亀井 克彦

Gliotoxin, one of the mycotoxins produced by Aspergillus fumigatus, has various, potent bioactivities. However, it has not been considered to be a toxic (or virulence) factor because of its slow production. The aim of the present study was to investigate the effects of aeration on the cytotoxicity of A. fumigatus culture filtrate, and to determine the optimal condition for the rapid production of gliotoxin from this fungus. Fungal culture filtrates were made in three different containers under various conditions of aeration and O-2 concentration. These filtrates were compared in terms of their cytotoxicity on murine macrophages and analyzed by gas chromatography. The culture filtrate showed high cytotoxicity when it was made under highly aerated conditions, but it was significantly less cytotoxic when prepared under non-aerated conditions. The cytotoxic activity became evident within 15 h of culture at 20% O-2, when the fungus had already started producing gliotoxin. The culture filtrates also contained some other as yet unidentified substances that might also to some extent contribute to the cytotoxicity. In light of these results, the authors propose that a highly aerated condition is responsible for the rapid production of gliotoxin, and that gliotoxin might play an important role in the respiratory infection by A. fumigatus, with other toxic substances acting additively or synergistically.

The lesions of histoplasmosis in dogs in Japan differ from those in dogs in North America. Affected dogs in Japan have had multiple granulomatous or ulcerated foci in skin or gingiva and have not had pulmonary or gastrointestinal lesions. The present report introduces a polymerase chain reaction (PCR) diagnosis of canine histoplasmosis and the characteristic of disease in Japan. The surgically removed skin ulcerate samples from a 5-years-old female Shiba-inu native to Japan without traveling out of the country were evaluated. Tissue samples had many yeast-like organisms in the macrophages. DNA was extracted from paraffin-embedded tissue samples. A nested PCR technique was applied. The detected sequence of the internal transcribed spacer of ribosomal RNA gene had 99.7% in homology with Ajellomyces capsulatus (the teleomorph of Histoplasma capsulatum). Clinical manifestations, historical background of equine epizootic lymphangitis in Japan, and a human autochthonous case of histoplasmosis farciminosi indicated that this dog might have been infected with H. capsulatum var. farciminosum as a heteroecism.

Invasive aspergillosis has become a serious problem in clinical practice, but the actual factor that confers virulence on the fungus has not been thoroughly elucidated. To identify and isolate the immunosuppressive substances produced by the fungus, the bioactivity of culture filtrates was assessed, and analyses of the culture filtrates were carried out. Culture filtrates from different strains of Aspergillus fumigatus were assessed for their effect on human polymorphonuclear leukocytes and murine macrophages. To assess their activities in vivo, their effect on the survival of mice infected by the fungus was also studied. Subsequently, the composition of the culture filtrates was analyzed by gas chromatography-mass spectrometry. The analyses revealed that the culture filtrates contained gliotoxin at concentrations of 3 to 4μg/ml, and some other unidentified compounds. The bioactivities of the culture filtrates were similar to those of gliotoxin. The fungal culture filtrate reduced the survival of infected mice, but the filtrate itself did not cause the death of mice. However, all the bioactivities could not be accounted for by gliotoxin itself. These results indicate that gliotoxin in the culture filtrates may be responsible for part of the immunosuppressive activity, but some other components produced by A. fumigatus contribute, in an additive or synergistic manner, to the virulence of the fungus.

Animal bones after being devitalized at death are strongly resistant to wear and tear and remain in the soil or environment much longer than other organic components from dead animals. Yet over the course of time they seem to disappear and thus our ecological surroundings are not cluttered with bone remnants. Mechanical factors creating compression or friction and chemical factors like pH of the soil and surroundings must together have provided concerted degrading effects. Microorganisms in the soil also help in this process by utilizing the organic components of devitalized bones. Certain highly pathogenic fungi that have been collected from soil from time to time and many other environmental fungi may take part in the degrading of the bone remnants. In this study, several strains from the highly pathogenic dimorphic fungi Coccidioides immitis, Blastomyces dermatitidis, Histoplasma spp., Paracoccidioides brasiliensis and also some strains of dematiaceous fungi (Exophiala spp. and Foncecaea pedrosoi) were inoculated to dissected and devitalized murine long bones that had been placed on solidified water agar plates to see if they would survive, grow and invade the bones. After being kept for 12 weeks at 25°C all the parts of the histological sections of these bones showed invasion by most of the strains used in this study, although the cortical component of the bony architecture seemed to be comparatively resistant to invasion. Their ability to grow and sporulate in the aforementioned nutrient-limiting condition hinted at a possible role of these fungi in the degradation of devitalized bones.

Pathogenic fungi that are non-native in Japan are highly virulent and present a significant health hazard to persons in the environment into which they are introduced. Little is known, however, about the precise trend of infection by imported mycoses in Japan. To clarify this issue, all available cases were collected through a search of MEDLINE and Japana Centra Revuo Medicine and analyzed. Also included in this analysis were cases not reported in the literature for which the authors provided identification of the fungi, diagnosis, or treatment. The analysis revealed that, for three diseases, the number of imported mycoses cases in Japan is much higher than previously reported: 31 cases of coccidioidomycosis, 34 cases of histoplasmosis, and 17 cases of paracoccidioidomycosis. Additionally, one case of penicilliosis marneffei was found. The most rapid increase in the incidence of these mycoses occurred from 1991 to 1995. Analysis of the patients' profiles provided the following information: (1) coccidioidomycosis infection in Japan is increasing very rapidly, (2) Japan might be an endemic area of histoplasmosis infection, (3) histoplasmosis is a potentially fatal disease; and (4) reliable serodiagnostic methods have been used only infrequently. Because of the increase of international travel and immigration, the incidence of imported mycoses in Japan is expected to continue rising, and mycoses that have never been reported in Japan, such as blastomycosis, might also be encountered in the near future. To cope with this newly emerging health problem to residents of Japan, the Japanese medical system must train its members to identify and treat mycoses.

The role of chlamydospores in the conversion process from a mycelial-to-yeast form using the slide culture method was studied. Three clinical isolates and two other isolates from armadillo, belonging to the fungal species Paracoccidioides brasiliensis, were cultured on Sabouraud dextrose agar (SDA), potato dextrose agar (PDA) and brain heart infusion dextrose agar (BHIDA). Initially, the mycelial forms of each isolate were grown at 25°C for 7, 14, 30 or 60 days on slide cultures and then the temperature was shifted to 35°C. Interestingly, the slide cultures of all the isolates at 25°C formed chlamydospores on either SDA or BHIDA, whereas, on PDA medium, aleurioconidia were formed. If the slide cultures on BHIDA were incubated at 35°C for 7 to 14 days, multiple budding forms could be observed. This phenomenon was not evident in the slide cultures of SDA or PDA. The results of this morphological study indicate that in P. brasiliensis, chlamydospores may play an important role in the conversion process from a mycelial-to-yeast form.

Nocardia sp. IFM 0896, an actinomycete with biochemical characteristics that differed from Nocardia brasiliensis, was isolated from a 71-year-old Japanese man with a history of tuberculosis and cancer. Although the isolate was tentatively identified as N. brasiliensis, the morphological and physiological characteristics of strain IFM 0896 were different from those of N. brasiliensis IFM 0236T. The results of 16S rRNA gene sequence phylogenies and PCR-RFLP analysis of a heat shock protein revealed that Nocardia sp. IFM 0896 belongs to the species N. pseudobrasiliensis. This is the first clinical isolation report of N. pseudobrasiliensis in Japan.

500床以上の一般病院508施設の感染症担当医を対象にアスペルギルス症の発生動向についてアンケート調査を実施し143施設163名の医師から回答が得られた.その結果,アスペルギルス症の診断・治療では3/4以上の医師が困った経験を有しており,診断では画像所見で本症が疑われても菌の分離ができず確定診断が困難な点が最も多く挙げられた.治療では使用可能な抗真菌薬が限られている点とアムホテリシンBの副作用が強いことが挙げられた.経験した疾患では肺アスペルギローマ,次いで侵襲性肺アスペルギルス症が多く,播種性アスペルギルス症の肺以外の感染臓器としては肝,脳,腎,心臓の順で多かった.アスペルギルス症の診断基準については,胸部X線等の画像,鏡検,血清検査,培養などを用いられていたが,診断基準の数が7〜8種類と多く,本症の診断の困難さを表していた.以上のことからアスペルギルス症の特異的診断法の開発と副作用のない新しい殺菌性抗菌薬の開発が必須であると考えられた

Paracoccidioidomycosis (PCM) is a deep mycosis caused by the thermo-dependent dimorphic fungus Paracoccidioides brasiliensis and is prevalent in Latin American countries. Diagnosis of PCM is sometimes difficult outside the endemic countries, thus a rapid and conclusive method for diagnosis of PCM has been anticipated. We compared the sensitivities of a nested PCR method for detecting the gp43 gene and a commercial kit for detecting (1 3) -j9-D-glucan in the blood of experimentally infected mice. Blood samples were collected from mice at 0 (soon after inoculation), 6, 12, 24, 48, and 72 hours and 5, 7, 10, 14, 17, 21, 24, 28 and 56 days after the intravenous inoculation of 106 yeast cells of P. brasiliensis, and were separated into clots and plasma. The (1→3) -β-D-glucan detection kit in the plasma showed positive reactions in some samples within 7 days and 28 and 56 days after infections. In contrast, the PCR method was more sensitive than the (1→3) -β-D-glucan detection kit throughout the observation period. The clot samples yielded more sensitive PCR-results than did the plasma samples. Although 24 hours is required for the PCR detection, it was confirmed to provide an accurate diagnosis of PCM.

Aspergillus fumigatus causes serious, life-threatening human infection, and is one of the most important pathogenic fungi. Little is known, however, about its mechanism of infection or its virulence factors. To learn about its virulence factors, the effect of the culture filtrate of A. fumigatus on macrophages was studied. When cocultured with A. fumigatus in 96-well microplates, murine peritoneal macrophages showed significant morphological changes indicating serious cellular damage, even when the macrophages were not in direct contact with the fungus. Then culture filtrates of Aspergillus spp., A, fumigatus, A. lavus, A. terreus and A. niger, were prepared by culturing the fungus in 96-well or 24-well microplates for 24 h, and the effect of the culture filtrates was determined by culturing macrophages with or without culture filtrate. When cultured with the culture filtrate of A. fumigatus at a concentration of 1 % or higher, macrophages demonstrated significant morphological changes, leading to their death. Treatment with heat greatly lowered the activity of the culture filtrate. In contrast, culture filtrates of A. terreus and A, flavus showed no detectable effect on macrophages, whereas A. niger did display a similar, but much weaker effect. Our study strongly suggests that A. fumigatus releases a toxic product (s) in the medium very rapidly, and this may be critically involved as the virulence factor in human infection, at least in part, by causing serious injury to macrophages.

ヒストプラズマ症は世界的に分布する真菌症で,日本では輸入真菌症の一つとして取り扱われており,ヒトの症例はこれ迄に30症例以上が報告されており,イヌでも国内感染例が1例報告されている.筆者らは東京都で飼育の雄,ミニチュアダックスフント(2歳7ヵ月)の肉芽腫性病変と熊本県で飼育の雌,シーズー(2歳4ヵ月)の顔面皮筋から,マクロファージ内に寄生しているヒトプラズマ様の酵母細胞を確認した.これらの病理組織のパラフィンブロックより抽出したDNAからリポソームRNA遺伝子のinternal transcribed spacer領域をPCR法により検出し,その塩基配列がAjellomyces capsulatusの同遺伝子領域と97.4%一致することを確認した.このことからこれらのイヌはA.capsulatusの不完全型であるHistoplasma capsulatusの感染であることが判明したが,これらのイヌは輸入歴や渡航歴がなく,国内で感染したと推測されるので,今後の疫学的調査が重要と考えられた

深在性真菌症に対する医療従事者の意識調査ならびに真菌血症についてアンケート調査を行い,253施設から回答を得た.その結果,意識調査においては,感染症法の四類感染症に規定されたコクシジオイデス症(輸入真菌症)が,保健所への届出が義務づけられた全数把握の感染症であることを知っていた医師が過半数に達していなかった.又,真菌症の診断は主に培養と鏡検に基づいて行われている一方で,診断基準の数は7〜8種類と多く,診断がいかに困難であるかを反映する結果となった.又,深在性真菌症の最近5年間の発生状況を知る為の調査では,真菌血症由来の菌種ではC.albicansが最も多く,それ以外の菌種ではC.glabrataやC.kruseiに僅かではあるが増加傾向がみられた.以上より,深在性真菌症の増加が指摘されている中で,今回の調査では真菌血症が減少傾向にあるという矛盾した結果が得られた

大学病院内の病棟や廊下,ナースステーションなどから分離されたMalassezia furfurの脂質資化性について調べた.その結果,油脂,ワックス,パラフィンなど様々な脂質を資化し,又,軟膏やクリームなど各種外用薬剤でも増殖がみられたことから,臨床現場におけるこれらの薬剤使用に際しては本菌の消長に注意を払う必要があると考えられた

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 muM, 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 greater than or equal to 200 muM 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.

51歳女.咳嗽,喀痰を主訴に近医を受診し,末梢血好酸球増多および胸部X線像で左上葉無気肺を認めた.気管支鏡にて粘液栓子の除去を行い無気肺は改善した.病理組織学的には好酸球浸潤と真菌菌糸を伴うmucoid impactionであり,喀痰培養によりSchizophyllum commune(スエヒロタケ)を分離し,本菌によるアレルギー性気管支肺真菌症様の病態を伴った気管支粘膜塞栓(MIB)と診断した.無治療で経過観察したが症状,陰影の増悪はなく退院となった.以後外来通院していたが,約8ヵ月後に咳嗽,喀痰が再度出現して右中葉無気肺を認め,気管支洗浄液からS.communeとAspergillus nigerが培養された.症状はitraconazole 200mg/日の投与で改善した.S.communeは肺真菌症の原因菌としては稀であり,文献的考察を加えて報告した

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.

A 51-year-old female was admitted to our hospital because of fever, cough, and hemoptysis. A chest radiograph showed a partial collapse of the left upper division and infected bullae in the left upper lobe. Bronchoscopic examination showed thick mucous plugs in the left upper bronchus. The isolates of the plugs proved to be Schizophyllum commune. Neither accumulation of eosinophils nor Charcot-Leyden crystals were present in the plugs. Mild ectatic changes of the left upper bronchus had been observed 17 years previously. We describe the first case of mucoid impaction, which was independent of the immunological reactions, caused by S. commune in association with bronchiectasis. (Internal Medicine 39:160-162, 2000)

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.

原因菌の検出或いは同定を目的として本センターに依頼のあった菌株を対象とし,通常の形態学的検討に加え交配試験を適宜併用して同定を行った.次いでSchizophyllum communeが分離された患者のプロフィール,臨床経過などを総合的に検討した.血清中のIgG抗体はS.communeから作成した抗原を用いELISA法にて判定した. 1)依頼された真菌(及び検体)の中で12例から本菌が検出された. 2)患者の約83%が女で,また92%が40歳以上であった. 3)全症例の約83%でアレルギー性気管支肺真菌症ないしはmucoid impaction of bronchi様の病態を呈していた. 4)血清中の抗体は82%の患者に検出された. 5)分離された本菌の58%が,通常の形態学的手法では同定不可能な一核菌糸体であった. 6)海外で紹介された症例の検討では,13例の文献的報告があり,多くは副鼻腔病変であったが,わが国と異なり半数は侵襲性病変を呈していた

A 69 yr old female was hospitalized for further examination of abnormal shadows on chest radiographs. She had a history of tuberculous pleurisy, rheumatoid arthritis and gold-induced interstitial pneumonia. On admission she still suffered from rheumatoid arthritis. A chest computed tomography scan on admission showed clusters of small nodules in subpleural regions of both lungs combined with bronchiectasis. Mycobacterium avium complex was cultured repeatedly from the sputum. Bronchoscopic examination disclosed white-yellow polypoid lesions in the orifice of the left B4 bronchus. Cultures of the brushing specimen of the polypoid lesions and bronchial aspirates from the B4 bronchus yielded smoky-grey mycelial colonies that were later identified as Scedosporium apiospermum. It was concluded that the polypoid bronchial lesions due to Scedosporium apiospermum were formed in the preexisting dilated bronchus caused by Mycobacterium avium complex pulmonary disease.

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 aias 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.

肺結核の既往があり，糖尿病，アルコール性肝硬変を有する 62 歳の男性が，平成 8 年 9 月中旬より 微熱，咳嗽，喀痰，血痰が出現し，同年 10 月 15 日に喀血し入院した.X 線学的に右上中肺野の濃い浸潤 影と肺結核遺残空洞及びその内腔に菌球を思わせる結節影を認め，気管支鏡で右上葉支からの出血を確認し た.喀痰や気管支洗浄液から糸状菌が検出され，Pseudallescheria boydii と同定された.miconazole 400 mg􏰀日の投与により，投与 4 日目以降の喀痰培養及び 29 日目の気管支洗浄液の培養から菌は消失した.胸 部 CT 上菌球様構造物も消退したため，miconazole の投与は 2 カ月間で終了した.その後も喀痰から菌は 検出されず，順調に経過した.本症例における感染と喀血には，糖尿病と栄養障害による免疫能低下とアル コール性肝硬変による血液凝固能低下が関与したものと考えられる.肺シュードアレシェリア症の報告は少 なく，貴重な症例と考えられる.

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.

51歳女.紅皮症に発症したCunninghamella bertholletiae(C.bertholletiae)による肺ムコール症を,文献的考察を加えて報告した.C.bertholletiaeによる感染症の報告例は極めて少なかったが,近年報告数は次第に増加しつつある.更にC.bertholletiaeの培養,同定が容易でないことを考慮すると,本症が過去に同定不能の真菌症,或いは単なるムコール症として処理されてきた可能性がある.臓器移植,AIDS等の増加に伴い今後とも本症の増加が予想されること,更に多くの症例が急速,かつ,重篤な経過を辿っていることを考慮すると,今後十分な注意が必要である

72歳女性. 平成元年9月左下葉無気肺にて入院, 気管支鏡的に粘液栓の除去を行い無気肺の改善を認め, 病理組織学的に肺真菌症の診断を得た. 組織学的にはアスペルギルスが疑われるも確定診断には至らなかった. amphotericin B ネブライザー吸入, flucytosine 経口投与により軽快退院. 平成6年8月中旬より全身倦怠感を自覚し近医を受診. 末梢血好酸球増多を指摘された. 数日後呼吸困難感出現し再び近医受診. 胸部X線写真上異常陰影を指摘され当院紹介入院となった. 左上葉無気肺を認め, 好酸球増多を伴うことより肺真菌症の再発を考え, 気管支鏡を施行した. 左上葉を閉塞する白色粘液栓を認め経気管支鏡的に抜去した. 粘液栓の病理組織学的検索では著明な好酸球浸潤と菌糸を認めた. 気管支鏡検体の培養よりスエヒロタケを同定し本菌によるABPMと診断した. 深在性肺真菌症の原因として本菌が同定されるのは, 極めて稀なため文献的検討を加え報告する.

チオグリコレート培地により,ICRマウスの腹腔マクロファージを誘導,分離した後,flucytosineの存在下でC.kruseiを加え,24時間後に逆培養しcolony unit数から抗菌力を判定した.1)マクロファージはC.kruseiに対し静菌作用を有する,2)flucytosineはC.kruseiに対し単独では0.1-1μg/mlの範囲では有意な抗菌作用を示さず,10μg/mlに至って初めて抗菌作用示す,3)マクロファージの存在下では,flucytosineは単独投与の場合の1/100の濃度に当たる0.1μg/mlの濃度から抗菌作用を示すこと,等が示された.この結果から,マクロファージとflucytosineがin vitroで協同作用を持っていることが明らかになった

It is known that Histoplasma capsulatum can resist the intraphagolysosomal environment and multiply inside macrophages. This resistance can be closely related to its pathogenicity. The mechanism of this resistance has been investigated, but it has not been clarified as yet. To learn about the metabolic condition of the yeast-form of H. capsulatum (isolates G217B and CDC 105) when ingested by macrophages, we investigated protein synthesis by ingested H. capsulatum with [35S]-methionine labeling. Cycloheximide at 5 to 10 micrograms/ml was used to preferentially inhibit macrophage uptake of [35S]-methionine without affecting H. capsulatum uptake. Protein synthesis by H. capsulatum in medium alone served as a positive control. The negative control consisted of macrophages with ingested heat-killed H. capsulatum. Analysis of cytosols with SDS-PAGE and fluorography disclosed that, respectively for G217B and CDC 105, ingested H. capsulatum synthesized 4 and 5 novel proteins, increased the synthesis of 9 and 17 proteins and decreased the synthesis of 9 and 10 constitutive proteins. Ten of these novel or increased proteins were apparently common to both strains. These metabolic changes in ingested H. capsulatum could reflect its adaptation to the intraphagolysosomal environment of macrophages and its ability to multiply there.

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.

Human pulmonary alveolar macrophages (PAM) play an important role in the anti-fungal pulmonary defense. To assess the anti-fungal capacity in cancer patients, PAM were examined for phagocytic and killing activities against Candida albicans. No significant difference was found in phagocytic activity between normal control and neoplastic groups. In contrast, the fungicidal activity of PAM was significantly decreased in cancer patients when cultured with autologous serum (7.70 +/- 3.96 in neoplastic group vs 13.40 +/- 4.18 in normal control gourp, p<0.01). Furthermore, the patients' PAM when cultured with normal serum, showed fungicidal activity comparable to that of PAM from healthy subjects (from 8.65 +/- 3.82 vs. 12.15 +/- 4.83 with normal serum, p<0.05), suggesting that some macrophage-suppressor factor may be present in the cancer patients' sera, and this factor may possibly be related to the predisposition of immunocompromised hosts to pulmonary fungal infection.

35歳女.気胸は死亡直前まで認められなかったが,巨大な腹部腫瘤を呈した

It is well known that some micro-organisms synthesize proteins when stressed by heat or other factors. The function of these proteins is not vet 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 [S-35]-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.

肺における C. neoformans に対する初期の感染防御を調べるため, マウスに対する病原性の異なる二株の菌を用いてヒトPAMとPMNの食菌能, 殺菌能と食菌に伴うO-2産生能について検討した. PAMの食菌能と殺菌能は莢膜の薄い弱毒株と比較して莢膜の厚い強毒株に対しては明らかに劣っており, PMNでも同様の結果であった. PAMとPMN間の食菌能, 殺菌能とO-2産生能の比較では差が認められなかった. また, 殺菌能とO-2産生能は相関しないことよりPAMとPMNにおけるC. neoformans の細胞内殺菌にO-2は関与しないと考えられた. 以上よりPAMとPMNの感染防御は弱毒株に対しては有効であるが強毒株に対しては有効ではなく, 肺におけ C. neoformans に対する感染防御を考える上で興味深い結果であった.

気管支肺胞洗浄にてPAMを採取し,被験者本人の新鮮血清とCandida albicansを種々の比率で加え,PAMの食菌能を顕微鏡的に観察し,逆培養からC. albicansの殺菌能を算出した.PAM 2.5×106/ml, C. albicans 2.5×107/ml,新鮮血清10%を加え,30分後に測定する系が至適条件と判明した.臨床応用では,正常対照群で食菌PAMの割合は47.5±8.3%,食菌PAM 1個当たりが食菌したC. albicansの平均個数は2.54±0.62,全PAM 100個当たりの被食菌C. albicansの総数は123.9±40.8, C. albicans 100個当たりの殺菌率は6.13±0.61%と安定した値を示した.肺疾患患者では,サルコイドーシス群と肺アスペルギルス症群で食菌能の増加傾向が認められ,前者では個々の食菌PAMの食菌活性が,後者では食菌PAMの割合が増加傾向を示した.殺菌能は悪性腫瘍群で低下する傾向が認められた

症例は43歳の男性で血痰, 呼吸困難を主訴に来院. 胸部X線写真上, 両側肺野にエアー・ブロンコグラムを伴う浸潤影を認め, 同時にHb 5.0g/dlと著明な貧血を認めた. 浸潤影は自然経過にて10日後にはほとんど消失した. 腎機能障害も認められたため, 経皮的腎生検及び経気管支的肺生検を施行した. 腎組織は半月体形成性腎炎の所見であり, 直接蛍光抗体法にて腎糸球体基底膜にIgAの線状沈着が認められたが, IgGの沈着は認めなかった. 肺組織では軽度の胞隔の肥厚と肺胞腔に多数の担鉄マクロファージの出現をみた. 以上からIgA抗基底膜抗体による Goodpasture 症候群と診断した. プレドニゾロン投与により貧血は順調に改善したが, 経過中細菌性肺炎が原因と思われるDICを併発し死亡した. 診断確定後の全経過は約13ヵ月であった.

急性気管支炎32例, 慢性呼吸器疾患の感染増悪51例及び肺炎16例の呼吸器感染症99例に対するCefteram pivoxil (CFTM-PI) の有用性を検討した。 1. 臨床効果は著明改善27例, 改善51例, やや改善9例, 不変10例, 悪化2例で, 改善率は78.8%であった。 2. 総合効果は著効12例, 有効9例, やや有効5例, 無効症例はなく, 有効率は80.8%であった。 3. 起炎菌別細菌学的効果は26株中21株消失し (消失率80.8%), 優れた抗菌力を示した。特にHaemophilus influenzae 10 株に対するCefteramのMICはβ-Lactamase産生性に関係なく, 接種菌量108, 106cells/ml共に, MICは0.05μg/ml以下であった。 4. 副作用は99例中4例に軽度の胃腸障害などがみられた。又, 臨床検査値異常では, GOT・GPTの軽度上昇が2例にみられたが, 2例とも投与前から異常値を示しており, 継続投与可能であり, 又, 投与終了後に改善した。 以上の結果から, CFTM-PIは急性呼吸器感染症, 及び慢性呼吸器疾患の感染増悪に対して有用な薬剤と思われた。

A 77-year-old man was found to have multiple pulmonary amyloidoma and arteriovenous (AV) fistula of the lungs. Massive deposits of amyloid were present in the vascular wall, which apparently caused the fistula.

症例は60歳男性で，胸部異常陰影の精査のために当科に入院。入院時自覚症状は殆どなく， 肺野に異常呼吸音も聴取されなかった。胸部X線上はびまん性の網状影・索状影が両側の上肺野に密であった。経気管支的肺生検にて組織球および少数のリンバ球，好酸球よりなる肉芽腫を認め，電子顕徹鏡での検索でも X body を有する典型的な histiocytosis X 細胞が認められ肺好酸球性肉芽腫症と診断した。無治療で経過観察を行っていたところ3カ月後の胸部単純X線写真にて，胸部異常陰影は減少傾向を示し，動脈血液ガス分析にても改善が認められた。診断確定後2年間経過しているが，胸部CTスキャンにてわずかに薄壁の輪状影が認められるだけで，増悪傾向はなく，自然寛解を示したと思われた。

Hermansky-Pudlak 症候群の2例を報告した. 症例1は乾性咳嗽と呼吸困難を主訴に来院した55歳の女性. Oculocutaneous albinism と胸部X線写真にて間質性肺炎の像を認めた. 両親は血族結婚であり, 妹が46歳で同疾患にて死亡している. 骨髄穿刺液よりセロイド様物質を有する典型的なマクロファージを証明した. Lumi-aggregometer により血小板凝集能の低下とATPの無放出を認め, 血小板の storage pool 中のADP, ATPは著減していた. 経気管支肺生検 (TBLB) では肺胞壁の肥厚が認められた. 症例2は43歳の女性. 労作時呼吸困難を主訴に当科受診し, oculocutaneous albinism と胸部X線写真にて間質性肺炎の所見を認めた. 両親は血族結婚であるが, 血縁者に同様の人なし. Lumi-aggregometer にて血小板凝集能は, ほぼ正常であったが, ATPの放出は全く認められず, 血小板の storage pool 中のADP, ATPは著減していた.