Tape stripping induces marked epidermal proliferation and altered TGF-alpha expression in non-lesional psoriatic skin.

Psoriasis is a chronic inflammatory disorder characterized by epidermal hyperproliferation. Although recent evidence suggests that T cell activation is a primary trigger for psoriasis lesions, there may be alterations in the keratinocyte growth regulatory pathways which induce epidermal hyperproliferation in psoriatic patients. To test this hypothesis, we investigated the proliferative activity of epidermal keratinocytes 48 h after tape stripping, one of the standard mechanical ways to stimulate the epidermis, in 20 psoriasis patients and in 18 controls. Epidermal cell kinetics were assessed with DNA flow cytometry, the mitotic index, bromodeoxyuridine incorporation, Ki-67 antigen expression and DNA polymerase alpha expression. The expression of TGF-alpha and EGF receptors, critical mediators of keratinocyte proliferation, were also investigated immunohistochemically. The results of multiparameter assays showed that the baseline proliferative activity in uninvolved skin was the same in psoriasis patients and normal controls. After tape stripping, although both psoriasis patients and the normal controls showed significant increases in epidermal cell proliferation, the values of all the parameters investigated were significantly greater in the psoriasis patients than in the normal controls. EGF receptors were overexpressed in basal and suprabasal keratinocytes after tape stripping in both the psoriasis patients and the normal controls. In contrast, overexpression of TGF-alpha was only observed in the patients with psoriasis, which may explain their increased proliferative response to trauma.

Effect of beclomethasone dipropionate inhalation on eosinophilic bronchitis in patients with silicosis.

The efficacy of beclomethasone dipropionate (CAS 5534-09-8, BDP, beclomethasone) inhalation therapy over the course of 12 months were evaluated in 42 patients with established chronic silicosis. Their pulmonary functions were monitored every 3 months and volume of sputum production was established daily. Subjects were divided randomly into two groups; 21 patients (BDP group) were treated with BDP (400 micrograms/day) by way of a metered-dose inhaler, while the 21 controls did not receive the BDP inhalation therapy. Although FVC (forced vital capacity), FEV1 (forced expiratory volume in 1 s), MMEF (maximal mean expiratory flow) and arterial blood oxygen tension did not improve significantly, sputum production significantly decreased in the BDP group. The patients who responded most dramatically to the treatment presented with sputum eosinophilia and elevated serum IgE levels prior to therapy. Pulmonary tuberculosis or exacerbation of chronic airway infection was not observed in any of the patients. These results suggest that corticosteroid inhalation therapy is helpful in the management of chronic silicosis, especially in patients with sputum eosinophilia. Positive atopic factors may be related to the pathogenesis of eosinophilic bronchitis, a complication of chronic silicosis.

Annular elastolytic giant cell granuloma: response to cyclosporin A.

A case of annular elastolytic giant cell granuloma with a good response to cyclosporin A is reported. A 62-year-old man developed multiple annular patches on the trunk with elevated and indurated borders. Biopsy specimens from the border showed granulomatous inflammation in the mid dermis with phagocytosis of elastic fibers by giant cells. Biopsy specimens from the center showed dense collagen formation without inflammation. Immunological investigation of perivascular infiltrating cells in the lesions revealed a predominance of CD4+ cells over CD8+ cells. Our case showed a good response to cyclosporin A (5 mg/kg/day) for eight weeks. There were no adverse effects and no recurrences for one month after discontinuation of cyclosporin A.

Action spectrum for bergamot-oil phototoxicity measured by sunburn cell counting.

The present study investigated the phototoxic effect of bergamot oil and its photosensitive component, bergapten, on sunburn cell (SBC) production in guinea pig skin. The back skin was pretreated with bergamot oil or bergapten and exposed to monochromatic light under various conditions. After irradiation, skin specimens were excised, and histological sections were prepared. The number of sunburn cells in the interfollicular epidermis was counted. The SBC formation by bergamot oil or bergapten plus UVB radiation was the same as that without pretreatment with any photosensitizer. In contrast, a significant number of SBCs were induced by bergamot oil or bergapten plus UVA radiation, but no SBCs were found after the treatment with UVA alone. The result indicates that bergamot oil or bergapten was photosensitized by UVA irradiation. The SBCs were linearly increased in a UV-dose dependent manner. On the basis of the regression lines, an action spectrum and spectral peak for the photosensitizers plus UVA were obtained. The action spectrum for bergamot oil- and bergapten-induced SBC formation was in the ranges of 325-365 nm and 325-350 nm, and their spectral peaks were at 335-345 nm and 335-350 nm, respectively. The data are in good accordance with those estimated from skin erythema reactions. Therefore, counting SBCs is a very useful parameter for quantitative evaluation of phototoxicity.

An adult case of histiocytosis X with a vulvar ulcer and multiple bone lesions.

A 62-year-old female with histiocytosis X presented with a vulvar ulcer. Multiple osteolytic lesions were later detected. Histological examination of the ulcerated skin showed diffuse proliferation of histiocytic cells with folded nuclei and pale eosinophilic cytoplasm. Immunohistochemistry revealed S100 protein and vimentin as well as CD1a, CD4, and HLA-DR antigens in the proliferating cells. Electron microscopy demonstrated Birbeck granules in the cytoplasm of the cells. The patient was successfully treated by complete surgical excision of the ulcer followed by radiotherapy for recurrent vulvar erythema.

Factor-XIIIa-positive cells in normal peripheral nerves and cutaneous neurofibromas of type-1 neurofibromatosis.

Cutaneous neurofibromas consist of heterogenous cell populations including Schwann cells, perineurial cells, and fibroblastlike cells. However, the histogenesis of neurofibromas, particularly the origin and nature of the fibroblastlike cells, is still controversial. Recently, cells containing blood coagulation factor XIIIa have been reported in cutaneous neurofibromas, although their identity is uncertain. In this report, by the combination of double immunohistochemical staining and immunoelectron microscopy, we demonstrate that factor-XIIIa-positive cells are distinct from Schwann cells, perineurial cells, endothelial cells, mast cells, and conventional macrophages, but correspond to the fibroblastlike cells in cutaneous neurofibromas. Such factor-XIIIa-positive cells in cutaneous neurofibromas, however, differ from conventional fibroblasts in the strong expression of HLA-DR antigen and lack of prolyl 4-hydroxylase. Similarly, so-called endoneurial fibroblasts and, occasionally, connective tissue cells within perineurium and epineurium in normal peripheral nerve fibers express factor XIIIa as well as HLA-DR antigen. The results suggest that fibroblastlike cells in cutaneous neurofibromas are probably derived from factor-XIIIa- and HLA-DR antigen-positive connective tissue cells in peripheral nerves. The role of such factor-XIIIa-positive cells in the growth and development of cutaneous neurofibromas is discussed.

Subcorneal pustular dermatosis associated with IgA myeloma and intraepidermal IgA deposits.

We report a 59-year-old woman who had subcorneal pustular dermatosis and IgA-kappa myeloma. Immunofluorescence tests showed intercellular IgA-kappa deposits in the upper portion of the lesional epidermis and circulating IgA-kappa anti-intercellular autoantibodies in a titer of 1:40. A combination chemotherapy for myeloma induced dramatic improvement of the skin lesions in accordance with a marked decrease in serum IgA levels as well as the disappearance of circulating anti-intercellular IgA autoantibodies, suggesting a pathogenetic link between skin lesions and IgA-kappa paraprotein produced by myeloma cells.

Immunoelectron microscopy of acute graft versus host disease of the skin after allogeneic bone marrow transplantation.

AIMS: To clarify the pathological mechanisms of acute cutaneous graft versus host disease (GvHD) following allogeneic bone marrow transplantation. METHODS: Skin biopsy specimens from five patients were examined by immunoelectron microscopy. A panel of monoclonal antibodies against T cell and natural killer cell subpopulations was used, including anti-CD4, -CD8, -CD16b, -CD56, -CD57, and -TCR delta 1 antibodies. RESULTS: All the specimens contained CD8+ cells, CD4+ cells, and CD56+ cells infiltrating the epidermis. Cells stained with anti-CD16b, -CD57, or -TCR delta 1 were very sparse or absent. Most of the CD8+ cells in the epidermis displayed morphological features of activated cytotoxic T lymphocytes and apposition of such cells to degenerating keratinocytes was shown. CD4+ cells outnumbered CD8+ cells in the epidermis in all five cases. Noticeable intercellular as well as intracellular oedema of keratinocytes was observed at the site of prominent CD4+ cell infiltration, suggesting that these also have a role as actual effector cells by secreting cytotoxic cytokines. CD56+ cells infiltrating the epidermis did not exhibit the characteristic ultrastructural morphology of the natural killer cells thus far examined, and their lineage remained uncertain. CONCLUSIONS: These data provide direct evidence that CD8+ cytotoxic T cells attack keratinocytes, and further suggest that CD4+ cells as well as CD56+ cells participate in the cellular pathogenesis of acute cutaneous GvHD.

Malignant lymphoma with myxoid change and sarcomatous features.

We report a case of unusual B-cell malignant lymphoma of the kidney and mediastinum. Renal biopsy showed prominent myxoid changes and sarcomatous features, leading to considerable difficulty in histologic diagnosis on routinely stained histologic sections. However, immunohistochemical staining for lymphocyte markers led to the final histologic diagnosis of B-cell malignant lymphoma. Although myxoid change is not generally found in malignant lymphoma, malignant lymphoma should not be excluded from consideration when one encounters a small round cell sarcoma with myxoid stroma, especially in extranodal soft tissue tumors.

[Evaluation criteria for chemotherapeutics for malignant skin carcinomas].

Malignant skin carcinomas occur in a large variety of forms, among them malignant melanoma with a poor prognosis, such as squamous cell carcinoma, basal cell carcinoma, appendix tumors of skin (e.g., sweat gland carcinoma, sebaceous gland carcinoma), metastatic carcinomas of skin, intraepidermal carcinomas (e.g., Bowen's disease, Paget's disease) and mesenchymal carcinomas including mycosis fungoides (cutaneous T cell lymphoma). Furthermore, not only do they present with varied clinical symptoms, some forming tumors or erythemas, some being infiltrative in nature and some being flat in shape, but the clinical symptoms also vary with time during treatment. All these conditions conspire to make the evaluation of chemotherapeutics complicated and difficult. In the field of dermatology topical drugs provide a no less powerful weapon than drugs for systemic administration with which to combat skin carcinomas and are simple and easy to administer. In consideration of those clinical and therapeutic aspects of malignant skin carcinomas new evaluation criteria for chemotherapeutics for topical and systemic administration have been established by adding three-way measurement to the conventional methods of one- and two-way measurement for measurable lesions along with the evaluation of the response of clinical symptoms to chemotherapeutics in unmeasurable carcinomas. The new version of criteria is based in its general framework on the Japan Society for Cancer Therapy's Evaluation Criteria for Chemotherapeutics for Solid Carcinomas by Koyama and Saito and the new version has been approved at the 26th general meeting of the Japan Society for Cancer Therapy (1988, Niigata).

Beta 2 microglobulin expression in normal melanocytes, nevocellular nevi, and malignant melanomas.

Expression of beta 2 microglobulin (beta 2M), a light chain of class 1 HLA antigen, was studied in normal melanocytes and in benign and malignant melanocytic tumors by use of immunohistochemical methods. By immunoelectron microscopy, normal melanocytes were shown to express beta 2M on the cell surface. In lentigo maligna melanomas and acral lentiginous melanomas, the mean percentages of beta 2M-positive tumor cells were significantly lower in thick (greater than 1.50 mm) primary lesions and metastases than in thin (less than or equal to 1.50 mm) primary lesions. The evidence suggests that melanocyte-derived melanoma clones with a low grade of malignancy preserve class 1 HLA expression, and that the clones with a high grade of malignancy tend to lose the antigen expression. Nevus cells in common nevi have little or no expression of beta 2M. In halo nevi, however, beta 2M were detected on nevus cells in the lesions associated with inflammatory infiltration. Immunohistochemical analyses of the cellular composition of the inflammatory cells in halo nevi demonstrated the presence of cytotoxic T cells together with helper/inducer T cells, Langerhans cells, and macrophages. It appears that nevus cells of halo nevi are destroyed by cytotoxic T cells and that class 1 HLA antigens expressed on nevus cells play an important role in the target cell recognition and lysis by specific cytotoxic T cells.

[A new variety of neurocutaneous melanosis: benign leptomeningeal melanocytoma associated with extensive Mongolian spot on the back].

A 38-year-old Japanese man presented with a blue macule on the back. A spinal meningeal tumor at the C3-C5 levels was detected radiologically and excised. The histological findings in the biopsy specimen from the blue macule were consistent with an extensive Mongolian spot. The histological diagnosis of the meningeal tumor was benign melanocytoma. The case was thought to be a new variety of neurocutaneous melanosis.

T cell lymphoma presenting clinical and morphological features resembling polymorphic reticulosis and lymphomatoid granulomatosis.

A male, 53 years old, complained of a mass on the left side of neck. The biopsy specimens revealed extensive necrotizing lesions with polymorphonuclear leukocyte infiltration. About three years later a recurrence from the same site was noted and the rebiopsy specimens showed features of malignant lymphoma of pleomorphic type. Subsequently multiple cutaneous nodules and then ulcerative lesions of the midfacial region developed and repeated biopsies were done. Immunological examination indicated that the lymphoid cells obtained from the skin lesion had predominantly T-lymphocyte marker. He died of massive hemorrhage from the nasopharyngeal lesion 51 months after the first admission. Autopsy revealed multiple organ involvements, including the nasopharynx, lungs, subcutaneous tissue, and adrenal gland. The morphological features in the present case were compatible with a diagnosis of lymphomatoid granulomatosis or polymorphic reticulosis (midline malignant reticulosis), and were thought to be best designated as T cell lymphoma.

Synthesis of basal lamina by epidermal cells in vitro.

In epidermal cell cultures grown on type I collagen, the in vitro synthesis of basal lamina was studied by electron microscopy and indirect immunofluorescence with anti-type IV collagen antibody. The newly-formed basal lamina and type IV collagen were observed in a linear pattern beneath the epidermal cells. The observations strongly suggest that the basal lamina containing type IV collagen is newly synthesized by the epidermal cells.

Basal lamina formation by epidermal cells in cell culture.

The formation of basal lamina in epidermal cell cultures was studied by electron microscopy. Epidermal cells were cultured on plastic dishes which were either uncoated or coated with collagen gel. The cells grew and stratified on the plastic substratum as well as on the collagen gel. While the cultures on the plastic surface showed no occurrence of hemidesmosomes and basal lamina at the interface with the plastic substratum, the cultures on the surface of the collagen gel showed development of hemidesmosomes leading to the focal occurrence of basal lamina at the interface of the collagen gel and the basal plasma membrane of basal cells. Thereafter, basal lamina occurred under the interhemidesmosomal areas in addition to the hemidesmosomal areas of the basal plasma membrane, forming a continuous layer by joining.