Cryptococcus neoformans, a facultative intracellular pathogen of macrophages, is unique among medically important fungi in its possession of a polysaccharide capsule. Capsule represents the organism's major virulence factor. In the absence of opsonins, binding of encapsulated C. neoformans to macrophages is minimal. Following incubation in serum, C. neoformans potently activates complement, resulting in surface deposition of the third component of complement. Macrophages bind and phagocytose opsonized C. neoformans via three major complement receptors (CR) for C3 fragments, designated CD35 (CR1), CD 11 b/CD 18 (CR3), and CD 11 cICD 18 (CR4). Antibody in normal human serum generally lacks opsonic activity, although vaccination can elicit anticapsular antibodies that are opsonic. The major component of cryptococcal capsule, glucuronoxylomannan (GXM), is shed from the fungus and circu-lates in the blood and cerebrospinal fluid of patients with cryptococcosis. Cellular receptors defined or GXM include CD 14, toll-like receptor-2, toll-like receptor-4, and CD 18. GXM binding to macro-phage receptors triggers activation of nuclear factor- _KB, but not mitogen-activated protein kinases. This results in no proinflammatory gene expression or release. C. neoformans also secretes mannoproteins, which are recognized by mannose receptors as well as by mannose-binding lectin, perhaps in conjunction with CD 14. Strategies directed at modulating how intact C. neoformans and its released components are recognized by phagocytes could lead to novel approaches to treating cryptococcosis

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Cryptococcosis is an opportunistic fungal infectious pathogen in immunocompromised patients with acquired immunodeficiency syndrome and hematological malignancies. The host defense to this pathogen is mediated mostly by cellular immunity. Th 1-type cytokines including IFN-7, IL-12 and IL-18 play a pivotal role in this process. Recently, innate immunity mediated by NK, NKT and y T cells has garnered much attention from investigators. NKT cell has been identified as a particular cell population which recognizes glycolipids and participates in the development of tumor immunity and autoimmune diseases. In the present review, the accumulating knowledge on the roles of NKT cells in host defense to infectious pathogens are summarized with our own data on cryptococcal infection.

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This understood without starting paper describes general histopathological features of deep seated mycoses in patients with acquired immunodeficiency syndrome (AIDS) detailed histological examination on cryptococcal lesions with a consideration of morphological modification caused by treatment with highly active antiretroviral therapy (HAART).
In a histopathological review of 164 patients with total human immunodeficiency virus (HIV) infection, the microscopical appearance of esophageal candidiasis which was common in those with single organ involvement revealed necrotic debris containing proliferating hyphae at the site of mucosal erosions without fungal invasion of underlying tissue. The incidence of oral and esophageal candidiasis was followed by that of pulmonary aspergillosis and Candida pneumonia. Nineteen patients including one treated with HAART had generalized cryptococcosis, representing the most common generalized fungal disease. The essential histologic features of the disease were yeast cell proliferation with a histiocytic response, but only minor lymphocytic and neutrophilic components. This was different from those induced by both Candida and Aspergillus infections. Three histologic patterns were recognized in the pulmonary cryptococcal lesions, two of which could be graded with respect to the degree and type of inflammatory reaction. The first was a mild one consisting of small scattered foci of intra-alveolar cryptococcal proliferation with a histiocytic response. The second pattern involved massive cryptococcal infection, which might have been simply more extensive than that in the former. Capillary involvement of alveolar septa was an important common finding in the eighteen patients who had not been treated with HAART. The absence of T cells and decreasing function of antigen presenting activity in histiocytes were confirmed by immunohistological examination. These findings suggest that the lungs of AIDS patients without HAART offer little resistance to bloodstream diss mination by Cryptococci. The third pattern demonstrated in the patient treated with HAART was characterized by the presence of CD4 + cells, greater response of histiocytes and multinucleated giant cell formation, and lack of massive capillary involvement.

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Neutrophil disfunction, caused by a decreased production of effective radical oxygen species by myeloperoxidase (MPO) and NADPH oxidase within the neutrophil, may result in susceptibility to opportunistic fungal infections. In vitro, MPO produces OC1, which kills bacteria and viruses. In the case of MPO deficiency, susceptibility to Candida albicans infection was observed. Furthermore, it was demonstrated that MPO knockout mice were primarily susceptible to C. albicans infection. With regards to NADPH oxidase deficiency, such a patient was found to have severe chronic granulomatous disease (CGD) due to Aspergillus infection. This deficiency may have resulted from a gene mutation and/or abnormality of the NADH oxidase components, particularly cytochrome b₅₅₈ (gp 91 ^phox and p 22 ^phox) in membrane and cytosol factors p 47 ^phox, p 67 ^phox, p 40^phox and others in neutrophil. Thus, irregular regulation of transcription factors for gene expression of phox molecules and MPO permits susceptibility to Aspergillus and Candida infections.

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Aspergillosis has become the biggest cause of death among mycoses in Japan. The main causative agent is Aspergillus fumigatus and its virulence factors have been variously investigated, yet much remains to be clarified.
We recently found that the culture filtrate of A. fumigatus has potent anti-leukocyte activity. It seriously damages macrophages and hampers the function of polymorphonuclear neutrophils. The filtrate is also active in vivo : when injected intraperitoneally, the culture filtrate lowered the survival of mice infected with A. fumigatus. This activity becomes overt within 24 hours of culture of the fungus. Although the mechanism of pathogenicity of A. fumigatus is believed to be somewhat complex, we suggest the activities shown in the culture filtrate may play a crucial role in the development of the infection.

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Thirty-one single ascospore cultures were obtained from one ascoma produced in mating of RV 26678 (+) (Institut de Medicine Tropicale, Antwerp, Belgium) and KMU 4169 (-) (Dept. Dermatology, Kanazawa Medical University, Uchinada, Japan), which are genetically different strains of Arthroderma benhamiae. The isolation was performed with the aid of an inverted microscope and a binocular microscope. The internal transcribed spacer (ITS) regions of the nuclear ribosomal RNA gene of all the ascospore cultures were analyzed by restriction fragment length polymorphism (RFLP) with the restriction enzyme Hinfl. The mating types of all the single-ascospore cultures were also checked. Eight cultures had mating type (+) and RV 26678 genotype, 10 had mating type (-) and RV 26678 genotype, 6 had mating type (+) and KMU 4169 genotype and 7 had mating type (-) and KMU 4169 genotype. There was no linkage between the mating types and the genotypes, implying that the genes control the mating behavior and the genes of ribosomal RNA are on different chromosomes from each other. The hybrids comprised half of the isolates and so they were actually from the ascospores and not from the microconidia or the peridial hyphae.

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Hortaea werneckii, a black yeast and the causative agent of tinea nigra (a superficial type of dermatomycosis), is a human pathogen and is also found in the environment. It is not highly pathogenic but in the last fifteen to twenty years has been isolated from various human and environmental sources in Japan. As far as we know, there has been no report on the isolation of H. werneckii from animals. Recently, we found a case of a guinea pig with dark superficial lesions on the palm and dorsal areas. Cultural and morphological studies of scrapings from the lesion showed that the causative agent was a black yeast, which was identified as H. werneckii by morphological study and molecular biological screening. Dl/D2 region of the 26S large subunit rDNA gene of this isolate was identical to those of 11 other H. werneckii isolates used as reference strains in this study. This is the first case recorded of tinea nigra caused by H, werneckii in a guinea pig.

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The fungicidal activities of thiocarbamate antifungal agent liranaftate were studied by determining the MIC and the MCC against Trichophyton rubrum with the Milliflex ®-100 Test System and by determining the time-kill curve in comparison to that of six reference agents.
Liranaftate and lanoconazole both showed excellent fungistatic activity against the conidia of T. rubrum. For each of these agents, the MIC after 14 days of contact was 0.009 ig/ml. The liranaftate-induced decrease in the MCC occurred from 9 days onwards; MCC at 14 days was 0.039 ig/ml. The MCC for tolciclate was also reduced from 9 days onwards, but that of amorolfine, lanoconazole, neticonazole, clotrimazole and bifonazole was not lowered up to 14 days. Similar results were obtained when the studies were performed with germinated conidia.
The time-kill curves showed that both liranaftate and tolciclate, at concentrations ranging from 2 to 32 times the MICs, achieved a decrease in viable counts to below the detection limit within 7 to 9 days. In experiments with low levels of inoculum, only amorolfine produced a decrease to below the detection level, and that occurred at 14 days; no reduction in viable counts was observed up to 14 days with the four azole agents.
Our data suggest that antifungal agents of the thiocarbamate class possess the most potent fungicidal activity against dermatophytes; these are followed in order by morpholine and azole antifungals.

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We report a case of seborrheic blepharitis treated with oral itraconazole during a short period. Direct examination using Parker KOH revealed numerous hyphae and spores of Malassezia in the scale. Low-dose itraconazole pulse therapy (200 mg daily, 7 days a month) was quite effective. This is the second case in which we also observed a unique fungal conformation which looked like tinea versicolor. The evidence strongly suggests that Malassezia is one of the major causative agents of Seborrheic Blepharitis.

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