The Role of the Supreme Court of Japan in the Field of Judicial Administration

This article focuses on the Japanese Supreme Court\u27s exercise of its power of judicial administration. The article places special emphasis on the management of the judiciary and on rulemaking, both quite novel to the Japanese court

The role of the corpus callosum in interhemispheric propagation of iron-induced epileptogenic activity in the rat.

In iron-induced epilepsy, partial section of the corpus callosum resulted in a decrease in rats showing dominant spike activity on the side of secondary focus and an increase in rats showing almost equal spike activity on the sides of primary and secondary focus in electrocorticograms (ECoGs). Changes in ECoG spike frequencies caused by sectioning the corpus callosum included an increase in unilateral spikes on the side of primary focus, a decrease in unilateral spikes on the side of secondary focus, and an increase in bilateral spikes appearing almost synchronously on both sides.</p

Regional difference in depolarization-elicited accumulation of cyclic AMP in cobalt-induced epileptic cortex of the rat.

The appearance of epileptiform discharges in electrocorticograms was induced by a unilateral injection of CoCl2 solution into the sensorimotor cortex of rats. Accumulation of cyclic AMP elicited by ouabain or a high concentration of potassium ions was determined in slices from different cortical areas of rats 9 or 10 days after the injection. In the anterior cortex, the depolarization-elicited accumulation of cyclic AMP was significantly higher in the cortical area ipsilateral to the injection site than in the contralateral cortical area. In the posterior cortex, a similar but not significant difference in the accumulation of cyclic AMP was noted.</p

Expression of Toll-Like Receptor 4 Contributes to Corneal Inflammation in Experimental Dry Eye Disease

Purpose. To investigate the corneal expression of toll-like receptor (TLR) 4 and determine its contribution to the immunopathogenesis of dry eye disease (DED). Methods. Seven to 8-week-old female C57BL/6 mice were housed in a controlled environment chamber and administered scopolamine to induce experimental DED. Mice received intravenous TLR4 inhibitor (Eritoran) to block systemic TLR4-mediated activity. The expression of TLR4 by the corneal epithelium and stroma was evaluated using real-time polymerase chain reaction and flow cytometry. Corneal fluorescein staining (CFS) was performed to evaluate clinical disease severity. The corneal expression of proinflammatory cytokines (IL-1β, IL-6, TNF, and CCL2), corneal infiltration of CD11b+ antigen-presenting cells, and lymph node frequency of mature MHC-IIhi CD11b+ cells were assessed. Results. The epithelial cells of normal corneas expressed TLR4 intracellularly; however, DED significantly increased the cell surface expression of TLR4. Similarly, flow cytometric analysis of stromal cells revealed a significant increase in the expression of TLR4 proteins by DED-induced corneas as compared with normal corneas. DED increased the mRNA expression of TLR4 in corneal stromal cells, but not epithelial cells. TLR4 inhibition decreased the severity of CFS and significantly reduced the mRNA expression of IL-1β, IL-6, and TNF. Furthermore, TLR4 inhibition significantly reduced the corneal infiltration of CD11b+ cells and the lymph node frequency of MHC-IIhi CD11b+ cells. Conclusions. These results suggest that DED increases the corneal expression of TLR4 and that TLR4 participates in the inflammatory response to ocular surface desiccating stress

Spin frustration in antiperovskite systems: (TTF˙+or TSF˙+)3[(Mo6X14)2−Y−]

Two novel antiperovskite charge-transfer (CT) solids composed of a tetraselenafulvalene radical cation (TSF˙+), a dianionic molybdenum cluster unit [Mo6X14]2−, and a halogen anion (Y−) (X, Y = Cl, Br) were prepared by electrocrystallization. Their crystal structures and magnetic properties with regard to spin frustration are discussed together with those of isostructural tetrathiafulvalene (TTF) CT solids previously reported. Both TSF and TTF salts have an apex sharing distorted octahedral spin lattice with a rhombohedral R[3 with combining macron] space group. The calculated overlap integrals based on the crystal structures and insulating nature of the TSF salts indicate that they are Mott insulators. Their spin susceptibilities obeyed the Curie–Weiss law and exhibited an antiferromagnetic ordering at lower temperatures for the TSF salts (Néel temperature, TN = 3.0 K for X = Y = Cl and 5.5 K for X = Y = Br) than the TTF salts. The Curie–Weiss temperatures (|ΘCW| ∼ 1.6–6.3 K) for the TSF salts are lower than those of the TTF salts. For the TSF salts, spin-flop behavior was detected at 3.2 T for X = Y = Cl and 1.5 T for X = Y = Br at 1.9 K. Due to both the distortion of the octahedral geometry of the spin lattice and the anisotropic molecular orientation, the geometrical spin frustrations in TSF and TTF systems are weakened

Serum Antibody Against NY-ESO-1 and XAGE1 Antigens Potentially Predicts Clinical Responses to Anti–Programmed Cell Death-1 Therapy in NSCLC

Introduction: Programmed cell death-1 (PD-1) inhibitors effectively treat NSCLC and prolong survival. Robust biomarkers for predicting clinical benefits of good response and long survival with anti-PD-1 therapy have yet to be identified; therefore, predictive biomarkers are needed to select patients with benefits. Methods: We conducted a prospective study to explore whether serum antibody against NY-ESO-1 and/or XAGE1 cancer-testis antigens predicted primarily good clinical response and secondarily long survival with anti-PD-1 therapy for NSCLC. The serum antibody was detected by enzyme-linked immunosorbent assay, and tumor immune microenvironment and mutation burden were analyzed by immunohistochemistry and next-generation sequencing. Results: In the discovery cohort (n = 13), six antibody-positive NSCLC cases responded to anti-PD-1 therapy (two complete and four partial responses), whereas seven antibody-negative NSCLC cases did not. Antibody positivity was associated with good response and survival, regardless of tumor programmed death ligand 1 (PD-L1) expression, mutation burden, and CD8+ T-cell infiltration. In the validation cohort (n = 75), 17 antibody-positive NSCLC cases responded well to anti-PD-1 therapy as compared with 58 negative NSCLC cases (objective response rate 65% versus 19%, p = 0.0006) and showed significantly prolonged progression-free survival and overall survival. Antibody titers highly correlated with tumor reduction rates. In the multivariate analysis, response biomarkers were tumor programmed death ligand 1 expression and antibody positivity, and only antibody positivity was a significantly better predictive biomarker of progression-free survival (hazard ratio = 0.4, p = 0.01) and overall survival (hazard ratio = 0.2, p = 0.004). Conclusions: Our results suggest that NY-ESO-1 and/or XAGE1 serum antibodies are useful biomarkers for predicting clinical benefits in anti-PD-1 therapy for NSCLC and probably for other cancers

NO-1886, a lipoprotein lipase activator, attenuates contraction of rat intestinal ring preparations

Various intestinal symptoms or diseases are closely associated with intestinal motility, which may be altered by metabolic disturbances associated with diabetes and obesity. It is therefore important that drugs used in the treatment of metabolic disorders should not have any adverse effects on the intestine. In the present study, we examined whether [4-(4-bromo-2-cyano-phenylcarbamoyl)-benzyl]-phosphonic acid diethyl ester (NO-1886), a lipoprotein lipase activator with anti-diabetic and/or anti-obese activity, affects stimulant-induced intestinal contractility. Administration of NO-1886 to intestinal ring preparations of ileum, rectum and colon isolated from Wistar rats attenuated or relaxed contraction induced by a high K+ environment or acetylcholine (ACh). This effect of NO-1886 was dependent on extracellular Ca2+ and intracellular myosin light chain kinase activity. Our results also showed that ACh-induced colonic contraction was significantly higher in the obese Otsuka Long-Evans Tokushima Fatty (OLETF) than in the non-obese Long-Evans Tokushima Otsuka (LETO) rats. The hypercontractility observed in the colons of OLETF rats occurred concomitantly with an elevation in muscarinic M3 ACh receptor protein levels. Administration of NO-1886 attenuated the obesity-induced hypercontractility of the colonic rings of OLETF rats. Thus, intestinal contractile system would be a novel pharmacological target of the lipoprotein lipase activator NO-1886

Dysregulation of RNF213 promotes cerebral hypoperfusion

RNF213 is a susceptibility gene for moyamoya disease, yet its exact functions remain unclear. To evaluate the role of RNF213 in adaptation of cerebral blood flow (CBF) under cerebral hypoperfusion, we performed bilateral common carotid artery stenosis surgery using external microcoils on Rnf213 knockout (KO) and vascular endothelial cell-specific Rnf213 mutant (human p.R4810K orthologue) transgenic (EC-Tg) mice. Temporal CBF changes were measured by arterial spin-labelling magnetic resonance imaging. In the cortical area, no significant difference in CBF was found before surgery between the genotypes. Three of eight (37.5%) KO mice died after surgery but all wild-type and EC-Tg mice survived hypoperfusion. KO mice had a significantly more severe reduction in CBF on day 7 than wild-type mice (KO, 29.7% of baseline level; wild-type, 49.3%; p = 0.038), while CBF restoration on day 28 was significantly impaired in both KO (50.0%) and EC-Tg (56.1%) mice compared with wild-type mice (69.5%; p = 0.031 and 0.037, respectively). Changes in the subcortical area also showed the same tendency as the cortical area. Additionally, histological analysis demonstrated that angiogenesis was impaired in both EC-Tg and KO mice. These results are indicative of the essential role of RNF213 in the maintenance of CBF