MICA/B expression in macrophage foam cells infiltrating atherosclerotic plaques

Infiltrating macrophages accumulate in fatty streak lesions and transform into foam cells, leading to the formation of atherosclerotic plaques. Inflammatory mechanisms underlying the plaque formation mediated by NKG2D-positive lymphocytes such as CD8⁺ T cells, natural killer cells and natural killer T cells have been extensively investigated. Yet, the involvement of the NKG2D system itself remains poorly understood. Recent work in mouse models has shown that blockade of an NKG2D receptor–ligand interaction reduces plaque formation and suppresses inflammation in aortae. In this study, we conducted immunohistochemical analysis of NKG2D ligand expression in autopsy-derived aortic specimens. Foam cells expressing NKG2D ligands MICA/B were found in advanced atherosclerotic lesions accompanied by a large necrotic core or hemorrhage. Human monocyte-derived macrophages treated in vitro with acetylated low-density lipoproteins enhanced expression of MICA/B and scavenger receptor A, thus accounting for NKG2D ligand expression in foam cells infiltrating atherosclerotic plaques. Our results suggest that, as in mice, the NKG2D system might be involved in the development of atherosclerosis in humans.     

Immunogenicity and Safety after Booster Vaccination of Diphtheria,Tetanus, and Acellular Pertussis in Young Adults: an Open Randomized Controlled Trial in Japan

The recent increase of pertussis in young adults in Japan is hypothesized to be due in part to waning protection from the acellular pertussis vaccine. While a booster immunization may prevent an epidemic of pertussis among these young adults, little is known about the safety and immunogenicity of such a booster with the diphtheria, tetanus, and acellular pertussis vaccine (DTaP), which is currently available in Japan. One hundred and eleven medical students with a mean age of 19.4 years were randomly divided into 2 groups of 55 and 56 subjects and received, respectively, 0.2 or 0.5 ml of DTaP. Immunogenicity was assessed by performing the immunoassay using serum, and the geometric mean concentration (GMC), GMC ratio (GMCR), seropositive rate, and booster response rate were calculated. Adverse reactions and adverse events were monitored for 7 days after vaccination. After booster vaccination in the two groups, significant increases were found in the antibodies against pertussis toxin, filamentous hemagglutinin, diphtheria toxoid, and tetanus toxoid, and the booster response rates for all subjects reached 100%. The GMCs and GMCRs against all antigens were significantly higher in the 0.5-ml group than in the 0.2-ml group. No serious adverse events were observed. Frequencies of local reactions were similar in the 2 groups, although the frequency of severe local swelling was significantly higher in the 0.5-ml group. These data support the acceptability of booster immunization using both 0.2 and 0.5 ml of DTaP for young adults for controlling pertussis. (This study was registered at UMIN-CTR under registration number UMIN000010672.)     

Prospective, randomized, single-blind comparison of effects of 6?months' treatment with atorvastatin versus pravastatin on leptin and angiogenic factors in patients with coronary artery disease

Leptin has been reported to exert an atherosclerotic effect by regulating expression of angiogenic factors that have been implicated in the pathogenesis of coronary artery disease (CAD). The purpose of this study was to investigate whether lipid-lowering therapy (LLT) with statins could affect leptin levels and angiogenic factors in patients with CAD. This study included 76 patients with CAD and 15 subjects without CAD (non-CAD). CAD patients were randomized to 6?months of intensive LLT with atorvastatin or moderate LLT with pravastatin. Plasma leptin, angiopoetin-2 (Ang-2), hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) levels were measured prior to statin therapy (baseline) and after 6?months. Baseline levels of leptin, Ang-2, HGF and VEGF were higher in the CAD group than in the non-CAD group (all P?<?0.05). Treatment with intensive LLT decreased leptin, Ang-2, HGF and VEGF levels, whereas moderate LLT did not change these levels. This study suggests that LLT with atorvastatin decreases leptin levels and angiogenic factors in patients with CAD, possibly contributing to the beneficial effects of LLT with atorvastatin in CAD.     

Fish to meat intake ratio and cooking oils are associated with hepatitis C virus carriers with persistently normal alanine aminotransferase levels

Aim: Dietary habits are involved in the development of chronic inflammation; however, the impact of dietary profiles of hepatitis C virus carriers with persistently normal alanine transaminase levels (HCV‐PNALT) remains unclear. The decision‐tree algorithm is a data‐mining statistical technique, which uncovers meaningful profiles of factors from a data collection. We aimed to investigate dietary profiles associated with HCV‐PNALT using a decision‐tree algorithm. Methods: Twenty‐seven HCV‐PNALT and 41 patients with chronic hepatitis C were enrolled in this study. Dietary habit was assessed using a validated semiquantitative food frequency questionnaire. A decision‐tree algorithm was created by dietary variables, and was evaluated by area under the receiver operating characteristic curve analysis (AUROC). Results: In multivariate analysis, fish to meat ratio, dairy product and cooking oils were identified as independent variables associated with HCV‐PNALT. The decision‐tree algorithm was created with two variables: a fish to meat ratio and cooking oils/ideal bodyweight. When subjects showed a fish to meat ratio of 1.24 or more, 68.8% of the subjects were HCV‐PNALT. On the other hand, 11.5% of the subjects were HCV‐PNALT when subjects showed a fish to meat ratio of less than 1.24 and cooking oil/ideal bodyweight of less than 0.23 g/kg. The difference in the proportion of HCV‐PNALT between these groups are significant (odds ratio 16.87, 95% CI 3.40–83.67, P = 0.0005). Fivefold cross‐validation of the decision‐tree algorithm showed an AUROC of 0.6947 (95% CI 0.5656–0.8238, P = 0.0067). Conclusion: The decision‐tree algorithm disclosed that fish to meat ratio and cooking oil/ideal bodyweight were associated with HCV‐PNALT.