クロミプラミン急性及び慢性投与下におけるモノアミン代謝のラット脳内変化

金沢大学医学部研究課題/領域番号:63770810, 研究期間(年度):1988出典：研究課題「クロミプラミン急性及び慢性投与下におけるモノアミン代謝のラット脳内変化」課題番号63770810（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-63770810/）を加工して作

Potential role of vacuolar H+–adenosine triphosphatase in neointimal formation in cultured human saphenous vein

AbstractObjective: Vacuolar H+–adenosine triphosphatase plays a pivotal role in pH regulation and molecular transport across the vacuolar membranes and is involved in cell proliferation and transformation. In the present study, possible involvement of vacuolar H+–adenosine triphosphatase in neointimal formation was investigated in an organ culture model of human saphenous vein. Methods and results: Cultured saphenous vein segments developed neointimal formation and marked thickening of the media within 14 days. Neointimal formation and medial thickening were completely inhibited by 10 nmol/L bafilomycin A1, a selective inhibitor of vacuolar H+-adenosine triphosphatase, although structurally related macrolide antibiotics FK-506 and erythromycin were without an effect. The neointimal cells were positive for α-smooth muscle actin and vimentin but negative for desmin, indicative of myofibroblasts. The emergence of myofibroblasts was inhibited, and endothelial cells were preserved in the saphenous vein segments treated with bafilomycin A1. Uptake of bromodeoxyuridine, a proliferation marker, by myofibroblasts was abrogated in the saphenous vein segments treated with 10 nmol/L bafilomycin A1. Detection of apoptotic cells by terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling concomitant with identification of desmin-expressing smooth muscle cells demonstrated that neointimal myofibroblasts, but not medial smooth muscle cells, that expressed desmin underwent apoptosis by treatment with bafilomycin A1. Conclusions: These results suggest that vacuolar H+–adenosine triphosphatase may be involved in myofibroblast growth that contributes to neointimal formation and medial thickening in cultured human saphenous vein. Increased sensitivity of myofibroblasts, but not endothelial cells, and differentiated smooth muscle cells to bafilomycin A1 may have potential therapeutic implications in the treatment for vein graft disease. (J Thorac Cardiovasc Surg 2000;119:998-1007

Enterokinase and IAV Infection

Cleavage and activation of hemagglutinin (HA) by trypsin-like proteases in influenza A virus (IAV) are essential prerequisites for its successful infection and spread. In host cells, some transmembrane serine proteases such as TMPRSS2, TMPRSS4 and HAT, along with plasmin in the bloodstream, have been reported to cleave the HA precursor (HA0) molecule into its active forms, HA1 and HA2. Some trypsinogens can also enhance IAV proliferation in some cell types (e.g., rat cardiomyoblasts). However, the precise activation mechanism for this process is unclear, because the expression level of the physiological activator of the trypsinogens, the TMPRSS15 enterokinase, is expected to be very low in such cells, with the exception of duodenal cells. Here, we show that at least two variant enterokinases are expressed in various human cell lines, including A549 lung-derived cells. The exogenous expression of these enterokinases was able to enhance the proliferation of IAV in 293T human kidney cells, but the proliferation was reduced by knocking down the endogenous enterokinase in A549 cells. The enterokinase was able to enhance HA processing in the cells, which activated trypsinogen in vitro and in the IAV-infected cells also. Therefore, we conclude that enterokinase plays a role in IAV infection and proliferation by activating trypsinogen to process viral HA in human cell lines

Oral immunotherapy combined with omalizumab for high–risk cow’s milk allergy : a randomized controlled trial

We evaluated the efficacy and safety of oral immunotherapy (OIT) combined with 24 weeks of omalizumab (OMB) at inducing desensitization in children with cow’s milk allergy (CM) compared with an untreated group. The present study was a prospective randomized controlled trial. Sixteen patients (age, 6–14 years) with high IgE levels to CM were enrolled in the present study. Patients were randomized 1:1 to receive OMB-OIT group or untreated group. The primary outcome was the induction of desensitization at 8 weeks after OMB was discontinued in OMB-OIT treated group and at 32 weeks after study entry. None of the 6 children in the untreated group developed desensitization to CM while all of the 10 children in the OIT-OMB treated group achieved desensitization (P < 0.001). A significantly decreased wheal diameter in response to a skin prick test using CM was found in the OMB-OIT treated group (P < 0.05). These data suggest that OIT combined with OMB using microwave heated CM may help to induce desensitization for children with high-risk CM allergy. This prospective randomized controlled trial was intended for 50 participants but was prematurely discontinued due to overwhelming superiority of OMB combined with microwave heated OIT over CM avoidance

Continuing mind for primary care medicine as total family care mailing list (TFC-ML) group

There were historically two great doctors for primary care (PC) medicine in Japan. They are Dr. Shigeaki Hinohara and Dr. Yoshikazu Tasaka. Tasaka was always active in medical treatment, organizational management, postgraduate education, and information dissemination using the Internet, and started Total Family Care Mailing List (TFC-ML) in 1998. TFC-ML included medical information with his comments every day for long. Even after his death in 2007, TFC-ML activity has been continued by many voluntary PC physicians. His TFC mind has been transmitted to future PC physicians. His inspiration may often come to TFC members for better total family care

Proliferation of parathyroid cells negatively correlates with expression of parathyroid hormone–related protein in secondary parathyroid hyperplasia

Proliferation of parathyroid cells negatively correlates with expression of parathyroid hormone-related protein in secondary parathyroid hyperplasia.BackgroundParathyroid hormone–related protein (PTHrP) is now suspected to act as an autocrine or paracrine regulator of cell growth or differentiation, although it was originally reported as a hypercalcemic substance in malignancies. This study was performed to assess the relationship between PTHrP expression and cell proliferation in human parathyroid glands.MethodsThe localization of PTH and PTHrP was studied in 42 samples of hyperplastic parathyroid from 14 long-term hemodialysis cases with immunohistochemistry and in situ hybridization. Results were compared with proliferative activity (proliferating cell nuclear antigen index: counts of proliferating cell nuclear antigen-positive cells/100 cells). The localization of the PTH/PTHrP receptor was also examined. Ten normal glands were studied as controls.ResultsIn hyperplasia, cells positive for PTH, PTHrP, or both were observed immunohistochemically. The areas expressing PTHrP mRNA completely coincided with those positive for PTHrP immunohistochemically. Oxyphilic or transitional oxyphilic cells were consistently positive for PTHrP. PTH/PTHrP receptors were located in the cytoplasmic membrane in most parathyroid cells. Proliferating cell nuclear antigen-positive cells were rare in normal glands with an index of 0.22 ± 0.09 (mean ± sem). They were significantly increased in hyperplastic cases but less for PTHrP-positive than for -negative cells (1.25 ± 0.16 as compared with 7.80 ± 0.52; P < 0.0001).ConclusionThe observed low level of proliferation of PTHrP-positive cells suggests a functional role for PTHrP as a possible growth suppressor in the human parathyroid

Developing Lesson Modules for Reconstruction of Perspectives on Peace and Meta-cognition of its Process

The aim of this study is to develop the module for peace education which helps learners to reconstruct their own perspectives on peace. Previous studies introducing lesson plans on peace education have limitation in that these lesson plans focus heavily on wars or issues unfamiliar to students. In addition, they were not intended to give opportunities to metacognize the reconstruction of perspectives on peace. The lesson module we developed consists of three section: introduction section, main section, closing section. The main section consists of six units, and we chose six concepts or theories with which learners reconstruct their perspectives on peace：(1)game theory, (2)Galtung’s theory of peace, (3)conflict resolution, (4)authoritarian personality, (5)labeling theory, and, (6)social identity. This lesson module includes not only various concepts or theories about peace but also the process through which learners reconstruct their own perspectives on peace and reflection on the process in order to cultivate peace-makers

The method of lesson study based on the structure of the subject: the case of primary social studies classroom

This study presents the case study of the lesson study in a primary social studies classroom in Japan. The result indicates to propose a new method of social studies lesson study. While previous method tended to pay less attention to the context of school and children because of the focus of generalization, this study highlights the reality of diverse children in a classroom settings. Throughout the study, we compared the two items: The structure of the subject, namely, triangle relation of goals, contents, and methods and learner 's learning structure. Comparing the two items, we could see the effect of the process of teaching and learning on the children. It means that we can propose the new method by focusing on the reality of the classroom

A Report on Overseas Teaching Practicum by Graduate Students in Elementary/Secondary Schools in the United States（Ⅺ）

This paper reports on the 11th overseas teaching practicum in the U.S. 12 students joined this year’s program and they observed and conducted lessons in English in three local public schools in North Carolina after careful and repeated preparation sessions in Japan. Many of them did lessons on crosscultural understandings and a few taught subject contents. Through the trail to convey messages in English, their foreign language, students learned the role of verbal and nonverbal language and the more universal way to explain topics to children who are unfamiliar with what re taught. And they also learned and noticed the cultural differences and similalities between the two countries. It seemed that students realized that the two countries share many things in common such as what chidren are like, teachers’ attitude toward children and challenges they are facing, and people’s kindness. These learning was no substitute experience for the participants and it is hoped that their experience will be passed to the next generation when they become teachers