Yusho Miura

Immunological studies on aphthous ulcer and erythema nodosum-like eruptions in Behcet's disease

Patients with Behcets disease show an intense delayed hypersensitivity (DH) reaction to a group of streptococcal bacteria. We have attempted to detect deposits of immune complexes and to analyse cytological reactions in the aphthous ulcers and erythema nodosum (EN)‐like eruptions. Deposits of IgM and positive fluorescence of anti‐streptococcal group D serum were found in vessel walls and sites infiltrated by inflammatory cells. Cytological analysis has revealed that the inflammatory infiltrating cells are mainly composed of activated T‐cells and macrophages in association with natural killer cells. These results suggest that DH reactions with antigen‐antibody mediated cytotoxicity may play an important role in causing the lesions of Behcets disease.

Natural killer cell numbers and function in peripheral lymphoid cells in Behcet's disease

We have studied NK cell activity and numbers in the peripheral blood obtained from patients with Behcets disease and from normal healthy controls. NK cell activity in the peripheral blood of patients in the clinically‐active stage of Behcets disease was significantly lower than that of patients in the inactive stage and normal controls. In contrast, it was observed that the actual number of NK cells was markedly increased in the peripheral blood of patients with active disease. The addition of α‐interferon (INF‐α) to these cells showed significant augmentation of NK cell activity. These results suggest that the patients with active Behcets disease lack a factor which activates NK cells.

Crystalline lamellae in the endothelial cells of a type of hemangioma characterized by the proliferation of immature endothelial cells and pericytes—angioblastoma (Nakagawa)

Two babies were found to have large hemangiomas. Histologically there were many islands of compactly packed mesenchymal cells in the deep dermis and subcutaneous tissue. Electron microscopically there was proliferation of immature endothelial cells and pericytes. Characteristic crystalline lamellae were in the endothelial cells. Our two cases seemed to be an independent entity from other benign angiomas because of the distinct clinical, histologic, and ultrastructural features. The suggested diagnosis was angioblastoma (Nakagawa; Miki and Matsumoto), hypertrophic hemangioma (Watson and McCarthy), and benign hemangioendothelioma (Stout).

TWO FORMS OF ADENOSINE DEAMINASE IN PIG EPIDERMIS (II)

Molecular heterogeneity of adenosine deaminase in pig epidermis is reported. Gel filtration of pig skin extracts with Sephadex G‐150 revealed the existence of two forms of adenosine deaminase. Molecular weights of the enzymes were around 30,000–40,000 and 300,000–350,000 respectively. Several catalytic properties of these two adenosine deaminases were quite similar: Km value, substrate specificity, pH activity profile, and the effect of coformycin, a strong inhibitor of adenosine deaminase.

Adenosine deaminase in human epidermis from healthy and psoriatic subjects

SummaryAdenosine deaminase, which catalyzes the irreversible hydrolytic deamination of adenosine and deoxyadenosine to inosine and deoxyinosine respectively, plays an important role in the degradation of adenine nucleotide and purine nucleotide salvage pathway metabolism. We investigated human epidermal adenosine deaminase activity using a radiochemical method, which enabled us to measure the adenosine deaminase activity of protein smples as small as several micrograms. We measured adenosine deaminase activity of microdissected pure epidermis of the healthy skin and the psoriatic affected and unaffected skin. It was shown that psoriatic affected epidermis had increased adenosine deaminase activity compared with the healthy epidermis (P<0.05) and the unaffected epidermis (P<0.01). There was no difference in enzyme activity between healthy and psoriatic unaffected epidermis. The increased adenosine deaminase activity in the psoriatic affected epidermis may reflect the accelerated salvage pathway of the nucleic acid metabolism probably associated with the hyperproliferative condition of the psoriatic epidermis.

Retinoid stimulates epidermal outgrowth of pig skin explants.

Using a pig explant culture system, the effects of retinoids on pig epidermal cells were studied. Ro 10‐9359 slightly stimulated epidermal outgrowth, but this effect was not significant. Ro 10‐1670 (a metabolite of Ro 10‐9359) significantly stimulated epidermal outgrowth. Cytochalasin B and colchicine markedly inhibited the stimulatory effect of Ro 10‐1670, but hydroxyurea or cycloheximide did not completely block this stimulatory effect. During a migratory period, cytochalasin B completely blocked it. Neither Ro 10‐1670 nor Ro 10‐9359 effected a change in mitotic index. Histological studies revealed that Ro 10‐1670‐treated epidermal cells did not form any keratin layers. These results suggest that Ro 10‐1670 stimulated outgrowth, particularly migratory outgrowth, of epidermal cells, resulting in reduced keratin formation.

Blue rubber-bleb nevus syndrome with Masson's vegetant intravascular hemangioendothelioma

A 14‐year‐old Japanese male showed numerous small cutaneous hemangiomas and severe anemia produced by internal hemorrhages from intestinal hemangiomas. Histological studies revealed ectatic vessels lined by a single layer of endothelial cells. Six hemangiomas, with fibrous walls of variable thickness, showed characteristics of vegetant intravascular hemangioendothelioma (Masson) in an organizing thrombus. Electron microscopy confirmed that the dilated cavities, were lined by a layer of flattened endothelial cells, surrounded by a few pericytes and/or smooth muscle cells. No appreciable abnormalities were found in the blood vessels located in the clinically normal skin.

Extractable immune complex in soluble substances from psoriatic scales.

SummarySoluble substances of psoriatic scales (Psoexts) were analysed immunologically to detect immune complex (IC) related to the immune reactions in psoriatic lesions and compared with extracts of scales from a patient with erythroderma due to pityriasis rubra pilaris (PRP-exts) as control. Immunoelectrophoretically IgG, IgA and C3 were detected in Pso-exts, but in PRP-exts only IgG was seen as immunological reactive substances. When analysed by Sephadex G-200 column chromatography, IgG and IgA eluates were found in Pso-exts with a molecular weight of more than 200,000 daltons. By Raji cell assay, the IgG and IgA eluates were shown to have IC characteristics and they were the IC composed of IgG-IgA, which was also confirmed using anti-IgG affinity chromatography. The IC seemed to be binding the epidermal proteins as antigen. Thesefindings suggest that deposits of immunoglobulins and complement in the stratum corneum of psoriatic lesions are not just secondary to the underlying inflammation in the dermis but that the IC detected is related to the immune reactions in psoriatic lesions.

The effects of db-cAMP and related compounds on the outgrowing epidermis in vitro.

Explant cultures of domestic pig skin were used to study the effects of db‐cAMP and related compounds on epidermal outgrowth and mitotic index in the outgrowing epidermis. Db‐cAMP and related compounds which elevated intracellular concentrations of cyclic AMP had inhibitory effects on epidermal outgrowth and mitotic index. Treatment with db‐cAMP in an early “migratory” phase revealed that db‐cAMP inhibited the migratory activities of epidermis in culture.

ADENOSINE DEAMINASE ACTIVITY IN PERIPHERAL LYMPHOCYTES OF PSORIASIS AND SÉZARY'S SYNDROME: POSSIBLE SIGNIFICANCE IN T-LYMPHOCYTE DYSFUNCTION

Adenosine deaminase (ADA) activity in peripheral lymphocytes were measured in 15 normal subjects, 15 psoriatic patients, and one patient with Sézarys syndrome.