Maki Takeda

The role of MT2-MMP in cancer progression

The role of MT2-MMP in cancer progression remains to be elucidated in spite of many reports on MT1-MMP. Using a human fibrosarcoma cell, HT1080 and a human gastric cancer cell, TMK-1, endogenous expression of MT1-MMP or MT2-MMP was suppressed by siRNA induction to examine the influence of cancer progression in vitro and in vivo. In HT1080 cells, positive both in MT1-MMP and MT2-MMP, the migration as well as the invasion was impaired by MT1-MMP or MT2-MMP suppression. Also cell proliferation in three dimensional (3D) condition was inhibited by MT1-MMP or MT2-MMP suppression and tumor growth in the nude mice transplanted with tumor cells were reduced either MT1-MMP or MT2-MMP suppression with a prolongation of survival time in vivo. MT2-MMP suppression induces more inhibitory effects on 3D proliferation and in vivo tumor growth than MT1-MMP. On the other hand, TMK-1 cells, negative in MT1-MMP and MMP-2 but positive in MT2-MMP, all the migratory, invasive, and 3D proliferative activities in TMK-1 are decreased only by MT2-MMP suppression. These results indicate MT2-MMP might be involved in the cancer progression more than or equal to MT1-MMP independently of MMP-2 and MT1-MMP.

Gastric Contraction Imaging System Using a 3-D Endoscope

This paper presents a gastric contraction imaging system for assessment of gastric motility using a 3-D endoscope. Gastrointestinal diseases are mainly based on morphological abnormalities. However, gastrointestinal symptoms are sometimes apparent without visible abnormalities. One of the major factors for these diseases is abnormal gastrointestinal motility. For assessment of gastric motility, a gastric motility imaging system is needed. To assess the dynamic motility of the stomach, the proposed system measures 3-D gastric contractions derived from a 3-D profile of the stomach wall obtained with a developed 3-D endoscope. After obtaining contraction waves, their frequency, amplitude, and speed of propagation can be calculated using a Gaussian function. The proposed system was evaluated for 3-D measurements of several objects with known geometries. The results showed that the surface profiles could be obtained with an error of <;10% of the distance between two different points on images. Subsequently, we evaluated the validity of a prototype system using a wave simulated model. In the experiment, the amplitude and position of waves could be measured with 1-mm accuracy. The present results suggest that the proposed system can measure the speed and amplitude of contractions. This system has low invasiveness and can assess the motility of the stomach wall directly in a 3-D manner. Our method can be used for examination of gastric morphological and functional abnormalities.

Emerging innovation towards safety in the clinical application of ESCs and iPSCs.

The Review by Behfar and colleagues (Cell therapy for cardiac repair—lessons from clinical trials. Nat. Rev. Cardiol. 11, 232–246; 2014)1 summarized that ‘first-generatio n’ cell therapies for heart failure2 using autologous cells are safe for use in humans. Conversely, ‘next-generation’ cell therapies, which include pluripotent stem cells such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), have major safety concerns, because contamination of undifferentiated cells might lead to teratoma formation.3 However, novel and efficient protocols for selective shutdown of tumour formation in these cells have been reported in several studies, which merit discussion (Table 1). Firstly, chemical inhibitors of survivin potently induce selective and complete cell death of undifferentiated human ESCs or iPSCs.4,5 A single pretreatment exposure to survivin inhibitors is sufficient to completely inhibit teratoma formation after transplantation.4 Importantly, differentiated cells derived from human ESCs or iPSCs maintain their functionality after treatment with survivin inhibitors.4 The survivin inhibitor QC has been widely used as nutritional supplement and no adverse effects have been reported.4 Secondly, chem ical inhibitors of oleate synthesis have been identified as compounds for selective elimination of human ESCs or iPSCs.6,7 Oleate synthesis inhibitors lead to apoptosis in human ESCs or iPSCs through Emerging innovation towards safety in the clinical application of ESCs and iPSCs

The Cleaning Effect of Shampooing Care by Adenosine Triphosphate Bioluminescence System

This paper discusses the cleaning effect of shampooing care by using Adenosine Triphosphate (ATP) bioluminescence system. Shampooing care is an important nursing one for patients who are difficult to care oneself. It is necessary to perform effective and comfortable care. So, we need to evaluate these effects quantitatively and qualitatively. We measured ATP, blood pressure, heart rate, heart rate variability, peripheral skin temperature and Visual Analog Scale (VAS) before and after shampooing. When we analyzed ATP adhering to head as “contamination” to evaluate that effect quantitatively, it found that the contamination of the scalp after shampooing decreased by 31%, and that of the hair decreased by 22%. The correlation between ATP and VAS showed that the more ATP decreased, the more subjects felt refresh. The physiological index was stable, and it found that the shampoo method in this study had little load on the body. We were able to clarify the cleaning effect of shampooing using rapid and simple method. These results showed can be the basic data that evaluated the effect by shampooing comprehensively.

Histone Modification Is Correlated With Reverse Left Ventricular Remodeling in Nonischemic Dilated Cardiomyopathy

BACKGROUND Although implantation of a left ventricular assist device (LVAD) induces reverse remodeling of the left ventricle in end-stage nonischemic dilated cardiomyopathy (DCM), the underlying mechanism is not fully understood. It has been shown that epigenetic modification, such as methylation or acetylation of the histone, is one of the most important upstream signals in cardiac failure. This study hypothesized that histone profiles may be modified by LVAD implantation for end-stage nonischemic DCM, in association with reverse left ventricular remodeling. METHODS Hemodynamic changes associated with histone modification profiles in the left ventricle were comprehensively assessed in 14 patients with a diagnosis of end-stage nonischemic DCM. These patients underwent LVAD implantation and subsequent cardiac transplantation in our institution (Osaka University Hospital, Osaka, Japan). Samples of normal left ventricle from 3 different people were used as a control. RESULTS After LVAD support for 2.5 ± 1.2 years, the study cohort showed a significant reverse remodeling of left ventricular function associated with histopathologic changes in the left ventricle, such as reduction of myocyte size. Although the left ventricle of the cohort histologically expressed less 3 histone methylation-related molecules (eg, H3 lysine 4 trimethylation [H3K4me3], H3 lysine 9 dimethylation [H3K9me2], and H3 lysine 9 trimethylation [H3K9me3]) compared with normal left ventricle, LVAD support reversed expression of these molecules, associated with up-regulation of H3 lysine 9 [H3K9] methyltransferase and suppressor of variegation 3-9 homologue 1 [SUV39H1] and with down-regulation of H3K9 demethylase and jumonji domains [JMJDs] in the LVAD-supported left ventricle. Moreover, expression of atrial natriuretic peptide and brain natriuretic peptide (ANP and BNP) was negatively correlated with that of H3K9me2 and H3K9me3. CONCLUSIONS The epigenetic state of cardiac myocytes (eg, as histone methylation) was substantially modulated in end-stage nonischemic DCM. LVAD support partially reversed the epigenetic state and its upstream signals, in association with pathologic and functional reverse remodeling.

Evaluation of the three-dimensional endoscope system for assessing the gastrointestinal motility

This paper described evaluation of the three-dimensional endoscope system for assessing the gastrointestinal motility. Gastrointestinal diseases are mainly based on the morphological or anatomical abnormity. However, sometimes the gastrointestinal symptoms are apparent without visible abnormalities. Such diseases are called functional gastrointestinal disorder, for example, functional dyspepsia, and irritable bowel syndrome. One of the major factors of these diseases is the gastrointestinal dysmotility. Assessment procedures for motor function are either invasive, or indirect. We thus propose a three-dimensional endoscope system for assessing the gastrointestinal motility. To assess the dynamic motility of the stomach, three-dimensional endoscopic imaging of stomach lining is performed. Propagating contraction waves are detected by subtracting estimated stomach geometry without contraction waves from one with contraction waves. After detecting constriction waves, their frequency, amplitude, and speed of propagation can be calculated. In this study, we evaluate the proposed system. First, we evaluate the developed three-dimensional endoscope system by a flat plane. This system can measure the geometry of the flat plane with an error of less than 10 percent of the distance between endoscope tip and the object. Then we confirm the validity of a prototype system by a wave simulated model. The detected wave is approximated by a Gaussian function. In the experiment, the amplitude and position of the wave can be measure with 1 mm accuracy. These results suggest that the proposed system can measure the speed and amplitude of contraction. In the future, we evaluate the proposed system in vivo experiments.

Biosignal-based relaxation evaluation of head-care robot

Such popular head care procedures as shampooing and scalp massages provide physical and mental relaxation. However, they place a big burden such as chapped hands on beauticians and other practitioners. Based on our robot hand technology, we have been developing a head care robot. In this paper, we quantitatively evaluated its relaxation effect using the following biosignals: accelerated plethymography (SDNN, HF/TP, LF/HF), heart rate (HR), blood pressure, salivary amylase (sAA) and peripheral skin temperature (PST). We compared the relaxation of our developed head care robot with the head care provided by nurses. In our experimental result with 54 subjects, the activity of the autonomic nerve system changed before and after head care procedures performed by both a human nurse and our proposed robot. Especially, in the proposed robot, we confirmed significant differences with the procedure performed by our proposed head care robot in five indexes: HF/TP, LF/HF, HR, sAA, and PST. The activity of the sympathetic nerve system decreased, because the values of its indexes significantly decreased: LF/HF, HR, and sAA. On the other hand, the activity of the parasympathetic nerve system increased, because of the increase of its indexes value: HF/TP and PST. Our developed head care robot provided satisfactory relaxation in just five minutes of use.

Evaluation of a compound eye type tactile endoscope

Minimally invasive surgical techniques for endoscope become widely used, for example, laparoscopic operation, NOTES (Natural Orifice Translumenal Endoscopic Surgery), robotic surgery and so on. There are so many demand and needs for endoscopic diagnosis. Especially, palpation is most important diagnosis on any surgery. However, conventional endoscopic system has no tactile sensibility. There are many studies about tactile sensor for medical application. These sensors can measure object at a point. It is necessary to sense in areas for palpation. To overcome this problem, we propose compound eye type tactile endoscope. The proposed system consists of TOMBO (Thin Observation Module by Bound Optics) and clear silicon rubber. Our proposed system can estimate hardness of target object by measuring deformation of a projected pattern on the silicon rubber. The purpose of this study is to evaluate the proposed system. At first, we introduce approximated models of the silicone and the object. We formulate the stiffness of object, the deformation of silicone, and the whole object. We investigate the accuracy of measured silicone’s lower surface for deformation of silicone by prototype system. Finally, we evaluate the calculated stiffness of the soft object.