免疫組織染色法によるヒストンH3リジン9の修飾とメチル化酵素の検出および骨格系細胞分化過程におけるそれらの局在変化

早大学位記番号:新6540早稲田大

Honesty mediates the relationship between serotonin and reaction to unfairness

How does one deal with unfair behaviors? This subject has long been investigated by various disciplines including philosophy, psychology, economics, and biology. However, our reactions to unfairness differ from one individual to another. Experimental economics studies using the ultimatum game (UG), in which players must decide whether to accept or reject fair or unfair offers, have also shown that there are substantial individual differences in reaction to unfairness. However, little is known about psychological as well as neurobiological mechanisms of this observation. We combined a molecular imaging technique, an economics game, and a personality inventory to elucidate the neurobiological mechanism of heterogeneous reactions to unfairness. Contrary to the common belief that aggressive personalities (impulsivity or hostility) are related to the high rejection rate of unfair offers in UG, we found that individuals with apparently peaceful personalities (straightforwardness and trust) rejected more often and were engaged in personally costly forms of retaliation. Furthermore, individuals with a low level of serotonin transporters in the dorsal raphe nucleus (DRN) are honest and trustful, and thus cannot tolerate unfairness, being candid in expressing their frustrations. In other words, higher central serotonin transmission might allow us to behave adroitly and opportunistically, being good at playing games while pursuing self-interest. We provide unique neurobiological evidence to account for individual differences of reaction to unfairness

Annexin A5 involvement in bone overgrowth at the enthesis

Little is known about the molecular mechanisms of enthesis formation in mature animals. Here, we report that annexin A5 (Anxa5) plays a critical role in the regulation of bone ridge outgrowth at the entheses. We found that Anxa5 is highly expressed in the entheses of postnatal and adult mice. In Anxa5‐deficient (Anxa5–/–) mice, the sizes of bone ridge outgrowths at the entheses of the tibiae and femur were increased after 7 weeks of age. Bone overgrowth was not observed at the fibrous enthesis where the fibrocartilage layer does not exist. More ALP‐expressing cells were observed in the fibrocartilage layer in Anxa5–/– mice than in wild‐type (WT) mice. Calcein and Alizarin Red double labeling revealed more mineralized areas in Anxa5–/– mice than WT mice. To examine the effects of mechanical forces, we performed tenotomy in which transmission of contractile forces by the tibial muscle was impaired by surgical muscle release. In tenotomized mice, bone overgrowth at the enthesis in Anxa5–/– mice was decreased to a level comparable to that in WT mice at 8 weeks after the operation. The tail‐suspended mice also showed a decrease in bone overgrowth to similar levels in Anxa5–/– and WT mice at 8 weeks after hindlimb unloading. These results suggest that bone overgrowth at the enthesis requires mechanical forces. We further examined effects of AnxaA5 gene knockdown (KD) in primary cultures of osteoblasts, chondrocytes, and tenocytes in vitro. AnxaA5 KD increased ALP expression in tenocytes and chondrocytes but not in osteoblasts, suggesting that increased ALP activity in the fibrocartilaginous tissue in AnxaA5 KO mice is directly caused by Anxa5 deletion in tenocytes or fibrocartilage cells. These data indicate that Anxa5 prevents bone overgrowth at the enthesis, whose formation is mediated through mechanical forces and modulating expression of mineralization regulators

Immunohistochemical detection of methylated histone H3 lysine 9 and histone methyltransferases and implication of their roles during skeletal cell differentiation

早大学位記番号:新6540博士(人間科学)早稲田大

Mid- term results of stryker® scorpio plus mobile bearing total knee arthroplasty

BACKGROUND: The mobile bearing knee system was introduced to lessen contact stress on the articular bearing surface and reduce polyethylene wear. The purpose of the current study was to investigate the mid-term results of patients undergoing total knee arthroplasties (TKAs) using Scorpio Plus Mobile Bearing Knee System (Stryker, Mahwah, NJ), and compare the outcomes between patients with osteoarthritis and osteonecrosis (OA·ON group) and patients with rheumatoid arthritis (RA group). METHODS: Eight males and 58 females were followed up for a period of 4.4- 7.6 years from June 1, 2003 to December 31, 2005. There were 53 knees with osteoarthritis, 17 knees with rheumatoid arthritis, and 6 knees with osteonecrosis. Clinical and radiographic follow- up was done using The Japanese Orthopedic Association knee rating score (JOA score) and Knee Society Total Knee Arthroplasty Roentgenographic Evaluation and Scoring System. RESULTS: With regard to the JOA score, there was significant improvement in both groups. The postoperative range of motion was between 0.8°and 116.8° in OA·ON group, and between 0.0° and 113.7° in RA group. There were no significant differences with the radiographic evaluation between two groups. Spontaneous dislocation of a polyethylene insert occurred in one patient, and deep infection was occurred in one patient. CONCLUSION: There was significant improvement with regard to the clinical and radiographic results of patients undergoing TKAs using the model. The risk of polyethylene insert dislocation related to the mobile bearing TKA is a cause for concern

潜在的連想テスト(Implicit Association Test)のリスク認知への応用

早大学位記番号:新7568早稲田大

Phase I clinical trial of autologous NK cell therapy using novel expansion method in patients with advanced digestive cancer

Table S2. Change in NK population in PBL

The Periplasmic Chaperone Network of Campylobacter jejuni: Evidence that SalC (Cj1289) and PpiD (Cj0694) Are Involved in Maintaining Outer Membrane Integrity

The outer membrane (OM) of Gram-negative pathogenic bacteria is a key structure in host–pathogen interactions that contains a plethora of proteins, performing a range of functions including adhesion, nutrient uptake, export of effectors and interaction with innate and adaptive components of the immune system. In addition, the OM can exclude drugs and thus contribute to antimicrobial resistance. The OM of the food-borne pathogen Campylobacter jejuni contains porins, adhesins and other virulence factors that must be specifically localized to this membrane, but the protein sorting mechanisms involved are only partially understood. In particular, chaperones are required to ferry OM proteins across the periplasm after they emerge from the Sec translocation system. The SurA-related chaperone PEB4 (Cj0596) is the only protein with a proven role in OM biogenesis and integrity in C. jejuni. In this work, we have constructed a set of isogenic deletion mutants in genes encoding both known and predicted chaperones (cj0596, cj0694, cj1069, cj1228c, and cj1289) using NCTC 11168H as the parental strain. These mutants were characterized using a range of assays to determine effects on growth, agglutination, biofilm formation, membrane permeability and hydrophobicity. We focused on Cj1289 and Cj0694, which our previous work suggested possessed both chaperone and peptidyl-proyl cis/trans isomerase (PPIase) domains. Mutants in either cj1289 or cj0694 showed growth defects, increased motility, agglutination and biofilm formation and severe OM permeability defects as measured by a lysozyme accessibility assay, that were comparable to those exhibited by the isogenic peb4 mutant. 2D-gel comparisons showed a general decrease in OM proteins in these mutants. We heterologously overproduced and purified Cj0694 and obtained evidence that this protein was an active PPIase, as judged by its acceleration of the refolding rate of reduced and alkylated ribonuclease T1 and that it also possessed holdase-type chaperone activity. Cj0694 is most similar to the PpiD class of chaperones but is unusual in possessing PPIase activity. Taken together, our data show that in addition to PEB4, Cj1289 (SalC; SurA-like chaperone) and Cj0694 (PpiD) are also key proteins involved in OM biogenesis and integrity in C. jejuni