Kiichiro Danno

Essential Contribution of Germline-Encoded Lysine Residues in Jγ1.2 Segment to the Recognition of Nonpeptide Antigens by Human γδ T Cells

Human γδ T cells display unique repertoires of Ag specificities largely imposed by selective usages of distinct Vγ and Vδ genes. Among them, Vγ2/Vδ2+ T cells predominate in the circulation of healthy adults and respond to various microbial small molecular mass nonpeptide Ags. The present results indicate that the primary Vγ2/Vδ2+ T cells stimulated with the distinct groups of nonpeptide Ags, including monoethyl pyrophosphate, isobutyl amine, and aminobisphosphonate, invariably exhibit Jγ1.2 in the Vγ2+ TCR-γ chains. Gene transfer studies revealed that most of the randomly cloned Vγ2/Jγ1.2+ TCR-γ genes bearing diverse Vγ/Jγ junctional sequences could confer the responsiveness to all these nonpeptide Ags, while none of the Vγ2/Jγ1.1+ or Vγ2/Jγ1.3+ TCR-γ genes could do so. Furthermore, mutation of the lysine residues encoded by the Jγ1.2 gene, which are unique in human Jγ1.2 and absent in other human or mouse Jγ segments, completely abrogated the responsiveness to all the nonpeptide Ags without affecting the response to anti-CD3 mAb. These results strongly suggested that the positively charged lysine residues in the TCR-γ chain CDR3 region encoded by the germline Jγ1.2 gene play a key role in the recognition of diverse small molecular mass nonpeptide Ags.

Near‐infrared irradiation stimulates cutaneous wound repair:laboratory experiments on possible mechanisms

Background/Aims: Several physical agents such as low‐energy lasers have been used in the treatment of chronic skin ulcers. This study was performed to investigate potential effects of a newly‐developed, specific near‐infrared light source on wound repair.

Atopic dermatitis‐like pruritic skin inflammation caused by feeding a special diet to HR‐1 hairless mice

Abstract:  Dry skin/barrier dysfunction is considered to be one of the characteristic features of atopic dermatitis (AD). When HR‐1 hairless mice are fed a special diet, HR‐AD, dry red skin is induced. We examined whether HR‐AD–fed mouse could be used as a model for AD by showing itch‐associated scratching behaviour and by analysing the immunological change. HR‐1 mice were fed HR‐AD from 4 weeks old. HR‐AD–fed mice showed severe dry skin symptoms accompanied by a decrease in dermal water content and an increase in transepidermal water loss and prolonged scratching bout duration on day 14 or 28. These symptoms became gradually worse until day 56. Marked epidermal hyperplasia and slight increase in CD4+ cells in the skin were observed from day 28. In contrast, increases in circulating T cells and serum immunoglobulin E were seen from day 41. Other skin‐infiltrating inflammatory cells, such as eosinophils and mast cells, were increased on day 56 but not on day 28. Though daily oral treatment with dexamethasone reduced the increased numbers of these cells, it did not affect the dry skin symptoms or the prolonged scratching episodes. In contrast, the development of dry skin was inhibited by feeding with 10% normal diet‐containing HR‐AD. The skin barrier dysfunction in HR‐AD–fed mice is closely associated with the development of AD‐like pruritus. Changes in the immunological parameters observed may be the consequence of skin barrier dysfunction. Our findings suggest that HR‐AD–fed mouse could be used as a dry skin‐based experimental model for AD.

Cyclosporin-A suppresses p53-dependent repair DNA synthesis and apoptosis following ultraviolet-B irradiation.

Background: The combination of cyclosporin‐A (CS‐A) and ultraviolet‐B (UV‐B) irradiation is not recommended in the treatment of psoriasis, because risks of UV‐B‐induced skin cancer are increased. The recommendation, however, has not well been confirmed by basic researches.

Effects of near‐infrared radiation on the epidermal proliferation and cutaneous immune function in mice

While ultraviolet radiation alters various cutaneous cell functions, little is known about the photobiological effects of infrared radiation (IR) on the skin except its local thermal effect. This study demonstrated that single exposure of mouse skin to near IR (0.7‐1.3 μm) reversibly suppressed the proliferating activity of the epidermis, the density of Langerhans cells, and the ability of skin to induce contact hypersensitivity reaction. During the exposure, the ear surface temperature was elevated from a mean of 27 to 31.2°C. The results suggest that near IR can modulate the epidermal proliferation and part of the skin immune system, with a mild thermal effect.

PEMPHIGUS VEGETANS WITH OESOPHAGEAL INVOLVEMENT : SUCCESSFUL TREATMENT WITH MINOCYCLINE AND NICOTINAMIDE

although probably rare, the coexistence of malignancy and EN should be borne in mind, especially when this dermatosis develops inexplicably in an elderly subject. In such cases, additional investigative procedures should be undertaken.^ Finally, as EN may also be associated with menstruation^ and pregnancy/ this raises the question of whether EN associated with irradiated or untreated uterine malignancy is due to shedding of an antigen by the neoplasm, or might it be due to release of the same hypothetical factor which gives rise to EN in association with menstruation or pregnancy? This problem deserves further investigation.

Combination Therapy with Low‐Dose Etretinate and Eicosapentaenoic Acid for Psoriasis Vulgaris

A randomized open study was undertaken to compare the therapeutic effects between low‐dose etretinate alone and low‐dose etretinate combined with eicosapentaenoic acid in 40 patients with chronic, stable psoriasis vulgaris. Better and more rapid improvement was obtained with the combination therapy for 12 weeks than with low‐dose etretinate monotherapy. Eicosapentaenoic acid was safe, and adverse reactions due to low‐dose etretinate were mild or tolerable. The combination regimen, therefore, has a satisfactory effect on psoriasis without marked adverse reactions.

A Case of Acne Fulminans in a Patient with Ulcerative Colitis Successfully Treated with Prednisolone and Diaminodiphenylsulfone: A Literature Review of Acne Fulminans, Rosacea Fulminans and Neutrophilic Dermatoses Occurring in the Setting of Inflammatory Bowel Disease

A 19-year-old Japanese man had been treated for ulcerative colitis for 2 years. He was admitted to our hospital with nodulocystic inflammatory papules and pustules on his face and chest, high-grade fever, arthralgia and general malaise. A biopsy specimen from a pustule showed prominent infiltration of neutrophils in the epidermis and dermis, particularly around hair follicles. We made a diagnosis of acne fulminans. The systemic administration of prednisolone at 30 mg daily for 1 week immediately improved his skin lesions and other symptoms; however, during tapering of prednisolone at 20 mg daily, skin lesions flared up. The addition of oral diaminodiphenylsulfone improved the skin lesions. Although there have been a few reports of acne fulminans associated with Crohn’s disease, this is the first case report of acne fulminans in a patient with ulcerative colitis. It is noteworthy that the addition of diaminodiphenylsulfone was effective for treating the relapse of acne fulminans in this case.

Sun Exposure Is an Aggravating Factor Responsible for the Recalcitrant Facial Erythema in Adult Patients with Atopic Dermatitis

Background: In Japan, a considerable number of adult patients with atopic dermatitis suffer from recalcitrant facial erythema that resists common treatment with topical corticosteroids and antihistamines. Objective: Our purpose was to investigate the potential role of sun exposure in the aggravation of these facial lesions. Methods: The history of photoaggravation was taken from 74 adult patients with atopic dermatitis who suffered from recalcitrant facial erythema. Repeated UVB and UVA phototests were performed in 36 patients. Surface markers of infiltrating cells in UVB-provoked lesions were characterized immunohistochemically. Results: Forty-one of 74 patients experienced an exacerbation of the facial lesions after sun exposure. UVB testing revealed an abnormal, papular response in 14 of 36 patients. All of the 14 patients complained of clinical aggravation after sun exposure. No abnormal reactions were observed at UVA testing. In UVB-provoked lesions, CD4+ cells were predominant to CD8+ cells. Conclusion: Exposure to UVB radiation may be responsible for the recalcitrant facial erythema in at least some of the patients with atopic dermatitis.

PUVA therapy: current concerns in Japan.

Photochemotherapy using methoxsalen in combination with long-wave ultraviolet light (PUVA) is an essential modality in the treatment of various skin diseases. Major therapeutic regimens include oral, topical and water-delivery methods. An adequate regimen should be chosen regarding cases of disease, extent of involvement and the age of patients. In Japan, however, treatment techniques and protocols have not yet been standardized. PUVA therapy may be a first choice in the early stages of mycosis fungoides and a second choice or an adjunctive measure in other diseases, such as psoriasis, vitiligo and atopic dermatitis, which have been disabling or resistant to conventional treatments. Japanese guidelines for PUVA therapy of psoriasis are being prepared to be produced. Risks and benefits must be weighed and the patient orientation is necessary to complete the treatment and also to minimize side-effects. Although possible risks for skin cancers in Japanese patients have been reported to be much lower, a careful monitoring of the patients skin changes is recommended. While action mechanisms are not completely understood, recent investigations suggest that both antiproliferative and immunomodulatory effects are involved. This review article deals with the recent progress in clinical and basic research on PUVA therapy, focusing on our current concerns.