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Table S1: Adverse events that occurred in >5% of patients. (PDF 99 kb)

Tubulocystic carcinoma of the bile duct is extremely rare and has not been reported in the literature. We reported a case of cystic neoplasm of the liver with distinct histopathological features that could not be clearly classified as of either mucinous or intraductal papillary neoplasm. A 68-year-old Japanese patient had a multicystic biliary tumor within the liver. This tumor was detected on follow-up of polymyalgia rheumatica. The exophytic, multicystic, 35 × 50 mm mass was composed of complex tubulocystic structures. We initially suspected cystadenocarcinoma of the liver and performed radical operation. However, pathology ultimately showed it to be very rare tubulocystic carcinoma that derived from the bile duct. We reviewed the literature and describe the process of our differential diagnosis.

Rotigotine is a dopamine receptor agonist indicated for the treatment of Parkinson's disease and moderate-to-severe restless legs syndrome. Continuous transdermal delivery of rotigotine via a silicon-based patch maintains stable plasma concentrations over 24 h. The objective of the study was to evaluate the pharmacokinetics, safety, and tolerability of a multiple-dose schedule of rotigotine transdermal patch in Japanese and Caucasian subjects. In this open-label, repeated-dose, parallel-group study (ClinicalTrials.gov: NCT01854216), healthy male and female subjects of Japanese or Caucasian ethnic origin were matched by gender, body mass index, and age. Subjects underwent a 9-day patch application period. 12 Japanese and 12 Caucasian subjects were included in the pharmacokinetic analyses. Mean apparent doses (actual amount of drug delivered) increased proportionally with rotigotine nominal dosages (1, 2, and 4 mg/24 h) and were similar for both ethnic groups, with large inter-individual variability. Mean plasma concentration-time profiles for unconjugated rotigotine were similar in both ethnic groups at day 3 for each dosage. Peak concentrations (C max,ss) and area under the concentration-time curves from pre-dose to the concentration measured 24 h after administration of patch (AUC(0-24,ss)) showed similar exposure in both groups; higher values in Japanese subjects were explained by differences in body weight. For total rotigotine, C max,ss and AUC(0-24,ss) values were higher in Caucasian subjects and could be explained by small differences in apparent dose. Rotigotine was generally well tolerated following multiple applications up to 4 mg/24 h. These findings suggest similar dosage requirements for rotigotine transdermal system in Japanese and Caucasian populations.

Many patients with myeloid malignancies are ineligible for conventional allogeneic hematopoietic stem cell transplantation (allo-HSCT) with myeloablative conditioning because of their age, medical problems, or the lack of a suitable HLA-identical related donor. The outcome of 9 patients with myeloid malignancies who underwent allo-HSCT following fludarabine- and busulfan- based reduced intensity conditioning (RIC) from unrelated or mismatched related donor is herein described. Six patients received bone marrow from an unrelated donor, two received a serologically mismatched related allograft, and one received serologically mismatched unrelated cord blood. All patients demonstrated successfully engraftment at a median of 15 days and showed complete donor chimerism of 9527772566420n day 28. One patient developed grade 3 regimen-related toxicity. Grade II to IV acute graft-versus-host disease (GVHD) and extensive type chronic GVHD developed in 6 and 4 patients, respectively. Of the two patients who received the second HSCT, one died of relapse and one died of acute GVHD. The remaining 7 patients are currently alive in remission. The overall survival at 4 years after allo-HSCT was 77.8%.0 These observations suggest that these RIC regimens enable rapid engraftment of stem cells from alternative donors with tolerable toxicities in patients who are not eligible for conventional HSCT.

Myeloproliferative neoplasms (MPN), a group of haematopoietic stem cell (HSC) disorders, are often accompanied by myelofibrosis. We previously identified the fusion of the ETV6 gene to the LYN gene (ETV6-LYN) in idiopathic myelofibrosis with ins(12;8)(p13;q11q21). The introduction of ETV6-LYN into HSCs resulted in fatal MPN with massive myelofibrosis in mice, implicating the rearranged LYN kinase in the pathogenesis of MPN with myelofibrosis. However, the signalling molecules directly downstream from and activated by ETV6-LYN remain unknown. In this study, we demonstrated that the direct activation of STAT5 by ETV6-LYN is crucial for the development of MPN. ETV6-LYN was constitutively active as a kinase through autophosphorylation. ETV6-LYN, but not its kinase-dead mutant, supported cytokine-free proliferation of haematopoietic cells. STAT5 was activated in a JAK2-independent manner in ETV6-LYN-expressing cells. ETV6-LYN interacted with STAT5 and directly activated STAT5 both in vitro and in vivo. Of note, ETV6-LYN did not support the formation of colonies by Stat5-deficient HSCs under cytokine-free conditions and the capacity of ETV6-LYN to induce MPN with myelofibrosis was profoundly attenuated in a Stat5-null background. These findings define STAT5 as a direct target of ETV6-LYN and unveil the LYN-STAT5 axis as a novel pathway to augment proliferative signals in MPN and leukaemia.

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官能的に評価された木材の表面粗さが, 客観的に測定できる木材の材質特性値とどのように関連しているかを, 主成分分析法を用いて解析した。その結果官能的な木材の粗さは触針法で測定されるHmaxによって大部分が説明でき, 針葉樹材では年輪に基づく凹凸の深さとピッチが, 広葉樹材では道管縦断面に基づく凹凸の深さとともに材の比重が宮能的な粗さに影響することが明らかになった。