Our results suggest that putative poor metabolizers of xanthine oxidase activities exist in a Japanese population and that a decreased 1,7-dimethyluric acid formation from caffeine in poor metabolizers of CYP2A6 appears to affect the metabolic ratio used for the assessment of CYP1A2 activity.

Panoramic radiographs and clinical records were used to investigate developmentally absent permanent teeth in 98 subjects with Down syndrome (trisomy-21). This retrospective study was based on the records and panoramic radiographs of subjects from approximately five years of age (the age at which mineralization of the permanent tooth germ could be identified) through to their most recent records. The time period covered by records ranged from 6 to 28 years. The majority of subjects with Down syndrome (63%) exhibited oligodontia, and many subjects were missing two or more teeth (53%). The most frequently absent teeth were the lower lateral incisors (23.3%), the upper second premolars (18.2%), the upper lateral incisors (16.5%), and the lower second premolars (15.3%). In general, the distribution of the developmentally absent teeth was similar for teeth in homologous positions (i.e., left and right canines, etc.) on either side of the midline or between the maxilla and the mandible. The only significant exceptions to this pattern were seen with the central incisors and the second molar. This study's findings suggest a high risk of oligodontia in subjects with Down syndrome.

The Chinese herbal medicine sho-saiko-to is a mixture of seven herbal components (Bupleurum root, Pinellia tuber, Scutellaria root, Jujube fruit, Ginseng root, Glycyrrhiza root and Ginger rhizome) that is widely administered to patients with chronic hepatitis in Japan. We assessed the effects of sho-saiko-to on the activity of cytochrome P450 (CYP) 1A2, CYP3A and xanthine oxidase (XO) in man. Twenty-six healthy subjects were studied to evaluate their baseline activity of CYP1A2 and XO by the respective urinary metabolic ratios of an 8-h urine sample after an oral 150-mg dose of caffeine and of CYP3A by a urinary excretion ratio of 6beta-hydroxycortisol (6beta-HC) to free cortisol (FC). Thereafter, the subjects received a twice-daily 2.5-g dose of sho-saiko-to for five days, and underwent the caffeine test on day 1 and day 5. The mean activity of CYP1A2 decreased by 16% on both day 1 and day 5 compared with the baseline (P=0.001). The mean activity of XO also significantly decreased by 25% on day 1 and 20% on day 5 (P<0.0001) compared with the baseline value. The activity of CYP3A tended to be lower on day 5 than the baseline (P=0.146). It is concluded that sho-saiko-to reduces CYP1A2 and XO activity in man.

Interleukin 12 (IL‐12)‐activated NK1.1+TCRα β+ (NKT2) and NK1.1+TCRα β– (NK) cells exhibit cytotoxic activity against a wide variety of tumor cells in the absence of prior sensitization. Here we demonstrate that the integrin adhesion receptor LFA‐1 (CD11a / CD18) regulates the cytotoxic activity of IL‐12‐activated NKT and NK cells against YAC‐1 and EL‐4 tumor cells. Differentiation in vivo and the expression of the cytolytic effector molecules perforin and Fas‐L were comparable in both IL‐12‐activated NKT and NK cells from LFA‐1– / – and LFA‐1+ / + mice. However, LFA‐1– / – IL‐12‐activated NKT and NK cells showed impaired conjugate formation with target cells. These results provide the first genetic evidence for a role for an adhesion receptor in killing by IL‐12‐activated NK cells.