Relationship between tooth loss and mortality in 80-year-old Japanese community-dwelling subjects

<p>Abstract</p> <p>Background</p> <p>Findings from several studies suggest associations between tooth loss and health outcomes, including malnutrition, poor quality of life, and mortality, in older individuals. However, limited information is available regarding whether those associations remain true in very elderly subjects after adequately considering confounding factors such as sex and smoking status. Herein, we determined whether the number of teeth in 80-year-old subjects is an independent predictor of mortality.</p> <p>Methods</p> <p>We initially contacted 1282 80-year-old community-dwelling individuals born in 1917, of whom 697 responded and participated in a baseline study, with follow-up examinations conducted 4 and 5.5 years later. Data from interviews and medical and oral examinations were obtained, and oral health was determined according to the number of teeth remaining in the oral cavity.</p> <p>Results</p> <p>A total of 108 and 157 subjects died in 4 years and 5.5 years, respectively, after the baseline study. Tooth loss was significantly associated with mortality at age 85.5, but not at age 84, after adjusting for potential confounders. When the analysis was stratified by sex, we found a stronger association in females in follow-up examinations conducted at both 4- and 5.5 years. On the other hand, the effect of tooth loss on mortality was not significantly different between smokers and non-smokers.</p> <p>Conclusion</p> <p>Tooth loss is a significant predictor of mortality independent of health factors, socio-economic status, and lifestyle in octogenarians, with a stronger association in females.</p

Dendritic cell-derived exosomes induce monocyte antigen-presentation and immune amplification in neoantigen vaccine therapy

Mature dendritic cells release exosomes; however, the immunological role of exosomes in dendritic cell vaccine therapy remains unclear. We examined the immunogenicity of neoantigen peptide-pulsed dendritic cell-derived exosomes (Neo-P DEX) and investigated their role in vaccine therapy. The quality of DEX derived from dendritic cell cultures was confirmed via electron microscopy, western blotting, flow cytometry, and CD63 ELISA. When DEX released from neoantigen-pulsed DCs was applied to monocytes, they showed dendritic cell-like properties such as surface antigen expression. Furthermore, monocytes receiving Neo-P DEX activated neoantigen-reactive T lymphocytes. Fluorescence-activated cell sorting (FACS) analysis showed that plasma exosomes after neoantigen-pulsed DC vaccine may contain more DEX compared to before the vaccine, suggesting that DEX released after DC vaccination may be involved in the amplification of tumor-specific immune responses by translocating to monocytes in the patient body and transforming them into antigen-presenting dendritic cells. This study suggests that dendritic cell exosomes may act as endogenous neoantigen vaccines or immune amplifiers

Anti-integrin αvβ6 antibody as a biomarker for diagnosing ulcerative colitis: a nationwide multicenter validation study

BACKGROUND: A serum biomarker for diagnosing ulcerative colitis (UC) remains to be established. Although we recently reported an anti-integrin αvβ6 antibody (V6 Ab) for diagnosing UC with high sensitivity and specificity, no large-scale validation study exists. This study aimed to validate the diagnostic value of V6 Ab for UC using a nationwide multicenter cohort study. METHODS: We measured V6 Ab titers in patients definitively diagnosed with UC, Crohn's disease (CD), or other gastrointestinal disorders (OGDs). The primary outcome was the diagnostic value of V6 Ab. Secondary outcomes were factors associated with false-negative results in patients with UC and false-positive results in patients without UC and the heterogeneity of the diagnostic value of V6 Ab among the participating facilities. RESULTS: We enrolled 1241, 796, and 206 patients with UC, CD, and OGD, respectively, from 28 Japanese high-volume referral centers. The diagnostic sensitivity of V6 Ab for UC was 87.7%, and its specificities for CD and OGDs were 82.0% and 87.4%, respectively. Multivariable logistic regression analysis showed that false-negative results were associated with older age at the time of sample collection, current smokers, lower partial Mayo score, and not receiving advanced therapies in patients with UC, and false-positive results were associated with colonic CD in patients with CD. No factor was associated with false-positive results in patients with OGDs. There were no significant differences in the diagnostic value of V6 Ab among the centers. CONCLUSIONS: The diagnostic value of V6 Ab for UC was validated in the large-scale nationwide multicenter study

Abstract 257: Autophagy in Endothelial Cell Has an Important Role for Hemostasis and Thrombosis

Autophagy has been reported to maintain intracellular homeostasis through lysosomal-mediated degradation of damaged organelles and proteins. Recent evidence suggests that autophagy regulates many physiological and pathological process including aging, reactive oxygen species levels, and inflammation. The role of autophagy in endothelial cell biology is poorly understood. Electron microscopic analysis of human umbilical vein endothelial cell (HUVEC) surprisingly demonstrated spontaneous fusion of autophagosomes with Weibel-Palade bodies, endothelial specific organelles containing abundant von Willebrand factor (VWF). Knockdown of the essential autophagy gene Atg7 resulted in a reduction in release of VWF from HUVECs after histamine (2.07±0.02 mU/mL vs. 1.30±0.02 mU/mL), or vascular endothelial growth factor (3.10±0.01 mU/mL vs. 1.22±0.03 mU/mL) stimulation. Pharmacological inhibition of autophagy showed similar results. We generated mice that have an endothelial specific deletion of Atg7. These mice have normal blood pressure (Control; 113±8/87±6 mmHg vs. Atg7 deficient; 119±7/88±4 mmHg) and normal vessel architecture. However, endothelial specific Atg7 deficient mice showed a reduction of plasma VWF and marked elevation of their bleeding times (The number of mice with bleeding time of more than 10min; Control=1/17, Atg7 deficient 6/9). Thus, an intact endothelial autophagy machinery is necessary for VWF secretion and hemostasis.</jats:p

Abstract 521: Role of Autophagy in Endothelial Cells for Atherosclerosis

Endothelial dysfunction is thought to play an important role for the development of atherosclerosis. Autophagy is the mechanism by which organelles, aggregated protein, and even lipid droplet are broken down. Since hyperlipidemia can cause endothelial cell dysfunction during the early stage of atherosclerosis, there may be link between atherosclerosis and endothelial autophagy. To address this issue, we generated endothelial specific Atg7 knockout in apoE deficient mice (Atg7 endo /apoE). En face analysis of Oil-red O stained whole aorta showed Atg7 endo /apoE double knockout mice had severe atherosclerosis. At 16 week old, apoE single knockout mice (apoE) had 9.7 % of oil-red O positive area while Atg7 endo /apoE mice had 18.6 % (n=10, 9 mice per group). The composition of macrophages, collagen, and lipid in atherosclerotic lesions were similar between control and Atg7 endo /apoE mice. Body weight and fat composition were also similar between the two groups, as were blood glucose, triglyceride, cholesterol, and fatty acid levels. At 24 weeks of age, en face analysis of aorta showed even more disparity in lesion size between control and Atg7 endo /apoE mice (apoE mice, 15.4%, Atg7 endo /apoE mice, 36.2%, n=10, 7 mice per group). Secretion of various chemokine, such as MCP-1 from Atg7 knockdown human umbilical vein endothelial cell (shATG7 HUVECs) was 10-fold higher that of control cells. These results suggest that autophagy deficiency in endothelial cells accelerate in vivo atherosclerosis. This augmentation may result from an enhanced inflammatory response. </jats:p