Divergent roles of Smad3 and PI3-kinase in murine adriamycin nephropathy indicate distinct mechanisms of proteinuria and fibrogenesis

Multiple transforming growth factor (TGF)-β-induced fibrogenic signals have been described in vitro. To evaluate mechanisms in vivo, we used an adriamycin nephropathy model in 129x1/Svj mice that display massive proteinuria by day 5 to7 and pathological findings similar to human focal segmental glomerulosclerosis by day 14. TGF-β mRNA expression increased after day 7 along with nuclear translocation of the TGF-β receptor-specific transcription factor Smad3. Inhibiting TGF-β prevented both pathological changes and type-I collagen and fibronectin mRNA expression, but proteinuria persisted. Renal Akt was phosphorylated in adriamycin-treated mice, suggesting PI3-kinase activation. Expression of mRNA for the p110γ isozyme of PI3-kinase was specifically increased and p110γ colocalized with nephrin by immunohistochemistry early in disease. Nephrin levels subsequently decreased. Inhibition of p110γ by AS605240 preserved nephrin expression and prevented proteinuria. In cultured podocytes, adriamycin stimulated p110γ expression. AS605240, but not a TGF-β receptor kinase inhibitor, prevented adriamycin-induced cytoskeletal disorganization and apoptosis, supporting a role for p110γ in podocyte injury. AS605240, at a dose that decreased proteinuria, prevented renal collagen mRNA expression in vivo but did not affect TGF-β-stimulated collagen induction in vitro. Thus, PI3-kinase p110γ mediates initial podocyte injury and proteinuria, both of which precede TGF-β-mediated glomerular scarring

Visualization of mandibular movement relative to the maxilla during mastication in mice: integration of kinematic analysis and reconstruction of a three-dimensional model of the maxillofacial structure

Background: Mastication is one of the most fundamental functions for the conservation of human life. To clarify the pathogenetic mechanism of various oral dysfunctions, the demand for devices for evaluating stomatognathic function has been increasing. The aim of the present study was to develop a system to reconstruct and visualize 3-dimensional (3D) mandibular movements relative to the maxilla, including dynamic transition of occlusal contacts between the upper and lower dentitions during mastication in mice.Methods: First, mandibular movements with six degrees of freedom were measured using a motion capture system comprising two high-speed cameras and four reflective markers. Second, 3D models of maxillofacial structure were reconstructed from micro-computed tomography images. Movement trajectories of anatomical landmark points on the mandible were then reproduced by integrating the kinematic data of mandibular movements with the anatomical data of maxillofacial structures. Lastly, 3D surface images of the upper dentition with the surrounding maxillofacial structures were transferred to each of the motion capture images to reproduce mandibular movements relative to the maxilla. We also performed electromyography (EMG) of masticatory muscles associated with mandibular movements.Results: The developed system could reproduce the 3D movement trajectories of arbitrary points on the mandible, such as incisor, molars and condylar points with high accuracy and could visualize dynamic transitions of occlusal contacts between upper and lower teeth associated with mandibular movements.Conclusions: The proposed system has potential to elucidate the mechanisms underlying motor coordination of masticatory muscles and to clarify their roles during mastication by taking advantage of the capability to record EMG data synchronously with mandibular movements. Such insights will enhance our understanding of the pathogenesis and diagnosis of oral motor disorders by allowing comparisons between normal mice and genetically modified mice with oral behavioral dysfunctions

Diagnosis of Myocardial Viability by Fluorodeoxyglucose Distribution at the Border Zone of a Low Uptake Region

Purpose: In cardiac 2-[F-18]fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET) examination, interpretation of myocardial viability in the low uptake region (LUR) has been difficult without additional perfusion imaging. We evaluated distribution patterns of FDG at the border zone of the LUR in the cardiac FDG-PET and established a novel parameter for diagnosing myocardial viability and for discriminating the LUR of normal variants. Materials and Methods: Cardiac FDG-PET was performed in patients with a myocardial ischemic event (n = 22) and in healthy volunteers (n = 22). Whether the myocardium was not a viable myocardium (not-VM) or an ischemic but viable myocardium (isch-VM) was defined by an echocardiogram under a low dose of dobutamine infusion as the gold standard. FDG images were displayed as gray scaled-bull’s eye mappings. FDG-plot profiles for LUR ( = true ischemic region in the patients or normal variant region in healthy subjects) were calculated. Maximal values of FDG change at the LUR border zone (a steepness index; Smax scale/pixel) were compared among not-VM, isch-VM, and normal myocardium. Results: Smax was significantly higher for n-VM compared to those with isch-VM or normal myocardium (ANOVA). A cut-off value of 0.30 in Smax demonstrated 100 % sensitivity and 83 % specificity for diagnosing n-VM and isch-VM. Smax less than 0.23 discriminated LUR in normal myocardium from the LUR in patients with both n-VM and isch-VM with a 94 % sensitivity and a 93 % specificity. Conclusion: Smax of the LUR in cardiac FDG-PET is a simple and useful parameter to diagnose n-VM and isch

遺伝子診断教育のための簡便な毛髪形態（EDAR）及び耳垢型（ABCC11）遺伝子多型解析法

Recently, progress in molecular biology is being made in various fields such as biology, agriculture and medical and pharmaceutical sciences. Students graduating from not only pharmaceutical departments but also general high schools will be required to have knowledge of molecular biology techniques for understanding prevailing technologies. However, it is difficult to include such experiments in a curriculum for students at general high schools and universities because of safety aspect, expensive materials and experimental equipment and time consumed. This report introduces the convenient experimental methods on human DNA polymorphisms for the genotyping of the hair thickness-determining gene EDAR on the chromosome 2 and the earwax type gene ABCC11 on the chromosome 16 using a PCR-RFLP method. This experiment enables each student to handle DNA safely. The total experiment time is less than 6 hours. The PCR-RFLP experiment proposed here is a suitable genotyping method to acquire molecular biological knowledge and techniques

Study on the way of educational practical training of special needs education in at the special needs class in the affiliated school, Hiroshima Univerisity

本研究は，附属学校の特別支援学級における教育実習において，実習終了後に行う公立特別支援学校での教育実習のさらなる充実を図り，学部の教育と附属の実習，公立特別支援学校での実習の連続性整備のためにプログラムの見直しや改善を図ると共に，そのあり方について検討する。附属東雲小学校・中学校は大学の特別支援教育学講座と連携し，教育実習の内容の検討や改善に向けての提言を受ける他，具体的な大学における取り組みとも連動するようにした。さらに，特別支援教育実習協議会を通して特別支援学校との連携を図り，実習校と学生へのアンケート調査によって課題を明らかにした。また，全国の附属学校特別支援学級の連絡協議会を活用し，教育実習における実情や課題を情報交換することで、情報の共有化を図り新たな知見も得た。このような取り組みを進めていく中で，実習の事前指導にあたり，公立特別支援学校との連携が不足していたことが課題としてあげられた。この課題を解決していくために，教育実習に対しての附属学校としての取り組みを改善すると共に，より具体的かつ実用的な指導や評価を行い，内容を引き継ぐシステムの構築が必要であることが明らかとなった。The purpose of this research is to improve the teaching practice at the public special support school which is carried out after completion of the educational practice of the attached school special support class and to improve the educational practice of the undergraduate school and the special special support school We reviewed the contents of teaching practice and examined improvement. Attached Shinonome Elementary School and Junior High School have a special support education course lecture of the Graduate school of pedagogy and a public education practice meeting with the public special support school, and from the questionnaire survey to each school and the student, lack of cooperation with the public special support school It was made clear that it was. In order to solve the problem, it is necessary to instruct teacher interns more practical guidance and evaluation, and to inherit the contents to the public special support school