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ABSTRACT: Aspergillus fumigatus is known to produce various immunosuppressive mycotoxins including gliotoxin. However, none of these mycotoxins has been confirmed as being directly related to the pathogenesis of aspergilli. Recent studies have made substantial progress in the determination of mycotoxins as virulence factors. Gliotoxin was found to be produced much faster than previously believed under certain culture conditions, such as at 37 degrees C and under high oxygen content, which is close to the environment in the host. Gliotoxin was also found to be detectable in the sera of aspergillosis mice and of aspergillosis patients. Based on these findings, it is becoming evident that gliotoxin is produced in the infected organs of patients of aspergillosis at a significant level. In addition to these known mycotoxins, A. fumigatus produces many mycotoxins apparently different from known toxins. From the aspect of gene analysis, the deletion of laeA was found to block the expression of metabolic gene clusters such as sterigmatocystin, and the gene is also expected to be related to the production of gliotoxin. The significance of mycotoxins as virulence factors will hopefully be clarified in the near future.
Medical Mycology 06/2005; 43 Suppl 1:S95-9. · 2.46 Impact Factor
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ABSTRACT: Candida dubliniensis is a newly described fungus that is frequently isolated from the oral cavities of HIV-positive patients. Although extensive studies have been performed on the phylogeny of C. dubliniensis, little is known about the pathogenic ecology of this yeast. Here we examined aspects related to C. dubliniensis in comparison with those of C. albicans. When injected intravenously into mice, C. dubliniensis had a higher survival rate than C. albicans. Histopathological analysis disclosed that C. dubliniensis remained mostly in the yeast form in the infected organs, whereas C. albicans changed into the mycelial form. The host inflammatory reaction was aggressive with C. dubliniensis infection and mild with C. albicans infection. Co-culture of the yeasts with human polymorphonuclear leukocytes disclosed that C. dubliniensis is more vulnerable to the fungicidal activity of leukocytes than C. albicans. C. dubliniensis was also more susceptible to the toxic effect of hydrogen peroxide. When cultured in vitro, C. dubliniensis grew more slowly than C. albicans, but the formation of germ tubes was faster. When the fungi were cultured in RPMI 1640, a fetal bovine serum supplement suppressed the growth of C. dubliniensis but enhanced that of C. albicans. These results clearly indicated that C. dubliniensis is less virulence than C. albicans.
Medical Mycology 07/2002; 40(3):249-57. · 2.46 Impact Factor
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ABSTRACT: The effect of activated lansoprazole (AG 2000), a novel benzimidazole proton pump inhibitor, against hypha formation of Candida albicans was examined in hypha-forming medium pH 7 (HFM7) after 20 h. AG 2000, at 50-800 microM, did not inhibit germ tube formation. However, it inhibited elongation of germ tubes to form hyphae and favored conversion of germ tubes to resume yeast growth at concentrations of > or =200 microM. Pre-treatment of AG 2000 with a sulfhydryl reagent (1:1), such as 2-mercaptoethanol. blocked the inhibitory property of AG 2000 on hypha formation.
Medical Mycology 07/2001; 39(3):283-5. · 2.46 Impact Factor
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Contributions to microbiology 02/2001; 9:45-57.
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ABSTRACT: A non-pigmented and asporogenic fungal strain without taxonomically useful characteristics was isolated from sputum of a patient with chronic bronchitis. Although the taxonomic position could not be determined based on traditional morphological criteria, the fungus was identified as an Aspergillus fumigatus mutant strain by molecular techniques including ITS sequence analysis and PCR identification system using a PCR primer pair specific for A. fumigatus. Usefulness of these molecular techniques for the identification of non-classifiable fungal strains in a clinical laboratory is discussed.
Nippon Ishinkin Gakkai Zasshi 02/2001; 42(2):91-3.
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T Iizasa, K Kamei,
M Chiyo,
M Suzuki,
M Baba,
T Toyosaki,
K Hiroshima,
H Ohwada,
S Kanno,
K Nishimura,
T Fujisawa
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ABSTRACT: We report a surgical case involving localized honeycomb lung with mucus, caused by colonization of a Schizophyllum commune, which displayed a tumorous shadow in the right upper mediastinum. A 74-year-old male with a history of tuberculosis in the 1970s was referred to Chiba University Hospital (Chiba, Japan) with an abnormal shadow evident in the chest roentgenogram. A transbronchial biopsy failed to yield a definite diagnosis. We resected the right upper lobe, which was found to contain a consolidative lesion filled with viscous mucus in the right upper lobe adjacent to the right upper mediastinum. Microscopic examination revealed a honeycomb lung formation with mucus in the destroyed space. Culture of the mucus yielded a whitish filamentous fungus, positively identified as S. commune. This is the first report of S. commune leading to a deposit of mucus and the formation of a consolidative lesion in the destroyed lung.
Respiration 02/2001; 68(2):201-3. · 2.26 Impact Factor
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ABSTRACT: Histoplasmosis is distributed in tropical, subtropical and temperate zones of the world. The disease is one of the imported mycoses in Japan. To date, although more than 30 human and one canine case of histoplasmosis have been reported in Japan, some including that of the canine might have been infected domestically, since the patients have no history of going abroad. The pathogen of histoplasmosis is thus believed to be present in our country. We examined skin biopsies from two dogs in Tokyo and Kumamoto, and found fungal elements 1-2 or 2-4 microEm in diameter in the macrophages. The homology of DNA sequences for the ITS rRNA gene were correspondent to Ajellomyces capsulatus at a rate of more than 97.4%. Therefore, the two dogs were diagnosed as having been infected with Histoplasma capsulatum which is the anamorph of A. capsulatus. Since the dogs had no history of having been outside Japan and had not been brought from an endemic area, they might have been infected domestically. Further epidemiological surveys on canine histoplasmosis may be able to estimate autochthonous human cases in Japan.
Nippon Ishinkin Gakkai Zasshi 02/2001; 42(4):229-35.
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K Kamei
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ABSTRACT: Infections caused by zygomycetes, which have been increasing in recent years, are known for their difficulty of diagnosis and treatment. Because little is known about this fungus and its infection, vigorous research is now in serious demand. As in many other systemic mycoses, animal model studies are essential in the investigation of zygomycosis, particularly for the study of pathogenesis, diagnosis and treatment. Unfortunately, such studies have been limited when compared with those of aspergillosis. To help investigating the disease, here in this review article, the profile of human zygomycosis is briefly described, followed by a review of the heretofore used animal models of zygomycosis. Among clinically important zygomycetes causing human infection, animal models are available for Absidia corymbifera, Rhizopus oryzae, R. microsporus var. rhizopodiformis, Rhizomucor pusillus and Cunninghamella bertholletiae. Mice are the most commonly used animals, but models using guinea pigs and rabbits are also available. Pretreatment of animals with cyclophosphamide, corticosteroid, alloxan or streptozocine is frequently done to create an immunocompromised state. Treatment with desferrioxamine, an iron chelator, is also used to make animal models. In terms of the route of infection, the airborne route is used for pathophysiological studies in pulmonary infection models, but sometimes intravenous injection is preferred, particularly for antifungal drug studies. When pathophysiological analysis is the purpose of the study, the animals must be cautiously examined both histopathologically and mycologically. For the most part, zygomycosis model studies can be performed in a similar manner to those of aspergillosis. However, Aspergillus spp. and zygomycetes are completely different fungi, and researchers should be aware of the specific, critical aspects when handling zygomycosis models, such as homogenization of infected organs and staining of pathological samples.
Mycopathologia 02/2001; 152(1):5-13. · 1.65 Impact Factor
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ABSTRACT: The lipophilic yeasts Malassezia species are the causative agents of tinea versicolor and known also to be a member of normal skin flora. They are commonly isolated from the skin of humans and animals, but not from the environment. This is the first report of the isolation of Malassezia sp. from the environment (a hospital floor). The results of assimilation tests of lipids and karyotyping showed that these isolates were M. furfur. They assimilated not only lipids including floor wax and car wax but also some ointments (except antifungal agents) used clinically. The results suggest that we need to take care when using such ointments to treat skin diseases.
Nippon Ishinkin Gakkai Zasshi 02/2001; 42(3):123-6.
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ABSTRACT: A yeast, repeatedly isolated from a post-surgical abdominal infection of a 75-year-old Japanese man, was genotyped as Candida dubliniensis. This is the first reported case in Asia of this recently described fungus.
Medical Mycology 03/2000; 38(1):81-3. · 2.46 Impact Factor
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ABSTRACT: Infections caused by Schizophyllum commune have recently been on the increase. We analyzed cases in which this fungus was isolated from clinical samples from 1991 to 1995. Regular morphological methods were first employed in the identification of S. commune, and when necessary, mating was made with a known S. commune isolate. IgG antibodies against S. commune in the patients' serum were determined by the ELISA method. Profiles of the cases were analyzed and the English-language medical literature was reviewed. S. commune was isolated from 12 patients. Eighty three percent of the patients were female, most of which presented with allergy-related pulmonary diseases, i. e. allergic bronchopulmonary mycosis or mucoid impaction of bronchi. IgG antibodies were detectable in nine of eleven patients examined (82%). Fifty eight percent of the isolates were monokaryotic, and therefore, unidentifiable by regular morphological methods. In contrast, analysis of the English literature disclosed that sinusitis is the most common form of infection, and that hyphal invasion into the tissue was seen in 50% of reported cases. Our study shows that S. commune should be regarded as a pathogenic fungus, and is infecting humans much more frequently than previously assumed. Further investigation is warranted.
Nippon Ishinkin Gakkai Zasshi 02/1999; 40(3):175-81.
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ABSTRACT: Pulmonary zygomycosis rarely occurs without pre-existing immunocompromised disease. A 72-year-old male was found to have a nodular shadow (3 cm x 4 cm) in the right S8 and S9 on a chest X-ray. Right lower lobectomy was performed and histological examination of the resected material demonstrated pulmonary zygomycosis. Hyphae stained positively not only with Grocott-Gomori methenamine silver staining, but also with an anti-Rhizopus oryzae polyclonal antibody.
Mycoses 02/1999; 42(11-12):675-7. · 2.25 Impact Factor
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ABSTRACT: A systematic cultural, cytological and microscopic study of voriconazole (VCZ) and fluconazole (FCZ) damage to Cryptococcus neoformans over time was made. When haemocytometer counts were compared with colony-forming units (cfu) viability decreased with increased drug concentration and prolonged treatment time up to 48 h. Percentage viability by vital staining correlated with cfu. Concentrations of VCZ were found to be 10-fold more potent than FCZ. At 72 h, percentage viability increased in cultures with lower drug concentrations, indicating outgrowth of surviving yeast cells. Drug treatment resulted in a cytological change in a large percentage of yeast cells characterized by a large central vacuole easily observed microscopically. Vital staining showed that there was no direct relationship between cytological changes and non-viability. These novel findings add a new approach for studying the antifungal action of VCZ and FCZ against C. neoformans and provide a new perspective on their antifungal action.
Medical Mycology 09/1998; 36(4):227-33. · 2.46 Impact Factor
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ABSTRACT: Voriconazole (VCZ), a new wide-spectrum antifungal triazole currently in development, was tested for activity against Cryptococcus neoformans (CN) var. gattii and var. neoformans in RPMI-1640 (RPMI) or RPMI plus human serum. In RPMI VCZ was 10-fold more inhibitory than FCZ for both varieties of CN. In the presence of human serum neither VCZ nor FCZ had enhanced activity against CN var. gattii. By contrast, both VCZ and FCZ had significantly increased activity in the presence of serum against CN var. neoformans. The lack of serum-enhancing activity for VCZ or FCZ against CN var. gattii may reflect the in vivo situation and predict less efficacy in CN var. gattii infections.
Mycopathologia 02/1998; 142(1):3-7. · 1.65 Impact Factor
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ABSTRACT: We describe, to our knowledge, the first case of allergic bronchopulmonary mycosis (ABPM) caused by the basidiomycetous fungus Schizophyllum commune in an otherwise healthy woman. Bronchoscopic analysis repeatedly disclosed S. commune hyphae in the bronchi of the lingular lobe; these hyphae were originally misidentified as Aspergillus because the presence of clamp connections was overlooked. A lingular infiltrate with ectatic proximal bronchi, eosinophilia, an elevated serum level of IgE, and antibodies to S. commune supported the diagnosis. It is sometimes difficult to isolate and identify S. commune in clinical specimens, and hence only a limited number of cases of ABPM might have been correctly diagnosed in the past. We suspect, therefore, that some cases of ABPM caused by an allergic reaction to S. commune may be misdiagnosed as allergic bronchopulmonary aspergillosis or eosinophilic pneumonia of unknown origin. The significance of S. commune in allergic bronchopulmonary diseases is discussed.
Clinical Infectious Diseases 04/1994; 18(3):305-9. · 9.15 Impact Factor
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ABSTRACT: A case of lymphangiomyomatosis (LAM) in a 35-year-old woman is reported. Because she was already severely dyspneic when she was admitted to our hospital, neither TBLB nor open lung biopsy was performed, and no accurate diagnosis was made. She died of respiratory failure three years after the development of exertional dyspnea, and autopsy revealed LAM. Pneumothorax, a well-known and frequent complication of LAM, did not occur until one month prior to her death. Although pneumothorax frequently complicates LAM, there are a few reports of cases in which pneumothorax did not occur during the course of the disease. We emphasize that LAM should be considered in the differential diagnosis of diffuse interstitial lung disease, even when the patient has no pneumothorax. The retroperitoneal tumor (15 x 10 x 10 cm), which was evident clinically, was later shown to be intra-abdominal involvement of LAM. Although only a few cases of LAM with a large retroperitoneal tumor have been reported, minor intra-abdominal involvement is relatively common. This case also suggested that the finding of a retroperitoneal tumor may be a diagnostic clue in LAM.
Nihon Kyōbu Shikkan Gakkai zasshi 06/1992; 30(5):892-7.
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ABSTRACT: It is well known that some micro-organisms synthesize proteins when stressed by heat or other factors. The function of these proteins is not yet clear, but some of them are believed to be related to resistance against a hostile environment. Histoplasma capsulatum is an intracellular pathogenic fungus that multiplies inside macrophages and resists macrophage microbicidal mechanisms. To study the defense mechanisms of H. capsulatum and mimic the hostile environment the fungus may encounter during infection, we investigated protein synthesis by H. capsulatum (isolate G217B) when stressed by heat (40 degrees C), low pH (pH 4), or oxidative products (H2O2) using [35S]-methionine labelling. Analysis of cytosol proteins by SDS-PAGE and fluorography disclosed that H. capsulatum increased synthesis of six constitutive proteins and decreased synthesis of six proteins when stressed at 40 degrees C. When stressed by pH 4 or H2O2, H. capsulatum increased the synthesis of eight and five constitutive proteins, respectively, and decreased the synthesis of three proteins. Estimation of superoxide dismutase (SOD) and catalase enzymatic activity in cytosols from stressed H. capsulatum did not reveal an increase of these enzymatic activities compared to cytosols from non-stressed H. capsulatum. These results suggest that H. capsulatum increases the synthesis of some constitutive proteins when stressed by heat, low pH or H2O2, which might relate to pathogenicity, and are thus worthy of further study. These induced proteins are apparently different from SOD or catalase.
Journal of medical and veterinary mycology: bi-monthly publication of the International Society for Human and Animal Mycology 02/1992; 30(5):385-93.
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ABSTRACT: The phagocytic and killing activities of human pulmonary alveolar macrophages (PAM) and polymorphonuclear leukocytes (PMN), and superoxide (O2-) production in phagocytizing PAM and PMN were studied by using a strongly and weakly virulent strains of Cryptococcus neoformans (C. neoformans) in mice. The strongly virulent strain was encapsulated with a thick capsule while the other had a thin one. The phagocytic and killing activities of PAM and PMN against the strongly virulent strain were lower than against the weakly virulent one. There was no significant difference between PAM and PMN in terms of phagocytic or killing activities and O2- production. It seems likely that O2- plays no defensive role in the intracellular killing of C. neoformans by PAM and PMN because no correlation was found between the killing activity and O2- production. These results indicate that human PAM and PMN play an effective role in host defense against the weakly virulent strain of C. neoformans encapsulated with a thin capsule but are not effective against the strongly virulent strain encapsulated with a thick capsule.
Nihon Kyōbu Shikkan Gakkai zasshi 10/1991; 29(9):1174-9.
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ABSTRACT: We evaluated the efficacy of Itraconazole (ITZ), a newly developed triazole antifungal agent, in 5 cases of pulmonary aspergilloma. A daily dose of 100-200 mg of ITZ was given orally for 5 to 20 months. In one patient, administration of ITZ was discontinued because of mild and transient hepatic injury. On computerized tomography and conventional roentgenogram of the chest, improvement was clearly observed in 2 of the remaining 4 cases. Symptomatic improvement, mainly disappearance of airway bleeding, was seen in 2 cases. Thus the overall improvement rate was 50% (two out of 4). No adverse response other than the hepatic injury mentioned above occurred. In one patient, who had two fungus balls previously, one of the fungus balls disappeared completely and the other decreased significantly in size during the course of treatment. In this case, the daily dose of ITZ was larger (200 mg once a day) and the plasma concentration of ITZ was extremely higher (2068 ng/ml) than in other cases (137-330 ng/ml). We conclude that ITZ is an efficacious drug in the treatment of pulmonary aspergilloma, and that this drug may be even more efficacious if we keep higher plasma concentration of ITZ.
Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases 08/1991; 65(7):808-12.
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ABSTRACT: The usefulness of cefteram pivoxil (CFTM-PI) was evaluated in 99 cases with respiratory tract infections: 32 cases with acute bronchitis, 51 cases with infectious exacerbations of chronic respiratory diseases and 16 cases with pneumonia. 1. The clinical efficacies included marked improvement in 27 cases, improvement in 51 cases, moderate improvement in 9 cases, no change in 10 cases and deterioration in 2 cases. The improvement rate was 78.8%. 2. Overall effects were excellent in 12 cases, good in 9 cases and fair in 5 cases. There was no case in which efficacy was not observed and the efficacy rate was 80.8%. 3. Bacteriological effects were classified according to the causative organisms. Eradication rate was 80.8% (21 of 26 strains), indicating an excellent antibacterial action of CFTM-PI. In particular, MICs of cefteram were below 0.05 microgram/ml against all 10 strains of Haemophilus influenzae regardless of beta-lactamase production even with an inoculum of 10(8) or 10(6) cells/ml. 4. Side effects rarely occurred and included a slight gastrointestinal irritation in 4 of 99 cases (4%). Two cases which had abnormal elevations of GOT and GPT had abnormal values prior to administration of CFTM-PI. The elevations were slight and it was possible to continue administration. The GOT and GPT values were improved after the end of administration. The above results indicate the usefulness of CFTM-PI in acute respiratory infections and infectious exacerbation of chronic respiratory diseases.
The Japanese journal of antibiotics 03/1990; 43(2):326-36.
