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Uyama T.,Kagawa University | Inoue M.,Tokushima University | Okamoto Y.,Tokushima University | Shinohara N.,Kagawa University | And 5 more authors.
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids | Year: 2013

Anandamide and other bioactive N-acylethanolamines (NAEs) are a class of lipid mediators and are produced from glycerophospholipids via N-acylphosphatidylethanolamines (NAPEs). Although the generation of NAPE by N-acylation of phosphatidylethanolamine is thought to be the rate-limiting step of NAE biosynthesis, the enzyme responsible, N-acyltransferase, remains poorly characterized. Recently, we found that five members of the HRAS-like suppressor (HRASLS) family, which were originally discovered as tumor suppressors, possess phospholipid-metabolizing activities including NAPE-forming N-acyltransferase activity, and proposed to call HRASLS1-5 phospholipase A/acyltransferase (PLA/AT)-1-5, respectively. Among the five members, PLA/AT-1 attracts attention because of its relatively high N-acyltransferase activity and predominant expression in testis, skeletal muscle, brain and heart of human, mouse and rat. Here, we examined the formation of NAPE by PLA/AT-1 in living cells. As analyzed by metabolic labeling with [14C]ethanolamine or [ 14C]palmitic acid, the transient expression of human, mouse and rat PLA/AT-1s in COS-7 cells as well as the stable expression of human PLA/AT-1 in HEK293 cells significantly increased the generation of NAPE and NAE. Liquid chromatography-tandem mass spectrometry also exhibited that the stable expression of PLA/AT-1 enhanced endogenous levels of NAPE, N- acylplasmenylethanolamine, NAE and glycerophospho-NAE. Furthermore, the knockdown of endogenous PLA/AT-1 in mouse ATDC5 cells lowered NAPE levels. Interestingly, the dysfunction of peroxisomes, which was caused by PLA/AT-2 and -3, was not observed in the PLA/AT-1-expressing HEK293 cells. Altogether, these results suggest that PLA/AT-1 is at least partly responsible for the generation of NAPE in mammalian cells. © 2013 Elsevier B.V. Source


Kageji T.,Tokushima University | Nagahiro S.,Tokushima University | Mizobuchi Y.,Tokushima University | Matsuzaki K.,Tokushima Prefectural Central Hospital | And 2 more authors.
Journal of Medical Investigation | Year: 2014

The purpose of this study was to evaluate the clinical outcome of boron neutron capture therapy (BNCT) and conventional treatment in patients with newly diagnosed glioblastoma. Since 1998 we treated 23 newly-diagosed GBM patients with BNCT without any additional chemotherapy. Their median survival time was 19.5 months; the 2-, 3-, and 5-year survival rates were 31.8%, 22.7%, and 9.1%, respectively. The clinical results of BNCT in patients with GBM are similar to those of recent conventional treatments based on radiotherapy with concomitant and adjuvant temozolomide. © 2014 by The University of Tokushima Faculty of Medicine. Source


Pooh R.K.,CRIFM Clinical Research Institute of Fetal Medicine PMC | Pooh K.H.,Shikoku Medical Center for Children and Adults
Donald School Journal of Ultrasound in Obstetrics and Gynecology | Year: 2013

Transvaginal high-resolution ultrasound and three-dimensional (3D) ultrasound has been establishing sono-embryology in the first trimester as well as neurosonography. Fetal brain is rapidly developing and changing its appearance week by week during pregnancy. The most important organ but it is quite hard to observe detailed structure of this organ by conventional transabdominal sonography. It is possible to observe the whole brain structure by magnetic resonance imaging in the post half of pregnancy, but it is difficult in the first half of gestation and transvaginal high-resolution 3D ultrasound is the most powerful modality. As for brain vascularization, main arteries and veins have been demonstrated and evaluated in various CNS conditions. Source


Yamaguchi Y.,Shikoku Medical Center for Children and Adults | Kojima T.,Tokushima University | Yoshinaga T.,Tokushima University
Progress in Biomedical Optics and Imaging - Proceedings of SPIE | Year: 2016

In clinical X-ray computed tomography (CT), filtered back-projection as a transform method and iterative reconstruction such as the maximum-likelihood expectation-maximization (ML-EM) method are known methods to reconstruct tomographic images. As the other reconstruction method, we have presented a continuous-time image reconstruction (CIR) system described by a nonlinear dynamical system, based on the idea of continuous methods for solving tomographic inverse problems. Recently, we have also proposed a multiplicative CIR system described by differential equations based on the minimization of a weighted Kullback-Leibler divergence. We prove theoretically that the divergence measure decreases along the solution to the CIR system, for consistent inverse problems. In consideration of the noisy nature of projections in clinical CT, the inverse problem belongs to the category of ill-posed problems. The performance of a noise-reduction scheme for a new (previously developed) CIR system was investigated by means of numerical experiments using a circular phantom image. Compared to the conventional CIR and the ML-EM methods, the proposed CIR method has an advantage on noisy projection with lower signal-to-noise ratios in terms of the divergence measure on the actual image under the same common measure observed via the projection data. The results lead to the conclusion that the multiplicative CIR method is more effective and robust for noise reduction in CT compared to the ML-EM as well as conventional CIR methods. © 2016 SPIE. Source


Tsuboi K.,Kagawa University | Okamoto Y.,Tokushima University | Rahman I.A.S.,Kagawa University | Uyama T.,Kagawa University | And 5 more authors.
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids | Year: 2015

Bioactive N-acylethanolamines include anti-inflammatory palmitoylethanolamide, anorexic oleoylethanolamide, and an endocannabinoid arachidonoylethanolamide (anandamide). In animal tissues, these molecules are biosynthesized from N-acylethanolamine phospholipids directly by phospholipase D-type enzyme or through multi-step routes via N-acylethanolamine lysophospholipids. We previously found that mouse brain has a lysophospholipase D (lysoPLD) activity hydrolyzing N-acylethanolamine lysophospholipids to N-acylethanolamines and that this activity could be partially attributed to glycerophosphodiesterase (GDE) 1. In the present study, we examined catalytic properties of GDE4, another member of the GDE family. When overexpressed in HEK293 cells, murine GDE4 mostly resided in the membrane fraction. Purified GDE4 showed lysoPLD activity toward various lysophospholipids, including N-acylethanolamine lysophospholipids as well as lysophosphatidylethanolamine and lysophosphatidylcholine. When HEK293 cells were metabolically labeled with N-[14C]palmitoylethanolamine lysophospholipid, the transient expression of GDE4 increased the [14C]palmitoylethanolamide level, while the knockdown of endogenous GDE4 decreased this level. These results suggested that GDE4 functions as an N-acylethanolamine-generating lysoPLD in living cells. Moreover, the expression of GDE4 increased most species of lysophosphatidic acid (LPA), which can be produced from various lysophospholipids by the lysoPLD activity of GDE4. GDE4 mRNA was widely distributed among mouse tissues including brain, stomach, ileum, colon, and testis. In conclusion, GDE4 may act as a lysoPLD, which is involved in the generation of N-acylethanolamines and LPA. © 2015 Elsevier B.V. All rights reserved. Source

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