The host-defense is composed of many elements or mechanisms which maintain the homeostasis of individuals by elimination of foreign materials such as microorganisms or harmful chemicals and of self derived harmful components. After invasion of microorganisms, the host-defense works as a sequential barrier of various elements proceeding from the early defense system without antigen recognition to the typical immune system with antigen recognition and clonal expansion. I have proposed a new entity “primitive T cell response” (PT response), which covers the gap between the early defense system and the typical immune system in terms of time-course and functional expression. Recently, I have indicated that about a half of these reactions are carried out by TCR-γ S T cells and the other half by TCR-αβ subsets with primitive functional patterns.

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The role of antigen 6 in the adherence process of Candida albicans serotype A to cultured keratinocytes was examined with a scanning electron microscope. The number of adhered organisms was significantly lower for the antigen 6-deficient mutant strain than that for the antigen 6-positive parent strain. Fibrilor strand-like structures bridging the organisms and the keratinocytes were found to develop during the later stages of the adherence. The keratinocyte growth was suppressed by co-culture with C. albicans, but was stimulated by the addition of diluted culture filtrate from C. albicans.

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Dermatophytosis is a unique infectious disease in that dermatophytes reside only in the barrier membrane of the body surface, i. e. in the stratum corneum. Dermatophytes in the stratum corneum cannot become direct targets of antibody response or phagocytosis.
Based on our data obtained in the studies of dermatophytosis with guinea pigs, we postulate that skin inflammation at the site of dermatophytosis plays an important role in the defence mechanism against dermatophytes by increasing turnover of the epidermis and stratum corneum, thereby fascilitating the elimination of the dermatophytes. Skin inflammation in dermatophytosis seems to be caused mainly by contact sensitivity to trichophytin and transepidermal neutrophil chemotaxis.
We examined the turnover of stratum corneum in experimental dermatophytosis using the dansyl chloride fluorometry technique. The turnover of the lesional stratum corneum seemed to be increased compared to control site.

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Preparation and analysis of experimental dermatophytosis are both of great importance in order that mechanisms of dermatophytosis might be elucidated. Tagami et al. demonstrated hypersensitivity to constituents of dermatophytes in experimental dermatophytosis on hairy skin in guinea pig, and found that the dermatophytosis induces epidermal hyperproliferation which facilitates elimination of the fungi. Fujita et al. established a reproducible model of tinea pedis in guinea pig and indicated that inflammatory tissue reactions are mediated by delayed hypersensitivity. Although experimental dermatophytosis on the back of hairless guinea pig resembles human tinea corporis, this model remains to be improved. From the fact that experimental tinea pedis never heals spontaneously, we assumed that hair apparatus has an important role in spontaneous healing of experimental dermatophytosis on hairy skin. Therefore, we analyzed morphological alterations of hair apparatus evoked by dermatophyte infection in guinea pig using immunohistochemical methods. Most of the hair apparatus began to involute and retract synchronously on day 16 after inoculation of fungi. In hair bulb, DNA synthesizing cells decreased in number significantly in comparison with those on day 14. It is assumed that fungal infection induced hair apparatus to involute by affecting hair cycle. Alterations of cellular dynamics in hair apparatus is one of the important factors in mechanisms of spontaneous healing in experimental dermatophytosis on hairy skin in guinea pig.

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Delayed-type hypersensitivity (DTH) response is recognized as one of the essential parts of the host defense against dermatophyte infections. T cell-derived cytokines (IFN-γ, GM-CSF, IL-2) are involved in the elicitation of the DTH response. We previously demonstrated that IFN-γ, IL-2 and GM-CSF were released by peripheral blood mononuclear cells (PBMC) from patients with non-chronic dermatophyte infection, suggesting the involvement of these cytokines in eradication of the dermatophytes from the stratum corneum of the skin. We also showed that the production of IFN-γ in response to stimulation with trichophytin was depressed in the PBMC obtained from patients who had chronic dermatophyte infection, when compared with that in the PBMC obtained from non-chronically infected patients. It is possible that decreased release of cytokines at the site of infection might explain the inability of chronically infected patients to eradicate dermatophytes from the skin.

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Cultures were taken by cotton swab method from tongues which had no lesions and showed no fungus by direct examination. Candida spp. were isolated from 23 of 27 cases on oral steroids, 22 of 51 cases with internal disease, and 31 of 132 controls. Of 76 isolated strains of Candida spp., 62 were identified as C. albicans A, 5 as C. albicans B, and 9 as other spp.
The detection rate of C. albicans on controls diffed with age; the rate under 60 years was 12 of 110 (10.9%), while that of 61 and over was 12 of 22 (54.5%). C. albicans was isolated from 18 of 21 (85.7%) cases on oral steroids, and 17 of 40 (42.5%) cases with internal disease under 60 years old.
C. albicans had thus increased on the tongue of many cases on oral steroids, those with internal disease, and controls 61 years and over even though no fungus was shown by direct examination. The detection of C. albicans by cotton swab method indicates the possibility of a compromised host.

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The imidazole compound is well established as one of the most valuable agents in the therapy of tinea, because it has a high antifungal activity as well as a broad antifungal spectrum. However, this agent has a little effectiveness for hyperkeratotic type of tinea pedis and manum. With regard to the antifungal activiy of imidazole compound, no correlation has been found between the in vitro MIC (minimum inhibitory concentration) value and the clinical efficacy. This study was undertaken to elucidate the reason why this compound has so littlee effectiveness for hyperkeratotic type of tinea.
The study focused on: 1) the influence of human cutaneous horny material on the in vitro antifungal activity (MIC value), 2) the action of absorption and liberation of antifungal agents on the human stratum corneum, and 3) the permeability and retention activity of antifungal agents in the human stratum corneum. In experiment 1, using 4% Sabouraud's dextrose broth with human cutaneous horny material, the MIC value of clotrimazole was higher by 64-256 times than that of control medium. This suggested that the human stratum corneum significantly reduced the antifungal activity of imidazole compound.
Based on the growth of dermatophytes on the medium with the sliced human stratum corneum topically treated with antifungal agent, comparative studies were performed on the absorption-liberation (experiment 2) and the permeability-retention activity (experiment 3) of clotrimazole and bifonazole solutions. These revealed that clotrimazole disappeared more rapidly from and was retained much less time in the human stratum corneum than bifonazole.
These experiments elucidated a part of the pharmacodynamic action of topical antifungal agents on the human stratum corneum, and experiment 3 seemed to be an especially simple and useful method to evaluate the permeability and the retention activity of agent without the use of any radioactive tracers.

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Total cellular DNAs from reference strains of Trichophyton (T.) rubrum and two teleomorphs of T. mentagrophytes, Arthrodrema (A.) benhamiae and A. vanbreuseghemii, were extracted from a small amount of lyophilized mycelia using the minipreparation method. The DNAs were digested with restriction enzym es followed by electrophoresing on agarose gels, and restriction profiles were compared with those of chromosomal and mitochondrial DNA purified by equilibrium centrifugation in CsCl. Using restriction enzymes Hae III and Msp, I, the profiles composed of clearly observed bands of total cellular DNAs were identical to those of mitochondrial DNAs. The results indicate that the method, which is less expensive and less time consuming than preparation of mitochondrial DNA, combined with appropriate restriction enzymes is useful for screening the molecular type among these dermatophyte species.

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Distribution of dermatophytes on the soles of the feet of twenty-seven, previously untreated patients with tinea pedis was investigated by a new direct culture method (foot-press method). The infected sole of each patient was directly pressed onto actidione-chloramphenicol-supplemented Sabouraud dextrose agar prepared in a large culture dish. Dermatophyte colonies were isolated from fifteen patients (56%). Nine of the isolated dermatophytes were Trichophyton rubrum (60%), and the rest were Trichophytok mentagrophytes (40%). Positive rate was higher in patients with widely-spread lesions and did not depend on species or disease type.

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Two cases of endogenous candida endophthalmitis which consulted our dermatological office are reported. Case 1: A 39-year-old man was diagnosed with subacute extradural haematoma. Following an intracranial intracranial operation, fever of unknown origin continued for about a month. During intravenous hyperalimentation (IVH), floating spots, failing sight and clouded vision were experienced in both his eyes. The patient was furthermore complicated by subcutaneous candidal abscess, candidal glossitis and oral candidiasis. Case 2: A 59-year-old man was diagnosed with cancer of the stomach. Following an operation, a pancreatic fistula was found. During IVH, he experienced floating spots and failing sight. Candida albicans was detected both under direct microscopic examination and from the culture of the resected vitreous body of the two cases.

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A 68-year-old Japanese male farmer visited our clinic with large red plaques on his face and hands. The lesion started one year and half prior to his first visit to our clinic as an acneiform eruption on the left eyebrow. At that time he visited the office of a dermatologist and was diagnosed as cutaneous sarcoidosis. He was treated with topical steroids. The lesion, however, gradually enlarged and other formed. On Feb. 8, 1994, he visited our clinic. Physical examination showed large red plaques covered with crust and scaly surfaces with some erosive parts on the face and hands. Histological findings revealed granulomatous infiltration in the upper dermis, composed of lymphocytes, histiocytes, plasma cells and giant cells. Grocott staining demonstrated fungal elements in the upper dermis. Candida albicans was cultured from the skin specimen. Based on the clinical, histological, and mycological findings, the patient was diagnosed with deep cutaneous candidiasis. The lesions were cured completely with the administration of itraconazole.

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