Defensins are a family of broad-spectrum antimicrobial peptides found abundantly in the cytoplasmic granules of mammalian neutrophils and Paneth cells of the small intestine. Defensins are known to form ion channels on the membranes of target cells. These channel formations and the cytotoxicity of defensins are intimately linked. We showed the morphological effects of defensins on the cytoplasmic membranes of Staphylococcus aureus by transmission electron microscopy. S. aureus exposed to defensins developed characteristic mesosome-like structures but did not show remarkable changes in cell walls. Defensins induced such structural changes not only at high concentration but also at low concentrations that were not bactericidal. We also showed that increasing the concentration of NaCl in the reaction mixture completely inhibited the occurrence of membranous changes of target cells exposed to defensins. These findings are, to our knowledge, the first report of morphological changes in gram-positive bacteria treated with defensins. Our results indicate that the first effect of defensins in S. aureus is to damage cytoplasmic membranes directly; they also support previous reports that the cell membrane is the principal target of defensins.

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Aims: The associations between low-density lipoprotein cholesterol (LDL-C) and the risk of cardiovascular disease (CVD) subtypes are not well established among the Japanese population. This study used longitudinal data from the Aichi Workers' Cohort Study to explore the association between LDL-C levels and the risk of coronary heart disease (CHD) and stroke subtypes. Methods: Pooled data of 8966 adults (7093men and 1903 women) who were recruited between (2002) and (2008) were used for the current analysis. Propensity scores for the LDL-C categories were generated using multinomial logistic regression. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from the inverse probability weighted Cox proportional hazards model for LDL-C category associations with risks of CHD, stroke subtypes, and CVD. Results: During a median follow-up of 12 years, 122 strokes (57 ischemic strokes, 25 intracerebral hemorrhage, and 40 unknown subtypes) and 82 cases of CHD were observed. LDL-C 160-mg/dL compared to LDL-C 100-119 mg/dL was positively and significantly associated with the risk of CHD (HR: 4.56; 95% CI: 1.91-10.9) but not with ischemic stroke (HR: 0.99; 95% CI: 0.44-2.22). LDL-C was inversely associated with the risk of intracerebral hemorrhage (P for trend=0.009). Conclusion:In middle-aged Japanese workers, LDL-C was significantly and positively associated with CHD, but not with ischemic stroke. LDL-C was inversely significantly associated with intracerebral hemorrhage.

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