Crucial Role of MLL for the Maintenance of Memory T Helper Type 2 Cell Responses

SummaryThe Mixed-Lineage Leukemia (MLL) gene, a mammalian homolog of the Drosophila trithorax, is implicated in regulating the maintenance of Hox gene expression and hematopoiesis. The physiological functions of MLL in the immune system remain largely unknown. Although MLL+/− CD4 T cells differentiate normally into antigen-specific effector Th1/Th2 cells in vitro, the ability of memory Th2 cells to produce Th2 cytokines was selectively reduced. Furthermore, histone modifications at the Th2 cytokine gene loci were not properly maintained in MLL+/− memory Th2 cells. The reduced expression of MLL in memory Th2 cells resulted in decreased GATA3 expression accompanied with impaired GATA3 locus histone modifications. The direct association of MLL with the GATA3 locus and the Th2 cytokine gene loci was demonstrated. Memory Th2 cell-dependent allergic airway inflammation was decreased in MLL+/− Th2 cell-transferred mice. Thus, a crucial role for MLL in the maintenance of memory Th2 cell function is indicated

Efficient production of infectious viruses requires enzymatic activity of Epstein-Barr virus protein kinase

AbstractThe Epstein-Barr virus (EBV) BGLF4 gene product is the only protein kinase encoded by the virus genome. In order to elucidate its physiological roles in viral productive replication, we here established a BGLF4-knockout mutant and a revertant virus. While the levels of viral DNA replication of the deficient mutant were equivalent to those of the wild-type and the revertant, virus production was significantly impaired. Expression of the BGLF4 protein in trans fully complemented the low yield of the mutant virus, while expression of a kinase-dead (K102I) form of the protein failed to restore the virus titer. These results demonstrate that BGLF4 plays a significant role in production of infectious viruses and that the kinase activity is crucial

Relationship between medical examination methods and actual conditions of life for preserving visual acuity in primary and junior high school: Verification of the current vision test

The deterioration of children’s eyesight is on the rise. Children's lives have changed in a short period of time, such as an increase in blue light due to the use of electronic devices. It is necessary to consider non-traditional content of health guidance for prevention. The accurate visual acuity test is important to examine the effects of visual acuity and environmental or living factors. We examined the accuracy of the visual acuity test with the three stage Landolt ring for children from the relationship with the eye axial length. After performing a normal detailed visual acuity test of the children and the correlation analysis with the eye axial length, we examined the distribution of the eye axis according to the results of the three-stage visual acuity test by the Landolt ring. The number of children measured eye axial length was 13. The correlation coefficient between detailed visual acuity test and eye axial length was negative. According to the results of the three-stage visual acuity test, the distribution of the eye axis is good for the right eye: the average eye axis of “A” was 23.44 mm, moderate: the average of “B” was 22.58 mm. The average of the left eye axis for “A” children is 23.34 mm, for “B” is 23.08 mm, and for “C” is 23.7 mm. The correlation coefficient between the detailed visual acuity test and the eye axial length was negative on both sides, namely a negative correlation between the visual acuity and the eye axial length. There was a possibility of not correspondence between the three-stage visual test and the eye axial length. In the case of children, it was considered that their visual performance and answers were different because of their mood and physical condition on the day

Relationship between medical examination methods and actual conditions of life for preserving visual acuity in primary and junior high school: Verification of the current vision test

The deterioration of children’s eyesight is on the rise. Children's lives have changed in a short period of time, such as an increase in blue light due to the use of electronic devices. It is necessary to consider non traditional content of health guidance for prevention. The accurate visual acuity test is important to examine the effects of visual acuity and environmental or living factors. We examined the accuracy of the visual acuity test with the three-stage Landolt ring for children from the relationship with the eye axial length. After performing a normal detailed visual acuity test of the children and the correlation analysis with the eye axial length, we examined the distribution of t he eye axis according to the results of the three stage visual acuity test by the Landolt ring The number of children measured eye axial length was 13. The correlation coefficient between detailed visual acuity test and eye axial length was negative. Ac cording to the results of the three-stage visual acuity test, the distribution of the eye axis is good for the right eye: the average eye axis of “A” was 23.44 mm, moderate: the average of “B” was 22.58 mm. The average of the left eye axis for “A” children is 23.34 mm, for “B” is 23.08 mm, and for “C” is 23.7 mm. The correlation coefficient between the detailed visual acuity test and the eye axial length was negative on both sides, namely a negative correlation between the visual acuity and the eye axial length. There was a possibility of not correspondence between the three-stage visual test and theeye axial length. In the case of children, it was considered that their visual performance and answers were different because of their mood and physical condition on the day

Damage of Membrane Functions in the Yeast Saccharomyces cerevisiae by Near-UV Irradiation

酵母Saccharomyces cerevisiaeに長波長紫外光を照射すると,酵母の生存率は光量に依存して急激に低下した.この現象の発現機構についての知見を得るために,細胞膜機能として非常に重要な透過障壁能と能動輸送能の長波長紫外照射による損傷について,光量一効果曲線を作成して調べた. 酵母に10J/mlの長波長紫外光を照射すると生存率は50%に低下する.この照射光量は,細胞膜の透過障壁能の破壊を引き起こし,細胞内のカリウムイオンおよびナトリウムイオンの非選択的漏出と細胞膜非透過性物質の細胞内への浸入をもたらした .5J/ml以下の光量は酵母の生存率にほとんど影響を与えないが,アミノ酸の取り込み速度の著しい低下とポンプあるいはチャンネル機構の損傷を予想させるカリウムイオンの選択的漏出をもたらした.また,動力学的解析結果から,アミノ酸の取り込み速度低下の要因は､細胞膜表面に存在するレセプターの損傷によるものではなく､受容以降の輸送系の損傷によることが示唆された

TGR5活性化はアナグリプチンによる糖尿病ラットに対する肝線維化抑制効果を増強する

Hyperglycemia and hyperinsulinemia activate the proliferative potential of hepatic stellate cells (HSCs) and promote hepatic fibrosis. Dipeptidyl peptidase-4 (DPP-4) inhibitors, antidiabetic agents, reportedly inhibit the HSC proliferation. Additionally, Takeda G protein-coupled receptor 5 (TGR5) agonists induce the systemic release of glucagon-like peptides from intestinal L cells, which maintains glycemic homeostasis. This study assessed the combined effect of TGR5 agonist and DPP-4 inhibitor on diabetes-based liver fibrosis development. Male diabetic rats received intraperitoneal injection of porcine serum (PS) to induce liver fibrosis, and they were orally administered the following agents: oleanolic acid (OA) as a TGR5 agonist, anagliptin (ANA) as a DPP-4 inhibitor, and a combination of both agents. Treatment with OA or ANA significantly improved glycemic status and attenuated intrahepatic steatosis and lipid peroxidation in diabetic rats. PS-induced liver fibrosis development was also drastically suppressed by treatment with either agent, and the combination of both reciprocally enhanced the antifibrotic effect. Fecal microbiome demonstrated that both agents inhibited the increase in the Firmicutes/Bacteroidetes ratio, an indicator of dysbiosis related to metabolic syndromes. Furthermore, ANA directly inhibited in vitro HSC proliferative and profibrogenic activities. Collectively, TGR5 agonist and DPP-4 inhibitor appears to be a novel strategy against liver fibrosis under diabetic conditions.博士（医学）・甲第766号・令和3年3月15日© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)

Radiation and Health in Kindergarten, Elementary, and Junior High Schools Consistently : Efforts to Enhance Health and Environmental Awareness from the Perspective of Health and Science Education

原発災害等による放射能に対する健康不安や風評対策として，平常時から子どもが安全な環境や，放射線についての知識や判断の仕方，身の回りの安全な生活について学習しておく必要性が高いと考え，本研究では，安全な環境や放射線についての正しい認識を深める学習のあり方を検討することを目的とした。 理科教育と保健指導の連携によって，本校の中学３年生に「放射線学習・放射線と健康」の指導を行い，指導の前後で評価した。実際の実践は，理科分野では中学生の放射線に対する科学的な認識を育成するために環境測定を実施し，データの集積や実験を通して科学的な根拠に基づいた学習を展開した。また,学校保健分野では保健指導として，理科で学習した知識を活かして日常生活や健康との関連を考えさせ，環境の変化に伴う生活・健康課題の改善を図るために自分で情報を収集する手段について指導した。理科と学校保健が連携した指導は，知識と実生活を結びつけ，よりよく生きようという生きる力を育む教育となると考えられた。今後は，学校保健と社会科や技術家庭科との連携も充実させることで，更に効果的な学習と成りえる。The purpose of this study was to consider instructions for maintaining a safe environment and correct awareness of radiation. Lessons on “Knowledge of Radiation” and “Radiation and Health” were given to ninth-grade students. Effects of learning were evaluated before and after classes. Teachers made students put environmental measurement to cultivate their scientific knowledge of radiation in science classes. Classes also addressed the scientific basis through data and experiments. In school health field, teachers asked students to consider relationships between daily life and health, using knowledge learned in science classes. Moreover, teachers guided the students’ means of collecting information to improve their daily life and ability to deal with health problems in the event of environmental changes. The instruction that linked science with school health tied daily lives to scientific knowledge. This instruction can make a contribution to an education that develops a “Zest for Living”. In the future, this instruction can be more effective by incorporating school health into social studies, industrial arts and homemaking

Synthesis and pharmacological characterization of potent, selective, and orally bioavailable isoindoline class dipeptidyl peptidase IV inhibitors

Focused structure-activity relationships of isoindoline class DPP-IV inhibitors have led to the discovery of 4b as a highly selective, potent inhibitor of DPP-IV. In vivo studies in Wistar/ST rats showed that 4b was converted into the strongly active metabolite 4l in high yield, resulting in good in vivo efficacy for antihyperglycemic activity

Omega-3 Polyunsaturated Fatty Acids Suppress the Cystic Lesion Formation of Peritoneal Endometriosis in Transgenic Mouse Models

Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) play a role in controlling pathological inflammatory reactions. Endometriosis is characterized by the presence of endometrial tissue on the peritoneum and an exaggerated inflammatory environment around ectopic tissues. Here peritoneal endometriosis was reproduced using a mouse model in which murine endometrial fragments were inoculated into the peritoneal cavity of mice. Fat-1 mice, in which omega-6 can be converted to omega-3 PUFAs, or wild type mice, in which it cannot, were used for the endometriosis model to address the actions of omega-3 PUFAs on the development of endometriotic lesions. The number and weight of cystic endometriotic lesions in fat-1 mice two weeks after inoculation were significantly less than half to those of controls. Mediator lipidomics revealed that cystic endometriotic lesions and peritoneal fluids were abundant in 12/15-hydroxyeicosapentaenoic acid (12/15-HEPE), derived from eicosapentaenoic acid (EPA), and their amount in fat-1 mice was significantly larger than that in controls. 12/15-Lipoxygenase (12/15-LOX)-knockout (KO) and control mice with or without EPA administration were assessed for the endometriosis model. EPA administration decreased the number of lesions in controls but not in 12/15-LOX-KO mice. The peritoneal fluids in EPA-fed 12/15-LOX-KO mice contained reduced levels of EPA metabolites such as 12/15-HEPE and EPA-derived resolvin E3 even after EPA administration. cDNA microarrays of endometriotic lesions revealed that Interleukin-6 (IL-6) expression in fat-1 mice was significantly lower than that in controls. These results suggest that both endogenous and exogenous EPA-derived PUFAs protect against the development of endometriosis through their anti-inflammatory effects and, in particular, the 12/15-LOX-pathway products of EPA may be key mediators to suppress endometriosis