By in vitro translation of mRNA's isolated from free and membrane-bound polysomes, direct evidence was obtained for the synthesis of two lysosomal hydrolases, ß-glucuronidase of the rat preputial gland and cathepsin D of mouse spleen, on polysomes bound to rough endoplasmic reticulum (ER) membranes. When the mRNA's for these two proteins were translated in the presence of microsomal membranes, the in vitro synthesized polypeptides were cotranslationally glycosylated and transferred into the microsomal lumen . Polypeptides synthesized in the absence of microsomal membranes were 2,000 daltons larger than the respective unglycosylated microsomal polypeptides found after short times of labeling in cultured rat liver cells treated with tunicamycin. This strongly suggests that nascent chains of the lysosomal enzymes bear transient amino terminal signals which determine synthesis on bound polysomes and are removed during the cotranslational insertion of the polypeptides into the ER membranes .In the line of cultured rat liver cells used for this work, newly synthesized lysosomal hydrolases showed a dual destination; -60% of the microsomal polypeptides detected after short times of labeling were subsequently processed proteolytically to lower molecular weight forms characteristic of the mature enzymes. The remainder was secreted from the cells without further proteolytic processing . As previously observed by other investigations in cultured fibroblasts (A . Gonzalez-Noriega, J . H . Grubbs, V. Talkad, and W. S. Sly, 1980, J. Cell Biol. 85 : 839-852; A. Hasilik and E. F. Neufeld, 1980, /. Biol. Chem ., 255:4937-4945 .) the lysosomotropic amine chloroquine prevented the proteolytic maturation of newly synthesized hydrolases and enhanced their secretion . In addition, unglycosylated hydrolases synthesized in cells treated with tunicamycin were exclusively exported from the cells without undergoing proteolytic processing . These results support the notions that modified sugar residues serve as sorting out signals which address the hydrolases to their lysosomal destination and that final proteolytic cleavage of hydrolase precursors takes place within the lysosome itself .Structural differences in the carbohydrate chains of intracellular and secreted precursors of cathepsin D were detected from their differential sensitivity to digestion with endoglycosidases H and D . These observations suggest that the hydrolases exported into the medium follow the normal secretory route and that some of their oligosaccharides are subject to modifications known to affect many secretory glycoproteins during their passage through the Golgi apparatus.
Background
Rikkunshito, a standardized Japanese herbal medicine, is thought to accelerate gastric emptying and relieve dyspepsia, although no large‐scale, randomized, placebo‐controlled trials of rikkunshito have been conducted. This study aimed to determine the efficacy and safety of rikkunshito for treating functional dyspepsia (FD).
Methods
FD patients received 2.5 g rikkunshito or placebo three times a day for 8 weeks in this multicenter, randomized, placebo‐controlled, parallel‐group trial. The primary end point was the proportion of responders at 8 weeks after starting test drug, determined by global patient assessment (GPA). The improvement in four major dyspepsia symptoms severity scale was also evaluated. In addition, plasma ghrelin levels were investigated before and after treatment.
Key Results
Two hundred forty‐seven patients were randomly assigned. In the eighth week, the rikkunshito group had more GPA responders (33.6%) than the placebo (23.8%), although this did not reach statistical significance (p = 0.09). Epigastric pain was significantly improved (p = 0.04) and postprandial fullness tended to improve (p = 0.06) in the rikkunshito group at week 8. Rikkunshito was relatively more effective among Helicobacter pylori‐infected participants (rikkunshito: 40.0% vs placebo: 20.5%, p = 0.07), and seemed less effective among H. pylori‐uninfected participants (rikkunshito: 29.3% vs placebo: 25.6%, p = 0.72). Among H. pylori‐positive individuals, acyl ghrelin levels were improved just in rikkunshito group. There were no severe adverse events in both groups.
Conclusions & Inferences
Administration of rikkunshito for 8 weeks reduced dyspepsia, particularly symptoms of epigastric pain and postprandial fullness. (UMIN Clinical Trials Registry, Number UMIN000003954).
In this study we described development of boys' and girls' games on the school playground at recess as they progressed across the first year of primary school in London (UK) and Minneapolis (USA) in order to document age-related trends in games during this period and to examine the predictive role of games in children's adjustment to school and more general social adjustment. Consistent with expectations, games accounted for a significant portion of children's, but especially boys', behavior during recess. American children played games more frequently, especially simple games, relative to English children. Consistent with expectation, the complexity of games increased, especially for boys, across the school year for children in both countries. We also examined the extent to which facility with games forecasted adjustment to school and social adjustment. Games predicted both, but only in the USA sample. Results are discussed in terms of games being an important developmental task for children of this age. Implications for future research and educational policy are discussed.
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