Activity In Liver Biopsies Research Articles

Phenylalanine hydroxylase activity in liver biopsies from hyperphenylalaninemia heterozygotes: deviation from proportionality with gene dosage.

Liver biopsy samples from the patients with hyperphenylalaninemia have an average of 5 percent of the normal hydroxylase activity. The parents of the patients have between 7.3 percent (excluding the value for one parent) and 10 percent of the normal hepatic hydroxylase activity. An explanation for these findings involves negative interallelic complementation, which involves protein-protein interaction between subunits in a multimeric enzyme. In support of this model is the evidence that rat liver phenylalanine hydroxylase is a multimeric protein composed of two electrophoretically distinguishable subunits.

Hepatotoxicity of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) in dogs: The use of serial percutaneous liver biopsies

Hepatotoxicity resulting from po administration of a single dose of CCNU to dogs was studied by weekly determinations of liver function tests and performance of percutaneous liver biopsies. Histochemical stains for glycogen and alkaline phosphatase in liver sections revealed an effect on these parameters within 1–2 weeks after dosage, the earliest sign of drug toxicity. Histopathologic changes were evident 7–14 days later, when increased activity of serum alanine aminotransferase was also present. Chemical indices of liver abnormalities were reversible, whereas glycogen depletion and increased alkaline phosphatase activity in liver biopsies persisted throughout the 2- to 3-month observation period. This study demonstrates the feasibility and usefulness of serial percutaneous liver biopsies in determining both the qualitative and quantitative features of developing and recovering from drug toxicity in the dog.

Correlation of alcohol and tolbutamide blood clearance rates with microsomal alcohol-metabolizing enzyme activity

Alcohol and tolbutamide metabolism was followed serially in a group of recently drinking, noncirrhotic chronic alcoholics along with measurement of NADP-dependent ethanol-metabolizing activity in liver biopsies. Paired comparisons in eight patients over 6 weeks and in five patients over 10 weeks showed the expected slowing in rate of alcohol and tolbutamide degradation occurring in the shorted interval and a decrease in NADP-dependent ethanol-metabolizing activity over the longer interval. Slowing of ethanol and tolbutamide clearances while the measured enzyme activity remained at its original level may indicate that ethanol and tolbutamide blood clearance is unrelated to the NADP-dependent microsomal ethanol-oxidizing system.

Radiochemical assays for p-hydroxyphenylpyruvate hydroxylase activity in human liver

Two radiochemical methods for the determination of p-hydroxyphenylpyruvate hydroxylase have been developed. The substrate, [U- 14C] p-hydroxyphenylpyruvate is prepared immediately before use by the action of l-amino acid oxidase on l-[U- 14C]tyrosine. For the measurement of enzyme activity in liver biopsies around 0.1 mg wet weight of liver is needed. A homogenate of liver tissue is incubated with the substrate and the formed homogentisate quantitated by scanning a thin-layer plate for the distribution of isotope. With this technique the enzyme activity in human liver was 0.34 (0.15–0.63) U/g of wet weight. When high sensitivity is not required a more rapid assay may be used, which is based on the determination of 14CO 2 formed in the conversion of p-hydroxyphenylpyruvate to homogentisate. With this assay about a hundred determinations can be carried out in one day. During storage at −60° for 2 months the enzyme activity in human liver remains constant.

Estimation of the total body vitamin B12 in the live subject.

1. Values for total body vitamin B12 were calculated for eighteen patients by giving a tracer dose of radioactive cyanocobalamin and measuring the radioactivity and microbiological activity in liver biopsies obtained at laparotomy. 2. The values for total body vitamin B12 ranged from 960 to 5984 μg with a mean of 2528 μg. Five values were greater and thirteen less than the mean. 3. Significant correlations were found between the serum vitamin B12 and total body vitamin B12, the serum vitamin B12 and the hepatic vitamin B12 and the hepatic B12 and the total body vitamin B12.

Dehydrogenase activity in liver biopsies from patients with cirrhosis.

The activity of succinic (SDH), NADH- and NADPH-dehydrogenase was determined by the Nitro-BT method. In biopsies from patients with moderate and severe cirrhosis a lower activity of SDH was observed than in biopsies from those without or with slight alterations. The findings may indicate that liver failure is caused by a decrease in SDH-activity in addition to a reduction in liver-cell mass by the fibrosis.