基板上における低次元スピン系の構築と微視的評価

学位の種別: 課程博士審査委員会委員 : （主査）東京大学准教授 長谷川 幸雄, 東京大学教授 福谷 克之, 東京大学教授 嶽山 正二郎, 東京大学教授 長谷川 修司, 東京大学准教授 加藤 岳生University of Tokyo(東京大学

Do calcineurin inhibitors influence the serum concentrations of mizoribine?

Background: Mizoribine (MZR) is an antimetabolite that inhibits inosine-monophosphate dehydrogenase and has been used for preventing rejection in renal transplantation. However, the effect of calcineurin inhibitors (CNIs) on the pharmacokinetics of MZR has not been shown. This study was performed to show the influence of CNIs (tacrolimus [Tac] or cyclosporine [CyA]) on the serum concentration of MZR.Methods: Thirty-four living-donor renal transplant recipients administered a four-drug immunosuppressive therapy regimen (steroid, CNIs, basiliximab and MZR 6 mg/kg/day) were investigated. 20 recipients were treated with Tac and 14 were with CyA. Serum concentrations of MZR were obtained retrospectively at 464 points and at 243 points for each. Population pharmacokinetic (PPK) analysis was used to make pharmacokinetic models of serum MZR. After statistically evaluating the correlation of the pharmacokinetic models with the actual data, areas under the curves (AUCs) of each CNI were also estimated in these models and statistically evaluated.Results: The mean values of the PPK parameters (absorption lag time, absorption rate constant [Ka], apparent volume of distribution [V/F] and oral clearance of MZR [CLMZR/F]) were 0.600 hr and 0.643 hr, 1.14/hr and 0.911/hr, 0.732×body weight (WT) (L) and 0.784×WT (L), and 1.64×creatinine clearance (CLcr) (L/hr) and 1.81×CLcr (L/hr), respectively. Moreover, the serum concentrations of MZR at all-time points were estimated with these parameters. The correlation coefficients between the individual actual and estimated serum concentrations of MZR in the Tac group and the CyA group were 0.988 and 0.992, respectively. The average value of the AUCs of MZR corrected by the CLcr in the Tac group, and the CyA group were 0.61±0.21 and 0.55±0.19 (average value±standard deviation) for each (p=0.19).Conclusion: These findings suggest the pharmacokinetics of MZR were well-described by 1-compartment model with first-order absorption. Moreover, concomitant use of CNIs, e.g., Tac and CyA, may have no significant influence on the pharmacokinetics of MZR

Conjugate Simulation of Flow and Heat Conduction with a New Method for Faster Calculation

ABSTRACT

Factors influencing long-term survival after aortic valve replacement.

In the aortic stenosis group, the left ventricular (LV) muscle mass index was a good parameter for predicting the prognosis. Associated mitral valve disease had no influence on long term survival after aortic valve replacement. In the aortic insufficiency group, associated mitral valve disease had a marked influence on the results of aortic valve replacement. In general, the aortic insufficiency group had less clinical improvement postoperatively than the aortic stenosis group. In the annuloaortic ectasia group, left ventricular enddiastolic pressure (LVEDP) might be the predictor to the prognosis. This group had the worst prognosis, of the three groups. Early operation should be considered for patients who have no, or only mild symptoms of, aortic valve disease.</p

Virulent Strain of Hepatitis E Virus Genotype 3, Japan

Virulence may be associated with mutation of the helicase domain (V239A), and source of the human infection may be swine

Serum NY-ESO-1 antibody as a predictive biomarker for postoperative recurrence of gastric cancer: a multicenter prospective observational study

The version of record of this article, first published in British Journal of Cancer, is available online at Publisher’s website: https://doi.org/10.1038/s41416-023-02540-3Background: No reliable marker has been identified to predict postoperative recurrence of gastric cancer. We designed a clinical trial to investigate the utility of serum NY-ESO-1 antibody responses as a predictive marker for postoperative recurrence in gastric cancer. Methods: A multicenter prospective study was conducted between 2012 and 2021. Patients with resectable cT3-4 gastric cancer were included. Postoperative NY-ESO-1 and p53 antibody responses were serially evaluated every 3 months for 1 year in patients with positive preoperative antibody responses. The recurrence rate was assessed by the positivity of antibody responses at 3 and 12 months postoperatively. Results: Among 1001 patients, preoperative NY-ESO-1 and p53 antibody responses were positive in 12.6% and 18.1% of patients, respectively. NY-ESO-1 antibody responses became negative postoperatively in non-recurrent patients (negativity rates; 45% and 78% at 3 and 12 months, respectively), but remained positive in recurrent patients (negativity rates; 9% and 8%, respectively). p53 antibody responses remained positive in non-recurrent patients. In multivariate analysis, NY-ESO-1 antibody positivity at 3 months (P < 0.03) and 12 months (P < 0.001) were independent prognostic factors for a shorter recurrence-free interval. Conclusions: Serum NY-ESO-1 antibodies may be a useful predictive marker for postoperative recurrence in gastric cancer. Clinical trial registration: UMIN000007925

Pink-Colored Grape Berry Is the Result of Short Insertion in Intron of Color Regulatory Gene

We report here that pink grape berries were obtained by a short insertion in the intron of the MybA1 gene, a gene that regulates grape berry color. Genetic variation was detected among the MybA1 genes from grapes cultivated worldwide. PCR analysis of the MybA1 gene demonstrated that the size of the MybA1 gene in the red allele differs among grapes. Oriental V. vinifera bearing pink berries has the longest MybA1 gene among grapes, whereas the shortest MybA1 gene was detected in occidental V. vinifera grapes. The nucleotide sequences of the MybA1 genes demonstrated that oriental V. vinifera has two additional gene fragments (44 bp and 111 bp) in the promoter region of the MybA1 gene in the red allele and another 33 bp fragment in the second intron of the MybA1 gene in the red allele. The short insertion in the intron decreased the transcription activity in the model system and retained MybA1 transcripts with unspliced intron in the total RNA. From the experiments using deletion mutants of the 33 bp short insertion, 16 bp of the 3′ end in the insertion is a key structure for a defect in splicing of MybA1 transcripts. Thus, a weakly colored grape berry might be a result of the short insertion in the intron of a color regulatory gene. This is new evidence concerning the molecular mechanism of the fate of grape berry color. These findings are expected to contribute to the further understanding of the color variation in grape berries, which is correlated with the evolutional events occurring in the MybA1 gene of grapes

クシロガワリュウイキ ノ イトウ HUCHO PERRYI サンランカセン ニ オケル レキノイドウ キョウキュウ ニ カンスル チョウサケンキュウ

北海道東部の緩蛇行河川において,サケ科魚類イトウHucho perryiの産卵床は,蛇行区間の崖が洗掘され,堆積したと思われる河床の礫底に造成される傾向にある。そこで本研究においては,崖が存在する蛇行区間と崖が存在しない蛇行区間の物理環境を測定し,礫の供給が崖に依存しているか否かを調査した。結果,両蛇行区間の比較において,川幅,流速,半径に有意差はなかったが,水深は崖のある蛇行で有意に浅く,礫サイズも崖のある蛇行で有意に大きかった。また融雪増水時に投入した礫に移動が認められなかったことから,礫の供給は上流域からではなく崖が洗掘されることにより供給されるものと推定された。In eastern Hokkaido, Kushiro river basin where the redd of japanese huchen is observed, the river cliff eroded, and gravel accumulated. In this study, the physical environment was measured in order to examine just how the river precipice is the supply source of the gravel. As a result, no significant differences were indicated in the river width, velocity and the radius but the river depth in the meander with river cliff is significantly shallower than the one without river cliff and the size of gravel in the meander with cliff is significantly larger than the one without river cliff. Additionally, there was no obvious migration of gravel by freshet of snow melting. In conclusion, it was extrapolated that the gravel was provided not from upstream but by the eroding of the river cliff