This study was designed to assess the role of macrophages in saphenous vein graft disease after coronary artery bypass grafting (CABG). Three newly harvested saphenous vein grafts (SVGs) and 6 SVGs removed from patients 8 to 15 years after CABG (3 were occluded soon after the operation and 3 became diseased after a long period) were immunostained for macrophages and investigated microscopically. No macrophages were detected in the newly harvested SVGs. In the grafts with early occlusion, macrophages were detected only in the superficial layer of the intima. In the grafts that became diseased after a long period, macrophage accumulation was detected at the site of atherosclerotic lesions. In the pathogenesis of arterial atherosclerotic lesions, vascular endothelial cell damage and subsequent subendothelial migration of monocytes/macrophages in the early phase are thought to be very important. This study revealed that macrophage migration into the intima of SVGs occurs soon after surgery and suggested it could be the basis of saphenous vein graft disease occurring long after CABG.

The effectiveness of recombinant human erythropoietin (rHuEPO) was evaluated in elderly patients who underwent coronary artery bypass grafting. A total of 133 patients were divided into three groups: those who were 70 years of age or older and received rHuEPO (group I; n=32), those who were also 70 years of age or older but did not receive rHuEPO (group II; n=35), and those who were 60 years or younger and received rHuEPO (group III; n=66). In 87.5% of group I, 42.9% of group II, and 98.5% of group III, homologous blood transfusion could be avoided. The percentage of patients without homologous blood transfusion was significantly higher in group I than in group II (p<0.001). The rate of homologous blood transfusion was significantly higher in group I than in group III (p<0.05), but rHuEPO had equal effects in terms of increase in hemoglobin level in the two groups. Furthermore, in patients without anemia, the rate of homologous blood transfusion was almost the same in the two groups. In conclusion, the administration of rHuEPO enables even elderly patients to undergo coronary artery bypass grafting without homologous blood transfusion.

Tooth crown morphogenesis is tightly regulated by the proliferation and differentiation of dental epithelial cells. Globoside (Gb4), a globo-series glycosphingolipid, is highly expressed during embryogenesis as well as organogenesis, including tooth development. We previously reported that Gb4 is dominantly expressed in the neutral lipid fraction of dental epithelial cells. However, because its functional role in tooth development remains unknown, we investigated the involvement of Gb4 in dental epithelial cell differentiation. The expression of Gb4 was detected in ameloblasts of postnatal mouse molars and incisors. A cell culture analysis using HAT-7 cells, a rat-derived dental epithelial cell line, revealed that Gb4 did not promote dental epithelial cell proliferation. Interestingly, exogenous administration of Gb4 enhanced the gene expression of enamel extracellular matrix proteins such as ameloblastin, amelogenin, and enamelin in dental epithelial cells as well as in developing tooth germs. Gb4 also induced the expression of TrkB, one of the key receptors required for ameloblast induction in dental epithelial cells. In contrast, Gb4 downregulated the expression of p75, a receptor for neurotrophins (including neurotrophin-4) and a marker of undifferentiated dental epithelial cells. In addition, we found that exogenous administration of Gb4 to dental epithelial cells stimulated the extracellular signal-regulated kinase and p38 mitogen-activated protein kinase signalling pathways. Furthermore, Gb4 induced the expression of epiprofin and Runx2, the positive regulators for ameloblastin gene transcription. Thus, our results suggest that Gb4 contributes to promoting the differentiation of dental epithelial cells into ameloblasts.