Masaki Ibe

Extracellular regulated kinase and c-Jun N-terminal kinase are activated in psoriatic involved epidermis.

Psoriatic skin shows markedly increased keratinocyte proliferation and altered differentiation with various abnormal signalling pathways. In the present study, we investigated the expression of mitogen-activated protein kinases in psoriatic skin. Immunohistochemical study showed increased extracellular regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) expression in the nuclei of involved epidermis. Western blot analyses confirmed the increased active phospho-ERK and phospho-JNK expression in the involved epidermis. In contrast, expression pattern of p38 was not different between the involved and uninvolved epidermis, which was confirmed by western blot analysis. These results indicate that psoriatic epidermis shows selective activation of ERK and JNK, which might be related to hyperproliferation and abnormal differentiation of psoriatic epidermis.

Similarly potent action of 1,25-dihydroxyvitamin D3 and its analogues, tacalcitol, calcipotriol, and maxacalcitol on normal human keratinocyte proliferation and differentiation

BACKGROUND The active vitamin D3 regulates proliferation and differentiation of epidermal keratinocytes. Recently topical vitamin D3, tacalcitol, calcipotriol, and maxacalcitol are widely used for psoriasis. OBJECTIVE To examine the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on cultured normal keratinocytes (NHK) and compared its effect with those of various vitamin D3 analogues. METHODS Cell proliferation of NHK cells was analyzed by MTS, BrdU and 3H-thymidine incorporation. The expression of involucrin, transglutaminase 1, keratin 5 and keratin 1 was investigated by western blot and PCR amplification and quantitative assay. Furthermore, we performed cornified cell envelope (CE) formation assay. RESULTS 1,25(OH)2D3, tacalcitol, calcipotriol, and maxacalcitol decreased NHK cell proliferation in a concentration-dependent manner and the maximal effect was observed at 10(-7) M. There was no significant difference in the anti-proliferative effect among the active vitamin D3 analogues. The expression of involucrin and transglutaminase 1 were induced by 1,25(OH)2D3 and its analogues in mRNA and protein levels. CE formation was also induced by 1,25(OH)2D3 and its analogues. There was no significant difference in the potency among these chemicals. Keratin 5 and 1 expression was not altered by these active vitamin D3 analogues. CONCLUSIONS The present study demonstrated that active vitamin D3 analogues, tacalcitol, calcipotriol, and maxacalcitol, suppress keratinocyte proliferation and induce differentiation with similar potency.

Satisfactory Remission Achieved by PUVA Therapy in Langerhans Cell Hisiocytosis in an Elderly Patient

Langerhans cell histiocytosis is currently regarded as a reactive proliferative process of Langerhans cells rather than a malignancy. The disease is characterized by Langerhans cell infiltration of skin, lung, bone and other organs. We report a 74‐year‐old man with Langerhans cell histiocytosis who had generalized hemorrhagic and crusted papules. He also had diabetes insipidus. Because he did not have any severe constitutional symptoms or failure of vital organs, we applied topical PUVA treatment to his skin lesions, which responded well to the therapy. Diabetes insipidus, however, remained, in spite of X ray radiotherapy for the pituiary lesion.

Pleomorphic Angioleiomyoma: Report of Two Cases With Immunohistochemical Studies

We describe two cases of pleomorphic angioleiomyoma. In one case, a 46-year-old man presented with a single nodule on his scrotum of 1 years duration, and in another, a 38-year-old woman presented with a single nodule on her right knee of 1 years duration. In both cases, histopathologic examination showed a well-circumscribed nodule composed of smooth muscle and numerous veins and capillaries. Contrary to the ordinary angioleiomyoma, marked nuclear pleomorphism was noted. Although mitoses were rare, immunohistochemistry revealed many tumor cells that were positive for proliferating cell nuclear antigen, Ki-67, and p53, indicating that the pleomorphic appearance does not simply represent a degenerative change of some tumor cells.

ATX-S10(Na)-PDT shows more potent effect on collagen metabolism of human normal and scleroderma dermal fibroblasts than ALA-PDT

Recent study revealed that photodynamic therapy (PDT) with a novel photosensitizer (ATX-S10(Na)) shows more potent effects for various skin diseases than ALA-PDT. The effect of ATX-S10(Na)-PDT on dermal fibroblasts is still unknown. Using dermal fibroblasts derived from normal and scleroderma patients, and mouse skin in vivo, we compared the effects of ATX-S10(Na)-PDT and ALA-PDT. Fibroblasts from normal, scleroderma patients or mice skin were treated with ATX-S10(Na)-PDT or ALA-PDT. After the PDT treatments, the expression of matrix metalloproteinases (MMPs) Tissue inhibitors of metalloproteinases (TIMPs) and collagen synthesis was assayed using ELISA and reverse transcription-PCR (RT-PCR). The expression of MMP-1 and MMP-3 was slightly decreased and collagen I mRNA was significantly increased in scleroderma fibroblasts compared with normal fibroblasts. Both ATX-S10(Na)-PDT and ALA-PDT increased the expression of MMP-1 and MMP-3 in protein and mRNA levels in both normal and scleroderma fibroblasts with more potent effect by ATX-S10(N)-PDT. Collagen I synthesis was markedly decreased by ATX-S10(Na)-PDT and by ALA-PDT again with more potent effect by ATX-S10(Na)-PDT in both normal and scleroderma fibroblasts. In mice skin the effect of PDT for MMPs and collagen I was also detected and the effect was more potent in ATX-S10(Na)-PDT. In contrast, MMP-2, TIMP-1, TIMP-2, and collagen III expression was not affected by the ATX-S10(Na)-PDT or ALA-PDT treatment. ATX-S10(Na)-PDT is more potent modulator for dermal matrix components than ALA-PDT and might be useful for scleroderma patients.

Analysis of psoriatic patients registered in Asahikawa Medical College Hospital from 1983 to 2007

Psoriasis is a chronic inflammatory skin disease, which has been increasing during the last 50 years in Japan. The aim of the present study is to analyze psoriatic patients registered from 1983–2007 in Asahikawa Medical College Hospital, which is located in the northern part of Japan. A total of 607 cases were registered at the first inspection in the Department of Dermatology, Asahikawa Medical College. Men (403 cases, 66.4%) were predominant over women (204 cases, 33.6%). The clinical types of psoriasis were psoriasis vulgaris (91.5%), guttate psoriasis (4.2%), psoriasis arthropathica (2.8%), psoriatic erythroderma (0.6%), generalized pustular psoriasis (0.6%), localized pustular psoriasis (0.15%) and infantile psoriasis (0.15%). Topical corticosteroids (78.1%) and vitamin D3 (18.1%) products were the main previous topical agents. Previous systemic treatments included etretinate (7.7%), cyclosporine (1.5%) and methotrexate (0.3%). Use of topical vitamin D3 and cyclosporine therapies have been gradually increasing during the past 25 years. Regarding the previous phototherapy, topical psoralen and ultraviolet A therapy (PUVA) (4.9%) was predominant over ultraviolet B (0.9%), and systemic PUVA (0.7%). Use of ultraviolet B phototherapy has been increasing during the past 5 years. The results are essentially similar to those of a survey of psoriasis in Japan from 1982–2001. Although the incidence of psoriasis might be higher in Hokkaido Prefecture, there is essentially no variation in the disease profile of psoriatic patients.

A case of a fixed drug eruption presenting with a butterfly rash-like exanthem in a patient with Sjögren's syndrome.

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