Hitoshi Yaguchi

The Expression of Endothelin‐1 and Its Binding Sites in Mouse Skin Increased after Ultraviolet B Irradiation or Local Injection of Tumor Necrosis Factor α

Endothelin (ET)‐1 is a 21‐amino acid peptide which has vasoconstrictor and growth regulatory activity. Recently, cultured keratinocytes have been reported to express ET‐1 and its receptor when irradiated by ultraviolet (UV) B. In order to further understand the role of ET‐1 in vivo during UVB‐induced inflammation, we examined the localization, intensity and time course of the expression levels of ET‐1 and its binding sites in UVB‐exposed BALB/c mouse skin. Frozen and paraffin sections prepared from mouse skin 48 h after treatment with UVB irradiation (0.36 or 0.72 J/cm2) or after injection with tumor necrosis factor (TNF)‐α (1.0 μg) or interleukin (IL)‐1α (0.05 μg) were incubated with monoclonal anti‐ET‐1 IgG and then visualized by peroxidase staining. In normal skin, faint ET‐1 immunoreactivity was observed in the epidermis, pilosebaceous structures and blood vessels. Upon exposure to UVB irradiation or administration of TNF‐α injection or IL‐1α injection, such immunoreactivity was found to be significantly enhanced. Subsequently, the frozen sections were incubated with 125I ET‐1 for 30 min, and visualized by autoradiographic technique. In normal skin, ET‐1 weakly bound to the skin, while UVB irradiation and TNF‐α injection significantly enhanced ET‐1 binding in the epidermis, pilosebaceous structures and blood vessels. Time course experiments (1, 2, 4 and 7 days) indicated that ET‐1 immunoreactivity and ET‐1 binding peaked 1 or 2 days after UVB irradiation or TNF‐α injection. These results suggest that the up‐regulated expression of ET‐1 and its binding sites in the epidermis and pilosebaceous structures may act as an autocrine/paracrine factor during UVB‐induced inflammation.

Vulvitis circumscripta plasmacellularis treated successfully with interferon alpha

A 74-year-old woman with vulvitis circumscripta plasmacellularis was successfully treated with intralesional injections of interferon alpha. Although the patient had been previously treated unsuccessfully for 5 years with topical administration of a potent corticosteroid, with cryotherapy, and with surgical procedures, the disease continually recurred. A course of interferon alpha resulted in a significant clinical improvement of the lesions, a histologically verified decrease of plasma cell infiltrate, and the disappearance of the antigen of herpes simplex virus that had been detected before treatment by direct immunofluorescence staining of the lesion. This clinical course demonstrates the effectiveness of local injections of interferon alpha into those lesions with vulvitis circumscripta plasmacellularis that did not previously respond to conventional therapy. Therefore an implication exists that herpes simplex virus infection may be one of the factors involved in the pathogenesis of this disease.

Esophageal strictures in children with recessive dystrophic epidermolysis bullosa: experience of balloon dilatation in nine cases.

BACKGROUND Recessive dystrophic epidermolysis bullosa is a rare disorder characterized by extreme vulnerability of the squamous epithelium and mucous membranes. Minor trauma such as is caused by swallowing solid food is followed by blistering and scarring. Stricture formation at the pharyngoesophageal junction (C6 or C7) is the severest complication of this disease. METHODS We evaluate the effectiveness of Microvasive Rigiflex balloon dilatation and extensive nutritional support as a primary treatment for this condition. Nine of 21 recessive dystrophic epidermolysis bullosa patients developed esophageal strictures at the level of the pharyngo-esophageal junction (C6). We treated them with intensive nutritional therapy followed by balloon dilatation, which produces longitudinal pressure and provides prompt relief from esophageal stricture. Eleven balloon dilatations have been performed in 9 patients. RESULTS All patients had poor physical development and were severely malnourished; extensive nutritional support was required before treatment could begin. Balloon dilatation was performed once in seven patients and twice in two patients. No recurrent stricture formation was observed after balloon dilatation. CONCLUSION Intensive nutritional support followed by balloon dilatation is the first choice of treatment for esophageal strictures complicating recessive epidermolysis bullosa. By following this regime, invasive surgery can be avoided.

SUCCESSFUL SURGICAL MANAGEMENT AND LONG-TERM FOLLOW-UP OF EPIDERMOLYSIS BULLOSA

Background. Esophageal stenosis and hand deformity are serious complications of recessive dystrophic epidermolysis bullosa that influence the prognosis of patients. To control such complications we have used surgical treatments with favorable results. Additional objectives were to summarize the results of long‐term follow‐up.

A Case of Unilateral, Systematized Linear Hair Follicle Nevi Associated with Epidermal Nevus-Like Lesions

Multiple hair follicle nevi are an extremely rare condition. In 1998, a case of unilateral multiple hair follicle nevi, ipsilateral alopecia and ipsilateral leptomeningeal angiomatosis of the brain was first reported from Japan. Very recently, hair follicle nevus in a distribution following Blaschko’s lines has also been reported. In this paper, we observed a congenital case of unilateral, systematized linear hair follicle nevi associated with congenital, ipsilateral, multiple plaque lesions resembling epidermal nevi but lacking leptomeningeal angiomatosis of the brain. These cases implicate the possibility of a novel neurocutaneous syndrome. Additional cases should be sought in order to determine whether this condition is pathophysiologically distinct.

EXPRESSION OF KERATOHYALIN‐TRICHOHYALIN HYBRID GRANULES IN MOLLUSCUM CONTAGIOSUM

Background. Recently, in the filiform papillae epithelium of mouse dorsal tongue, we showed the presence of hybrid granules in which filaggrin and trichohyalin were both present, but physically segregated. Further, trichohyalin was also detected in scattered granular cells of a number of hyperplastic skin diseases.

Histopathological studies of Sporothrix schenckii-inoculated mice. Possible functions of polymorphonuclear leukocytes in normal and immunocompromised (congenitally athymic nude) mice.

Defense mechanisms against Sporothrix schenckii were studied using mouse models. After an intracutaneous injection of the yeast form of S. schenckii to the dorsal skin of the congenitally athymic nude and normal heterozygote littermate mice, nodules were formed. They regressed and disappeared in 10 weeks in the case of normal mice. On the other hand, nodules and then ulceration developed progressively in nude mice until all animals expired by dissemination of microorganisms at the 11th week of inoculation. Histopathologically the migrated cells were similar in both the normal and the nude mice, particularly during the early phase (within 24 h), with infiltration by PMNs being predominant. Fragmentation of S. schenckii commenced early during the 12-24 h stage of inoculation in the normal mice, while such fragmentation was scarce in nude mice even though numerous PMNs accumulated. Microscopic observations in the early stages (within 24 h of inoculation) suggested that the lack of killing activity by PMNs in nude mice contributes more to the impaired defense than the lack of macrophage activation by T-cells.

A case of diffuse plane normolipemic xanthomatosis associated with pancytopenia and monoclonal gammopathy.

We report a case of diffuse plane normolipemic xanthomatosis (DPNX) which showed poorly demarcated, uncommon, yellow macules symmetrically distributed on the nape, axillae and inguinal folds accompanied by severe, persistent itching. Histopathological and ultrastructural studies of skin biopsy specimens revealed the existence of some foamy cells and the deposition of neutral fat in the upper papillary dermis. Laboratory investigations and bone marrow aspirate smears showed that our patient had myelodysplastic syndrome (MDS) associated with pancytopenia and monoclonal gammopathy of undetermined significance. Because our patient had neither a malignant hematological disorder nor a severe systemic disease, monoclonal gammopathy might explain the pathogenesis of DPNX in the present case.

Immunohistochemical localization of cathepsin L and cystatin A in normal skin and skin tumors

Cathepsin L, a cysteine proteinase, and cystatin A, an inhibitor of cysteine proteinases, are thought to regulate the invasion and metastasis of malignant cells. In this study, the expression of cathepsin L and cystatin A in skin tumors was investigated immunohistochemically in order to examine the relationship between these two enzymes in the pathophysiology of malignant cells. Formalin‐fixed and paraffin embedded specimens from normal skin, seborrheic keratoses, and squamous cell carcinomas were reacted with polyclonal antibodies against rat cathepsin L or cystatin α which cross‐react to human cathepsin L and cystatin A, respectively. The consequent immunostaining of these enzymes was observed to be strong in normal skin (4 cases) and seborrheic keratosis (6 cases). In well‐differentiated squamous cell carcinoma (SCC) (9 cases), staining for cathepsin L and cystatin A was moderately positive in differentiated tumor cells and negative in undifferentiated SCC (5 cases). The degree of staining of these enzymes was inversely correlated with the differentiation of the malignant cells. These results suggest that the immunohistochemical analysis of cathepsin L and cystatin A is a useful indicator for an aspect of malignancy in human epidermal keratinocytes.

Immunolocalization of epimorphin in skin

Epimorphin was originally identified as a mesenchymal cell surface-associated protein that modulates epithelial morphogenesis in embryonic skin and lung epithelia. A previous report which utilized embryonic mouse skin, showed that epimorphin was localized non-homogeneously in a region adjacent to the epidermis and in a mesenchymal cell condensation located in front of growing hair follicles. We report herein a further detailed localization of this protein in adult mouse skin using immunoelectron microscopy. Epimorphin was found to be localized on the undersurface of basal cells, in the cytoplasm of cell processes of fibroblasts, as well as on the plasma membrane of fibroblasts, endothelial cells, pericytes, perineurium and endomysium. Our present finding indicated that epimorphin is one of the factors involved in multiple biological functions in a variety of structures derived from various origins and that it is not a specific epithelial morphogenetic factor.