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Biomedical subjects
Publications and source records attributed to C S Davidson.
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The effect of dietary protein content on the diurnal variations in plasma neutral amino acid levels was studied in normal human subjects. For three consecutive 5-day periods, subjects consumed diets containing 0, 75, or 150 g of egg protein per day. Blood samples were drawn at 4-hr intervals on the 4th and 5th days of each period. Consumption of the protein-free diet caused plasma concentrations of all amino acids studied to fall in the late morning and afternoon, while the 150-g protein diet elicited increases in these levels during the daytime. Ingestion of the diet containing 75 g of egg protein tended to diminish the amplitudes of the daily rhythms in plasma amino acid levels, but most amino acids still exhibited small but significant elevations late in the evening. At all times of day, plasma concentrations of the large neutral amino acids studied (i.e., aromatic and branched-chain amino acids, and methionine) varied directly with the protein content of the diet. In contrast, the relationships between dietary protein content and the plasma concentrations of glycine and alanine, two small neutral amino acids, were inverse. The ratios of plasma tryptophan, tyrosine, and phenylalanine levels to the sum of the concentrations of other large neutral amino acids tended to fall as the protein content of the diet was increased. The corresponding ratio for valine increased as protein was added to the diet, while the leucine and isoleucine ratios were not correlated with dietary protein content. Since diet-induced changes in plasma trypotphan and tyrosine ratios in animals are known to cause parallel alterations in brain tryptophan and tyrosine levels, and thus in the rates of brain serotonin and catecholamine synthesis, our data suggest that ingestion of carbohydrates and protein may also normally affected brain monoamine synthesis in humans.
The effect of varying dietary protein content on the daily rhythms in plasma neutral amino acid concentrations was studied in patients with chronic cirrhosis. For two consecutive 5-day periods, subjects consumed diets containing either 0 or 75 g of protein per day. Blood samples were drawn at 4-hr intervals on the 4th and 5th days of each dietary period. For most of the neutral amino acids, the changes in plasma concentration associated with time of day or with variations in dietary protein content were similar to those observed previously in normal subjects. Ingestion of the protein-free diet caused significant reductions in the daytime level of all amino acids studied, except for tryptophan, the concentration of which did not change during the 24-hr period. Ingestion of the 75-g protein diet caused plasma levels of most of theamino acids to increase slightly during the day; these increments were not statistically significant for tryptophan, tyrosine, leucine, and methionine. The absolute plasma concentrations of most of the neutral amino acids were also in the normal range; exceptions included methonine, tyrosine, and phenylalanine, whose plasma levels were significantly elevated above normal valves. The plasma ratios of tryptophan, tyrosine, and phenylalanine concentrations to the sum of the concentrations of other large neutral amino acids increased during the day uhen the protein-free diet was ingested; this effect was moderated by the addition of protein to the food. The plasma ratios for the branched-chain amino acids were depressed below normal; those for tyrosine, phenylalanine, and methionine were significantly increased. The plasma tryptophan ratio was within the normal range. These findings provide a basis for anticipating that the uptake from blood into brain of several of the large neutral amino acids may be modified in patients with chronic cirrhosis.
Concentrations of immunoreactive insulin and of glucose were measured in plasma samples taken at 4-hour intervals from cirrhotic and normal control subjects ingesting diets containing various amounts of protein. In both groups, insulin levels were highest after meals, between 11 a.m. and 7 p.m.; in cirrhotic subjects, but not in controls, plasma glucose levels were also higher at these times. Insulin and glucose concentrations in plasma from cirrhotic subjects were higher than those from control subjects at all times measured. Peak daytime insulin levels were about 150 muU/ml in plasma from cirrhotic subjects, and 40--50 muU/ml in plasma from controls; nocturnal levels were 20--30 muU/ml in cirrhotics versus 10 muU/ml or less in controls. The protein content of the diet was unrelated to plasma insulin levels at all times of day or night examined. These data thus show that plasma insulin levels are persistently elevated in cirrhotics, remaining higher than normal throughout the 24-hour period.
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F-antigen is a liver-specific antigen detected with antibody, raised in allogeneic (CBA) mice, to BALB/c mouse liver extract. The authors have confirmed the hepatic specificity of this antigen by showing it to be absent in extracts of extrahepatic organs of mouse and human origin. It is present in liver extracts of guinea pigs, rats, and rabbits, as well as in liver extracts from mouse and human sources. The antigen was present in the circulation of rabbits with acute carbon tetrachloride-induced hepatocellular injury. It was also demonstrated in the sera of 3 of 8 patients with acute hepatitis B antigen-positive hepatitis and in 1 of 4 patients with chronic active hepatitis. It was absent from the sera of 121 other patients with a variety of hepatic and nonhepatic diseases, and from the sera of 20 healthy subjects. The antigen is immunologically distinct from hepatitis B antigen, from the liver-specific lipoprotein antigen LP-2 of Meyer zum Buschenfeld, and from each of 15 individual human serum proteins tested.
Mononuclear-cell responses to liver extracts were studied by a migration-inhibition assay in patients with alcoholic liver disease, viral hepatitis, chronic alcoholism without evidence of liver disease, and in healthy individuals. Patients with acute alcoholic hepatitis demonstrated liver-antigen-induced inhibition of migration (migration index [M.I]equal 0-58 plus or minus 0-08, mean plus or minus S.D.), while patients with cirrhosis, alcoholism, and acute viral hepatitis, as well as healthy volunteers, did not demonstrate such a response (M.I. 0-92 plus or minus 0-13, 0-90 lus or minus 0-10, 0-86 plus or minus 0-18, 0-99 plus or minus 0-04, respectively). It is concluded that cell-mediated immunity to normal or damaged liver tissue may act to perpetuate alcoholic hepatitis and thereby contribute to the development of cirrhosis.
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