Six patients with cryptococcal meningitis were admitted to the First Department of Internal Medicine of Yokohama City University School of Medicine in the last 15 years. Three of 6 patients were treated with intravenous amphotericin B alone (Group I) and the remaining three patients were treated with combining with flucytosine (Group II).
In this report, only two side effects, BUN elevation and bone marrow suppression (e. g. granulocytopenia), were discussed in the above two groups. Only one patient treated with amphotericin B alone had both of BUN elevation and bone marrow suppression and the remaining two patients had neither of two. On the other hand, all of three patients treated with combination therapy (Group II) had both of these two side effects. And no patients which had either of these two side effects were observed in the two groups. At least in part because amphotericin B administration has resulted in azotemia, combination therapy has resulted in granulocytopenia much more often than flucytosine alone. Therefore, during the combination therapy, the greatest care must be taken about flucytosine induced bone marrow suppression, which concomitantly occured with azotemia of amphotericin B nephrotoxicity.

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This study was performed to examine cutaneous lesions as one of a series of experiments using Fusarium oxysporum. The lesions were induced by an intracutaneous inoculation of live microconidia of F. oxysporum to rabbits in the following 3 groups: untreated controls, animals sensitized to formalin-killed F. oxysporum cells, and those treated with cyclophosphamide and mitomycin C.
In the control animals, the cutaneous lesions started to form a skin abscess and ulcer at the early stage, and were surrounded by macrophages (Mφ). Later, the ulcer healed by regeneration of epidermis and the abscess was reduced, then subsequently replaced by a small granuloma including degraded fungal elements. In the sensitized animals the fungal cutaneous lesions were similar to those in the control animals but more prominent. Although in the drug-treated animals, polymorphonuclear leukocyte infiltration was scarcely observed at the early stage, the lesions became similar to those in the animals of the other two groups. Fungal growth was not present in the lesions of the control and sensitized animals, but was considerable in the early lesions of the drug-treated. Cultures of the inoculated fungi from the cutaneous lesions were positive until the 7th day in all groups of animals.
These results were somewhat similar to those of the experimental cutaneous candidosis. However, it was characteristic in this experiment that the fungal lesions healed leaving a small granuloma containing fungal elements.

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From 383 (38.3%) of a total 1000 of soil samples, collected from Hokkaido prefecture, the northeastern district of Japan, keratinophilic fungi have been isolated using hair baiting technique. The fungi isolated were as follows: 318 strains of Trichophyton ajelloi (including 90 strains of Arthroderma uncinatum), 59 of Microsporum cookei (including 13 of Nannizzia cajetani), 32 of Chrysosporium keratinophilum, 23 of C. tropicum, 15 of Chrysosporium anamorph of Arthroderma tuberculatum, 6 of T. terrestre (including 3 of A. insingulare and one of A. quadrifidum), 4 of Chrysosporium sp., 2 of M. canis (including one of N. otae), one of M. gypseum, and one of Ctenomyces serratus. This is the first isolation of N. otae from soil.
Results of the study indicate that the distributional pattern of keratinophilic fungi in soils from Hokkaido prefecture is markedly different from that in the southern parts of Japan, especially in the frequent occurrence of T. ajelloi and the scarcity of M. gypseum. The unexpected isolation of N. otae and its anamorph, and the (+) and (-) strains of M. canis from the soil sample might reflect the peculiar distribution of M. canis in Hokkaido prefecture, where it is one of the most important dermatophytes.

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The inhibition of squalene epoxidase by thiocarbamate derivative, naphthiomate T was investigated with microsomes from Candida albicans and rat liver. Squalene epoxidase was found to be much sensitive to naphthiomate T with C. albicans than with rat liver. Furthermore, the epoxidase inhibition of C. albicans microsomes showed a non-competitive kinetics with respect to the substrate squalene and was not antagonized by the addition of the soluble fraction (activating factor). There was no evidence for an irreversible nature in epoxidase inhibition of C. albicans.

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Local heat therapy is considered to be effective and safe for treatment of chromoblastomycosis. The mechanism underlying the effectiveness of the therapy, however, is not yet fully elucidated. To clarify this mechanism, we studied the effects of temperature on the growth of 25 strains (5 species) of pathogenic dematiaceous fungi, the human skin surface temperature after application of various kinds of pocket warmers and the depth of fungal elements in the tissue in 7 cases of chromoblastomycosis. Maximal temperatures for the growth of F. pedrosoi, E. jeanselmei, E. dermatitidis, P. verrucosa and C. trichoides were found to be 39°C, 36-38°C, 40-42°C, 37°C and more than 45°C, respectively. Although F. pedrosoi, E. jeanselmei and P. verrucosa were killed by the 25th, 5th and 5th incubation day at 41°C, respectively, E. dermatitidis and C. trichoides were still alive until the 25th incubation day at this temperature. After application of a pocket warmer, the tissue temperature at the depth of 3-4mm rose to 40.5°C, while the temperature of the skin surface reached 42°C. Histologically, fungal elements were observed 1.5mm below the surface and the thickness of inflammatory cell infiltration reached 4mm from the skin surface. From these data, we believe that local heat therapy could be an effective treatment for chromoblastomycosis caused by F. pedrosoi, E. jeanselmei and P. verrucosa. In addition to its fungicidal effect, however the possibility that heat therapy has an enhancing effect on host immunity should also be recognized.

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A simple resazurin-coupled fluoroassay for serum D-arabinitol is described. This method involves two coupled enzymatic reactions, D-arabinitol dehydrogenase and diaphorase. The increase of fluorescence produced by the reduction of resazurin was determined with an excitation wavelength of 560nm and an emission wavelength of 580nm.
We serially determined serum D-arabinitol in a patient with acute lymphoblastic leukemia complicated with multiple Candida liver abscesses. When numerous small low density areas were recognized in the liver and the spleen by CT, serum D-arabinitol concentrations and D-arabinitol/creatinine ratios were found to be significantly increased, 10-20 fold above normal.

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The effect of a new azole antimycotic bifonazole on the ultrastructure of hyphal growth of Trichophyton mentagrophytes grown by the slide-culture technique was studied by high resolution scanning electron microscopy. With bifonazole at concentrations ranging from 2 to 500ng/ml, much lower than the MIC value of the drug for this test strain (0.63μg/ml), hyphal growth was significantly inhibited and several ultrastructural changes of the hyphae were produced. These were characterized by: (1) inhibition of hyphal growth showing wavy, curling, bending and twisted hyphae; (2) various abnormal features of growing hyphae and the wrinkled structure; (3) distortion of hyphae (exfoliation of hyphal walls, excretion of amorphous materials with resultant formation of film or seat extending between adjacent hyphae). These ultrastructural changes of the hyphae became more prominent with increasing concentration of the drug. These results strongly suggest that subinhibitory concentrations of bifonazole profoundly affect the normal growth and induce degenerative changes of the hyphae of T. mentagrophytes, probably by affecting some essential metabolism or structure of the cell.

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Crude enzyme solution was prepared from the supernate of cultured S. schenckii by filtration and partially purified with DEAE-cellulose column chromatography. The enzyme fraction which degraded azocoll (insoluble denatured collagen) was pooled and characterized. Optimum pH of hydrolytic activity of azocoll was found to be 4.0 and the activity was inhibited by pepstatin. The enzyme also showed degrading activity of native acid soluble calf skin collagen on SDS polyacrylamide gel electrophoresis.
From these studies, it was confirmed that S. schenckii produced collagenolytic proteinase. This suggests that the collagenolytic proteinase may play an important role in the pathogenesis of S. schenckii.

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