Chemokines Up-Regulated in Epithelial Cells Control Senescence-Associated T Cell Accumulation in Salivary Glands of Aged and Sjögren’s Syndrome Model Mice

Immunosenescence is characterized by age-associated changes in immunological functions. Although age- and autoimmune-related sialadenitis cause dry mouth (xerostomia), the roles of immunosenescence and cellular senescence in the pathogenesis of sialadenitis remain unknown. We demonstrated that acquired immune cells rather than innate immune cells infiltrated the salivary glands (SG) of aged mice. An analysis of isolated epithelial cells from SG revealed that the expression levels of the chemokine CXCL13 were elevated in aged mice. Senescence-associated T cells (SA-Ts), which secrete large amounts of atypical pro-inflammatory cytokines, are involved in the pathogenesis of metabolic disorders and autoimmune diseases. The present results showed that SA-Ts and B cells, which express the CXCL13 receptor CXCR5, accumulated in the SG of aged mice, particularly females. CD4⁺ T cells derived from aged mice exhibited stronger in vitro migratory activity toward CXCL13 than those from young mice. In a mouse model of Sjögren’s syndrome (SS), SA-Ts also accumulated in SG, presumably via CXCL12-CXCR4 signaling. Collectively, the present results indicate that SA-Ts accumulate in SG, contribute to the pathogenesis of age- and SS-related sialadenitis by up-regulating chemokines in epithelial cells, and have potential as therapeutic targets for the treatment of xerostomia caused by these types of sialadenitis.     

A Bayesian propensity score adjustment for latent variable modeling and MCMC algorithm

The estimation of the differences among groups in observational studies is frequently inaccurate owing to a bias caused by differences in the distributions of covariates. In order to estimate the average treatment effects when the treatment variable is binary, Rosenbaum and Rubin [1983. The central role of the propensity score in observational studies for causal effects. Biometrika 70, 41-55] proposed an adjustment method for pre-treatment variables using propensity scores. Imbens [2000. The role of the propensity score in estimating dose-response functions. Biometrika 87, 706-710] extended the propensity score methodology for estimation of average treatment effects with multivalued treatments.However, these studies focused only on estimating the marginal mean structure. In many substantive sciences such as the biological and social sciences, a general estimation method is required to deal with more complex analyses other than regression, such as testing group differences on latent variables. For latent variable models, the EM algorithm or the traditional Monte Carlo methods are necessary. However, in propensity score adjustment, these methods cannot be used because the full distribution is not specified.In this paper, we propose a quasi-Bayesian estimation method for general parametric models that integrate out the distributions of covariates using propensity scores. Although the proposed Bayes estimates are shown to be consistent, they can be calculated by existing Markov chain Monte Carlo methods such as Gibbs sampler. The proposed method is useful to estimate parameters in latent variable models, while the previous methods were unable to provide valid estimates for complex models such as latent variable models.We also illustrated the procedure using the data obtained from the US National Longitudinal Survey of Children and Youth (NLSY1979-2002) for estimating the effect of maternal smoking during pregnancy on the development of the child's cognitive functioning.     

Polarization characteristics of poly(vinyl alcohol) films containing metal iodide

The polarization properties of iodine complex layer deposited by oxidation of poly(vinyl alcohol) (PVA) containing metal iodide were investigated. Heat-resistant polarizing films with high polarization efficiency were produced by oxidizing and stretching the PVA containing metal iodide. The results indicate that i) the polarization efficiency of a polarizing film prepared by oxidation of a PVA film containing 1 mmol or more of potassium iodide (KI)/g PVA at 0°C for 120 s in a 10 wt.-% aqueous solution of H₂O₂ and a degree of stretching of 400% is high, ii) the heat resistance of the polarizing film in this experiment is higher than that of a filter prepared from a commercial PVA film.     

Case performed: simultaneous surgery for left coronary ostial stenosis and gastric cancer

This report describes a case in which a 68-year-old male underwent two operations simultaneously for left coronary ostial stenosis and gastric cancer. Successfully performed procedures were a single coronary artery grafting with the saphenous vein to the left anterior descending artery, and a subtotal gastrectomy using the Billroth II method. The postoperative course was uneventful and the patient was discharged from the hospital in good condition after 42 days. At present, one-year postoperative, the patient has been visiting the outpatient clinic in healthy condition.     

A case of congenital tricuspid regurgitation associated with atrial septal defect and peripheral pulmonary stenosis

This report describes a 5-year-old girl with congenital tricuspid regurgitation associated with an atrial septal defect and peripheral pulmonary stenosis. The girl was diagnosed with the heart murmur at birth and recently developed the cardiomegaly. Cardiac echocardiography and catheterization showed severe tricuspid regurgitation, an atrial septal defect of the secundum type and peripheral pulmonary stenosis. In the operative findings, the tricuspid annulus was dilated to 33 mm in diameter, and leaflets were attached normally to the antomic annulus. There was a large cleft of the anterior leaflet of the tricuspid valve. Suture of the cleft and annuloplasty of the tricuspid valve, suture closure of the atrial septal defect and patch dilatation of peripheral pulmonary stenosis were successfully performed. Including this case, 19 other cases with congenital tricuspid regurgitation undergoing surgery were reported to date.     

Inhibitory effect of lead on the proliferation of cultured vascular endothelial cells

We investigated the effect of lead nitrate (0.5, 1.0, 2.0 or 5.0 microM) on the proliferation of cultured bovine aortic endothelial cells. After exposure to lead, the number of cells and the incorporation of [3H]thymidine into the acid-insoluble fraction of the cells were reduced in parallel in a concentration-dependent manner. Histologically, lead treatment resulted in a decrease in the cell number accompanied by a change in the cell shape from polygonal to spindle; however, no degenerative change was observed except in 5.0 microM lead-treated cells. Furthermore, stimulation of [3H]thymidine incorporation by either basic or acidic fibroblast growth factor was significantly reduced by lead. However, the leakage of lactate dehydrogenase into the medium from the cells, a marker of nonspecific cell damage, was not changed by lead. From these results, it was revealed that lead inhibits the proliferation of cultured vascular endothelial cells without nonspecific cell damage. Although lead does not destroy the monolayer of endothelial cells, the metal may exhibit its noxious effect in the repair process of the vascular endothelium.     

Development of 170 GHz/500 kW gyrotron

A development of 170GHz/500kW level gyrotron was carried out as R&D work of ITER. The oscillation mode is TE_31,8. In a short pulse experiment, the maximum power of 750kW was achieved at 85kV/40A. The efficiency was 22%. In the depressed collector operation, 500kW/36%/50ms was obtained. The maximum efficiency of 40% was obtained at P_RF=470kW whereas the power decrease by the electron trapping was observed. Pulse extension was done up to 10s at P_RF=170kW with the depressed collector operation. The power was limited by the temperature increase of the output window.