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The pathogenic autoantibodies in MG depend on specific helper T cells. They recognise acetylcholine receptor (AchR) derived peptide epitopes when presented by HLA-class II molecules on antigen presenting cells. These [...]

RATIONALE AND OBJECTIVES: Hepatocyte growth factor (HGF) is a potent regenerative factor generated after a lung injury, and HGF supplementation after surgical reduction has been shown to enhance compensatory growth in remnant lungs and improve pathophysiologic conditions in a rat model of emphysema. Adipose tissue-derived stromal cells (ASCs) produce a large amount of angiogenic factors, including HGF. After lung volume reduction surgery (LVRS), we treated rats by implanting HGF-secreting ASCs with a scaffold onto the remnant lung tissue to determine the usefulness of this technique for treating respiratory dysfunction. Methods and MAIN RESULTS: Cells were isolated from rat inguinal adipose tissue and characterized by flow cytometry. ASCs were cultured on a polyglycolic acid felt sheet as a sealant material, and were shown to secrete significantly greater amounts of HGF than other angiogenic factors. Next, ASCs on polyglycolic acid felt sheets were used to cover the cut edge of the remaining lungs after LVRS for emphysema in rats. One week after implantation of the ASCs, both alveolar and vascular regeneration were significantly accelerated as compared with the rats that underwent LVRS alone. Consequently, gas exchange and exercise tolerance were also significantly restored, with these good results persisting for more than 1 mo. CONCLUSIONS: The present findings demonstrate the therapeutic potential of cell therapy using ASCs with a scaffold for selective delivery of HGF to remnant lungs, which resulted in enhancement of compensatory growth, after surgical resection. This approach may provide a new strategy for lung tissue engineering to improve LVRS outcome. [ABSTRACT FROM AUTHOR]

Cefoselis is a widely used ß-lactam antibiotic, but occasionally induces seizures and convulsion in elder and renal failure patients. However, ß-lactams are known not to pass through the blood-brain barrier (BBB). In this study, we examined the BBB penetration of cefoselis in normal and renal failure rats by means of brain microdialysis. Cefoselis was dose-dependently appeared in brain extracellular fluid in proportion to its blood level. The elimination constant from brain extracellular fluid (apparent) was slightly lower than that from blood. These results indicated that cefoselis might penetrate the BBB or be discharged by a certain transport system. In contrast to the result of cefoselis, cefazolin, a leading drug of cephalosporins, could not be detected in the brain extracellular fluid after an intravenous injection. In renal dysfunction rats, the elimination half-lives of cefoselis from both blood and brain were extensively prolonged. This would be one of responsible factors inducing seizures seen in patients. However, the additional factor, such as decrease in brain function related to aging, would be involved in seizures in patient received cefoselis, because an extremely high dose was required to induce seizures even in renal failure rats. A local administration of cefoselis into the hippocampus through the microdialysis probe caused a striking elevation of extracellular glutamate, with a minimum increase in ?-aminobutyric acid (GABA). However, a systematic cefoselis administration via the tail vein did not elevate extracellular glutamate and GABA concentrations in the hippocampus of renal failure rats that exhibited marked seizures. These results suggested that not the stimulation of glutamate release, but the blockade of GABA receptors might be responsible for the seizure induced by cefoselis. [ABSTRACT FROM AUTHOR]

Summary. The role of glutamate in the N-methyl-4-phenyl-dihydropyridinium (MPP+) toxicity has been argued in the past decade. However, the effects of glutamate efflux and NMDA antagonist on MPP+-induced dopamine overflow have not been documented. To clarify this, we perfused MPP+ through a microdialysis probe in the striatum of freely moving mature C57BL/6 mice. The 60-min perfusion of 10 and 100 μM MPP+ strikingly increased dopamine levels to 28- and 93-fold of the basal values, respectively. In contrast, an administration of MPP+ did not induce marked glutamate release: the MPP+-perfusion slightly increased the glutamate level at 100 μM, but not at 10 μM. The addition of 100 μM (+)-MK-801 or 200 μM (±)-AP-7 to the perfusate did not attenuate MPP+-induced dopamine overflow. The extent of dopamine release only depended on the amount of MPP+ accumulation into the cells. These results indicated that, at least in the striatum, neither glutamate release nor the NMDA antagonist, including (+)-MK-801, could regulate MPP+-evoked dopamine overflow. [ABSTRACT FROM AUTHOR]

Attempts to determine whether class II transactivator (CIITA) is responsible for the impaired up-regulation of major histocompatibility complex II molecules. Evaluation of the surface marker expression on thymic epithelial cells; Relationship between CIITA and the phenotypic characteristics of lymphocytes; Characteristics of thymoma.

To identify the substrate specificity of lipoprotein lipase (LPL) for triacylglycerol-rich lipoproteins with monoacid-rich triacylglycerols, monoacid-rich lipoproteins were prepared and kinetic parameters of LPL were characterized. Male broiler chickens were fed 8 g/100 g fat diets differing only in the fat source: palm oil (tripalmitin-rich), olive oil (triolein-rich), safflower oil (trilinolein-rich) and linseed oil (trilinolenin-rich). After diets were fed for 3 d, chickens were starved for 2 d and then force-fed emulsions containing one of the monoacid-triacylglycerols: tripalmitin, triolein, trilinolein or trilinolenin. The triacylglycerols in chylomicrons and very low density lipoprotein (VLDL) of chickens force-fed tripalmitin, triolein or trilinolein contained the corresponding acid at more than 70% of total acids. Linolenic acid was incorporated into chylomicrons and VLDL to a lower extent (51.2 and 57.2%, respectively) in chickens force-fed trilinolein. Major apolipoproteins and lipid compositions were not significantly different among all lipoproteins isolated from chickens fed the different fats. Vmax of LPL was significantly higher (P < 0.05) for palmitic acid-rich chylomicrons and VLDL and decreased with increasing chain length and unsaturation of monoacid: 16:0>18:1>18:2>18:3. The electron spin resonance analysis, order parameter (S), decreased with monoacid chain length and unsaturation. In addition, the Vmax of LPL increased linearly (P < 0.01, r = 0. 912) with an increase in the palmitic acid content of the lipoprotein triacylglycerols. These findings suggest that lipoprotein catalysis by LPL is modulated by the palmitic acid content of the lipoprotein triacylglycerol, which affects the fluidity of lipoproteins. [ABSTRACT FROM AUTHOR]