Aggregated dilated pores.

We report a 74-year-old Japanese man who had a 10-year history of approximately 20 open comedones crowded onto his lateral neck. An excisional biopsy revealed that each comedo was histologically a dilated pore. Dilated pores are usually solitary. The multiple and aggregated dilated pores seen in our case have never been reported.

A case of linear IgA disease: an immunofluorescent study using confocal laser scan microscopy.

A 79-year-old Japanese woman presented with erythema and bullae on her trunk and limbs. Histological examination of the skin lesions showed subepidermal bullae and polymorphonuclear leukocyte infiltration into the papillary dermis. A direct immunofluorescent study showed the linear deposition of IgA, but not of IgG or IgM, in the basement membrane zone. Indirect immunofluorescence of the serum using confocal laser scan microscopy showed IgA, but not IgG, reactivity in the basement membrane zone. In double immunostaining experiments, IgA reactivity was also observed on the epidermal side; laminin 5 was detected on the dermal side.

A case of Bednar tumor. Immunohistochemical positivity for CD34.

A 42-year-old Japanese man with a Bednar tumor is described. The skin showed a slightly elevated, red, partially dark blue, dermal nodule growing into the deep subcutaneous tissue. The histological specimen showed two types of tumor cells, spindle-formed cells with no melanin granules and melanin-laden cells. Immunohistochemical stainings for CD34 and S-100 protein revealed that the former cells showed positivity only for CD34, while the latter were only positive for S-100 protein. These results suggest that the Bednar tumor is a dermatofibrosarcoma protuberans in which melanin-laden cells coexist.

Primary cutaneous cryptococcosis and Cryptococcus neoformans serotype D.

We report a healthy, 73-year-old Japanese woman who presented with primary cryptococcosis on the skin of both cheeks. She had initially developed an erythematous, partly ulcerated lesion on the right cheek 2 weeks earlier following an injury. There was no regional lymphadenopathy, and chest X-rays were normal. Histopathological findings showed granulomatous cell infiltration. Periodic acid Schiff staining revealed spores that were identified by the indirect immunoperoxidase staining method as Cryptococcus neoformans. The isolate was identified as C. neoformans var. neoformans serotype D. The skin lesions healed in 1 month without antifungal therapy. A literature review indicates that this serotype tends to produce cutaneous lesions without systemic involvement.

Extrafacial granuloma faciale.

Granuloma faciale nearly always occurs on the face; extrafacial lesions are extremely rare. This is the tenth reported case. Extrafacial granuloma faciale closely resembles erythema elevatum diutinum; however, they are distinct entities which can be differentiated from each other.

Multiple xanthogranulomas in an adult.

Xanthogranulomas develop in adults as well as in children; however, adult cases with multiple lesions are very rare. We report an adult who developed both multiple cutaneous lesions on the face and trunk and lesions on the conjunctiva, oral mucosa and genitalia. We believe that this is the first such case described.

Blue-gray pigmentation in a patient receiving doxorubicin.

A 64-year-old Japanese female who was treated for hepatocellular carcinoma with doxorubicin developed diffuse blue-gray pigmentation of the face, fading out on the upper trunk. Skin biopsy revealed many melanin granules in the upper dermis. It is believed that the pigmentation was induced by doxorubicin.

Immunoblot assay as an aid to the diagnoses of unclassified cases of pemphigus.

With use of an immunoblot assay for both the normal human epidermal extracts and the bovine desmosome preparation, we investigated sera from 18 patients with pemphigus, who exhibited atypical clinical or histologic features and whose diagnoses were difficult to identify. Four sera yielded a 130-kd protein band in the epidermal extracts, which is characteristic of pemphigus vulgaris. A 150-kd protein was identified by nine sera in the epidermal extracts and/or the desmosome preparation, which is known as a pemphigus foliaceus antigen. Five sera demonstrated neither antigen. These results suggest that the immunoblot technique is useful to distinguish pemphigus vulgaris from pemphigus foliaceus and can be a good tool for the diagnosis of pemphigus, especially unclassified cases.

Primary localized cutaneous nodular amyloidosis: case report and biochemical analysis of amyloid.

We report a patient with scalp lesions of primary localized cutaneous nodular amyloidosis. The extensive examination revealed no systemic involvement. Analysis of glycosaminoglycans (GAGs) in amyloid deposits showed a twofold increase as compared with normal skin, which was due to the increase in dermatan sulfate. Local disorders of GAG metabolism may be related to the amyloid fibril formation. Amyloid fibrils were purified and identified electron-microscopically, which consisted of two major 12,000- and 13,000-dalton and minor 29,000- and 48,000-dalton peptides. Western blotting analysis showed a minor 29,000-dalton peptide reactive with antibodies against both kappa and lambda light chains of immunoglobulin. There is a possibility that some components of amyloid in some cases of primary localized cutaneous nodular amyloidosis may consist of both kappa and lambda immunoglobulin light chains.

Placental glutathione-S-transferase-pi mRNA is abundantly expressed in human skin.

Four overlapping cDNA clones were isolated from a lambda gt11 human placenta cDNA library using purified human IgG antibody, from a patient with bullous pemphigoid. The sequence was homologous to human placenta glutathione-S-transferase-pi (GST-pi). Using the placenta clone, epidermal cDNA clones were isolated from a human keratinocyte library. Expression of GST-pi mRNA in human skin, cultured keratinocytes and fibroblasts, and disorders of squamous hyperplasia was demonstrated by Northern blotting and in situ hybridization. Human epidermal and placental cDNA clones hybridized to the same genomic DNA fragments. Hybridization of placental cDNA to interspecific somatic cell hybrids showed retention of chromosome 11, confirming the assignment of GST 3 to the long arm of chromosome 11 by molecular means. Anti-GST-pi antibody did not give a basement membrane zone pattern, although some normal and BP sera contained antibodies to GST-pi. Human skin expresses glutathione-S-transferase-pi, which belongs to an enzyme family important for detoxification and carcinogenesis.

Detection of pemphigus vulgaris and pemphigus foliaceus antigens by immunoblot analysis using different antigen sources.

In an immunoblot analysis with human epidermal extract as a source of antigens, all (28/28) pemphigus vulgaris (Pv) sera showed a specific reactivity with a 130-kD protein. Several, but not all, Pv sera reacted with similar antigens in both a bovine muzzle desmosome preparation and extract of cultured human squamous carcinoma cells. On the other hand, some pemphigus foliaceus (Pf) sera exhibited reactivity with a 150-kD protein, which is most likely desmoglein I, in both the human epidermal extract and the bovine desmosome preparation, but no Pf serum reacted with this antigen in the squamous carcinoma cell extract. Furthermore, 4/16 Pv sera also reacted with a 150-kD protein in the desmosome preparation, which seemed to be the same as Pf antigen. These results show a relationship between antigens of both Pf and Pv and desmosomes, as well as heterogeneities of both Pv and Pf antigens in terms of antigenic molecules or epitopes. Furthermore, this study presents the possibility that immunoblot analysis can be routinely used for differentiation of Pv and Pf antibodies.

Immunoblot analyses of Brazilian pemphigus foliaceus antigen using different antigen sources.

We investigated the Brazilian pemphigus foliaceus (BPf) antigen applying the immunoblotting method to two different antigen sources using 27 patients' sera. Twelve BPf sera reacted specifically with a 150 kD protein in extract of dispase separated human epidermis, while 18 sera yielded a similar protein band in bovine muzzle desmosomal preparation. The diversity of staining intensities between the two samples suggested the heterogeneity of BPf antigens in terms of epitopes. Japanese sporadic pemphigus foliaceus (Pf) sera showed similar results but Japanese pemphigus vulgaris (Pv) sera recognized different antigens of 130 kD or 135 kD, suggesting that BPf is similar to Japanese Pf but is distinct from Pv in respect to the antigenic substance. Furthermore, the present study showed that immunoblot analysis using different antigen sources should be a valuable tool to determine clinical types of pemphigus.

Expression of pemphigus vulgaris antigen in cultured human keratinocytes: effect of inhibitors, tunicamycin, and lectins.

We have investigated expression of pemphigus vulgaris antigen(s) in cultured human keratinocytes induced by the addition of extracellular calcium. Cycloheximide (10(-4) M) inhibited pemphigus antigen expression and stratification but actinomycin D (2 micrograms/ml) had no effect. Tunicamycin, which inhibits dolichol pyrophosphate-mediated glycosylation of asparaginyl residues specifically, was used to study the role of glycosylation. When calcium switching was carried out in the presence of tunicamycin, human keratinocytes did not stratify, and the expression of pemphigus antigen was partially inhibited and limited to cell-cell contact areas. Analysis of biosynthetically labeled proteins showed that the synthesis of high-molecular-weight proteins was markedly reduced in the tunicamycin-treated cells. A reciprocal blocking test demonstrated that concanavalin A and wheat germ agglutinin receptor share an epitope with pemphigus vulgaris antigen(s). These results suggest that Ca++, newly synthesized protein, and N-asparaginyl glycosylation are required for normal pemphigus antigen expression and epidermal stratification in vitro. Pemphigus vulgaris antigen may have a highly glycosylated, high-molecular-weight protein chain with carbohydrates playing an important role in epidermal cell morphology, adhesion, and stability of cell surface antigens.

Biochemical changes in desmosomes of bovine muzzle epidermis during differentiation.

Biochemical changes taking place in desmosomes during differentiation have been studied. Bovine muzzle epidermis was sliced horizontally into 6 layers, 0.2 mm thick, and desmosomes were isolated from each layer. These were then analyzed by polyacrylamide gel electrophoresis. The electrophoretic patterns of desmosomal proteins from the 6 layers were found to be qualitatively similar to each other, but there was an increase in the ratio of the amount of 150 kD glycoprotein (desmoglein I) relative to 240 and 210 kD proteins (desmoplakins) in the upper layers of the epidermis. This finding was supported by the similar increase observed in electrophoretic patterns of proteins extracted directly from each layer of the epidermis in electrophoretic sample buffer. In order to study the fate of desmosomal components in the stratum corneum, serial skin surface biopsies were stained with antisera against desmosomal components using indirect immunofluorescence techniques. This experiment showed that desmosomal proteins and glycoproteins persist in the stratum corneum but quantitatively decrease in the outer layers. This decrease may play a significant role in desquamation.