CD74 interacts with APP and suppresses the production of Aβ

<p>Abstract</p> <p>Background</p> <p>Alzheimer disease (AD) is characterized by senile plaques, which are mainly composed of β amyloid (Aβ) peptides. Aβ is cleaved off from amyloid precursor protein (APP) with consecutive proteolytic processing by β-secretase and γ-secretase.</p> <p>Results</p> <p>Here, we show that CD74, the invariant chain of class II major histocompatibility complex, interacts with APP and serves as a negative regulator of Aβ. CD74 resembles other APP interacters such as BRI2 and BRI3, since all of them reduce the level of Aβ. However, unlike BRIs, CD74 does not reduce the secretion of sAPPα or sAPPβ. Interestingly, in HeLa cells, over expression of CD74 steers APP, but not Notch, to large vacuoles created by CD74.</p> <p>Conclusion</p> <p>Taken together, we propose that CD74 inhibits Aβ production by interacting with and derailing normal trafficking of APP.</p

Pathological Examination of Experimentally Induced Periodontal Polyp in Mice

The mechanism in the formation of periodontal polyp has been established in several histological studies but details on cell differentiation and/or proliferation have not been elucidated. In the present study, we established a convenient and possible experimental system using ddY mice. Briefly, pentobarbital sodium (Somnopentyl) was injected into the abdominal cavity of the mouse followed by access cavity preparation on maxillary first molar using low speed ½ round bur (Merufa Inc), exposing the pulp and then allowed to perforate the floor of the pulp chamber. Observation was done over time until 6 months using micro CT (m_CT) image photography. Results with transmission image using m_CT showed theexpansion in the width of the periodontal ligament in the furcation area. The lesion was excised as one mass and examined histopathologically. The granulation tissue was covered with stratified squamous epithelium. The present experimental technique has been confirmed to be effective in analyzing the formation of periodontal polyp induced by mechanical perforation

Potential of Panoramic Radiography as a Screening Method for Oral Hypofunction in the Evaluation of Hyoid Bone Position

The hyoid bone is located in the middle of the cervical muscles involved in oral masticatory function. The position of the hyoid bone is commonly determined by lateral cephalometric analysis. Although cephalometric radiography is commonly used in orthodontic treatment, the modality remains rare; routine dental care would benefit from precise identification of hyoid bone location using a more common modality, such as panoramic radiography. The purpose of this study was to investigate the usefulness of panoramic radiography compared to lateral cephalometric radiography for evaluating hyoid bone position as a potential screening method for oral hypofunction. The study included 347 patients referred for both a panoramic radiograph and a lateral cephalometric radiograph. The patients were divided into the following five groups according to the appearance of the hyoid bone in the panoramic radiograph: Group 1: hyoid bone could not be observed, or part of the greater horn was observed; Group 2: part of the hyoid body was observed, but not the most supero-anterior point of the hyoid bone; Group 3: the most supero-anterior point of the hyoid bone was observed; Group 4: all of the hyoid body was observed; Group 5: the hyoid body overlapped the mandible. The gold standard for measurement of hyoid bone position is the lateral cephalometric radiograph. Hyoid bone position as revealed by lateral cephalometric radiograph was compared among the groups. Hyoid bones that were observed in higher positions on lateral cephalometric radiograph were also observed in higher positions on panoramic radiograph. Hyoid bone position can be assessed by panoramic radiography, and this modality might be useful as a screening method for oral hypofunction

A novel dysphagia screening method using panoramic radiography

The purpose of this study was to establish a screening method for dysphagia using panoramic radiography. Seventy patients who had undergone panoramic radiography and videofluorographic swallowing study（VF）were selected. Exclusion criteria were surgery related to tumors, jaw deformity, and poor-quality panoramic radiograph images. Patients were diagnosed with dysphagia based on VF findings and accordingly categorized into Dysphagia（＋）or Dysphagia（−）groups. The control group consisted of 129 individuals who had undergone panoramic radiography for dental treatment. Exclusion criteria were the same as in the Dysphagia（＋）and Dysphagia（−）groups. Two maxillofacial radiologists assessed the vertical and horizontal position of the hyoid bone and measured the distance from the tongue to the palate. The vertical hyoid bone position was significantly lower in the Dysphagia（＋）group than in the control group. The distance from the tongue to the palate was significantly shorter in the control group, measuring 8.5±5.9mm as compared to 15.0±9.5 in the Dysphagia（＋）group and 14.9±10.0 in the Dysphagia（−）group. At least 77％ of patients were diagnosed with dysphagia or suspected of dysphagia because the hyoid body was below the mandibular line on panoramic radiography. Panoramic radiography may be a useful tool for predicting the risk of dysphagia as it reveals the vertical hyoid bone position and the distance from the tongue to the palate

PrP in M2 macrophages and influenza

The cellular prion protein, PrPC, is a glycosylphosphatidylinositol anchored-membrane glycoprotein expressed most abundantly in neuronal and to a lesser extent in non-neuronal cells. Its conformational conversion into the amyloidogenic isoform in neurons is a key pathogenic event in prion diseases, including Creutzfeldt-Jakob disease in humans and scrapie and bovine spongiform encephalopathy in animals. However, the normal functions of PrPC remain largely unknown, particularly in non-neuronal cells. Here we show that stimulation of PrPC with anti-PrP monoclonal antibodies (mAbs) protected mice from lethal infection with influenza A viruses (IAVs), with abundant accumulation of anti-inflammatory M2 macrophages with activated Src family kinases (SFKs) in infected lungs. A SFK inhibitor dasatinib inhibited M2 macrophage accumulation in IAV-infected lungs after treatment with anti-PrP mAbs and abolished the anti-PrP mAb-induced protective activity against lethal influenza infection in mice. We also show that stimulation of PrPC with anti-PrP mAbs induced M2 polarization in peritoneal macrophages through SFK activation in vitro and in vivo. These results indicate that PrPC could activate SFK in macrophages and induce macrophage polarization to an anti-inflammatory M2 phenotype after stimulation with anti-PrP mAbs, thereby eliciting protective activity against lethal infection with IAVs in mice after treatment with anti-PrP mAbs. These results also highlight PrPC as a novel therapeutic target for IAV infection

マウスにおける実験的根尖部炎症病変の確立

Abstract: Although studies on the formation of apical periodontitis have somehow been carried out but detailed cellular dynamics remain unclear. We recently established an experiment that could easily be performed using ddY mice. First, under general anesthesia using isoflurane inhalation, the coronal portion of the maxillary first molar was penetrated using a round bur and drill with water irrigation causing pulp exposure until the root apex. Micro computed tomography (R_mCT) was taken over time during observation. Four weeks later, R_mCT confirmed the presence of a radiolucent image at the apex of the tooth, which was then removed for histological examination. The results showed that granulation tissue with fibrosis had gradually formed at the periphery of the abscess. The present method confirmed the effectiveness of the experimental mode to exmine the formation of chronic inflammatory lesions at the root apex.根尖部炎症病変のマウスモデルを作製した。マウスをイソフラン吸入により麻酔し、上顎第1大臼歯の歯冠部をラウンドバーにより貫通させた後、水の灌注により穴をあけて根尖まで歯髄を露出させた。処置の4週間後、根尖部にX線透過性部位が存在することが、マイクロコンピュータートモグラフィーにより確認された。この部位について組織学的検査を行った結果、線維増生を示す肉芽組織が膿瘍の周辺に徐々に形成されることが明らかになった。以上より、本モデルは根尖部の慢性炎症病変の形成を調べる上で有用であることが示された

ピルビンサン ダッスイソ コウソ フクゴウタイ イジョウショウ ジョジ カンジャ ノ イデンシ シンダン システム ノ カクリツ

Pyruvate dehydrogenase (PDH) complex deficiency is one of the important causes of congenital lactic acidemia and mostly due to defect in the α subunit of PDH (E1α), of which gene is located on the X chromosome. The diagnosis of the PDH E1α deficiency is usually established by the measurement of the PDH complex activity in cultured cells. However, some female patients, who are heterozygous for the mutant allele, cannot be diagnosed only by the assay of PDH complex activity, because of the skewed X-chromosome inactivation in cultured cells. Then, we established DNA diagnostic system for PDH E1α deficiency using X inactivation assay, no RI PCR-SSCP, and direct sequencing. With this DNA diagnostic system we could diagnose 4 female patients as PDH E1α deficiency from 14 female patients who were suspected PDH complex deficiency from the clinical features and concentrations of lactate and pyruvate in the blood but showed normal PDH complex activity in their cultured cells. These results indicate that this DNA diagnostic system for PDH E1 αdeficiency is very useful

焼結ルチル二酸化チタン上の骨芽細胞様細胞の増殖およびアルカリホスファターゼ活性

The purpose of this study is creation of biomaterials from titanium dioxide (TiO2). This TiO2 has known for photocatalysis and osteogenesis. For the purpose of applying this function to orthodontic brackets and coating materials for implant, the relationship between surface of sintered and cell proliferation were examined. In addition, crystal structure and the surface property of sintering TiO2 were investigated. TiO2 were sintered at 1300°C for use as samples. We examined surface roughness, x-ray diffraction and scanning electron microscopy to make observations of the surface properties and texture. Moreover, mouse osteoblast-like cell line, MC3T3-E1 was cultured on sintered TiO2 in order to evaluate the cell proliferation and ALP. For the samples sintered at 1300°C, the crystalline phase of rutile-type TiO2 was confirmed.5000-fold magnified SEMimages of the surface of the unsintered samples, needle-like TiO2 crystals were pressure welded and showed mutual overlap, with pores occurring among the crystals. Sintering at 1300°C produced numerous small pores. Rutile TiO2 as a starting material was sintered at 1300°C and subjected to a cell culture experiment in which MC3T3-E1 cells were cultured on the sample, followed by viable cell counting and cell morphology observationon days 7, 14, 21, and 28 of culture. In the test of cell proliferation, sintered at 1300°C samples was found to remarkable cell proliferation even after time had passed. ALP activity of cells on 1300°C TiO2 sample, the values were 110% and 126% on days 14 and 28 of culture, respectively. These changes were calculated using polystyrene dish as the reference condition. Thus, TiO2 sintered at 1300°C showed good compatibility and increase in the ALP activity in MC3T3-E1 cells