No abstract

CD4+ Th1 cells play a critical role in the induction of cell-mediated immune responses that are important for the eradication of intracellular pathogens. Peptide-25 is the major Th1 epitope for Ag85B of Mycobacterium tuberculosis and is immunogenic in I-Ab mice. To elucidate the role of the TCR and IFN-gamma/IL-12 signals in Th1 induction, we generated TCR transgenic mice (P25 TCR-Tg) expressing TCR alpha- and beta-chains of Peptide-25-reactive cloned T cells and analyzed Th1 development of CD4+ T cells from P25 TCR-Tg. Naive CD4+ T cells from P25 TCR-Tg differentiate into both Th1 and Th2 cells upon stimulation with anti-CD3. Naive CD4+ T cells from P25 TCR-Tg preferentially develop Th1 cells upon Peptide-25 stimulation in the presence of I-Ab splenic antigen-presenting cells under neutral conditions. In contrast, a mutant of Peptide-25 can induce solely Th2 differentiation. Peptide-25-induced Th1 differentiation is observed even in the presence of anti-IFN-gamma and anti-IL-12. Furthermore, naive CD4+ T cells from STAT1 deficient P25 TCR-Tg also differentiate into Th1 cells upon Peptide-25 stimulation. Moreover, Peptide-25-loaded I-Ab-transfected Chinese hamster ovary cells induce Th1 differentiation of naive CD4+ T cells from P25 TCR-Tg in the absence of IFN-gamma or IL-12. These results imply that interaction between Peptide-25/I-Ab and TCR may primarily influence determination of the fate of naive CD4+ T cells in their differentiation towards the Th1 subset.

A fluorescent aptamer sensor was applied to the analysis of extracellular chemical transmitter dynamics. We utilized a tocopherol-labeled aptamer, which allowed the direct anchoring of the fluorescent aptamer on the cell surface while retaining its performance as a fluorescent sensor. The fast-responsive fluorescent DNA aptamer sensor, which targets adenine compounds, was anchored on the surface of brain astrocytes. Fluorescence imaging of the aptamer-anchored astrocytes enabled the real-time monitoring of release of adenine compounds as a gliotransmitter, which was synchronized with calcium wave propagation in neighboring cells.

SummaryThe influence of the chronic intake of a newly developed sweetener named "Neosugar" (fructooligosaccharide) on body weight gain, organ weight, serum lipids, fecal excretion and intestinal function was investigated in rats. The following results were obtained. 1) Body weight gain was diminished more severely in rats fed on 20% Neosugar diet than in rats fed on 10% Neosugar diet. 2) The wet weights of cecum and colon were greatly increased by Neosugar feeding. 3) Fecal wet weight was significantly increased and gastrointestinal transit time was shortened by Neosugar feeding compared with those of the control group. 4) Serum triacylglycerol levels were significantly lower in rats fed Neosugar, whereas serum cholesterol levels were similar to those of the control group. 5) Fecal excretions of neutral sterol and volatile fatty acids were significantly increased by Neosugar feeding. These results were quite similar, with the exception of diarrhea to those obtained using a dietary fi ber such as glucomannan. Therefore, Neosugar with a pleasant-tasting sweetness appears to be an unavailable oligosaccharide with a dietary fi ber-like action. Key Words Neosugar, fructooligosaccharide, dietary fiber, chronic in take, sweetener, undigestibility, gastrointestinal A dietary preference for sweet foods accompanied by an excessive intake of energy leads inevitably to obesity in people who continue to consume more energy than they burn. In this sense, pleasant-tasting, non-energy sweetener that is entirely safe would make it possible to enjoy sweetened food and at the same time, to avoid both obesity and its complications such as diabetes mellitus. The newly developed 111

The digestion of Neosugar, a mixture of 1F-(1-beta-fructofuranosyl)n-1 sucrose [n = 2, 1-kestose (GF2); n = 3, nystose (GF3); n = 4, 1F-beta-fructofuranosyl nystose (GF4)] was investigated in vitro and in vivo by using the rat. The results obtained were as follows. GF2 and GF3 were not hydrolyzed by a pancreatic homogenate. The GF2- and GF3-hydrolyzing activities of the enzymes in the intestinal mucosa homogenate were negligible compared with the activities of maltase and sucrase. GF2 and GF3 added to the incubation mixture did not affect the activities of sucrase and maltase in the intestinal mucosa. Long-term ingestion of Neosugar did not cause induction or suppression of GF2- and GF3-hydrolyzing enzymes in the small intestine. [U-14C]Neosugar injected intravenously was rapidly excreted in the urine without having undergone any degradation. These results indicate that Neosugar, which consists of GF2, GF3 and GF4, is scarcely hydrolyzed by the digestive enzymes of the gastrointestinal tract and internal organs, and that suggests to us that Neosugar is not utilized as an energy source in the body.