Clonal hematopoiesis was prevalent in aplastic anemia. Some mutations were related to clinical outcomes. A highly biased set of mutations is evidence of Darwinian selection in the failed bone marrow environment. The pattern of somatic clones in individual patients over time was variable and frequently unpredictable. (Funded by Grant-in-Aid for Scientific Research and others.).

Early on, laparoscopic liver resection (LLR) was limited to partial resection, but major LLR is no longer rare. A difficulty scoring system is required to guide surgeons in advancing from simple to highly technical laparoscopic resections. Subjects were 90 patients who had undergone pure LLR at three medical institutions (30 patients/institution) from January 2011 to April 2014. Surgical difficulty was assessed by the operator using an index of 1-10 with the following divisions: 1-3 low difficulty, 4-6 intermediate difficulty, and 7-10 high difficulty. Weighted kappa statistic was used to calculate the concordance between the operators' and reviewers' (expert surgeon) difficulty index. Inter-rater agreement (weighted kappa statistic) between the operators' and reviewers' assessments was 0.89 with the three-level difficulty index and 0.80 with the 10-level difficulty index. A 10-level difficulty index by linear modeling based on clinical information revealed a weighted kappa statistic of 0.72 and that scored by the extent of liver resection, tumor location, tumor size, liver function, and tumor proximity to major vessels revealed a weighted kappa statistic of 0.68. We proposed a new scoring system to predict difficulty of various LLRs preoperatively. The calculated score well reflected difficulty.

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Interleukin (IL)-17-producing T helper (Th17) cells are crucial for host defense against extracellular microbes and pathogenesis of autoimmune diseases. Here we show that the AP-1 transcription factor JunB is required for Th17 cell development. Junb-deficient CD4+ T cells are able to develop in vitro into various helper T subsets except Th17. The RNA-seq transcriptome analysis reveals that JunB is crucial for the Th17-specific gene expression program. Junb-deficient mice are completely resistant to experimental autoimmune encephalomyelitis, a Th17-mediated inflammatory disease, and naive T helper cells from such mice fail to differentiate into Th17 cells. JunB appears to activate Th17 signature genes by forming a heterodimer with BATF, another AP-1 factor essential for Th17 differentiation. The mechanism whereby JunB controls Th17 cell development likely involves activation of the genes for the Th17 lineage-specifying orphan receptors RORγt and RORα and reduced expression of Foxp3, a transcription factor known to antagonize RORγt function.

To identify HLA alleles closely involved in the autoantigen presentation in acquired aplastic anemia (AA), we studied the HLA allelic loss frequencies of 312 AA patients, including 43 patients with loss of heterozygosity of 6p chromosome (6pLOH). An analysis of the HLA alleles contained in the lost haplotype revealed to be the most frequently lost allele. When we examined 28 AA (12 6pLOH[+] and 16 6pLOH[-]) patients with for the presence of leukocytes lacking HLA-B4002 (B4002) using a new monoclonal antibody specific to this allele, B4002 granulocytes were detected not only in all 6pLOH(+) patients but also in 9 (56%) of the 16 6pLOH(-) patients. Furthermore, 10 (83%) of the 12 6pLOH(+) patients possessed 1.0% to 78% B4002 granulocytes that retained the HLA-A allele on the same haplotype (B4002A), suggesting the frequent coexistence of granulocytes that underwent mutations restricted to with 6pLOH(+) (B4002A) granulocytes. Deep sequencing of the of sorted B4002A granulocytes revealed various somatic mutations, such as frameshift, nonsense, and splice site mutations, in all 15 patients studied. Surprisingly, missense mutations in the α-3 domain of that are not involved in the antigen presentation were detected exclusively in the B4002 granulocytes of 3 patients possessing B4002 granulocytes. The markedly high prevalence of leukocytes lacking HLA-B4002 as a result of either 6pLOH or structural gene mutations, or both, suggests that antigen presentation by hematopoietic stem/progenitor cells to cytotoxic T cells via the HLA-B allele plays a critical role in the pathogenesis of AA.

Laparoscopic hepatectomy (LH) has become popular as a surgical treatment for liver diseases, and numerous recent studies indicate that it is safe and has advantages in selected patients. Because of the magnified view offered by the laparoscope under pneumoperitoneal pressure, LH results in less bleeding than open laparotomy. However, gas embolism is an important concern that has been discussed in the literature, and experimental studies have shown that LH is associated with a high incidence of gas embolism. Major hepatectomies are done laparoscopically in some centers, even though the risk of gas embolism is believed to be higher than for minor hepatectomy due to the wide transection plane with dissection of major hepatic veins and long operative time. At many high-volume centers, LH is performed at a pneumoperitoneal pressure less than 12 mmHg, and reports indicate that the rate of clinically severe gas embolism is low. However, more studies will be necessary to elucidate the optimal pneumoperitoneal pressure and the incidence of gas embolism during LH.

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