Contribution of transglutaminases and their substrate proteins to the formation of cornified cell envelope in oral mucosal epithelium

松本歯科大学大学院歯学独立研究科博士（歯学）学位申請論

口腔粘膜上皮における角質化細胞エンベロープ形成へのトランスグルタミナーゼと基質たんぱく質の寄与

Cornified envelope formation is crucial for the final differentiation of keratinized epithelium.However,the mechanisms of cornified envelope formation in the oral epithelium remain unclear.The aim of this study was to clarify the differences in the distribution and expression of cornified envelope related proteins and genes between keratinized and non-keratinized oral epithelia.We immunohistochemically investigated the distribution patterns of transglutaminase1(TG1),transglutaminase3(TG3),and their substrate proteins involucrin(IVL),loricrin(LOR),and small pro[1]line rich proteins(SPRs),in 19 keratinized and 14 non-keratinized oral epithelium samples.TG1 and TG3 mRNA levels were investigated in both types of epithelium by real time reverse transcription polymerase chain reaction(RT-PCR)using paraf[1]fin-embedded specimens.Data were analyzed to identify factors involved in cornified envelope formation.We demonstrate that 11 localization patterns show statistically significant differences between keratinized and non-keratinized oral epithelia.These factors clearly drove the separation of the two groups during cluster analysis.TG1 mRNA levels in keratinized oral epithelium were significantly higher than those in non-keratinized oral epithelium.In conclusion,the characteristic distribution of trans[1]glutaminases and their substrates and the mRNA levels of TG1 can regulate cornified envelope formation in keratinized oral epithelium, together with the contribution of TG3 first reported in this paper2021博士（歯学）松本歯科大

Management of coronary disease in patients with advanced kidney disease

BACKGROUND Clinical trials that have assessed the effect of revascularization in patients with stable coronary disease have routinely excluded those with advanced chronic kidney disease. METHODS We randomly assigned 777 patients with advanced kidney disease and moderate or severe ischemia on stress testing to be treated with an initial invasive strategy consisting of coronary angiography and revascularization (if appropriate) added to medical therapy or an initial conservative strategy consisting of medical therapy alone and angiography reserved for those in whom medical therapy had failed. The primary outcome was a composite of death or nonfatal myocardial infarction. A key secondary outcome was a composite of death, nonfatal myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. RESULTS At a median follow-up of 2.2 years, a primary outcome event had occurred in 123 patients in the invasive-strategy group and in 129 patients in the conservative-strategy group (estimated 3-year event rate, 36.4% vs. 36.7%; adjusted hazard ratio, 1.01; 95% confidence interval [CI], 0.79 to 1.29; P=0.95). Results for the key secondary outcome were similar (38.5% vs. 39.7%; hazard ratio, 1.01; 95% CI, 0.79 to 1.29). The invasive strategy was associated with a higher incidence of stroke than the conservative strategy (hazard ratio, 3.76; 95% CI, 1.52 to 9.32; P=0.004) and with a higher incidence of death or initiation of dialysis (hazard ratio, 1.48; 95% CI, 1.04 to 2.11; P=0.03). CONCLUSIONS Among patients with stable coronary disease, advanced chronic kidney disease, and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of death or nonfatal myocardial infarction

Health status after invasive or conservative care in coronary and advanced kidney disease

BACKGROUND In the ISCHEMIA-CKD trial, the primary analysis showed no significant difference in the risk of death or myocardial infarction with initial angiography and revascularization plus guideline-based medical therapy (invasive strategy) as compared with guideline-based medical therapy alone (conservative strategy) in participants with stable ischemic heart disease, moderate or severe ischemia, and advanced chronic kidney disease (an estimated glomerular filtration rate of <30 ml per minute per 1.73 m2 or receipt of dialysis). A secondary objective of the trial was to assess angina-related health status. METHODS We assessed health status with the Seattle Angina Questionnaire (SAQ) before randomization and at 1.5, 3, and 6 months and every 6 months thereafter. The primary outcome of this analysis was the SAQ Summary score (ranging from 0 to 100, with higher scores indicating less frequent angina and better function and quality of life). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate the treatment effect with the invasive strategy. RESULTS Health status was assessed in 705 of 777 participants. Nearly half the participants (49%) had had no angina during the month before randomization. At 3 months, the estimated mean difference between the invasive-strategy group and the conservative-strategy group in the SAQ Summary score was 2.1 points (95% credible interval, 120.4 to 4.6), a result that favored the invasive strategy. The mean difference in score at 3 months was largest among participants with daily or weekly angina at baseline (10.1 points; 95% credible interval, 0.0 to 19.9), smaller among those with monthly angina at baseline (2.2 points; 95% credible interval, 122.0 to 6.2), and nearly absent among those without angina at baseline (0.6 points; 95% credible interval, 121.9 to 3.3). By 6 months, the between-group difference in the overall trial population was attenuated (0.5 points; 95% credible interval, 122.2 to 3.4). CONCLUSIONS Participants with stable ischemic heart disease, moderate or severe ischemia, and advanced chronic kidney disease did not have substantial or sustained benefits with regard to angina-related health status with an initially invasive strategy as compared with a conservative strategy

Performance of the ALICE Electromagnetic Calorimeter

International audienceThe performance of the electromagnetic calorimeter of theALICE experiment during operation in 2010–2018 at the Large HadronCollider is presented. After a short introduction into the design,readout, and trigger capabilities of the detector, the proceduresfor data taking, reconstruction, and validation are explained. Themethods used for the calibration and various derived corrections arepresented in detail. Subsequently, the capabilities of thecalorimeter to reconstruct and measure photons, light mesons,electrons and jets are discussed. The performance of thecalorimeter is illustrated mainly with data obtained with test beamsat the Proton Synchrotron and Super Proton Synchrotron or inproton-proton collisions at √s = 13 TeV, and compared tosimulations

Measurement of the low-energy antitriton inelastic cross section

In this Letter, the first measurement of the inelastic cross section for antitriton−nucleus interactions is reported, covering the momentum range of 0.8≤p<2.4 GeV/c. The measurement is carried out using data recorded with the ALICE detector in pp and Pb−Pb collisions at a centre-of-mass energy per nucleon of 13 TeV and 5.02 TeV, respectively. The detector material serves as an absorber for antitriton nuclei. The raw yield of (anti)triton nuclei measured with the ALICE apparatus is compared to the results from detailed ALICE simulations based on the GEANT4 toolkit for the propagation of (anti)particles through matter, allowing one to quantify the inelastic interaction probability in the detector material. This analysis complements the measurement of the inelastic cross section of antinuclei up to A=3 carried out by the ALICE Collaboration, and demonstrates the feasibility of the study of the isospin dependence of inelastic interaction cross section with the analysis techniques presented in this Letter

First measurement of the ∣t∣|t|-dependence of incoherent J/ψ\psi photonuclear production

International audienceThe first measurement of the cross section for incoherent photonuclear production of J/$\psi$ vector meson as a function of the Mandelstam $|t|$ variable is presented. The measurement was carried out with the ALICE detector at midrapidity, $|y|<0.8$, using ultra-peripheral collisions of Pb nuclei at a centre-of-mass energy per nucleon pair $\sqrt{s_{\mathrm{NN}}} = 5.02$ TeV. This rapidity interval corresponds to a Bjorken-$x$ range $(0.3$$-$$1.4)\times 10^{-3}$. Cross sections are reported in five $|t|$ intervals in the range $0.04<|t|<1$~GeV$^2$ and compared to the predictions of different models. Models that ignore quantum fluctuations of the gluon density in the colliding hadron predict a $|t|$-dependence of the cross section much steeper than in data. The inclusion of such fluctuations in the same models provides a better description of the data

First measurement of the ∣t∣|t|-dependence of incoherent J/ψ\psi photonuclear production

International audienceThe first measurement of the cross section for incoherent photonuclear production of J/$\psi$ vector meson as a function of the Mandelstam $|t|$ variable is presented. The measurement was carried out with the ALICE detector at midrapidity, $|y|<0.8$, using ultra-peripheral collisions of Pb nuclei at a centre-of-mass energy per nucleon pair $\sqrt{s_{\mathrm{NN}}} = 5.02$ TeV. This rapidity interval corresponds to a Bjorken-$x$ range $(0.3$$-$$1.4)\times 10^{-3}$. Cross sections are reported in five $|t|$ intervals in the range $0.04<|t|<1$~GeV$^2$ and compared to the predictions of different models. Models that ignore quantum fluctuations of the gluon density in the colliding hadron predict a $|t|$-dependence of the cross section much steeper than in data. The inclusion of such fluctuations in the same models provides a better description of the data

Measurement of the low-energy antitriton inelastic cross section

International audienceIn this Letter, the first measurement of the inelastic cross section for antitriton$-$nucleus interactions is reported, covering the momentum range of $0.8 \leq p < 2.4$ GeV/$c$. The measurement is carried out using data recorded with the ALICE detector in pp and Pb$-$Pb collisions at a centre-of-mass energy per nucleon of 13 TeV and 5.02 TeV, respectively. The detector material serves as an absorber for antitriton nuclei. The raw yield of (anti)triton nuclei measured with the ALICE apparatus is compared to the results from detailed ALICE simulations based on the GEANT4 toolkit for the propagation of (anti)particles through matter, allowing one to quantify the inelastic interaction probability in the detector material. This analysis complements the measurement of the inelastic cross section of antinuclei up to $A=3$ carried out by the ALICE Collaboration, and demonstrates the feasibility of the study of the isospin dependence of inelastic interaction cross section with the analysis techniques presented in this Letter