Glycolipid α-C-galactosylceramide is a distinct inducer of dendritic cell function during innate and adaptive immune responses of mice

α-Galactosylceramide (α-GalCer) is the prototype compound for studying the presentation of glycolipids on CD1d molecules to natural killer T (NKT) lymphocytes. A single i.v. dose of glycolipid triggers a cascade of events involving the production of several cytokines over the course of a day, a short-lived activation of NKT and natural killer (NK) cells, and a more prolonged adaptive T cell immune response if certain antigens are given together with α-GalCer. We find that a recently described analogue, α-C-galactosylceramide (α-C-GalCer), more potently induces these innate and adaptive immune responses in mice. α-C-GalCer acts as a more effective trigger for IL-12 and IFN-γ production, although it minimally elicits IL-4 and TNF-α release into the serum. Also, α-C-GalCer better mobilizes NKT and natural killer cells to resist B16 melanoma. To help understand these effects, we find that α-C-GalCer binds more stably to dendritic cells than α-GalCer and that dendritic cells loaded with α-C-GalCer induce larger and more long lasting NKT cell responses in vivo. When glycolipid is targeted to dendritic cells in spleen together with antigens in dying cells, such as irradiated tumor cells, α-C-GalCer is active as an adjuvant for T cell-mediated immunity at lower doses, just 20 ng per mouse, where it is also able to up-regulate the required CD40L costimulatory molecule on NKT cells. Therefore, α-C-GalCer represents a glycolipid that binds more stably to dendritic cells and acts as a more effective link between innate and adaptive immunity in vivo

Activation of natural killer T cells by α-galactosylceramide rapidly induces the full maturation of dendritic cells in vivo and thereby acts as an adjuvant for combined CD4 and CD8 T cell immunity to a coadministered protein

The maturation of dendritic cells (DCs) allows these antigen-presenting cells to initiate immunity. We pursued this concept in situ by studying the adjuvant action α-galactosylceramide (αGalCer) in mice. A single i.v. injection of glycolipid induced the full maturation of splenic DCs, beginning within 4 h. Maturation was manifest by marked increases in costimulator and major histocompatibility complex class II expression, interferon (IFN)-γ production, and stimulation of the mixed leukocyte reaction. These changes were not induced directly by αGalCer but required natural killer T (NKT) cells acting independently of the MyD88 adaptor protein. To establish that DC maturation was responsible for the adjuvant role of αGalCer, mice were given αGalCer together with soluble or cell-associated ovalbumin antigen. Th1 type CD4+ and CD8+ T cell responses developed, and the mice became resistant to challenge with ovalbumin-expressing tumor. DCs from mice given ovalbumin plus adjuvant, but not the non-DCs, stimulated ovalbumin-specific proliferative responses and importantly, induced antigen-specific, IFN-γ producing, CD4+ and CD8+ T cells upon transfer into naive animals. In the latter instance, immune priming did not require further exposure to ovalbumin, αGalCer, NKT, or NK cells. Therefore a single dose of αGalCer i.v. rapidly stimulates the full maturation of DCs in situ, and this accounts for the induction of combined Th1 CD4+ and CD8+ T cell immunity to a coadministered protein

Effect of intracoronary thrombectomy on 30-day mortality in non-diabetic patients with acute hyperglycemia after acute myocardial infarction

SummaryBackgroundThere is limited evidence about useful therapeutic interventions for patients with acute hyperglycemia (AH) after acute myocardial infarction (AMI).MethodsWe studied 2433 consecutive non-diabetic AMI patients who underwent percutaneous coronary intervention (PCI) within 24h after the onset. Patients were divided into two groups according to the presence or absence of AH (admission serum glucose level ≥11.1mmol/l). We assessed the association between intracoronary thrombectomy and the clinical outcome in AMI patients with AH.ResultsPatients with AH had more risk factors than those without AH. The 30-day mortality rate of patients with AH was significantly higher than that of those without (11.7% vs 1.7%, p<0.001). Among patients with AH, the 30-day mortality rate was significantly lower for those with intracoronary thrombectomy than those without it (4.9% vs 17.2%, p=0.004). Among patients without AH, however, the 30-day mortality rate was similar between those with and without intracoronary thrombectomy (1.5% vs 1.9%, p=NS). Multivariate analysis showed that intracoronary thrombectomy was associated with an improved 30-day mortality rate for patients with AH (hazard ratio: HR 0.184, 95% CI 0.057–0.598, p=0.005).ConclusionsIn AMI patients with AH, intracoronary thrombectomy prior to PCI might improve the 30-day mortality rate

Effect of TU-100 in NASH

Background : Non-alcoholic steatohepatitis (NASH) is associated with a higher risk of hepatocellular carcinoma (HCC), and the importance of the gut–liver axis has been recognized in NASH-associated HCC. We investigated the effect of TU-100 on the intestinal microbiome and hepatocarcinogenesis in a NASH model. Methods : Seven-week-old Tsumura Suzuki obese diabetes mice, a model that shows the spontaneous onset of NASH and HCC, were used. They were divided into a TU-100 treated group and a control group. Mice were sacrificed at 24 and 48 weeks to evaluate hepatic steatosis, fibrosis, carcinogenesis, cytokine expression, and microbiome abundance. Results : At 24 weeks, the TU-100 group showed significantly lower expression of IL6, IL1B, and ACTA2 mRNA in the liver (P < 0.05). At 48 weeks, the TU-100 group showed significantly lower levels of serum alanine aminotransferase. The TU-100 group also showed a lower rate of NASH than the control group (28% vs 72% ; P = 0.1). Tumor diameter was significantly smaller in the TU-100 group compared with that in the control group (P < 0.05). Regarding the intestinal microbiome, the genera Blautia and Ruminococcus were increased in the TU-100 group (P < 0.05), whereas Dorea and Erysipelotrichaceae were decreased in the TU-100 group (P < 0.05). Conclusions : TU-100 regulates the intestinal microbiome and may suppress subsequent hepatocarcinogenesis in the NASH model

X box-binding protein１を介した小胞体ストレス応答不全は非アルコール性脂肪肝炎モデルマウスにおける肝部分切除後の肝再生不良の主要な要因である

Background Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Poor regeneration after hepatectomy in NAFLD is well recognized, but the mechanism is unclear. Endoplasmic reticulum (ER) stress plays an important role in the development of NAFLD. Here, we show that an impaired ER stress response contributes to poor liver regeneration in partially hepatectomized mice. Methods Non-alcoholic fatty liver (NAFL) or non-alcoholic steatohepatitis (NASH) was induced in mice using our patented feed and 70% partial hepatectomy (PH) was performed. Mice were sacrificed 0, 4, 8, 24, or 48 hours, or 7 days after PH, and liver regeneration and the mRNA expression of ER stress markers were assessed. Results NAFLD activity score was calculated as 4–6 points for NAFL and 7 points for NASH. NASH was characterized by inflammation and high ER stress marker expression before PH. After PH, NASH mice showed poorer liver regeneration than controls. High expression of proinflammatory cytokine genes was present in NASH mice 4 hours after PH. Xbp1-s mRNA expression was high in control and NAFL mice after PH, but no higher in NASH mice. Conclusions Dysfunction of the ER stress response might be a cause of poor liver regeneration in NASH

Quality of Early Childhood Education and Care and Child Development Evaluation Research in Higashi-hiroshima.: A report of 2021

In this study, we clarified how the quality of childcare at preschool childcare facilities (kindergartens, nursery schools, certified children’s kindergartens ) in the city is affected by the implementation status of the “Higashi-Hiroshima City Early Childhood Education and Childcare Action Plan.” The Action Plan includes, (1) the creation of an attractive childcare environment that nurtures the five abilities, (2) the promotion of natural childcare, (3) the enhancement of public childcare, and (4) the training and collaboration of childcare coordinators. Specifically, first, we clarified how teachers played a role in the growth of children from 0 years to preschool age through the implementation of the Higashi-Hiroshima City Early Childhood Education and Childcare Action Plan; second, we also evaluated parental childcare

Periodical structure of vortices in a semiconductor single wafer spin cleaner

We experimentally and numerically investigated large-scale structures formed by vortices in a single wafer spin cleaner. The Q-criterion identified the vortices developed in the cleaner as the flow regions with positive second invariant of the velocity gradient tensor obtained by both the PIV and LES. The time-series two-components PIV data shows that small-vortices were clustered near and under the edge of the rotating disk and were periodically emanated from there to the housing wall of the cleaner. The emanation frequency was increased with increasing in the angular velocity of the rotating disk. Three-dimensional LES reveal that six longitudinal vortices were spirally developed from under the edge of the rotating disk to the housing wall. This structure stably rotated slower than the disk speed. Fourier analysis of the LES data agreed with that of the PIV data. This supports that the passages of the stable spiral vortices on the PIV measurement region resulted in the periodical emanation of the clustered small-vortices observed in the PIV. Such a very large-scale spiral structure will induce reattachment of contaminants on the wafer surface, and should be destructed for development of much higher efficient cleaner

New acoustic respiratory sound monitoring with artificial intelligence

Monitored anesthesia care (MAC) often causes airway complications, particularly posing an elevated risk of aspiration and airway obstruction in obese patients. This study aimed to quantify the levels of aspiration and airway obstruction using an artificial intelligence (AI)-based acoustic analysis algorithm, assessing its utility in identifying airway complications in obese patients. To verify the correlation between the stridor quantitative value (STQV) calculated by acoustic analysis and body weight, and to further evaluate fluid retention and airway obstruction, STQV calculated exhaled breath sounds collected at the neck region, was compared before and after injection of 3 ml of water in the oral cavity and at the start and end of the MAC procedures. STQV measured immediately following the initiation of MAC exhibited a weak correlation with body mass index. Furhtermore, STQV values before and after water injection increased predominantly after injection, further increased at the end of MAC. AI-based analysis of cervical respiratory sounds can enhance the safety of airway management during MAC by quantifying airway obstruction and fluid retention in obese patients

Multiple granulomatous lung lesions in a patient with Epstein-Barr-virus-induced mononucleosis and new-onset systemic lupus erythematosus: a case report

INTRODUCTION: Granulomatous lesions are commonly encountered abnormalities in pulmonary pathology, and often pose a diagnostic challenge. We report an unusual case of granulomatous lung disease with uncommon characteristics, which developed following Epstein-Barr-virus-induced mononucleosis and new-onset systemic lupus erythematosus. We aim to highlight a diagnostic approach for the condition and to raise awareness of the possibility of it being related to the immunological reaction caused by Epstein-Barr virus infection. CASE PRESENTATION: A 36-year-old Japanese man, who had been diagnosed with Epstein-Barr-virus-induced infectious mononucleosis, new-onset systemic lupus erythematosus, and secondary Sjögren’s syndrome three weeks previously, presented to our facility with fever and diffuse pulmonary infiltrates. A computed tomography scan of the chest revealed multiple small nodules in both lungs. Fiberoptic bronchoscopy with bronchoalveolar lavage revealed lymphocytosis with predominance of T lymphocytes. A histological examination of a lung biopsy taken during video-assisted thoracic surgery showed randomly distributed tiny granulomatous lesions with infiltration of eosinophils. The differential diagnoses included hypersensitivity pneumonitis, sarcoidosis, and pulmonary involvement of Crohn’s disease, systemic lupus erythematosus, and Sjögren’s syndrome, but the clinical and pathological findings were not consistent with any of these. Our patient’s condition did not improve; therefore, prednisolone therapy was started because of the possibility of specific immunological reactions associated with Epstein-Barr virus infection. After steroid treatment, our patient showed radiological and clinical improvement. CONCLUSIONS: To the best of our knowledge, this is the first case of a patient developing randomly distributed multiple granulomatous lung lesions with eosinophilic infiltrates after Epstein-Barr virus infection and systemic lupus erythematosus. On the basis of our data, we hypothesize that Epstein-Barr virus infection altered the immune response of our predisposed patient and contributed to the pathogenesis of the lung lesions. Our patient’s clinical response to steroid treatment was excellent