Factors responsible for elevation of 1-h postchallenge plasma glucose levels in Japanese men

The 1-h postchallenge plasma glucose (1-h PG) level is considered to be a good index of the development of glucose intolerance and type 2 diabetes as well as of diabetic complications. In some cases, in Japanese, 1-h PG is elevated despite normal fasting glucose during oral glucose tolerance test (OGTT), but the factors responsible remain unclear. In the present study, subjects with normal glucose tolerance (NGT), isolated impaired fasting glucose (IFG), and isolated impaired glucose tolerance (IGT) were divided into subgroups at 1-h PG of 10.0 mM, and the four indices of insulin secretion and insulin sensitivity were compared. In all three categories, the insulinogenic index in subjects with elevated 1-h PG was remarkably lower than in those without elevated 1-h PG. In addition, the insulinogenic index was the strongest factor in elevated 1-h PG according to the multiple regression analysis. Interestingly, one third of the NGT subjects enrolled in this study had elevated 1-h PG. These subjects showed significantly elevated area under the curve of glucose (G-AUC) compared to NGT subjects without 1-h PG elevation. Thus, elevated 1-h PG in Japanese subjects indicates mildly impaired glucose tolerance due to decreased early-phase insulin secretion.     

Recommendation of lamivudine‐to‐entecavir switching treatment in chronic hepatitis B responders: Randomized controlled trial

Aim: In the 2007–2008 guidelines of the study group (Ministry of Health, Labor and Welfare of Japan), lamivudine (LAM)‐continuous treatment was recommended in patients treated with LAM for more than 3 years who maintained hepatitis B virus (HBV) DNA less than 2.6 log copies/mL, because in these patients LAM resistance might exist and switching treatment to entecavir (ETV) might cause ETV resistance. However, there was no evidence on whether switching treatment to ETV‐ or LAM‐continuous treatment was better in those patients. In the present study, we performed a randomized controlled trial of LAM‐to‐ETV switching treatment. Methods: Twenty‐seven patients treated with LAM for more than 3 years whose HBV DNA levels were less than 2.6 log copies/mL were enrolled and randomly divided into two groups, LAM‐continued group or switching to ETV group. Then, we examined incidence of virological breakthrough (VBT) and breakthrough hepatitis (BTH) in each group. Results: There was no BTH in any of the patients. VBT was observed in six patients of the LAM group (6/15, 40%), and no patient of the ETV group (0/11, 0%) (P = 0.02). The differences of the proportion of cumulated VBT using a log–rank test with Kaplan–Meier analysis were significant between the LAM and ETV groups (P = 0.025). Conclusion: In patients treated with LAM for more than 3 years maintaining HBV DNA less than 2.6 log copies/mL, switching treatment to ETV is recommended at least during the 2 years' follow‐up period.     

Three-year follow-up on the effects of a smoking prevention program for elementary school children with a quasi-experimental design in Japan

OBJECTIVE: We performed the follow-up tests for three years for junior high school students by the quasi-experimental design to investigate the medium-term effect of smoking prevention education in the elementary school. METHODS: The intervention group consisted of 106 school students of three elementary schools and received a smoking prevention program in the elementary school. Moreover, the follow-up tests were conducted at each grade of junior high school, and the booster program was mailed. The comparison group consisted of 193 school students of another three elementary schools without the program. RESULTS: The intervention effects were recognized on knowledge up to the second grade of junior high school for boys and up to the third grade for girls, on awareness of the importance of not smoking at the second grade, and on the intention of smoking at the age of 20 for girls up to the first grade. On the other hand, the intervention effects were not recognized on smoking experience for boys and girls. However, increase of the rate of smoking experience was not significant in the intervention group, while it was significant in the comparison group. CONCLUSION: The effect of the program for three years was judged to be moderate.     

Establishment of stable cell lines with high expression of heterodimers of human 4F2hc and human amino acid transporter LAT1 or LAT2 and delineation of their differential interaction with α-alkyl moieties

System L is a major transport system for cellular uptake of neutral amino acids. Among system L transporters, L-type amino acid transporter 1 (LAT1) is responsible for the nutrient uptake in cancer cells, whereas L-type amino acid transporter 2 (LAT2) is a transporter for non-cancer cells. In this study, we have established HEK293 cell lines stably expressing high levels of human LAT1 and LAT2 forming heterodimers with native human 4F2hc of the cells. We have found that L-[(14)C]alanine is an appropriate substrate to examine the function of LAT2, whereas L-[(14)C]leucine is used for LAT1. By using L-[(14)C]alanine on LAT2, we have for the first time directly evaluated the function of human LAT2 expressed in mammalian cells and obtained its reliable kinetics. Using α-alkyl amino acids including α-methyl-alanine and α-ethyl-L-alanine, we have demonstrated that α-alkyl groups interfere with the interaction with LAT2. These cell lines with higher practical advantages would be useful for screening and analyzing compounds to develop LAT1-specific drugs that can be used for cancer diagnosis and therapeutics. The strategy that we took to establish the cell lines would also be applicable to the other heterodimeric transporters with important therapeutic implications.     

Angiotensin II receptor blocker reduces oxidative stress and attenuates hypoxia-induced left ventricular remodeling in apolipoprotein E-knockout mice.

Elevated superoxide formation in cardiac extracts of apolipoprotein E-knockout (apoE-KO) mice has been reported. In addition, we previously reported that hypoxia increased oxidative stress in the aortas of apoE-KO mice, although we did not examine the effect of hypoxia on the heart. The aim of this study was to investigate the effect of chronic hypoxia on the left ventricular (LV) remodeling in apoE-KO mice treated with or without an angiotensin II receptor blocker. Male apoE-KO mice (n=83) and wild-type mice (n=34) at 15 weeks of age were kept under hypoxic conditions (oxygen, 10.0+/-0.5%) and treated with olmesartan (3 mg/kg/day) or vehicle for 3 weeks. Although LV pressure was not changed, hypoxia caused hypertrophy of cardiomyocytes and increased interstitial fibrosis in the LV myocardium. Furthermore, nuclear factor-kappaB (NF-kappaB) and matrix metalloproteinase (MMP)-9 activities were increased in apoE-KO mice exposed to chronic hypoxia. Olmesartan effectively suppressed the 4-hydroxy-2-nonenal protein expression and NF-kappaB and MMP-9 activities, and preserved the fine structure of the LV myocardium without affecting the LV pressure. In conclusion, olmesartan reduced oxidative stress, and attenuated the hypoxia-induced LV remodeling, in part through the inhibition of NF-kappaB and MMP-9 activities, in apoE-KO mice.     

Sequential analysis of cadherin expression in a 4-year-old girl with intracranial ependymoma

Introduction Cadherins are Ca²⁺-dependent cell-to-cell adhesion molecules that play an important role in tissue construction and morphogenesis in multicellular organisms. Cadherin involvement in tumor metastasis has recently been reported. Case report We investigated the expression of E-cadherin and N-cadherin in paraffin-embedded sequential surgical specimens and autopsy specimens from a 4-year-old girl with recurrent ependymoma, subsequent to cerebrospinal fluid (CSF) dissemination. We observed low expression of E-cadherin in all surgical specimens and autopsy specimens. In contrast, expression of N-cadherin was high in all surgical specimens, but was decreased in autopsy specimens. Conclusion Decreased expression of N-cadherin may be associated with CSF dissemination and may serve as a useful marker for CSF dissemination in patients with intracranial ependymoma.     

Effects of prednisolone on specifically expressed genes in pediatric acute B-lymphoblastic leukemia

Although glucocorticoid is essential in the treatment of pediatric acute lymphoblastic leukemia (ALL), their precise mechanisms of action remain unclear. We used DNA microarray to evaluate prednisolone-regulated genes in pre-B-ALL cells from 2 pediatric patients. We found up-regulation of 26 genes in ALL cells from both patients, compared with peripheral normal B lymphocytes before maintenance chemotherapy. Treatment with prednisolone for 48 hours induced down-regulation of 5 genes (terminal deoxynucleotidyl transferase, heparin-binding epidermal growth factorlike growth factor, pre-B-lymphocyte genes 1 and 3, and immunoglobulin lambda-like polypeptide) among 26 specifically expressed genes in pre-B-ALL cells from both patients.