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Histone deacetylases (HDACs) are involved in the deacetylation of core histones, which is an important event in transcription regulation in eukaryotes through alterations in the chromatin structure. We cloned cDNAs and genomic DNAs encoding two chicken HDACs (chHDAC-1 and -2), which are preferentially localized in nuclei. Treatment with trichostatin A reduced the HDAC activities in immunoprecipitates obtained with anti-chHDAC-1 and -2 antisera. Using gene targeting techniques, we generated homozygous DT40 mutants, ⌬chHDAC-1 and -2, devoid of two alleles of the chH-DAC-1 and -2 genes, respectively. The protein patterns on two-dimensional PAGE definitely changed for ⌬chH-DAC-2, and the amounts of the IgM H-and L-chains increased in it. Of the two IgM H-chain forms, the secreted form (s) increased in ⌬chHDAC-2, but the membrane-bound form (m) decreased. The IgM H-chain gene was transcribed more in ⌬chHDAC-2 than in DT40 cells. In the mutant, the alternative processing of IgM H-chain pre-mRNA preferentially occurred, resulting in an increase in the amount of s mRNA, whereas the stability of the two types of mRNA, s and m, was unchanged. In DT40 cells, treatment with trichostatin A increased both the amounts of IgM H-chain mRNAs and the switch from m to s mRNAs. Based on these results, we propose a model for a role of chHDAC-2 in both the transcription and alternative processing steps, resulting in control of the amount of the s IgM H-chain in the DT40 cell line.

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Using endoscopic ultrasonography (EUS), it is practicable to diagnose subepithelial lesions (SEL) with originating layer, echo level, and internal echo pattern etc. Lipoma, lymphangioma, and cyst have characteristic features; therefore, there is no need for endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA). Ectopic pancreas and glomus tumors, which originate from the third and fourth layers, are frequently seen in the antrum. However, ectopic pancreas located in the fundus or body is large and originates from the third and fourth layers (thickening of fourth layer). Each subepithelial lesion has characteristic findings. However, imaging differentiation of tumors originating from the fourth layer is very difficult, even if contrast echo is used. Therefore, EUS‐FNA should be done in these tumors, but the diagnostic yield for small lesions is not sufficient for clinical demands. Generally, those tumors, including small ones, should be first followed up in 6 months, then yearly follow up in cases of no significant change in size and features. When those tumors become larger than 1–2 cm, EUS‐FNA is recommended. Furthermore, unusual SEL and SEL with malignant findings such as nodular, heterogeneous, anechoic area, and ulceration indicate EUS‐FNA. Cap‐attached forward‐viewing echoendoscope is very helpful for EUS‐FNA of small SEL.

Interferon-gamma (IFN-gamma), vitamin D3 (VD), and retinoic acid (RA) induce differentiation of human monoblastic leukemia U937 cells to macrophage-like cells with potential superoxide anion-generating activity upon further stimulation. Here we report that U937 cells thus differentiated show various responses to apoptotic induction with a cytotoxic anti-Fas antibody and tumor necrosis factor (TNF). VD-or RA-treated U937 cells acquired resistance against Fas- or TNF receptor (TNFR)-mediated apoptosis, whereas apoptotic cell death was accelerated in IFN-gamma-treated cells. By flow cytometric analyses, no decrease in expression of surface Fas antigen or p55 TNFR was observed in differentiated U937 cells. Cell surface expression of CD11b was seen only when differentiation was induced with VD or RA but not with IFN-gamma. The growth of VD- or RA-treated cells was retarded but IFN-gamma-treated cells were prolific. These findings suggest that the differentiation state differs with the inducer and that the cellular response to apoptotic induction is closely related to the state including the cell cycle.