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Structural diversity of complex sphingolipids is important for maintenance of various cellular functions; however, the overall picture of the significance of this structural diversity remains largely unknown. To investigate the physiological importance of the structural diversity of complex sphingolipids, we here constructed a complex sphingolipid structural diversity disruption library in budding yeast, which comprises 11 mutants including with combinations of deletions of sphingolipid-metabolizing enzyme genes. The sensitivity of the mutants to various environmental stresses revealed that the more the structural variation of complex sphingolipids is limited, the more stress sensitivity tends to increase. Moreover, it was found that in mutant cells with only one subtype of complex sphingolipid, Slt2 MAP kinase and Msn2/4 transcriptional factors are essential for maintenance of a normal growth and compensation for reduced tolerance of multiple stresses caused by loss of complex sphingolipid diversity. Slt2 and Msn2/4 are involved in compensation for impaired integrity of cell walls and plasma membranes caused by loss of complex sphingolipid diversity, respectively. From these findings, it was suggested that loss of structural diversity of complex sphingolipids affects the environment of the cell surface, including both plasma membranes and cell walls, which could cause multiple environmental stress hypersensitivity.

Previously, we found that yeast exhibits a strong growth defect with the combination of a lack of gene involved in structural modification of sphingolipids and repression of the phosphatidylserine synthase gene. Here we found that the double gene mutation causes reactive oxygen species-mediated cell growth defect, which is suppressed by deletion of LEM3 encoding the subunit of phospholipid flippase.

Lipomatous angiomyofibroblastoma is extremely rare, with only 16 cases reported to date. We herein describe an additional case arising in the left vulvar region of a 49-year-old woman. The resected 5.3-cm yellowish tumor predominantly consisted of fat cells (85% of the tumor), together with medium- and small-sized vessels, multifocal fibrotic areas and pseudoangiomatous spaces. Spindle, rounded, and/or epithelioid tumor cells proliferated in a nest and/or cord-like pattern, or singly within perivascular fibrous tissues and between fat cells. The tumor cells were positive for vimentin, estrogen receptor, progesterone receptor, B-cell lymphoma 2, and CD10, but were negative for desmin, cytokeratin, epithelial membrane antigen, S-100 protein, human melanoma black 45, C-kit and p40. Ultrastructural examination revealed that these tumor cells exhibited fibroblastic characteristics. Lipomatous angiomyofibroblastoma should be discriminated from other lipomatous tumors, including spindle cell lipoma, angiomyolipoma and cellular angiofibroma containing numerous fat cells.

We present a case of cryptococcosis with adrenal insufficiency and meningitis in a healthy host without any risk factors. Antifungal therapy did not reduce the cryptococcal antigen titers of the cerebrospinal fluid and serum or the bilateral adrenal gland enlargement. It was suggested that the adrenal glands were the focus of persistent fungemia. Removal of both adrenal glands brought about a response to antifungal therapy. We conclude that if antifungal therapy is ineffective, bilateral adrenalectomy is an effective measure for treatment of such patients. Cryptococcosis is a possible cause of primary adrenal insufficiency in immunocompetent patients.

Heterotopic ossification can be found in neovascularized aortic valves with end-stage valvular disease, but its histopathological characteristics are not fully understood. The present study found ossification and neovessels in 21 (28%) and 54 (72%) of 75 surgically removed dysfunctional aortic valves, respectively; there was a significant association between them (P