NF-кB signaling in the stress response: Cellular response to environmental carcinogen

[Curriculum Vitae & Summary] International Symposium on Tumor Biology in Kanazawa 2004 / Kanazawa, Japan February 12 and 13, 200

Alkane inducible proteins in Geobacillus thermoleovorans B23

<p>Abstract</p> <p>Background</p> <p>Initial step of β-oxidation is catalyzed by acyl-CoA dehydrogenase in prokaryotes and mitochondria, while acyl-CoA oxidase primarily functions in the peroxisomes of eukaryotes. Oxidase reaction accompanies emission of toxic by-product reactive oxygen molecules including superoxide anion, and superoxide dismutase and catalase activities are essential to detoxify them in the peroxisomes. Although there is an argument about whether primitive life was born and evolved under high temperature conditions, thermophilic archaea apparently share living systems with both bacteria and eukaryotes. We hypothesized that alkane degradation pathways in thermophilic microorganisms could be premature and useful to understand their evolution.</p> <p>Results</p> <p>An extremely thermophilic and alkane degrading <it>Geobacillus thermoleovorans </it>B23 was previously isolated from a deep subsurface oil reservoir in Japan. In the present study, we identified novel membrane proteins (P16, P21) and superoxide dismutase (P24) whose production levels were significantly increased upon alkane degradation. Unlike other bacteria acyl-CoA oxidase and catalase activities were also increased in strain B23 by addition of alkane.</p> <p>Conclusion</p> <p>We first suggested that peroxisomal β-oxidation system exists in bacteria. This eukaryotic-type alkane degradation pathway in thermophilic bacterial cells might be a vestige of primitive living cell systems that had evolved into eukaryotes.</p

Safety and efficacy of pirfenidone in idiopathic pulmonary fibrosis in clinical practice

SummaryBackgroudPrevious pirfenidone trials have only involved patients with mild-to-moderate idiopathic pulmonary fibrosis (IPF). The aim of this study was to investigate the safety and efficacy of pirfenidone in patients with mild-to-severe IPF in clinical practice.MethodsThe clinical records of 76 patients who were diagnosed with IPF and received pirfenidone were reviewed.ResultsThe most frequent adverse event was anorexia, although the grade of anorexia in most patients was mild. Dose reduction of pirfenidone improved anorexia in 84% affected patients, which resulted in a high medication compliance rate. The mean forced vital capacity (FVC) at the initiation of pirfenidone therapy in this study was approximately 10% lower than that in previous clinical trials. The mean change in FVC during the 6-month period prior to the therapy initiation was −188 mL, which improved to −19 mL during the 6-month period after therapy. Significant attenuation in percentage predicted diffusion capacity of the lung for carbon monoxide decline was also achieved after pirfenidone therapy initiation. The efficacy of pirfenidone in attenuating the degree of FVC decline was higher in the group with FVC decline of ≥150 mL during the 6-month period prior to therapy initiation. The levels of serum markers, such as KL-6 and SP-D, were also lowered by the therapy.ConclusionsThese results showed that pirfenidone was well-tolerated and had beneficial effects in patients with mild-to-severe and/or progressive IPF. The degree of disease progression prior to the initiation of pirfenidone therapy had an impact on the response to the therapy

Selective vulnerability of human-induced pluripotent stem cells to dihydroorotate dehydrogenase inhibition during mesenchymal stem/stromal cell purification

間葉系幹細胞から未分化iPS細胞を選択除去する方法を開発: iPS細胞由来間葉系幹細胞の再生医療利用に期待. 京都大学プレスリリース. 2023-03-01.The use of induced mesenchymal stem/stromal cells (iMSCs) derived from human induced pluripotent stem cells (hiPSCs) in regenerative medicine involves the risk of teratoma formation due to hiPSCs contamination in iMSCs. Therefore, eradicating the remaining undifferentiated hiPSCs is crucial for the effectiveness of the strategy. The present study demonstrates the Brequinar (BRQ)-induced inhibition of dihydroorotate dehydrogenase (DHODH), a key enzyme in de novo pyrimidine biosynthesis, selectively induces apoptosis, cell cycle arrest, and differentiation; furthermore, it promotes transcriptional changes and prevents the growth of 3-dimensional hiPSC aggregates. Contrastingly, BRQ-treated iMSCs showed no changes in survival, differentiation potential, or gene expression. The results suggest that BRQ is a potential agent for the effective purification of iMSCs from a mixed population of iMSCs and hiPSCs, which is a crucial step in successful iMSC-based therapy

A novel technique for the measurement of the avalanche fluctuation of gaseous detectors

We have developed a novel technique for the measurement of the avalanche fluctuation of gaseous detectors using a UV laser. The technique is simple and requires a short data-taking time of about ten minutes. Furthermore, it is applicable for relatively low gas gains. Our experimental setup as well as the measurement principle, and the results obtained with a stack of Gas Electron Multipliers (GEMs) operated in several gas mixtures are presented.Comment: 7 pages, 7 figures. For the proceedings of VCI2016, to be published in Nucl. Instrum. Methods Phys. Res.

Use of Balloon Enteroscopy in Preoperative Diagnosis of Neurofibromatosis-Associated Gastrointestinal Stromal Tumours of the Small Bowel: A Case Report

Neurofibromatosis type I (NF1) is one of the most common inheritable disorders and is associated with an increased risk of gastrointestinal stromal tumours (GISTs). However, the predominant location of these lesions in the small bowel makes them difficult to diagnose. We report the successful use of balloon enteroscopy in conjunction with conventional methods for clinical diagnosis of jejunal GISTs in a 70-year-old man with NF1 who presented with melaena. The importance of screening NF1 patients for GISTs and the complementary role of balloon enteroscopy with capsule endoscopy in such diagnoses is discussed