シンカブ ヨヤクケン ハッコウ ノ カシ ト ソノ レンサ

末永敏和教授退職記念

Prospective study of lung function and abdominal aortic aneurysm risk: The Atherosclerosis Risk in Communities study

Abstract Background and aims No prospective study has investigated whether individuals with respiratory impairments, including chronic obstructive pulmonary disease (COPD) and restrictive lung disease (RLD), are at increased risk of abdominal aortic aneurysm (AAA). We aimed to prospectively investigate whether those respiratory impairments are associated with increased AAA risk. Methods In 1987–1989, the Atherosclerosis Risk in Communities (ARIC) study followed 14,269 participants aged 45–64 years, without a history of AAA surgery, through 2011. Participants were classified into four groups, “COPD” [forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <lower limit of normal (LLN)], “RLD” (FEV1/FVC ≥ LLN and FVC < LLN), “respiratory symptoms with normal spirometry” (without RLD or COPD), and “normal” (without respiratory symptoms, RLD or COPD, reference group). Results During the 284,969 person-years of follow-up, 534 incident AAA events were documented. In an age, sex, and race-adjusted proportional hazards model, individuals with respiratory impairments had a significantly higher risk of AAA than the normal reference group. After adjustment for AAA risk factors, including smoking status and pack-years of smoking, AAA risk was no longer significant in the respiratory symptoms with normal spirometry group [HR (95% CI), 1.25 (0.98–1.60)], but was still increased in the other two groups [RLD: 1.45 (1.04–2.02) and COPD: 1.66 (1.34–2.05)]. Moreover, continuous measures of FEV1/FVC, FEV1 and FVC were associated inversely with risk of AAA. Conclusions In the prospective population-based cohort study, obstructive and restrictive spirometric patterns were associated with increased risk of AAA independent of smoking, suggesting that COPD and RLD may increase the risk of AAA. Highlights • No prospective study has examined the association between lung function and abdominal aortic aneurysm (AAA). • We examined this association using a prospective population-based study in the US. • Chronic obstructive pulmonary disease (COPD) and restrictive diseases patterns were associated with increased AAA risk. • This study suggested COPD and restrictive lung diseases may increase AAA risk

Association of Educational Attainment With Lifetime Risk of Cardiovascular Disease: The Atherosclerosis Risk in Communities Study

Estimates of lifetime risk may help raise awareness of the extent to which educational inequalities are associated with risk of cardiovascular disease (CVD). To estimate lifetime risks of CVD according to categories of educational attainment. Participants were followed from 1987 through December 31, 2013. All CVD events (coronary heart disease, heart failure, and stroke) were confirmed by physician review and International Classification of Diseases codes. A total of 13 948 whites and African Americans who were 45 to 64 years old and free of CVD at baseline were included from 4 US communities (Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and suburbs of Minneapolis, Minnesota). The data analysis was performed from June 7 to August 31, 2016. Educational attainment. We used a life table approach to estimate lifetime risks of CVD from age 45 through 85 years according to educational attainment. We adjusted for competing risks of death from underlying causes other than CVD. The sample of 13 948 participants was 56% female and 27% African American. During 269 210 person-years of follow-up, we documented 4512 CVD events and 2401 non-CVD deaths. Educational attainment displayed an inverse dose-response relation with cumulative risk of CVD, which became evident in middle age, with the most striking gap between those not completing vs completing high school. In men, lifetime risks of CVD were 59.0% (95% CI, 54.0%-64.1%) for grade school, 52.5% (95% CI, 47.7%-56.8%) for high school education without graduation, 50.9% (95% CI, 47.3%-53.9%) for high school graduation, 47.2% (95% CI, 41.5%-52.5%) for vocational school, 46.4% (95% CI, 42.8%-49.6%) for college with or without graduation, and 42.2% (95% CI, 36.6%-47.0%) for graduate/professional school; in women, 50.8% (95% CI, 45.7%-55.8%), 49.3% (95% CI, 45.1%-53.1%), 36.3% (95% CI, 33.4%-39.1%), 32.2% (95% CI, 26.0%-37.3%), 32.8% (95% CI, 29.1%-35.9%), and 28.0% (95% CI, 21.9%-33.3%), respectively. Educational attainment was inversely associated with CVD even within categories of family income, income change, occupation, or parental educational level. More than 1 in 2 individuals with less than high school education had a lifetime CVD event. Educational attainment was inversely associated with the lifetime risk of CVD, regardless of other important socioeconomic characteristics. Our findings emphasize the need for further efforts to reduce CVD inequalities related to educational disparities

Identification of novel mast cell genes by serial analysis of gene expression in cord blood-derived mast cells

AbstractThe gene expression profile of human cord blood-derived mast cells (MCs) was investigated using serial analysis of gene expression (SAGE). A total of 22 914 tags, representing 9181 unique transcripts, were sequenced. By selecting tags that were detected more frequently in MCs than in other tissues, genes characteristic of MCs were enriched. Reverse transcription-PCR and the high-density oligonucleotide array hybridization confirmed the validity of our SAGE result. About 70% of the selected genes were previously uncharacterized. Northern blot analysis showed the MC-specific expression of selected genes. This inventory will be useful to identify novel genes with important functions in MCs

Impact of cardiac support device combined with slow-release prostacyclin agonist in a canine ischemic cardiomyopathy model

BackgroundThe cardiac support device supports the heart and mechanically reduces left ventricular (LV) diastolic wall stress. Although it has been shown to halt LV remodeling in dilated cardiomyopathy, its therapeutic efficacy is limited by its lack of biological effects. In contrast, the slow-release synthetic prostacyclin agonist ONO-1301 enhances reversal of LV remodeling through biological mechanisms such as angiogenesis and attenuation of fibrosis. We therefore hypothesized that ONO-1301 plus a cardiac support device might be beneficial for the treatment of ischemic cardiomyopathy.MethodsTwenty-four dogs with induced anterior wall infarction were assigned randomly to 1 of 4 groups at 1 week postinfarction as follows: cardiac support device alone, cardiac support device plus ONO-1301 (hybrid therapy), ONO-1301 alone, or sham control.ResultsAt 8 weeks post-infarction, LV wall stress was reduced significantly in the hybrid therapy group compared with the other groups. Myocardial blood flow, measured by positron emission tomography, and vascular density were significantly higher in the hybrid therapy group compared with the cardiac support device alone and sham groups. The hybrid therapy group also showed the least interstitial fibrosis, the greatest recovery of LV systolic and diastolic functions, assessed by multidetector computed tomography and cardiac catheterization, and the lowest plasma N-terminal pro-B-type natriuretic peptide levels (P < .05).ConclusionsThe combination of a cardiac support device and the prostacyclin agonist ONO-1301 elicited a greater reversal of LV remodeling than either treatment alone, suggesting the potential of this hybrid therapy for the clinical treatment of ischemia-induced heart failure

Effects of the acute and chronic restraint stresses on the central histaminergic neuron system of Fischer rat

pdf Title: Effects of the acute and chronic restraint stresses on the central histaminergic neuron syste

RUNX inhibitor suppresses graft‐versus‐host disease through targeting RUNX‐NFATC2 axis

Patients with refractory graft-versus-host disease (GVHD) have a dismal prognosis. Therefore, novel therapeutic targets are still needed to be identified. Runt-related transcriptional factor (RUNX) family transcription factors are essential transcription factors that mediate the essential roles in effector T cells. However, whether RUNX targeting can suppress, and GVHD is yet unknown. Here, we showed that RUNX family members have a redundant role in directly transactivating NFATC2 expression in T cells. We also found that our novel RUNX inhibitor, Chb-M’, which is the inhibitor that switches off the entire RUNX family by alkylating agent–conjugated pyrrole-imidazole (PI) polyamides, inhibited T-cell receptor mediated T cell proliferation and allogenic T cell response. These were designed to specifically bind to consensus RUNX-binding sequences (TGTGGT). Chb-M’ also suppressed the expression of NFATC2 and pro-inflammatory cytokine genes in vitro. Using xenogeneic GVHD model, mice injected by Chb-M’ showed almost no sign of GVHD. Especially, the CD4 T cell was decreased and GVHD-associated cytokines including tissue necrosis factor-α and granulocyte-macrophage colony-stimulating factor were reduced in the peripheral blood of Chb-M’ injected mice. Taken together, our data demonstrates that RUNX family transcriptionally upregulates NFATC2 in T cells, and RUNX-NFATC2 axis can be a novel therapeutic target against GVHD