In this work, the zebrafish model organism was developed to obtain a minivertebrate host system for a Candida albicans infection study. We demonstrated that C. albicans can colonize and invade zebrafish at multiple anatomical sites and kill the fish in a dose-dependent manner. Inside zebrafish, we monitored the progression of the C. albicans yeast-to-hypha transition by tracking morphogenesis, and we monitored the corresponding gene expression of the pathogen and the early host immune response. We performed a zebrafish survival assay with different C. albicans strains (SC5314, ATCC 10231, an hgc1 mutant, and a cph1/efg1 double mutant) to determine each strain's virulence, and the results were similar to findings reported in previous mouse model studies. Finally, using zebrafish embryos, we monitored C. albicans infection and visualized the interaction between pathogen and host myelomonocytic cells in vivo. Taken together, the results of this work demonstrate that zebrafish can be a useful host model to study C. albicans pathogenesis, and they highlight the advantages of using the zebrafish model in future invasive fungal research.

Background-Open lung biopsy is often performed to confirm the diagnosis in patients with suspected fibrosing alveolids. The superior sensitivity and specificity of high resolution computed tomography (CT) over chest radiography in various diffuse lung diseases suggest that the characteristic appearance of fibrosing alveolitis on high resolution CT might render biopsy confirmation unnecessary. Methods-The chest radiographs and high resolution CT scans of 86 patients (41 with fibrosing alveolitis and 45 with various other diffuse lung diseases) were examined individually and independently by two observers. No clinical information was given and the observers gave a level of confidence when the diagnosis was thought to be fibrosing alveolitis. Results-The observers correctly and confidently discriminated between fibrosing alveolitis and other diffuse lung diseases on high resolution CT with an accuracy of 88% and on chest radiography with an accuracy of 76%. The false negative rate for fibrosing alveolitis diminished from 29% on chest radiography to 11% on high resolution CT. The false positive rate on chest radiography was 190/o and on high resolution CT 13%; the false positive diagnoses on CT were the result of a few conditions (extrinsic allergic alveolitis, sarcoidosis, cryptogenic organising pneumonia, and pulmonary eosinophilia) which mimicked some of the CT features of fibrosing alveolitis. The superficial similarity of the CT patterns of these conditions are discussed. Conclusions-High resolution CT is superior to chest radiography in establishing the diagnosis of fibrosing alveolitis and the typical CT appearances are virtually pathognomonic. The diagnostic advantages of CT over chest radiography should further reduce the need for open lung biopsy in this condition. (Thorax 1993;48:334-338)

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