This study reports the findings of an electron microscopic search for so-called non-A, non-B nuclear particles in liver biopsies from patients with mainly chronic or prolonged liver disease and from chimpanzees. In patients without hepatitis B virus or acute hepatitis A virus serological markers, non-A, non-B-like nuclear particles were seen in hepatocytes in 28 of 31 cases of presumed non-A, non-B hepatitis, but also in 11 of 12 cases of liver disease not usually attributed to hepatitis viruses. They were also seen in 22 of 24 patients with HBsAg, in 3 of 3 patients with anti-HBc and no HBsAg, in 1 of 2 patients with hepatitis A, in a case of cytomegalovirus hepatitis, and in 16 of 19 patients whose serology was not available or inconclusive. The particles were present in 1 of 8 untreated HBsAg-negative chimpanzees and in 2 of 2 HBsAg-positive chimpanzees. They appeared in 4 of 4 chimpanzees developing non-A, non-B hepatitis following exposure to various inocula. Three patterns of particle aggregates were distinguished, all of which had been shown by others in non-A, non-B hepatitis. Dense aggregates were predominant, while others have shown intermediate aggregates more often; reasons for this difference could be technical. No pattern was specific for any condition. Either non-A, non-B-like nuclear particles, although associated with non-A, non-B hepatitis, are not specific for this condition, or non-A, non-B hepatitis viruses are extremely more common than is currently appreciated.

Animals↗

PubMedDate not supplied

Enhancement by secretin of the apparently maximal hepatic transport of bilirubin in the rat.

The effect of secretin (0.4 C.U. per hr per 100 gm body weight) on bile flow and the apparent maximal hepatic transport of bilirubin (Tm) was investigated in the rat. When secretin was administered during an already established bilirubin-Tm condition, it increased bile flow and bilirubin-Tm by 15 to 20% over a 30- to 50-min period. Enhancement of bilirubin output correlated with augmented flow and was sustained by an increased rate of excretion of monoglucuronides. When secretin was given for 90 min before bilirubin loading, it enhanced biliary bilirubin concentration and output, largely as diglucuronides. Bilirubin-Tm correlated positively with glururonyltransferase activity in liver homogenates. In the isolated perfused rat liver, injection of secretin in the portal cannula failed to produce choleresis. Bilirubin uridine diphosphate-glucuronyltransferase activity was lower than in intact rats and higher after treatment than in controls. The effect of secretin had an early effect on hepatocytic bile flow and a later effect on conjugation. Maximal hepatic bilirubin output was modulated both by flow and conjugation rate; the two mechanism may act independently.

Animals↗

PubMedDate not supplied

Effects of ioglycamide on the hepatic transport of bilirubin and its mono- and diconjugates in the rat.

Bilirubin seems to share the biliary excretion pathway with other organic anions, but not with bile acids. We studied the effects of the organic anion ioglycamide, an iodinated contrast agent, on bilirubin metabolism in Wistar rats. This compound does not undergo conjugation and is characterized by a maximal biliary secretory rate (Tm). The results show that in spite of producing a 3-fold increase in bile flow, ioglycamide excretion under Tm conditions decreased the output of unconjugated bilirubin and its monoconjugate by approximately 90%. Diconjugated bilirubin decreased by only 50% and became by far the predominant pigment in bile (86.5 +/- 6.0% of total pigment vs. 61.0 +/- 4.0% in basal conditions, n = 12). Unconjugated and monoconjugated bilirubins changed in parallel suggesting that the former arises from the monoconjugates. In serum, diconjugated bilirubin augmented from trace amounts to 1.15 +/- 0.17 mumole per liter. Total conjugated pigments in serum increased from 5 to 85% of total bilirubin. Bile acid output remained unchanged. Pretreatment of rats with ioglycamide altered neither the activity of bilirubin UDP-glucuronyltransferase nor the ratio of diconjugate to monoconjugate formed at both low (25 microM) and high (164 microM) bilirubin concentrations. The observed biological effects of ioglycamide were dose-dependent and fully reversible. We suggest that ioglycamide interferes with the excretion of conjugated bilirubins ("bilirubinostasis"). The monoconjugates retained in the hepatocyte might then undergo more efficient transformation to diconjugates, the latter thus becoming the most important bile pigments in serum and bile.

Animals↗

PubMedDate not supplied

[Primary biliary cirrhosis. Clinical, biological and histological study (author's transl)].

Explore the source record for details and available documents.

Aged↗

PubMedDate not supplied

Glucagon enhances bile flow, bilirubin uridine diphosphate-glucuronyltransferase activity and biliary bilirubin monoconjugate excretion in the rat.

Intravenous infusion of glucagon (100 micrograms/hr/100 g body weight) in rats produces a 20 to 35% increase in bile flow and enhances the activity of hepatic bilirubin uridine diphosphate-glucuronyltransferase to 132% after a 90 min infusion. When a bilirubin load is given to produce a constant and apparently maximal biliary bilirubin excretion rate (or transport maximum) the administration of glucagon increased the bilirubin transport maximum. The excretion rate of bilirubin monoglucuronides was more enhanced than that of diglucuronide. The enhanced rate of glucuronidation, assayed in vitro, correlated with the augmented biliary output and inversely with the plasma unconjugated bilirubin levels. It is concluded that glucagon, at the dosage used, leads to a higher formation rate of bilirubin monoconjugates and that the choleresis, also induced by the hormone, enhances the biliary secretion of the monoconjugates formed. The enhanced conjugation results in a decreased plasma concentration of unconjugated bile pigment and the associated choleresis leads to a decreased di- to monoconjugate ratio, opposite to what has been observed during bilirubinostasis and cholestasis. The secretory efficacy, as assessed from the bile-to-plasma concentration ratio, is enhanced for all bilirubin pigments after glucagon administration.

Animals↗

PubMedDate not supplied

[Chronic hepatitis].

Explore the source record for details and available documents.

Hepatitis↗

PubMedDate not supplied

Prevalence and significance of anti-HCV antibodies.

The actual ELISA test for anti-HCV defects an antibody to a non-structural part of the virus. It is present in 0.3 to 1.5% of the blood donors and in about 60% of patients with chronic non-A, non-B hepatitis. Seroconversion occurs 4 to 6 months after the beginning of the disease. The risk of a sporadic transmission is very low but unknown. An ALT elevation occurred only in 7% of the sexual partners of positive chronic liver patients but nobody seroconverted. Vertical, mother to infant, transmission is rare. In all risk groups for HCV infection such as drug abuse, multiple transfusion, haemodialysis, the presence of the antibody is increased between 15 to 80%. There is also evidence that HCV may be an oncogenic factor for hepatocellular carcinoma. It is present in 30 to 60% of the cases.

Blood Donors↗

PubMedDate not supplied

[Mitochondrial antigens and their antibodies].

In the mitochondria nine antigens and their corresponding antibodies are already known. They can be subdivided in three groups. The first one (M2-M4-M6-M8) appears during the evolution of primary biliary cirrhosis. The antibody against M2 is practically pathognomic for this disease. The M9-antibody is found in PBC with a slow and favourable evolution. The antibodies against M4-M8 are signs of a worse prognosis and a more rapid evolution into terminal cirrhosis. The second group is connected with infections and collagen diseases. The M1-antibody is directed against cardiolipin and diagnostic for syphilis. The M5-antibody appears in definite collagenoses. The M7-antibody is found in certain forms of acute and chronic cardiomyopathy. The third group of antibodies is induced by drugs: the anti-M3 by Venocuran containing a.o. phenopyrazone and the anti-M6 by Iproniazid. The role of the antigens and their antibodies concerning the aetiology and pathogenesis of the relevant diseases, especially primary biliary cirrhosis, is not known.

Autoantibodies↗

PubMedDate not supplied