Expression of Ascorbate Peroxidase Derived from Cyanidioschyzon merolae in Mammalian Cells

Background: Ascorbate peroxidase (APX) derived from Cyanidioschyzon merolae, a primitive red alga living in high temperature and acidic environments, has a greater anti-oxidative capacity than similar peroxidases occurring in other plants. In the present study, we examined the ability of Cyanidioschyzon merolae-derived APX (cAPX) to increase anti-oxidative capacity when expressed in mammalian cells. Materials and Methods: The cAPX gene was introduced into the mouse fibroblast-like cell line C3H10T1/2. Production of reactive oxygen species (ROS) and/or cell viability was assessed after heat, H2O2 and acid stimulation. Results: Heat and H2O2 stimulation caused ROS production. cAPX-expressing cells were more tolerant to oxidative stress induced by heat, H2O2 and acid stimulations than control cells lacking cAPX. Conclusion: Introduction of cAPX increases anti-oxidative capacity in mammalian cells

Suitable Image Parameters and Analytical Method for Quantitatively Measuring Cerebral Blood Flow Volume with Phase-Contrast Magnetic Resonance Imaging

The aim of this study was to determine suitable image parameters and an analytical method for phase-contrast magnetic resonance imaging (PC-MRI) as a means of measuring cerebral blood flow volume. This was done by constructing an experimental model and applying the results to a clinical application. The experimental model was constructed from the aorta of a bull and circulating isotonic saline. The image parameters of PC-MRI (repetition time, flip angle, matrix, velocity rate encoding, and the use of square pixels) were studied with percent flow volume (the ratio of actual flow volume to measured flow volume). The most suitable image parameters for accurate blood flow measurement were as follows: repetition time, 50 msec; flip angle, 20 degrees; and a 512 x 256 matrix without square pixels. Furthermore, velocity rate encoding should be set ranging from the maximum flow velocity in the vessel to five times this value. The correction in measuring blood flow was done with the intensity of the region of interest established in the background. With these parameters for PC-MRI, percent flow volume was greater than 90%. Using the image parameters for PC-MRI and the analytical method described above, we evaluated cerebral blood flow volume in 12 patients with occlusive disease of the major cervical arteries. The results were compared with conventional xenon computed tomography. The values found with both methods showed good correlation. Thus, we concluded that PC-MRI was a noninvasive method for evaluating cerebral blood flow in patients with occlusive disease of the major cervical arteries.</p

Cognitive behavioral therapy with interoceptive exposure and complementary video materials for irritable bowel syndrome (IBS): protocol for a multicenter randomized controlled trial in Japan

BackgroundThere is growing evidence of the treatment efficacy of cognitive behavioral therapy (CBT) for irritable bowel syndrome (IBS). CBT is recommended by several practice guidelines for patients with IBS if lifestyle advice or pharmacotherapy has been ineffective. Manual-based CBT using interoceptive exposure (IE), which focuses on the anxiety response to abdominal symptoms, has been reported to be more effective than other types of CBT. One flaw of CBT use in general practice is that it is time and effort consuming for therapists. Therefore, we developed a set of complementary video materials that include psycho-education and homework instructions for CBT patients, reducing time spent in face-to-face sessions while maintaining treatment effects. The purpose of this study is to examine the effects of CBT-IE with complementary video materials (CBT-IE-w/vid) in a multicenter randomized controlled trial (RCT).MethodsThis study will be a multicenter, parallel-design RCT. Participants diagnosed with IBS according to the Rome IV diagnostic criteria will be randomized to either the treatment as usual (TAU) group or the CBT-IE-w/vid + TAU group. CBT-IE-w/vid consists of 10 sessions (approximately 30 min face-to-face therapy + viewing a video prior to each session). Patients in the CBT-IE-w/vid group will be instructed to pre- view 3- to 13-min videos at home prior to each face-to-face therapy visit at a hospital. The primary outcome is the severity of IBS symptoms. All participants will be assessed at baseline, mid-treatment, post-treatment, and follow-up (3 months after post assessment). The sample will include 60 participants in each group.DiscussionTo our knowledge, this study will be the first RCT of manual-based CBT for IBS in Japan. By using psycho-educational video materials, the time and cost of therapy will be reduced. Manual based CBTs for IBS have not been widely adopted in Japan to date. If our CBT-IE-w/vid program is confirmed to be more effective than TAU, it will facilitate dissemination of cost-effective manual-based CBT in clinical settings

High Serum Advanced Glycation End Products Are Associated with Decreased Insulin Secretion in Patients with Type 2 Diabetes: A Brief Report

Advanced glycation end products (AGEs) are important in the pathophysiology of type 2 diabetes mellitus (T2DM). They directly cause insulin secretory defects in animal and cell culture models and may promote insulin resistance in nondiabetic subjects. We have developed a highly sensitive liquid chromatography-tandem mass spectrometry method for measuring AGEs in human serum. Here, we use this method to investigate the relationship between AGEs and insulin secretion and resistance in patients with T2DM. Methods. Our study involved 15 participants with T2DM not on medication and 20 nondiabetic healthy participants. We measured the AGE carboxyethyllysine (CEL), carboxymethyllysine (CML), and methyl-glyoxal-hydro-imidazolone (MG-H1). Plasma glucose and insulin were measured in these participants during a meal tolerance test, and the glucose disposal rate was measured during a euglycemic-hyperinsulinemic clamp. Results. CML and CEL levels were significantly higher in T2DM than non-DM participants. CML showed a significant negative correlation with insulin secretion, HOMA-%B, and a significant positive correlation with the insulin sensitivity index in T2DM participants. There was no correlation between any of the AGEs measured and glucose disposal rate. Conclusions. These results suggest that AGE might play a role in the development or prediction of insulin secretory defects in type 2 diabetes

Characterization of follistatin-related gene as a negative regulatory factor for activin family members during mouse heart development

Follistatin-related gene (FLRG) encodes a secretory glycoprotein that has characteristic cysteine-rich follistatin domains. FLRG protein binds to and neutralizes several transforming growth factor-β (TGF-β) superfamily members, including myostatin (MSTN), which is a potent negative regulator of skeletal muscle mass. We have previously reported that FLRG was abundantly expressed in fetal and adult mouse heart. In this study, we analyzed the expression of FLRG mRNA during mouse heart development. FLRG mRNA was continuously expressed in the embryonic heart, whereas it was very low in skeletal muscles. By contrast, MSTN mRNA was highly expressed in embryonic skeletal muscles, whereas the expression of MSTN mRNA was rather low in the heart. In situ hybridization and immunohistochemical analysis revealed that FLRG expressed in smooth muscle of the aorta and pulmonary artery, valve leaflets of mitral and tricuspid valves, and cardiac muscles in the ventricle of mouse embryonic heart. However, MSTN was expressed in very limited areas, such as valve leaflets of pulmonary and aortic valves, the top of the ventricular and atrial septa. Interestingly, the expression of MSTN was complementary to that of FLRG, especially in the valvular apparatus. Biochemical analyses with surface plasmon resonance biosensor and reporter assays demonstrated that FLRG hardly dissociates from MSTN and activin once it bound to them, and efficiently inhibits these activities. Our results suggest that FLRG could function as a negative regulator of activin family members including MSTN during heart development

A Senior Recital

Program listing performers and works performe

Doctoral Chamber Recital

List of performers and performances