Excitatory and inhibitory amino acid neurotransmitters and ammonia metabolism in hepatic failure rats.

The molar ratio of excitatory amino acid neurotransmitters (glutamate and aspartate) to inhibitory amino acid neurotransmitters (r-aminobutyric acid, GABA, and glycine) in the brain was diminished in acute hepatic failure rats with hyperammonemia, brain edema, and abnormal electroencephalograms. The ratio was further decreased with a marked elevation of arterial and brain ammonia levels 30 min after ammonium acetate was administered i.p.

Plasma amino acid imbalance in alcoholic liver cirrhosis.

Plasma amino acid concentrations and plasma glucagon and serum insulin levels were studied in male patients with compensated alcoholic and nonalcoholic liver cirrhosis. Age, nutritional status, and liver function tests were similar in both groups; none of the patients presented hepatic encephalopathy. Plasma valine and leucine concentrations were lower, and tyrosine, higher in alcoholic than nonalcoholic liver cirrhosis.

Glutamic acid and glutamine levels in serum and cerebrospinal fluid in hepatic encephalopathy.

Significant elevation of glutamic acid and glutamine concentrations in CSF was observed in hepatic encephalopathic patients with fulminant hepatitis and liver cirrhosis. However, the ratios of CSF glutamic acid to CSF glutamine levels and of CSF to serum glutamic acid and glutamine levels were significantly higher only in cirrhotic patients with hepatic encephalopathy. CSF glutamine levels were positively correlated with blood ammonia and CSF tyrosine levels in cirrhotic patients.

[Preparation of conjugates of adriamycin with antibodies to alpha-fetoprotein and their properties].

For its selective accumulation into tumor cells, the antitumor drug adriamycin (ADM) was attached to specific antibodies reactive against alpha-fetoprotein, a carcinoembryonic protein, and the antibody and antitumor activities of the resulting conjugate were investigated. Using the glutaraldehyde or carbodiimide binding methods, preparations containing 4-5 moles of ADM per mole of antibody were obtained. They retained 60-75% of the original antibody activity.

Effects of branched-chain alpha-keto acids on plasma amino acid concentrations in carbon tetrachloride-intoxicated rats.

Plasma branched-chain amino acid levels during continuous intravenous infusion of sodium salts of branched-chain alpha-keto acid were much higher in CCl4-intoxicated rats than in control rats. However, increases after intragastric administration were diminished in both groups. Increased plasma alloisoleucine levels following administration of R,S-alpha-keto-beta-methylvaleric acid were reduced greatly by using only S-alpha-keto-beta-methylvaleric acid.

Purification and characterization of rat liver cytosol catalase.

Rat liver cytosol catalase was purified by making use of its interaction with deoxycholate and by the various methods used to purify peroxisomal catalase. The purified preparation was both enzymatically and immunologically identical with the purified peroxisomal catalase, but differed in its chromatographic behaviour and electrophoretic mobility. Amino acid analysis also revealed a slight difference between the two catalase molecules.

Characteristic features of plasma amino acid, plasma pancreatic glucagon, serum insulin concentrations in cirrhotic patients with histories of chronic alcohol consumption.

Plasma amino acid, plasma pancreatic glucagon and serum insulin levels were simultaneously measured in cirrhotic patients with (drinkers) and without a history of alcohol drinking (non-drinkers), as compared to those in alcoholics without liver disease. Clinical characteristics in drinkers and non-drinkers, such as the extent of liver dysfunction, which may affect plasma amino acid levels, were strictly matched. Plasma pancreatic glucagon levels in the drinker group were much higher than those in the non-drinker group.

Effect of continued drinking on prognosis of alcoholic liver cirrhosis.

The prognoses of patients with alcoholic liver cirrhosis were compared between those who continued to drink and those who stopped. Clinical criteria were strictly set so as to control other variables affecting the prognoses. Four-year survival was significantly higher in the patients who stopped drinking than in those who continued to drink.

Serum neutral amino acid concentrations in cirrhotic patients with impaired carbohydrate metabolism.

Serum neutral amino acid levels in cirrhotic patients with abnormal oral glucose tolerance test patterns were not different from those of subjects without impaired carbohydrate metabolism. However, the characteristic features of serum aminograms in the patients, that is, increased levels of tyrosine, decreased levels of valine and leucine and the diminished ratio of branched chain amino acids to phenylalanine and tyrosine levels, were less pronounced in those treated with insulin. This finding is clinically important for evaluating the serum aminogram of cirrhotic patients under insulin therapy.

A simple and rapid method for determining blood ammonia levels.

Blood ammonia levels in patients with various liver diseases were determined quantitatively by a simple and rapid method using the Amitest Meter System. The results were compared to those obtained by an enzymatic method and were well correlated. This simple Amitest is also useful in animal experiments, particularly when there is a need to determine blood ammonia levels serially.

Brain tyrosine hydroxylase activity and calculated amount of brain dopa synthesized in carbon tetrachloride-intoxicated rats.

Tyrosine hydroxylase activity in the corpus striatum was measured in a large dose of carbon tetrachloride (CC14)-intoxicated rats in order to confirm whether brain catecholamine contents decrease in acute hepatic failure or not. Theoretical amounts of dopa synthesized in the brain of the treated animals were calculated according to an equation of enzyme kinetics. Tyrosine hydroxylase activities in CCl4-injured rats were similar to those in control rats, and calculated amounts of brain dopa in liver-injured rats were rather higher as compared to those in untreated animals.

Alterations in neutral amino acid transport across the blood-brain barrier in hepatic failure.

The accelerated transport of the blood neutral amino acids into the brain in encephalopathic patients with fulminant hepatitis and advanced liver cirrhosis was demonstrated not only by determining the cerebrospinal fluid (CSF) aminogram but also by calculating the predicted velocity of the amino acid transport through the blood-brain barrier. Significant elevation in CSF aromatic amino acid (AAA) and methionine levels was observed in the encephalopathic patients. Arousal from hepatic encephalopathy by drip infusion of a branched chain amino acid (BCAA)-enriched solution was obtained coincidentally with the elevated BCAA levels and diminished concentrations of AAA and methionine in CSF.

Effect of azathioprine and carbon tetrachloride on induction of hyperplastic liver nodule and hepatocellular carcinoma by diethylnitrosamine and N-2-fluorenylacetamide in rats.

The enhancing or inhibitory action of the hepatotoxic agents, carbon tetrachloride (CCl4) and azathioprine (AZP), on the evolution of hyperplastic liver nodule (HN) and hepatocellular carcinoma (HCC) in diethylnitrosamine (DEN)- and N-2-fluorenylacetamide (FAA)-treated rats (control group) was tested. The area of gamma-glutamyl transpeptidase(gamma-GTP)-positive HN and/or foci in the eighth week was remarkably small in rats fed on a diet containing FAA and AZP (the AZP group), but was quite large in rats fed a diet containing FAA in addition to repeated CCl4 injections (the CCl4 group). HCC was first detected in the 21st week and the incidence of HCC within the 36 weeks of the experiment was very high in the CCl4 group.

Effects of intraduodenal feeding of a branched-chain amino acid-rich solution on ammonia-induced encephalopathy in liver-injured rats.

A preventive effect of intraduodenal prefeeding of a branched-chain amino acid (BCAA)-rich solution on ammonia-induced encephalopathy was investigated with carbon tetrachloride CC14-injured rats with the elevated levels of blood ammonia. Five out of six cirrhotic rats, to which an electrolyte solution alone was preinfused for 24 hours, fell into coma following ammonia acetate injection and two comatose rats died. However, no cirrhotic rats preinfused with a BCAA-rich solution died and only two out of the six showed coma with complete recovery.

Effects of insulin and glucagon on serum amino acid concentrations in liver disease.

The effects of insulin and glucagon administration on serum amino acid levels were investigated in patients with severe liver disease, since simultaneous injection of pancreatic hormones has been recently introduced as a therapeutic approach. The changes in serum amino acid concentrations, as observed 3 h after ceasing a 3 h infusion of insulin and glucagon in 500 ml glucose solution, were an elevation of serum branched chain amino acid (BACA) levels and of the molar ratio of BCAA/aromatic amino acid (AAA) levels in patients with liver cirrhosis. Similar increases of serum BCAA levels during the infusion were also observed in patients with fulminant hepatitis.

Characteristics change in serum amino acid levels in different types of hepatic encephalopathy.

Serum amino acid patterns in patients with different types of hepatic encephalopathy were investigated. Marked elevations in most of serum amino acids observed in untreated patients with acute type of fulminant hepatitis were not remarkable in the patients who have already treated; particularly branched chain amino acids (BCAA), phenylalanine and tyrosine were much lower in the latter group. However, elevation of serum methionine levels and lower ratio of BCAA/(phenylalanine + tyrosine) were similarly observed in both groups.

Primary carcinoma of the gallbladder and the extrahepatic bile duct.

The clinical records of 68 patients with primary carcinoma of the gallbladder (39 cases) and the extrahepatic biliary tracts (29 cases) were comparatively reviewed. The survivals with carcinoma of the gallbladder were limited to five patients operated upon because of cholelithiasis and/or cholecystitis. The majority of the cases preoperatively diagnosed as cancer of the gallbladder were not able to undergo radical cholecystectomy.