[Systemic mastocytosis with refractory ascites successfully treated with interferon-α and a leukotriene receptor antagonist].

A 67-year-old male was referred to our hospital because of anemia, thrombocytopenia, and massive ascites. A diagnosis of systemic mastocytosis was made based on the observation of many mast cells in his bone marrow, elevated serum tryptase levels, and the presence of c-kit point mutation Asp816Val. Dasatinib and cladribine were ineffective, and a large volume of ascites was removed approximately every 3 days. Then, following an asthma attack, the patient was treated with pranlukast, a leukotriene receptor antagonist (LTRA). After LTRA treatment initiation, the frequency of ascites drainage decreased, and no puncture was necessary from the 10th day after the start of LTRA. Interferon α (IFN-α) was administered from the 15th day after the start of LTRA. Thereafter, his anemia and thrombocytopenia gradually improved, the ascites disappeared, the mast cells in his bone marrow were significantly reduced, and the Asp816Val mutation disappeared. Because persistent monocytosis was evident, he was suspected of chronic myelomonocytic leukemia but has not been diagnosed and is undergoing watchful waiting. This was considered to be a rare case of refractory ascites in which IFN-α was effective and LTRA might have been beneficial.

Significance of the neutrophil myeloperoxidase index in patients with atherosclerotic diseases.

The pattern of changes in the neutrophil myeloperoxidase (MPO) levels in various atherosclerotic conditions was analyzed by assessing the mean myeloperoxidase index (MPXI), which is calculated during the routine complete blood count (CBC) performed using the flow-cytochemistry blood autoanalyzer ADVIA120/2120 (Siemens), and plasma MPO concentrations. MPXI values of ischemic heart disease (IHD) patients did not differ from those of healthy volunteers. However, MPXI values of IHD patients with arteriosclerosis obliterans (ASO) (-6.1 ± 1.8) were significantly lower than those of IHD patients without ASO (0.8 ± 0.5). In contrast, the MPO values in IHD patients with ASO were significantly elevated. In subjects without IHD, while the MPXI values in mild cases of ASO (Fontaine's stages I/II, 3.4 ± 0.8) were significantly higher than those of healthy volunteers (0.4 ± 0.4), the values of those with severe ASO (stages III/IV, 0.3 ± 0.8) were significantly lower than those of mild cases. However, when ASO patients developed IHD, the MPXI values dramatically decreased (stages I/II, -7.3 ± 1.9; stages III/IV, -5.2 ± 1.6). These results indicate that MPXI is elevated in mild, but not in severe, ASO cases, and that MPXI decreases dramatically when ASO patients develop IHD. MPXI may constitute an informative independent biomarker for diagnosis and follow-up of IHD complicated by ASO.

The transcriptional mediator subunit MED1/TRAP220 in stromal cells is involved in hematopoietic stem/progenitor cell support through osteopontin expression.

MED1/TRAP220, a subunit of the transcriptional Mediator/TRAP complex, is crucial for various biological events through its interaction with distinct activators, such as nuclear receptors and GATA family activators. In hematopoiesis, MED1 plays a pivotal role in optimal nuclear receptor-mediated myelomonopoiesis and GATA-1-induced erythropoiesis. In this study, we present evidence that MED1 in stromal cells is involved in supporting hematopoietic stem and/or progenitor cells (HSPCs) through osteopontin (OPN) expression. We found that the proliferation of bone marrow (BM) cells cocultured with MED1 knockout (Med1(-/-)) mouse embryonic fibroblasts (MEFs) was significantly suppressed compared to the control. Furthermore, the number of long-term culture-initiating cells (LTC-ICs) was attenuated for BM cells cocultured with Med1(-/-) MEFs. The vitamin D receptor (VDR)- and Runx2-mediated expression of OPN, as well as Mediator recruitment to the Opn promoter, was specifically attenuated in the Med1(-/-) MEFs. Addition of OPN to these MEFs restored the growth of cocultured BM cells and the number of LTC-ICs, both of which were attenuated by the addition of the anti-OPN antibody to Med1(+/+) MEFs and to BM stromal cells. Consequently, MED1 in niche appears to play an important role in supporting HSPCs by upregulating VDR- and Runx2-mediated transcription on the Opn promoter.