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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.


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.


PubMed | Red Cross, Saitama University, JR Sendai Hospital, Miyanosawa Koike Child Clinic and 30 more.
Type: | Journal: Diabetic medicine : a journal of the British Diabetic Association | Year: 2016

To examine the contribution of the FUT2 gene and ABO blood type to the development of Type 1 diabetes in Japanese children.We analysed FUT2 variants and ABO genotypes in a total of 531 Japanese children diagnosed with Type 1 diabetes and 448 control subjects. The possible association of FUT2 variants and ABO genotypes with the onset of Type 1 diabetes was statistically examined.The se2 genotype (c.385A>T) of the FUT2 gene was found to confer susceptibility to Type 1A diabetes in a recessive effects model [odds ratio for se2/se2, 1.68 (95% CI 1.20-2.35); corrected P value = 0.0075].The FUT2 gene contributed to the development of Type 1 diabetes in the present cohort of Japanese children. This article is protected by copyright. All rights reserved.


PubMed | Red Cross, Fukuoka University, Showa University, Tohoku University and 34 more.
Type: Journal Article | Journal: Journal of human genetics | Year: 2016

The purpose of this study is to summarize the results from a survey on awareness of genetic counseling for pregnant women who wish to receive non-invasive prenatal testing (NIPT) in Japan. As a component of a clinical study by the Japan NIPT Consortium, genetic counseling was conducted for women who wished to receive NIPT, and a questionnaire concerning both NIPT and genetic counseling was given twice: once after pre-test counseling and again when test results were reported. The responses of 7292 women were analyzed. They expressed high satisfaction with the genetic counseling system of the NIPT Consortium (94%). The number of respondents who indicated that genetic counseling is necessary for NIPT increased over time. Furthermore, they highly valued genetic counseling provided by skilled clinicians, such as clinical geneticists or genetic counselors. The vast majority (90%) responded that there was sufficient opportunity to consider the test ahead of time. Meanwhile, women who received positive test results had a poor opinion and expressed a low-degree satisfaction. We confirmed that the pre-test genetic counseling that we conducted creates an opportunity for pregnant women to sufficiently consider prenatal testing, promotes its understanding and has possibilities to effectively facilitate informed decision making after adequate consideration. A more careful and thorough approach is considered to be necessary for women who received positive test results.


PubMed | Shikoku Medical Center for Children and Adults, Tokyo Metropolitan Childrens Medical Center and Chiba University
Type: Case Reports | Journal: Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy | Year: 2016

Many types of weak pathogenic microorganisms often cause opportunistic infections in extremely preterm infants. Paecilomyces formosus is one such opportunistic fungus that can lead to a serious infection. Here, we report the clinical course of P.formosus infection in an extremely preterm infant.An extremely preterm male infant was born at 23 weeks of gestation. Six days after birth, he developed yellowish-brown nodules on the skin of the back extending to the buttocks. P.formosus was identified by culture of samples from the cutaneous lesions. We treated the infection with intravenous micafungin and lanoconazole ointment application. The skin lesions improved dramatically and healed without scar tissue formation.Neonatologists should consider opportunistic P.formosus infections. This is the first report to describe that micafungin is effective for P.formosus cutaneous infection in extremely premature infants.


PubMed | Shikoku Medical Center for Children and Adults, Tokyo Metropolitan Childrens Medical Center and Keio University
Type: | Journal: Human genome variation | Year: 2016

Heterozygous kinase domain mutations or homozygous extracellular domain mutations in


Kuboi T.,Shikoku Medical Center for Children and Adults | Okazaki K.,Shikoku Medical Center for Children and Adults | Kusaka T.,Kagawa UniversityKagawa | Shimada A.,Tokushima University
Pediatrics International | Year: 2015

Congenital dacryocystocele is a relatively rare type of nasolacrimal duct obstruction that may induce respiratory distress during the early neonatal period. We encountered a case of bilateral congenital dacryocystoceles with intranasal cysts in a premature infant delivered at 34 weeks of gestation. The patient developed symptoms of respiratory failure immediately after birth, but no ophthalmologic symptoms. Treatment with nasal continuous positive airway pressure via a nasal mask, instead of a nasal prong, effectively relieved the symptoms. Early diagnosis and appropriate treatment are critical for infants with nasal obstruction. © 2015 Japan Pediatric Society.


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.


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.


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.

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