Tumor Growth Enhances Cross-Presentation Leading to Limited T Cell Activation without Tolerance

Using a tumor model of spontaneously arising insulinomas expressing a defined tumor-associated antigen, we investigated whether tumor growth promotes cross-presentation and tolerance of tumor-specific T cells. We found that an advanced tumor burden enhanced cross-presentation of tumor-associated antigens to high avidity tumor-specific T cells, inducing T cell proliferation and limited effector function in vivo. However, contrary to other models, tumor-specific T cells were not tolerized despite a high tumor burden. In fact, in tumor-bearing mice, persistence and responsiveness of adoptively transferred tumor-specific T cells were enhanced. Accordingly, a potent T cell–mediated antitumor response could be elicited by intravenous administration of tumor-derived peptide and agonistic anti-CD40 antibody or viral immunization and reimmunization. Thus, in this model, tumor growth promotes activation of high avidity tumor-specific T cells instead of tolerance. Therefore, the host remains responsive to T cell immunotherapy

松本歯科大学病院における小児全身麻酔下集中歯科治療の検討 : 過去11年間の環境要因の変遷について

We investigated the actual child-rearing environment, considering factors such as hygiene training, among 177 children (102 boys, 75 girls) ranging from 1 year and 9 months to 7 years and 2 months in age who underwent intensive dental treatment under general anesthesia in the Department of Pediatric Dentistry, Matsumoto Dental University Hospital between January 1990 and December 2000. The following results were obtained. 1) The annual number of patients slightly increased between 1992 and 1994. Thereafter, the annual number of patients decreased slightly each year. 2) The mean age attreatmentwas 3 years and 7 months (44.5±12.9 months). 3) Concerning the regional distribution, more than 50% of the children came from Nagano Prefecture areas other than Shiojiri City, where our university is located. 4) With respect to feeding methods during infancy, most children were breast fed or mixed breast and bottle fed. Furthermore, any feeding irregularity was noted. 5) The mean interval from birth until the start of weaning was 7.5±4.1 months. The mean interval until completion of weaning was 16.0±6.3 months. 6) 95.5% of the children habitually brushed their teeth. The frequency of tooth brushing was "once a day" or "sometimes" in 69.5% of the children. 7) Overall, 46.9% of the children had received fluoride application

Efficacy and Safety of Esaxerenone in Hypertensive Patients with Diabetic Kidney Disease: A Multicenter, Open-Label, Prospective Study

Introduction Clinical data of esaxerenone in hypertensive patients with diabetic kidney disease (DKD) are lacking. We evaluated the efficacy and safety of esaxerenone in patients with DKD and an inadequate response to blood pressure (BP)-lowering treatment. Methods In this multicenter, open-label, prospective study, patients were divided into urinary albumin-to-creatinine ratio subcohorts (UACR  Results In total, 113 patients were enrolled. Morning home SBP/DBP significantly decreased from baseline to EOT in the total population (− 11.6/− 5.2 mmHg, both p  Conclusion Esaxerenone demonstrated a BP-lowering effect and improved albuminuria. The effects were consistent regardless of the severity of albuminuria without clinically relevant serum potassium elevation and eGFR reduction

Detection of the Onset of Ischemia and Carcinogenesis by Hypoxia-Inducible Transcription Factor-Based In Vivo Bioluminescence Imaging

An animal model for the early detection of common fatal diseases such as ischemic diseases and cancer is desirable for the development of new drugs and treatment strategies. Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that regulates oxygen homeostasis and plays key roles in a number of diseases, including cancer. Here, we established transgenic (Tg) mice that carry HRE/ODD-luciferase (HOL) gene, which generates bioluminescence in an HIF-1-dependent manner and was successfully used in this study to monitor HIF-1 activity in ischemic tissues. To monitor carcinogenesis in vivo, we mated HOL mice with rasH2 Tg mice, which are highly sensitive to carcinogens and are used for short-term carcinogenicity assessments. After rasH2-HOL Tg mice were treated with N-methyl-N-nitrosourea, bioluminescence was detected noninvasively as early as 9 weeks in tissues that contained papillomas and malignant lesions. These results suggest that the Tg mouse lines we established hold significant potential for monitoring the early onset of both ischemia and carcinogenesis and that these lines will be useful for screening chemicals for carcinogenic potential

Observation of 60 GHz and 20 GHz Multiple Photon-Photon Resonances Using Active Multimode Interferometer Laser Diodes

1 × N active multimode interferometer laser diodes to achieve two photon-photon resonances (PPRs