therapy for AD through psychosomatic stress care.

Administration, Inhalation↗