Shinobu Matsuo

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.

Transforming growth factor β1 inhibits IL-3- and IL-4-dependent mouse connective tissue-type mast cell proliferation

Transforming growth factor Β1 (TGFΒ1) is a regulator of cell proliferation and differentiation. Using a mouse peritoneal cell-derived mast cell culture system, we investigated the effects of TGFΒ1 on mast cell proliferation. TGFΒ1 inhibited IL-3- and IL-4-dependent connective tissue-type mast cell proliferation. The effect was concentration dependent: 50% inhibition was observed with 1.0 ng/ml TGFΒ1 and the maximal inhibitory effect (no proliferation), was observed with 10 ng/ml. Flow cytometric analysis suggested that the inhibitory effect of TGFΒ1 was due to blocking of both G1 and G2 phases. Both control and TGFΒ1-treated mast cells showed similar histamine release induced by the calcium ionophore, A23187. TGFΒ1 seems to be an important negative regulator of connective tissue-type mast cell proliferation with apparently no appreciable effect on mast cell function.

Superoxide dismutase in epidermis (1).

Superoxide dismutase (SOD), which catalytically scavenges superoxide anion (O–2), constitutes an essential defense against the toxicity of oxygen. We investigated the enzyme activity of pig skin epidermis. SOD activity was determined by monitoring the inhibitory effect of SOD on red formazan formation from neotetrazolium, which depends on (O–2) generation. (O–2) was generated by the hypoxanthine‐xanthine oxidase reaction. Pig epidermis contained significant amounts of heat‐labile SOD activity which was proportional to the added epidermal homogenate. The optimal pH of the reaction was between pH 8.2 and 8.5. Metallochelating agents such as cyanide, sodium azide, and diethyldithiocarbamate (DDC) inhibited the epidermal SOD activity in a dose‐dependent manner. It has been known that two types of SOD, a Cu, Zn‐type and a Mn‐type, are present in eukaryotes; that the latter is insensitive to cyanide inhibition. Using this property, the main SOD present in the epidermis was hypothesized to be the Cu, Zn‐type (8.6 ±1.1 unit/mg protein; around 75%); the Mn‐type was a minor component (2.8 ± 0.2 unit/mg protein; around 25%). SOD staining following acrylamide disc gel electrophoresis revealed two epidermal SOD bands, one of which was abolished by the addition of cyanide. These results are consistent with the view that pig epidermis contains two types of SOD, a Cu, Zn‐type and a Mn‐type; the former appears to be predominant.

Effects of FK506 and Cyclosporin a on proliferation, histamine release and phenotype of murine mast cells

Using mouse peritoneal cavity mast cells, we investigated the effects of FK506 and cyclosporin A (CsA) on cell proliferation and histamine release induced by anti-IgE antibody, calcium ionophore (A23187), or neuropeptide (substance P). Both FK506 and CsA inhibited cytokine-dependent mast cell proliferation in a dose-dependent manner. The inhibitory effects of these compounds on mast cell proliferation was reversible; the removal of the chemicals from the incubation medium resulted in the reinitiation of mast cell proliferation. Flow cytometric analysis suggested that the inhibitory effect of FK506 and CsA was mostly due to G1/S boundary block, although a significant number of G2-arrested cells were also observed following FK506 treatment. Both FK506- and CsA-treated mast cells showed a similar inhibition of histamine release induced by A23187. However, CsA at higher concentrations inhibited the histamine release induced by anti-IgE antibody or substance P more markedly than FK506. Cellular histamine content was decreased by CsA treatment while FK506 had no effect. The staining properties of peritoneal mast cells changed from connective tissue-type mast cell-like to mucosal mast cell-like during CsA treatment but not during FK506 treatment. Thus FK506 and CsA have different effects on mast cell proliferation as well as histamine release, that might be associated with a phenotypic change of the cells during culture.

Keratoacanthoma Developing on a Pigmented Patch in Incontinentia pigmenti

Cutaneous manifestations of incontinentia pigmenti (IP) have classically been described as three sequential stages: an initial vesicobullous stage, a verrucous stage and a stage of swirled pigmentation. Verrucous lesions tend to last longer than vesicobullous eruptions, often persisting until 1 year of age. However, adult patients with verrucous lesions are rare. We report a case of keratoacanthoma with marked dyskeratosis on a pigmented patch in a 20-year-old woman. This tumor, like subungual keratotic tumors of IP, might have been developed as one of the late manifestations of the disease.

A Case of Bullous Pemphigoid with Antibodies against Intercellular 130 KD Antigen

Pemphigus and bullous pemphigoid are two typical autoimmune bullous diseases that involve circulating autoantibodies directed against the epidermal cell surface and the epidermal basement membrane zone, respectively. The coexistence of pemphigus and bullous pemphigoid is rare. We describe a case of a 79‐year‐old man who had tense bullae and erythematous, erosive lesions on his trunk and four extremities. Histopathology revealed subepidermal blister formation without any evidence of intraepidermal acantholytic changes. Direct immunofluorescence study demonstrated deposition of IgG on the epidermal intercellular spaces, as well as along the basement membrane zone; C3 was detected only on the latter. Indirect immunofluorescence study using monkey esophagus as a substrate demonstrated the presence of circulating antibodies against both junctional and intercellular antigens. In order to analyze the precise nature of this patients antibodies, indirect immunofluorescence study using cultured human keratinocytes and immunoblot analyses were performed. Pemphigus vulgaris sera showed smooth and uniform staining on intercellular spaces. The patients serum showed a granular and uneven staining pattern. Immunoblot analysis showed that the patients serum reacted with the typical 230 kd (bullous pemphigoid) antigen and 130 kd antigen, which is close to the pemphigus vulgaris antigen.

Repression of involucrin gene expression by transcriptional enhancer factor 1 (TEF-1)

Involucrin is one of the precursor proteins of keratinocyte cornified envelope that is formed beneath the inner surface of the cell membrane during terminal differentiation. Although involucrin is specifically expressed in the upper squamous cells of the epidermis, the precise regulatory mechanism of involucrin gene expression remains unknown. Transcriptional enhancer factor 1 (TEF-1), which binds to SV40 enhancer, is a nuclear protein expressed in various types of cells including keratinocytes. Immunohistochemical study has revealed that TEF-1 protein is highly expressed on the basal cell layer of the epidermis. To examine the possible regulatory mechanism of involucrin gene expression by TEF-1 protein, we analysed involucrin promoter activity of the INV-CAT vector, which was constructed by connecting the 5′ upstream region of the involucrin gene (−801 bp upstream from the transcription start site and downstream including the untranslated first exon) to the chloramphenicol acetyltransferase (CAT) reporter gene. The INV-CAT vector was transfected to SV40-transformed human keratinocytes (SVHK). Cotransfection of the TEF-1 expression vector significantly repressed INV-CAT promoter activity in a dose-dependent manner. The repression was also observed by transfection of the GAL4-TEF-1 vector, which was constructed by replacement of the TEF-1 DNA binding domain by the GAL4 activator domain. This suggests that TEF-1-induced repression is due to interference/squelching of a limiting transcriptional intermediary factor that is essential for involucrin expression. Analysis of the deleted INV-CAT vector suggested that the region from −599 to −495 of the involucrin gene, which contains two possible TEF-1 binding sites, was critical for the repression of the involucrin gene by TEF-1. By gel retardation analysis, the specific DNA binding of SVHK cell nuclear extracts and the recombinant TEF-1 protein was confirmed. TEF-1-dependent repression of involucrin gene expression might explain the suprabasal involucrin expression in the epidermis.

Lyme disease in Japan. Analysis of Borrelia species using rRNA gene restriction fragment length polymorphism.

BACKGROUND Lyme disease is sporadically observed in Japan since the first report in 1987. We have experienced 19 cases of Lyme disease. In 12 out of 13 trials we succeeded in isolating Borrelia strains (JEM1-12) from erythema migrans (EM) lesions. Recently, Borrelia burgdorferi sensu lato was classified into at least three distinct subgroups, B. burgdorferi sensu stricto, B. garinii and B. afzelii. OBJECTIVE In order to characterize Lyme disease in Japan, we summarized the clinical features of our cases and investigated the nature of the isolated Borrelia strains. METHODS The 12 Borrelia strains were analyzed by restriction fragment length polymorphism (RFLP) of ribosomal RNA gene. RESULTS Most of our 19 patients were in stage I with EM as the main clinical manifestation. RFLP analysis using 12 strains isolated from the patients indicated that 8 strains (group IV, V) were different from the three aforementioned genospecies. CONCLUSION Clinical data from the present study substantiate the view that Japanese Lyme disease has a relatively milder course. We speculate that this may be related to the specific Borrelia strains in Japan.

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.

Cholera toxin- and forskolin-induced cyclic AMP accumulations of pig skin (epidermis): Modulation by chemicals which reveal the beta-adrenergic augmentation effect

Effects of cholera toxin and forskolin on pig epidermal adenylate cyclase system were investigated. Both agents increased cyclic AMP levels of epidermis. Marked accumulations were observed in the presence of cyclic AMP phosphodiesterase inhibitor, isobutylmethylxanthine (IBMX). It has been known that hormone-stimulated adenylate cyclase responses are modified by various chemical treatments. Following long term incubation with hydrocortisone, Ro10-1670, and colchicine, the epidermal beta-adrenergic adenylate cyclase response was increased without the alteration of cyclic AMP phosphodiesterase activity. Adenosine-, and histamine-adenylate cyclase responses were unchanged by hydrocortisone treatment, and were decreased by Ro10-1670 and colchicine treatments. Following the long term incubation with these chemicals, effects of cholera toxin and forskolin were investigated. Colchicine-treated skin revealed the increased cholera toxin-, and forskolin-induced cyclic AMP accumulations. Neither hydrocortisone- nor Ro10-1670-treated skin revealed alterations of cholera toxin-, and forskolin-effect. The stimulatory effect of colchicine on the cholera toxin-, and forskolin-effect was observed at doses of the beta-adrenergic augmentation effect. Our results indicate that among the chemicals which reveal the beta-adrenergic augmentation effect, colchicine is unique in that it also increases cholera toxin-, and forskolin-induced cyclic AMP accumulations of epidermis.