The plasma concentration of 1,5-anhydro-D-glucitol (AG) was measured in 135 newly diagnosed patients who were referred for oral glucose tolerance tests. AG concentrations in the nondiabetic patients indicated that the mean value of normal AG concentration was 21.8 micrograms/ml (SD = 5.9 micrograms/ml, range 9.6-38.8 micrograms/ml). This distribution of AG concentration was significantly different from that in patients with impaired glucose tolerance (IGT) (13.3 +/- 5.4 micrograms/ml) and definitely different from that in diabetic patients (2.1 +/- 1.8 micrograms/ml). In a standard glucagon test, it was suggested that the decrease of plasma AG was affected not only by glycemic control of the patients but also by pancreatic cell secretory activity. The reduction of AG concentration was more marked in IDDM patients than in NIDDM patients. In longitudinal studies, AG concentration was shown to be sensitive to glycemic control. However, its recovery showed a tendency toward much delay after the improvement of fasting blood glucose or HbA1 concentrations. On the other hand, AG concentration showed negligible diurnal change and no immediate change as a result of diet, oral glucose load, or acute shift of the insulin level in both normal and diabetic subjects.

Induced pluripotent stem (iPS) cells provide powerful tools for studying disease mechanisms and developing therapies for diseases. The 8p11 myeloproliferative syndrome (EMS) is an aggressive chronic myeloproliferative disorder (MPD) that is caused by constitutive activation of fibroblast growth factor receptor 1. EMS is rare and, consequently, effective treatment for this disease has not been established. Here, iPS cells were generated from an EMS patient (EMS-iPS cells) to assist the development of effective therapies for EMS. When iPS cells were co-cultured with murine embryonic stromal cells, EMS-iPS cells produced more hematopoietic progenitor and hematopoietic cells, and CD34+ cells derived from EMS-iPS cells exhibited 3.2–7.2-fold more macrophage and erythroid colony forming units (CFUs) than those derived from control iPS cells. These data indicate that EMS-iPS cells have an increased hematopoietic differentiation capacity, which is characteristic of MPDs. To determine whether a tyrosine kinase inhibitor (TKI) could suppress the increased number of CFUs formed by EMS-iPS-induced CD34+ cells, cells were treated with one of four TKIs (CHIR258, PKC 412, ponatinib, and imatinib). CHIR258, PKC 412, and ponatinib reduced the number of CFUs formed by EMS-iPS-induced CD34+ cells in a dose-dependent manner, whereas imatinib did not. Similar effects were observed on primary peripheral blood cells (more than 90% of which were blasts) isolated from the patient. This study provides evidence that the EMS-iPS cell line is a useful tool for the screening of drugs to treat EMS and to investigate the mechanism underlying this disease.

O6-Methylguanine, O4-methylthymine and O4-ethylthymine were determined by a recently developed, highly sensitive and specific method (PREPI, pre-fractionation, 32P-post-labeling and immunoprecipitation) in human liver DNA obtained from 15 autopsy specimens and in 15 peripheral blood leukocyte DNA samples obtained from healthy volunteers. All the cases had no obvious history of recent occupational or therapeutic exposure to alkylating agents. In the human liver DNA O6-methylguanine was detected in 13 cases at levels of 1.1-6.7 adducts/10(7) guanine; two cases were below the detection limit of approximately 1.1 x 10(-8). O4-Methylthymine and O4-ethylthymine were detected in all the liver samples at levels of 0.1-14 adducts and 0.5-140 adducts/10(7) thymine respectively. The mean value of the ratio of O6-methylguanine to O4-methylthymine was about 6. Among the three DNA adducts measured there was no significant correlation between any two combinations of adducts. In peripheral leukocytes of healthy volunteers O6-methylguanine was detected at 0.7-4.6 adducts/10(8) guanine, this being approximately 3-6% of that in livers. Neither O4-methylthymine nor O4-ethylthymine was above the detection limits. These results suggest that humans are exposed to exogenous and/or endogenous methylating and ethylating agents in daily life.