Medullary thymic epithelial cell depletion leads to autoimmune hepatitis

TRAF6, an E3 ubiquitin protein ligase, plays a critical role in T cell tolerance by regulating medullary thymic epithelial cell (mTEC) development. mTECs regulate T cell tolerance by ectopically expressing self-antigens and eliminating autoreactive T cells in the thymus. Here we show that mice with mTEC depletion due to conditional deletion of Traf6 expression in murine thymic epithelial cells (Traf6ΔTEC mice) showed a surprisingly narrow spectrum of autoimmunity affecting the liver. The liver inflammation in Traf6ΔTEC mice exhibited all the histological and immunological characteristics of human autoimmune hepatitis (AIH). The role of T cells in AIH establishment was supported by intrahepatic T cell population changes and AIH development after transfer of liver T cells into immunodeficient mice. Despite a 50% reduction in natural Treg thymic output, peripheral tolerance in Traf6ΔTEC mice was normal, whereas compensatory T regulatory mechanisms were evident in the liver of these animals. These data indicate that mTECs exert a cell-autonomous role in central T cell tolerance and organ-specific autoimmunity, but play a redundant role in peripheral tolerance. These findings also demonstrate that Traf6ΔTEC mice are a relevant model with which to study the pathophysiology of AIH, as well as autoantigen-specific T cell responses and regulatory mechanisms underlying this disease.     

Differential effects of central fructose and glucose on hypothalamic malonyl-CoA and food intake

The American diet, especially that of adolescents, contains highly palatable foods of high-energy content and large amounts of high-fructose sweeteners. These factors are believed to contribute to the obesity epidemic and insulin resistance. Previous investigations revealed that the central metabolism of glucose suppresses food intake mediated by the hypothalamic AMP-kinase/malonyl–CoA signaling system. Unlike glucose, centrally administered fructose increases food intake. Evidence presented herein indicates that the more rapid initial steps of central fructose metabolism deplete hypothalamic ATP level, whereas the slower regulated steps of glucose metabolism elevate hypothalamic ATP level. Consistent with effects on the [ATP]/[AMP] ratio, fructose increases phosphorylation/activation of hypothalamic AMP kinase causing phosphorylation/inactivation of acetyl–CoA carboxylase, whereas glucose has the inverse effects. The changes provoked by central fructose administration reduce hypothalamic malonyl–CoA level and thereby increase food intake. These findings explain the paradoxical fructose effect on food intake and lend credence to the malonyl–CoA hypothesis.     

Effect of Granulocyte Colony-Stimulating Factor on Chemotherapeutic Activity of Cytosine Arabinoside in Acute Leukemic Cell Lines

Recent studies have shown the presence of receptors for granulocyte colony-stimulating factor (G-CSF) on lymphoid leukemic cells. To determine the effect of G-CSF on chemotherapeutic activity of cytosine arabinoside (Ara-C) on lymphoid as well as myeloid leukemic cells, we evaluated cell counts, apoptosis, and growth inhibition in HL-60, KG-1, Molt-4, Jijoye, and CCRF-CEM cell lines after incubation with Ara-C (0.1 and 1 micromol/L) and/or 5 ng/mL G-CSE G-CSF potentiated the effect of Ara-C on 2 of 3 lymphoid leukemic cell lines (Molt-4 and Jijoye), whereas it decreased the apoptosis and the effect of Ara-C on myeloid cell lines (HL-60 and KG-1).     

Development of web-based diabetic patient management system using short message service (SMS)

We developed a blood glucose management system using the Internet and short message service (SMS) which can lessen the social economic burden and materialize an individualized diabetes mellitus management. A total of 185 diabetic patients participated in this study and their mean age was 42.4 years old (8-79 year-old). Participants sent their self-measured blood glucose levels, medication and its dosages, amount of meal, and degree of exercise to their health providers in this specialized web-based diabetes management system for 3 months. The health providers consisting of endocrinology specialists, dietitians, and nurses sent recommendations for individualized diabetes management according to the data on the web. Laboratory tests including lipid profiles and glycated hemoglobin (HbA1c), and a survey of satisfaction about this system were performed before and after the study period. The mean HbA1c improved from 7.5 +/- 1.5 to 7.0 +/- 1.1% after using the management program (P = 0.003). The mean serum triglyceride and HDL-cholesterol levels turned for the better also. HbA1c improved from 8.4 +/- 1.2 to 7.5 +/- 1.0% after applying this program to patients with the HbA1c of 7% or higher at baseline (P = 0.010). We propose this web-based diabetic patient management system as a new tool for communication between health care providers and patients.