Our data obtained from subjects whose CYP3A activities were also induced by carbamazepine itself coincided with their results. In these studies of Asian subjects the induced CYP3A activities in the CYP3A*3/*3 subjects lacking CYP3A5 were not inferior to those in the rest. Large racial differences in the frequencies of the CYP3A5 variants and haplotypes have been reported. 1,4 The mechanism(s) regulating the hepatic CYP3A expression may also be different among races because the level of CYP3A4 messenger ribonucleic acid did not correlate with the level of CYP3A5 messenger ribonucleic acid in livers in Japanese subjects in contrast to the coregulatory expression of CYP3A4 and CYP3A5 in livers in white subjects. 4,5 Mouly et al 2 questioned whether the effect of CYP3A5 genotype observed in healthy volunteers might be evident in treated patients with human immunodeficiency virus, and this remains unanswered. The clinical impact of the CYP3A5*3 genotypes should thus be clarified further with regard to the influences of substrates, multigene haplotypes, races, and environmental factors. 1,2

Cathepsin G is a serine protease secreted by activated neutrophils that play a role in the inflammatory response. Because neutrophils are known to be invading leukocytes in various tumors, their products may influence the characteristics of tumor cells such as the growth state, motility, and the adhesiveness between cells or the extracellular matrix. Here, we demonstrate that cathepsin G induces cell-cell adhesion of MCF-7 human breast cancer cells resulting from the contact inhibition of cell movement on fibronectin but not on type IV collagen. Cathepsin G subsequently induced cell condensation, a very compact cell colony, resulting due to the increased strength of E-cadherin-mediated cell-cell adhesion. Cathepsin G action is protease activity-dependent and was inhibited by the presence of serine protease inhibitors. Cathepsin G promotes E-cadherin/catenin complex formation and Rap1 activation in MCF-7 cells, which reportedly regulates E-cadherin-based cell-cell junctions. Cathepsin G also promotes E-cadherin/protein kinase D1 (PKD1) complex formation, and Go6976, the selective PKD1 inhibitor, suppressed the cathepsin G-induced cell condensation. Our findings provide the first evidence that cathepsin G regulates E-cadherin function, suggesting that cathepsin G has a novel modulatory role against tumor cell-cell adhesion.

Mediterranean basin, corresponding to the Old Silk Road, an ancient trading route stretching between the Mediterranean, the Middle East, and the Far East 3 with an estimated prevalence of 13.5-20 cases per 100,000 people in Japan, Korea, China, Iran, and Saudi Arabia. 2 In Japan, the estimated prevalence of BD was reported as 14.9 per 100,000 people in 2002. 4 According to the diagnostic criteria published by the Japanese Ministry of Health, Labour and Welfare, 5,6 the major symptoms of BD include recurrent oral and genital ulceration, skin lesions such as erythema nodosum, subcutaneous thrombophlebitis, pseudofolliculitis and acneiform nodules, and ocular

This is a report on a statistical study comparing the Kaup index and the level of tobacco consumption of patients with idiopathic spontaneous pneumothorax and those of healthy subjects. A statistically significant difference was found between the average Kaupindex of the patients with idiopathic spontaneous pneumothorax and that of normal healthy individuals in Japan as published by the Ministry of Health and Welfare. A statistically significant difference was also found in the physical features between 2,433 males with idiopathic pneumothorax and 1,906 healthy males when compared by means of the Kaup index. Again, a statistically significant difference was noted in the level of tobacco consumption between the males with idiopathic pneumothoraxand normal males whencomparedby means of the Brinkmann index. The Kaup index of idiopathic pneumothorax patients was lower than that of healthy subjects, while the level of tobacco consumption of the former was higher. Idiopathic spontaneous pneumothorax is related to thin and tall individuals and the level of tobacco consumption amongsuch patients is higher than among healthy subjects.