動物由来の皮膚糸状菌を中心に検討を加え,皮膚糸状菌群の生物学的及び系統学的性状を追究した.
まずわが国における皮膚糸状菌症の動物から起因菌を分離同定して菌相を明らかにすると同時にこれらの菌の生態学的特徴を解析した.次に完全世代の観点から菌種の分類同定の重要性を検討し,疫学的および生態学的意義を追究した.また主にキチン合成酵素を対象として分子生物学的検討も行い,各菌種菌株間の関連性を解析し,完全世代による生物学的分類と分子生物学的系統関係の相関性を考察した.

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Trichophyton mentagrophytesの菌液を健常人の踵部角質に塗布し,様々な温度,湿度にて培養し,経時的に観察することにより,菌の角質内侵入に要する時間を検討した.一般に糸状菌培養の至適温度とされる27℃よりも,35℃の方が菌の角質内侵入が早期より観察された.湿度100%では,温度15℃においても菌の侵入が見られたことから,湿度は温度よりも重要な要因であると思われた.T.mentagrophytesとT.rubrumの2種の菌を用いて行った実験では,最も早期に角質内への侵入像が観察された日数は,湿度100%においてT.mentagrophytesで1日,T.rubrumで1.5日,湿度95%においてT.mentagrophytesで1.5日,T.rubrumの4日であった.第4趾間の1日を通じての湿度は95%以下と推定された結果から,毎日足を充分洗浄していれば,足白癬の発症は確実に予防できるものと思われた.角質の切断面に菌液を塗布した系では,100%のみならず95%の湿度においても,両菌共0.5日後に角質内への侵入像が観察された.また,表面側への塗布では侵入像が認められなかった85%以下の湿度においても侵入像が認められた.以上の結果から,微細な外傷による角質細胞膜の破壊は,湿度や温度同様,重要な発症要因である可能性が推測された.

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Partial cDNA cloning of a putative membrane transporter protein gene expressed in Sporothrix schenckii and DNA polymorphism of the isolated gene are described here. DNA fragments were isolated from S. schenckii, and the deduced amino acid sequence from one of the fragments contained a region homologous to the conserved sequence of the membrane transporter protein family. 188-bp fragments encoding the homologous region were amplified from many strains of S. schenckii, and were subjected to polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) analysis. The results demonstrated that the strains of S. schenckii were divided into three groups, and several base substitutions among these groups were observed. This finding agreed with the classification of S. schenckii strains based on the mitochondrial DNA diversity, because the three groups were clearly located on the branches of the phylogenetic tree constructed by digestion profiles of mitochondrial DNA with restriction enzymes. The correlation of the results of PCR-SSCP analysis with the mitochondrial DNA diversity might indicate linkage of the mutation of the membrane transporter protein gene with the evolution of S. schenckii, suggesting the protein plays an essential role in S. schenckii.

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66歳女性の左前腕に生じた黒色真菌感染症の症例を報告した.臨床的に単発性,暗紅色の扁平隆起性小結節を呈し,病理組織像は,真皮から皮下組織におよぶ慢性炎症性肉芽腫で,組織内菌要素としてはsclerotic cellは見られず,菌糸型のみであった.分離菌はExophiala spiniferaと同定された.本菌の感染症は本邦では3例目である.治療はイトリゾール200mg/日の内服と局所の温熱療法を行い,臨床的に治癒したかに見えたが,内服92日目に切除したところ,同菌を検出した.黒色真菌感染症では,小さな病変であれば外科的切除がより確実な治療法であると思われた.

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A 38-year-old Japanese AIDS patient delveloped papular lesions which rapidly increased in number, eroded and crusted, and spread over not only skin but also the mucosal surface. High fever, sore throat, malaise and hepatosplenomegaly were also noted, and he died despite 2 months of intensive treatment. An autopsy revealed numerous histiocytes infected with Penicillium marneffei in the lymph nodes, liver, spleen, bone marrow, skin, and mucosal surface of the oral cavity to the pharynx. This case is thought to be the first Japanese case of penicilliosis marneffei.

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1993年1月から1997年12月末までの間に昭和大学藤が丘病院皮膚科を受診した皮膚粘膜のカンジダ症患者618例に関し,病型,起因菌などについての統計学的検討を行った.過去の報告に較ベカンジダ性間擦疹の比率が増加し,乳児寄生菌性紅斑の比率が低下,爪カンジダ症や絆創膏などの貼付部に生じるカンジダ症など,従来の病型とは異なるカンジダ症が比較的多数認められた.最近の496例については培養を試みた.培養成功率は79.2%であった.その多くはCandida albicans serotype Aであった.全症例の中で,悪性腫瘍などの免疫不全と関連する疾患および状態の保有率は22.7%,脳神経疾患などの長期臥床と関連する疾患および状態の保有率は23.3%であった.

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A patient treated with itraconazole (ITCZ) under the diagnosis of Aspergillus flavus-induced chronic hypertrophic pachymeningitis is presented. The reason for the successful cure of this patient was investigated by the pharmacokinetic analysis of serum levels of ITCZ. Concurrently administered digoxin was also investigated for its drug-drug interaction.
The patient (a 75-year-old male) developed ophthalmopathy, and was diagnosed as having A. flavus hypertrophic pachymeningitis by pachymeninx biopsy. After admission, he was treated with FLCZ, AMPH, 5-FC and MCZ. The infection tended to subside with the AMPH administration. Since renal insufficiency was induced by AMPH and the other antifungal drugs were ineffective, daily administration of 200mg of ITCZ was initiated, and the inflammatory signs and symptoms gradually subsided. The symptoms did not recur during the 36 months of itraconazole treatment after discharge, and it was concluded that ITCZ was effective for A. flavus hypertrophic pachymeningitis.
Pharmacokinetic parameters of ITCZ and OH-ITCZ as follows: ITCZ: C_max 93.2ng/ml, T_1/2β 11 hours, AUC_0-24 999ng·h/ml, OH-ITCZ: C_max 159.4ng/ml, T_1/2β 16.2 hours, AUC_0-24 of 1391ng·h/ml. Both ITCZ and OH-ITCZ reached steady states seven days after administration began. The ITCZ and OH-ITCZ levels in serum collected 36 months after the initiation of administration were 452.9ng/ml and 1233.6ng/ml, respectively. C_max and AUC_0-24 of ITCZ and OH-ITCZ on the second day were markedly lower than those in healthy adults reported by Oguchi et al., and hypoalbuminemia observed at administration on that day was considered the most probable cause. It was assumed that the most plausible reason for a successful cure even at a low dose of ITCZ was the increase of distribution to tissue by the increase of the unbound form.
Digoxin was concurrently given to this patient at 0.125mg/day, but the blood digoxin level was not elevated.
Consideration of the blood level of albumin is believed to be important for evaluating the blood concentration of ITCZ.

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Aspergillus fumigatus is an opportunistic pathogen, especially in an immunocompromised host. This fungus grows in a hyphal form in infected tissues; therefore, new tests to examine hyphal susceptibility are needed. In this study, we measured the mycotic activity of miconazole (MCZ) contained in human serum against A. fumigatus using the BioCell-Tracer method. Three serum samples were obtained from the same patient who was injected with 600mg b. i. d. MCZ daily for 2 days. The concentrations of MCZ in the serum sample were 8.8, 3.5, and 1.6μg/ml, respectively.
The serum containing 8.8μg/ml of MCZ inhibited hyphal growth 90 minutes after administration, and the hypha stopped growing. The serum containing 3.5μg/ml MCZ stopped hypha growth 100 minutes after administration, but re-growth of the hypha was observed at this concentration of MCZ. Serum containing 1.6μg/ml did not inhibite hyphal growth, nor did control serum have any inhibitory activity foward hyphae. Based on these results, we conclude that the BioCell-Tracer is a useful method for determining the effects on filamentous fungi of antifungal agents in the serum.

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