Medical Mycology Journal
Online ISSN : 2186-165X
Print ISSN : 2185-6486
ISSN-L : 2185-6486
Volume 58, Issue 4
Displaying 1-10 of 10 articles from this issue
Medical Mycology Journal
Original Article
  • Yuichiro Kurone, Ken-ichi Ishibashi, Daisuke Yamanaka, Noriko N. Miura ...
    2017 Volume 58 Issue 4 Pages E121-E129
    Published: 2017
    Released on J-STAGE: November 30, 2017
    JOURNAL FREE ACCESS
    Aspergillus is a medically important fungal genus that causes a life-threatening infection known as aspergillosis in immunocompromised patients. β-1,3-Glucan is detected in the plasma of patients with aspergillosis and appears to be useful for the diagnosis of aspergillosis. In this study, we cultured Aspergillus spp. in a chemically defined liquid medium and prepared an Aspergillus water-soluble fraction (ASWS) from the culture supernatants. ASWS was found to be primarily composed of polysaccharides and proteins. Nuclear magnetic resonance analysis suggested that ASWS is a complex carbohydrate, consisting of α-1,3-glucan, β-1,3-glucan, galactomannan, and protein. The ASWS from Aspergillus fumigatus showed limulus factor G activity, whereas zymolyase-treated ASWS did not. ASWS was eliminated from the blood more rapidly than Aspergillus solubilized cell wall β-glucan. We analyzed the reactivity of human immunoglobulin towards ASWS by an enzyme-linked immunosorbent assay. Anti-ASWS antibodies were detected in human sera, with titers differing among individuals. This study demonstrated that the ASWS corresponds to the limulus factor G-activating substance found in the blood of patients with aspergillosis.
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Review
  • Yasuhiko Matsumoto, Masaki Ishii, Kiminori Shimizu, Susumu Kawamoto, K ...
    2017 Volume 58 Issue 4 Pages E131-E137
    Published: 2017
    Released on J-STAGE: November 30, 2017
    JOURNAL FREE ACCESS
    The development of effective drugs against fungal diseases involves performing infection experiments in animals to evaluate candidate therapeutic compounds. Cryptococcus neoformans is a pathogenic fungus that causes deep mycosis, resulting in respiratory illness and meningitis. Here we describe a silkworm system established to evaluate the safety and efficacy of therapeutic drugs against infection by Cryptococcus neoformans and the advantages of this system over other animal models. The silkworm assay system has two major advantages: 1) silkworms are less expensive to rear and their use is less problematic than that of mammals in terms of animal welfare, and 2) in vivo screenings for identifying candidate drugs can be easily performed using a large number of silkworms. The pharmacokinetics of compounds are consistent between silkworms and mammals. Moreover, the ED50 values of antibiotics are concordant between mammalian and silkworm infection models. Furthermore, the body size of silkworms makes them easy to handle in experimental procedures compared with other invertebrate infectious experimental systems, and accurate amounts of pathogens and chemicals can be injected fairly easily. These advantages of silkworms as a host animal make them useful for screening candidate drugs for cryptococcosis.
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Short Report
  • Kazuko Okamoto-Shibayama, Yuichiro Kikuchi, Eitoyo Kokubu, Kazuyuki Is ...
    2017 Volume 58 Issue 4 Pages E139-E143
    Published: 2017
    Released on J-STAGE: November 30, 2017
    JOURNAL FREE ACCESS
    Surface antigen protein 2 (Csa2) is a member of the Candida albicans Common in Fungal Extracellular Membranes (CFEM) protein superfamily. We previously established its role in iron acquisition in C. albicans. However, the other roles of Csa2 remain unknown. Here, we compared growth, morphological transition, and biofilm formation among wild-type, Csa2-mutant, and complemented strains of C. albicans. Deletion of the Csa2 gene resulted in smaller and reduced colony growth, significant attenuation of the dimorphic transition under serum-inducing conditions, and reduced biofilm formation; complementation restored these levels to those of the wild-type. Our findings demonstrated that Csa2 participated in yeast-to-hyphae morphological switching under serum-inducing conditions and contributed to the biofilm formation of C. albicans. This work, therefore, provides novel insights into the potential roles of Csa2 in virulence of C. albicans.
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Nippon Ishinkin Gakkai Zasshi
Original Articles
  • Eri Ikeda, Soko Watanabe, Mizuki Sawada, Junya Ninomiya, Itaru Dekio, ...
    2017 Volume 58 Issue 4 Pages J105-J111
    Published: 2017
    Released on J-STAGE: November 30, 2017
    JOURNAL FREE ACCESS
      67-year-old female patient developed drug-induced liver dysfunction after taking oral itraconazole (ITCZ) for the treatment of kerion celsi. Red papules appeared on the temporal area of the patient one month prior to her visit to our clinic. The patient presented with a nodule with yellow crust, erosion, infiltration, and hair loss on the area. Diagnosis of kerion celsi caused by Trichophyton rubrum was made from clinical, pathological, and mycological findings. Laboratory data showed normal liver function, and the patient was not taking any other medication, thus, daily oral ITCZ 100 mg was started. The skin lesion improved, but severe liver dysfunction was found 1 month after starting ITCZ. Oral ITCZ was therefore terminated, and the patient was admitted to a medical ward for the treatment of liver dysfunction. Hepatobiliary enzymes increased after admission: AST 232 IU/L, ALT 465 IU/L, T-bil 6.1 mg/dL, and D-bil 3.9 mg/dL. The patient was kept at rest and was given oral ursodeoxycholic acid. Hepatobiliary enzymes returned to normal level 2 1/2 months after starting ITCZ. The skin lesion healed without further treatment. No recurrence was observed. It is noteworthy that liver function has to be carefully monitored during treatment with oral ITCZ.
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  • Masayuki Hasuko, Ryo Shiomi, Yoshinori Takahashi, Kazuhiko Motoba, Hir ...
    2017 Volume 58 Issue 4 Pages J113-J119
    Published: 2017
    Released on J-STAGE: November 30, 2017
    JOURNAL FREE ACCESS
     Affinity of Luliconazole (LLCZ), an antifungal drug used for topical treatment of onychomycosis in Japan, to nail keratin was demonstrated. Efinaconazole (EFCZ) was used as a reference drug. Drugs at fixed concentrations were added to 4 ml of buffer solution containing 40 mg of nail keratin powder prepared from healthy volunteers or from tinea unguium patients. The mixtures were shaken at 37℃, and adsorption and desorption rates of the drug in nail keratin were measured. Theoretical analysis using the Freundlich adsorption isotherm was applied to eliminate effects of testing conditions on the results. Results showed that compared with EFCZ, LLCZ exhibited high adsorption rates and low desorption rates in nail keratins. These results were verified by Freundlich analysis, in which adsorption coefficient (KadsF) and desorption coefficient (KadsF) of LLCZ were 5–7 times and about 2 times higher than EFCZ, respectively. In addition, antifungal activity against Trichophyton rubrum of the desorbed LLCZ samples was determined using disk diffusion assay. In conclusion, LLCZ is considered to possess high affinity to nail keratin. LLCZ, therefore, can be retained in the nail as a reservoir and continuously desorbed at the infection site to exhibit antifungal activity against pathogenic fungi. The pharmacokinetics of LLCZ in the nail is believed to differ from that of EFCZ. As adsorption and desorption rates of the two drugs in nail keratin tended to be different between healthy volunteers and patients, further detailed study is needed.
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Reviews
  • Rui Kano
    2017 Volume 58 Issue 4 Pages J121-J126
    Published: 2017
    Released on J-STAGE: November 30, 2017
    JOURNAL FREE ACCESS
     Canine and feline upper respiratory tract (URT) infection due to Aspergillus spp. is considered an emerging disease, with the number of reported cases continuing to rise in Japan. Aspergillus fumigatus has been the most frequently reported etiologic agent of sino-orbital aspergillosis in dogs and cats; the other Aspergillus species, Aspergillus felis, Aspergillus fischeri, Aspergillus udagawae, Aspergillus viridinutans, and A. fumigatus, have also been implicated in feline cases. The minimum inhibitory concentrations (MICs) of antifungal drugs are elevated for these cryptic species compared with A. fumigatus. Some reports showed that the feline infections due to cryptic species did not respond to treatment with antifungal drugs. These results suggest that species identification and antifungal susceptibility testing of infecting agents are important to ensure effective treatment of feline URT aspergillosis.
     Feline cryptococcosis in Japan is typically attributed to Cryptococcus neoformans var. grubii. We isolated a fluconazole-resistant strain of C. grubii from a feline cryptococcosis. The predicted amino acid sequence of the lanosterol 14-α demethylase gene (ERG11) protein in the isolate was identical to that of the C. grubii reference strain. RT-PCR analysis of ERG11 and ATP binding cassette (ABC) transporter-encoding gene (AFR1) indicated that the isolate had increased transcription factor function for ERG11 and AFR1 compared with fluconazole-susceptible strains. This observation, in combination with the lack of resistance to other azoles (that is, lack of cross resistance), suggests that resistance in our isolate was the result of overexpression of the endogenous ERG11 and ABC transporter.
     Further ecological and epidemiological studies on small animal mycoses in Japan are needed to monitor the emergence of antifungal drug resistant strains.
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  • Masatomo Kimura
    2017 Volume 58 Issue 4 Pages J127-J132
    Published: 2017
    Released on J-STAGE: November 30, 2017
    JOURNAL FREE ACCESS
     Fungal sinusitis is divided into two categories depending on mucosal invasion by fungus, i.e., invasive and noninvasive. Invasive fungal sinusitis is further divided into acute and chronic disease based on time course. Noninvasive fungal sinusitis includes chronic noninvasive sinusitis (fungal ball type) and allergic fungal sinusitis. Chronic noninvasive sinusitis is the most predominant fungal sinusitis in Japan, followed by allergic fungal sinusitis. Invasive fungal sinusitis is rare. Hyphal tissue invasion is seen in invasive fungal sinusitis. Acute invasive fungal sinusitis demonstrates hyphal vascular invasion while chronic invasive fungal sinusitis usually does not. Fungal tissue invasion is never found in noninvasive sinusitis. A fungal ball may exist adjacent to sinus mucosa, but its hyphae never invade the mucosa. Fungal balls sometimes contain conidial heads and calcium oxalate, which aid in identifying the fungus in the tissue. Allergic fungal sinusitis is characterized by allergic mucin that is admixed with numerous eosinophils and sparsely scattered fungal elements. Histopathology is important in classifying fungal sinusitis, especially in confirming tissue invasion by the fungus.
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  • Masato Tashiro, Koichi Izumikawa
    2017 Volume 58 Issue 4 Pages J133-J139
    Published: 2017
    Released on J-STAGE: November 30, 2017
    JOURNAL FREE ACCESS
     The human body is a hostile environment for Aspergillus species, which originally live outside the human body. There are lots of elimination mechanisms against Aspergillus inhaled into the human body, such as high body temperature, soluble lung components, mucociliary clearance mechanism, or responses of phagocytes. Aspergillus fumigatus, which is the primary causative agent of human infections among the human pathogenic species of Aspergillus, defend itself from the hostile human body environment by various mechanisms, such as thermotolerance, mycotoxin production, and characteristic morphological features. Here we review mechanisms of defense in Aspergillus against elimination from the human body.
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  • Taminori Obayashi
    2017 Volume 58 Issue 4 Pages J141-J147
    Published: 2017
    Released on J-STAGE: November 30, 2017
    JOURNAL FREE ACCESS
     In 1985, a (1→3)-β-D-glucan assay based on the discovery of a (1→3)-β-D-glucan-sensitive coagulation factor in the horseshoe crab amebocytes was developed in Japan, as a test aid in the diagnosis of invasive fungal infections. After many clinical trials, it has now been incorporated in practice guidelines both in Japan and abroad for the diagnosis and management of invasive fungal infection, and is now available worldwide. In Japan, however, two commercial kits that differ widely in sensitivity to (1→3)-β-D-glucan are used; namely, the colorimetric and the turbidimetric assays. Thus, attention must be paid when comparing measurement values between the two tests. In most cases, one pg/ml of the latter corresponds to about 7 pg/ml of the former. This raises the cutoff value of the turbidimetric assay far higher than that of the colorimetric assay, raising concern about missing many true cases of invasive fungal infections. The detection limit of the turbidimetric method is equivalent to as high as 60 pg/ml if converted to the colorimetric measurement. Thus, early diagnosis will be difficult to make based on detection of a rise in the β-D-glucan level in the lower range of concentration. The kits used overseas also differ in sensitivity; thus, global standardization or harmonization will be required to establish inter-assay data comparability and to enhance the usefulness of the tests. In the future, genetic engineering may provide an alternative source of the coagulation pathway enzymes other than the horseshoe crabs, in accordance with the global trends in animal protection, and bring about new opportunities for standardization.
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