Observation of confined current ribbon in JET plasmas.

We report the identification of a localized current structure inside the JET plasma. It is a field-aligned closed helical ribbon, carrying current in the same direction as the background current profile (cocurrent), rotating toroidally with the ion velocity (corotating). It appears to be located at a flat spot in the plasma pressure profile, at the top of the pedestal. The structure appears spontaneously in low density, high rotation plasmas, and can last up to 1.4 s, a time comparable to a local resistive time. It considerably delays the appearance of the first edge localized mode.

Control of neoclassical tearing modes by sawtooth control.

The onset of a neoclassical tearing mode (NTM) depends on the existence of a large enough seed island. It is shown in the Joint European Torus that NTMs can be readily destabilized by long-period sawteeth, such as obtained by sawtooth stabilization from ion-cyclotron heating or current drive. This has important implications for burning plasma scenarios, as alpha particles strongly stabilize the sawteeth. It is also shown that, by adding heating and current drive just outside the inversion radius, sawteeth are destabilized, resulting in shorter sawtooth periods and larger beta values being obtained without NTMs.

Grafts of supplementary thymuses injected with allogeneic pancreatic islets protect nonobese diabetic mice against diabetes.

In nonobese diabetic (NOD) mice, the autoimmune attack of the beta-cells in pancreatic islets is now believed to result from abnormal thymic selection. Accordingly, grafts of thymic epithelium from NOD donors to athymic recipients promote autoimmune islet inflammation in normal strains, and intrathymic islet grafts decrease the incidence of disease in NOD animals. Two competing hypotheses of abnormal thymic selection in diabetic mice have been proposed: deficient negative selection with poor elimination of aggressive organ-specific T cells vs. deficient positive selection of protective T regulatory cells. We have now addressed these alternatives by grafting, into young NOD mice whose own thymus was left intact, newborn NOD thymuses containing allogeneic pancreatic islets. If the NOD defect represented poor negative selection, these animals would develop disease at control rates, as the generation of autoreactive T cells proceeds undisturbed in the autologous thymus. In contrast, if NOD thymuses are defective in the production of T regulatory cells, lower disease incidence is expected in the chimeras, as more protective cells can be produced in the grafted thymus. The results show a reduced incidence of diabetes in the chimeras (24%) as compared with control (72%) NOD mice, throughout adult life. We conclude that amelioration of NOD mice by intrathymic islet grafts is not caused by enhanced negative selection and suggest that autoimmune diabetes in this system is the result of inefficient generation of T regulatory cells in the thymus.

Influence of diet on lactate, alanine and serine turnover and incorporation into glucose in the dog.

Four diets containing 0 to 62% of energy from carbohydrate and 24% to 48% of energy from protein were fed to young dogs. The influence of these diets on the turnover of [U-14C]-L-lactate, [U-14C]-L-alanine and [U-14C]-L-serine and on the incorporation of these gluconeogenic precursors into plasma glucose of the dog was established. Blood lactate levels were lowered when high-protein diets were fed but were not influenced by the level of carbohydrate in the diet or by a 48-hour fast. Plasma alanine and serine levels were elevated in dogs fed the high-protein diets and were lowered by a 48-hour fast. Turnover of lactate was increased in dogs fed high-carbohydrate diets whereas turnover of alanine and serine was increased in dogs fed the high-protein diets. Following a 48-hour fast, 14C-lactate conversion to plasma glucose was lower in dogs fed the high-protein diets than in dogs fed the lower protein diets whereas 14C-alanine and 14C-serine conversion to plasma glucose was increased in dogs fed the high-protein. Thus, the diet consumed altered the relative importance of these gluconeogenic precursors to the maintenance of plasma glucose.

Influence of diet on glucose tolerance, on the rate of glucose utilization and on gluconeogenic enzyme activities in the dog.

Four diets containing 0 to 62% of energy from carbohydrate and 24% to 48% of energy from protein were fed to young dogs. Two of the diets (diets LPLC and HPLC) were carbohydrate-free and two of the diets (diets HPHC and HPLC) contained 46% to 48% protein. The influence of these diets on several parameters of glucose metabolism was ascertained. Following an intravenous glucose load, plasma glucose levels were higher in dogs fed carbohydrate-free diets (diets LPLC and HPLC) than observed in dogs fed carbohydrate-containing diets (diet LPHC and HPHC). Consumption of high-protein diets (diets HPHC and HPLC) also impaired glucose tolerance. Estimates of glucose utilization were obtained. Dogs fed carbohydrate-containing diets exhibited a higher rate of glucose utilization than did dogs fed the carbohydrate-free diets. Fasting the dogs for 48 hours reduced the glucose replacement rate in dogs fed the carbohydrate-containing diets but did not influence the rate of glucose utilization in dogs fed the carbohydrate-free diets. The activities of phosphoenolpyruvate carboxykinase (PEPCK) and of pyruvate carboxylase (PYCAR) in livers and kidneys of these dogs were influenced by the diets fed. Mitochondrial PEPCK and PYCAR activities in both liver and kidney were increased in dogs fed the carbohydrate-free diets. Consumption of the high-protein diets actually decreased the activities of PEPCK in liver and kidney mitochondria.

Effects of dietary carbohydrate, fat and protein on growth, body composition and blood metabolite levels in the dog.

Six semipurified canned diets ranging in composition from 0 to 62% of energy from carbohydrate and from 20% to 48% of energy from protein were fed to female beagle dogs for 8 months. Additionally, three commercial-type diets were also fed. The effects of these diets on growth, body composition and selected blood metabolite levels in the dogs were studied. The dogs readily consumed each of the nine diets fed. The level of carbohydrate, fat or protein in the diet did not influence body weight gain during the first 16 weeks nor was nitrogen balance affected by the diets. At the end of the 32-week study, dogs fed the high-carbohydrate (62% of energy) diet contained less body fat but an equal-free mass, than did dogs fed lower-carbohydrate (20--42% of energy) diets with a similar quantity of protein. Consumption of carbohydrate-free diets did not influence postprandial levels of circulating glucose or insulin in the dogs. Plasma cholesterol levels were elevated in dogs consuming in the diets high in fat but plasma triglyceride levels were not influenced by the diets fed. Consumption of high-protein (46--48% of energy) diets elevated plasma urea nitrogen levels but had minimal influence on plasma amino acid levels. The general response of these young dogs was not markedly influenced by consumption of diets ranging from carbohydrate-free to high-carbohydrate and from adequate-protein to high-protein.

Blood metabolites and glucose metabolism in the fed and fasted chicken.

The effect of fasting on blood metabolites and glucose metabolism in the chicken was studied. Parameters of glucose metabolism were estimated in vivo using a single injection of [2-3H]-glucose or [6-3H]-glucose in combination with [U-14C]-glucose. Plasma glucose, blood lactate and blood acetoacetate levels were not significantly changed in chickens fasted for 72 hours. Pyruvate levels in chickens fasted for 24 hours were higher than those observed in blood from birds fasted 0 to 72 hours. Further, the lactate to pyruvate ratio was lower in chickens fasted for 24 to 72 hours than in fed chickens. Fasting chickens for 24 or 72 hours resulted in three- to fivefold increase in blood beta-hydroxybutyrate levels and a significant increase in beta-hydroxybutyrate to acetoacetate ratio. Plasma levels of alanine and serine were increased after a 24 hour fast but were not further changed when fasting was extended to 72 hours. Plasma aspartate and glutamate levels were not significantly changed in chickens fasted for 24 hours but were markedly decreased in chickens fasted for 72 hours. Plasma levels of glycine were significantly lower in chickens fasted 24 or 72 hours than in fed birds. Glucose replacement rates estimated with [2-3H]-glucose in chickens fasted 0,24 and 72 hours were 14.3, 9.1 and 9.4 mg glucose/minute/kg body weight, respectively. Fasting up to 72 hours did not influence the total body glucose mass in the chickens. The degree of glucose-carbon recycling in 24-hour fasted chickens estimated by using [2-3H]- and [U-14C]-glucose or [6-3H]- and [U-14C]-glucose averaged 42% to 52% and 27% to 30%, respectively. These observations indicate that rate of glucose utilization in the chicken is rapid and that substantial recycling of glucose carbon occurs in fasted chickens.

Studies of the effect of dietary cholesterol on hepatic protein synthesis, reduced glutathione levels and serine dehydratase activity in the rat.

A basal diet or a basal diet plus 1% of cholesterol and 0.33% cholic acid was fed to rats for varying lengths of time and (1) the activities of liver phosphoenolpyruvate-carboxykinase (PEP-CK), tyrosine transaminase (TT), and serine dehydratase (SD); (2) the rate of total hepatic protein synthesis and (3) the concentration of hepatic reduced glutathione (GSH) were quantitated. The specific activity of PEP-CK was significantly depressed by cholesterol plus cholic acid feeding, while the specific activity of TT was unchanged. No significant effect of dietary cholesterol plus cholic acid was found on the total liver activities. In contrast, SD specific activity was increased 3-fold. The rate of (U-14C)-L-leucine incorporation into total TCA precipitable protein following ingestion of cholesterol plus acid was significantly reduced when the data were expressed as dpm (U-14C)-L-leucine/mg protein. After correcting this expression for specific radioactivity of the liver tissue free leucine pool, no significant effect of dietary cholesterol plus cholic acid on hepatic protein synthesis existed. In fact, the amount of 14C-leucine incorporated into protein on a total liver basis was 50% greater for the cholesterol group. On a per gram of liver basis, the concentration of GSH in the liver of rats fed a cholesterol plus cholic acid diet was significantly decreased. Considering the liver enlargement in rats fed cholesterol plus cholic acid, total organ GSH was found to be significantly greater than for rats fed a basal diet.

Butanediol and lipid metabolism.

Young growing rats, chicks and pigs were fed diets containing graded levels of 1,3-butanediol (BD). Replacement of up to 20% of the dietary carbohydrate energy with BD did not affect body weight gain or food efficiency in these species. Blood beta-hydroxybutyrate levels were markedly elevated when BD was added to the diet. Plasma triglyceride response varied with species. In the rat, plasma triglyceride levels were decreased when BD was added to a high-carbohydrate diet. Plasma triglyceride levels were increased when BD-containing diets were fed to pigs and unchanged when chicks consumed diets containing BD. The hepatic lactate:pyruvate ratio was increased in rats fed BD and decreased in chicks fed BD. Hepatic long-chain acyl CoA levels were increased in rats, but not in chicks, fed BD. Addition of BD to a high-carbohydrate diet markedly decreased the rate of fatty acid synthesis, as measured in vitro or in vivo, in rat liver but not in rat or pig adipose tissue. Hepatic fatty acid synthesis in the chick was not affected by replacement of up to 18% of the dietary carbohydrate with BD. We propose that the hepatic conversion of BD to beta-hydroxybutyrate in the rat shifts the cytoplasmic redox state, reduces the glycolytic rate, and reduces substrate availability for fatty acid synthesis. Further, the concomitant shift in the mitochondrial redox state allows long-chain acyl CoA levels to increase. The overall effect is a decrease in the rate of fatty acid synthesis in livers of rats fed BD.

Influence of dietary 1,3-butanediol on wieght gain, blood, and liver metabolites and lipogenesis in the pig and chick.

The influence of dietary 1,3-butanediol (BD) on body weight gain, blood and liver metabolites, and on lipogenesis in pigs and chicks was studied. Body weight gain and energy intake of both pigs and chicks were depressed when the dietary energy derived from BD exceeded about 20 percent. Circulating beta-hydroxybutyrate and acetoacetate levels were markedly increased by dietary BD. Plasma triglyceride levels were increased in pigs and unchanged in chicks fed BD-containing diets. In vitro rates of fatty acid synthesis and the activities of fatty acid synthetase and malic enzyme in pig adipose tissue were not affected by the dietary BD. Neither addition of 18 percent dietary energy in the form of BD to the diet nor addition of BD to the incubation buffer affected glucose conversion to fatty acids by chick liver slices. Dietary BD did not affect long-chain acyl CoA levels in freeze-clamped chick liver but did increase the free CoA levels slightly. The hepatic lactate: pyruvate ratio was decreased when chicks were fed a BD-containing diet.