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Biomedical subjects

J Fevery

Publications and source records attributed to J Fevery.

At least 199 records · Page 11Linked to original sources

Long-term follow-up of chronic active hepatitis of moderate severity.

A group of patients with only moderately active chronic hepatitis has been studied. The follow-up was long (mean 87 months). All patients except one were treated with prednisone and/or azathioprine. Of the hepatitis B virus positive patients two-thirds developed cirrhosis between the second and fifth year of evolution, while in the hepatitis B negative group this occurred in less than one-third. The transition to cirrhosis was clinically silent. The patients were all allowed to do their normal work except in the terminal stages of cirrhosis. Five patients died of causes related to the disease: three patients with cirrhosis and hepatocellular carcinoma, one with gallbladder carcinoma, and one from bleeding varices. The high incidence of tumour, especially liver-cell carcinoma, may be due to a cumulative effect of the presence of hepatitis B virus, cirrhotic transformation, and immuno-suppression. The other patients are currently in apparently good health.

Adult↗

Comparison in different species of biliary bilirubin-IX alpha conjugates with the activities of hepatic and renal bilirubin-IX alpha-uridine diphosphate glycosyltransferases.

The bilrubin-IXalpha conjugates in bile and the activities of bilirubin-IX alpha--UDP-glycosyltransferases in liver and kidney were determined for ten species of mammals and for the chicken. 1. In the mammalian species, bilirubin-IX alpha glucuronide was the predominant bile pigment. Excretion of neutral glycosides was unimportant, except in the cat, the mouse, the rabbit and the dog, where glucose and xylose represented 12--41% of total conjugating groups bound to bilirubin-IX alpha. In chicken bile, glucoside and glucuronide conjugates were of equal importance. They probably represent only a small fraction of the total bile pigment. 2. The transferase activities in liver showed pronounced species variation. This was also apparent with regard to activation by digitonin, pH optimum and relative activities of transferases acting on either UDP-glucuronic acid or neutral UDP-sugars. 3. Man, the dog, the cat and the rat excrete bilirubin-IX alpha largely as diconjugated derivatives. In general, diconjugated bilirubin-IX alpha could also be synthesized in vitro with liver homogenate, bilirubin-IX alpha and UDP-sugar. In contrast, for the other species examined, bilirubin pigments consisted predominantly of monoconjugated bilirubin-IX alpha. Synthesis in vitro with UDP-glucuronic acid, UDP-glucose or UDP-xylose as the sugar donor led exclusively to the formation of monoconjugated bilirubin-IX alpha. 4. The transferase activities in the kidney were restricted to the cortex and were important only for the rat and the dog. No activity at all could be detected for several species, including man. 5. Comparison of the transferase activities in liver with reported values of the maximal rate of excretion in bile suggests a close linkage between conjugation and biliary secretion of bilirubin-IX alpha.

Animals↗

Characterization of the major diazo-positive pigments in bile of homozygous Gunn rats.

Bilinoid pigments in bile of homozygous Gunn rats (jj) were analysed either after formation of dipyrrolic ethyl anthranilate azo derivatives or as the unmodified parent tetrapyrroles. 1. T.l.c. of the azo derivatives revealed seven major unconjugated components which were structurally characterized by chemical tests, spectrophotometry and mass spectrometry. In addition, two minor components were identified as azodipyrrole (A+B)-glucoside and azodipyrrole (A+B)-beta-d-glucuronide. 2. Extraction and t.l.c. of the tetrapyrrolic pigments showed 13 major yellow diazo-positive bands. Four of them, accounting for 59% of total diazo-positive material, were identified as unconjugated bilirubin-IXalpha, -IXbeta, -IXgamma and -IXdelta. A fifth band (16%) was characterized as a mixture of two isomeric monohydroxyl derivatives and another band (8%) as a dihydroxyl derivative of bilirubin-IXalpha. 3. Although unconjugated bilirubin-IXalpha constitutes one-third of total diazo-positive material in bile of our strain of Gunn rats, the daily amount excreted represented only about 3-4% of daily bilirubin production. 4. Phototherapy caused a 2.2-fold increase in the biliary output of diazo-positive bilinoids, but did not affect markedly their composition. However, an additional diazo-negative pigment, accounting for one-third of total yellow colour, was observed but was not identified. Mass-spectral data on two dipyrrolic azopigments have been deposited as Supplementary Publication SUP 50076 (3 pages) with the British Library Lending Division, Boston Spa, Wetherby, W. Yorkshire LS23 7BQ, U.K., from whom copies may be obtained on the terms given in Biochem. J. (1977) 161, 1.

Animals↗

Perinatal development of bilirubin UDP-glycosyltransferase activities in rat liver.

Bilirubin UDP-glucuronyltransferase and UDP-xylosyltransferase activity could already be demonstrated in rat liver from day 19 of fetal life onwards (4 days before birth). Bilirubin-glucuronide was present in hepatocytes of 21-day-old fetal liver strongly suggesting that the enzyme detected in vitro was really active in vivo. This further supports the theory that secretion from the cell is also immature. The known deficiency of UDP-glucose dehydrogenase in fetal and neonatal rat liver could lead to decreased intracellular concentrations of UDP-glucuronic acid and possibly to increased concentrations of UDP-glucose. However, no glucosides were present in the fetal hepatocytes.

Animals↗

Unconjugated bilirubin and an increased proportion of bilirubin monoconjugates in the bile of patients with Gilbert's syndrome and Crigler-Najjar disease.

Bilirubin pigments were studied in the bile of 20 normal adults, 25 patients with Gilbert's syndrome, 9 children with Crigler-Najjar disease, and 6 patients with hemolysis, to determine how a deficiency of hepatic bilirubin UDP-glucuronosyltransferase would affect the end products of bilirubin biotransformation. In the bile from patients with Gilbert's syndrome, a striking increase was found in the proportion of bilirubin monoconjugates (48.6+/-9.8% of total conjugates) relative to that in normal bile (27.2+/-7.8%). This increase was even more pronounced in children with Crigler-Najjar disease, in whom, even in the most severe cases, glucuronide could always be demonstrated in the bile. Furthermore, unconjugated bilirubin-IXalpha was unquestionably present in the bile of these children and amounted to 30-57% of their total bilirubin pigments (<1% in the controls). It was not possible to predict from the biliary bilirubin composition whether a child would respond to phenobarbital therapy or not. Bile composition was normal in patients with hemolysis, except when there was associated deficiency of hepatic glucuronosyltransferase. Therefore, the observed alterations were not a simple consequence of unconjugated hyperbilirubinemia. The present findings suggest that Crigler-Najjar disease represents a more pronounced expression than Gilbert's syndrome of a common biochemical defect. Hepatic bilirubin UDP-glucuronosyltransferase deficiency leads to decreased formation of diconjugates with an ensuing increase in the proportion of bilirubin monoconjugates in bile; in the most severe cases, an elevated content of biliary unconjugated bilirubin is also found.

Adolescent↗

Hepatitis B surface antigen (HBsAg) in the liver of patients with hepatitis; a comparison with serological detection.

Chronic hepatitis was diagnosed on liver biopsy of 76 patients; 52 (68%)had HBsAg. Of the 52 patients with HBsAg, 23% had HBsAg shown by immunofluorescence on the liver, while it could not be detected with radioimmunoassay on the serum; 77% had HBsAg detectable in liver and in serum, and none had HBsAg in serum only. HBsAg was detected more frequently in chronic aggressive hepatitis and active cirrhosis than in chronic persistent hepatitis and cirrhosis with little activity. No correlation was found in the different forms of chronic hepatitis between the HBsAg status on the one hand, and levels of transaminases, gammaglobulins, and auto-antibodies on the other. Acute hepatitis was diagnosed on liver biopsy of 24 patients; 50% had HBsAg. Liver tissue positivity was very low in the fully developed stage compared to serum positivity. In 146 patients with other liver ailments, both liver and serum were negative for HBsAg.

Acute Disease↗

Distribution patterns of hepatitis B surface antigen (HBsAg) in the liver of hepatitis patients.

One hundred liver biopsies from 100 hepatitis patients were examined by the indirect immunofluorescent technique for the detection of HBsAg. Of the 60 positive specimens 52 were diagnosed as various types of chronic hepatitis and 8 were acute hepatitis. Four main distribution patterns of HBsAg were obtained: full cytoplasmic fluorescence with diffuse lobular distribution; cytoplasmic fluorescence with spotty distribution; peripheral fluorescence in the cell membrane and/or cell peripheries; and focal cytoplasmic positivity. There was an inverse relationship between the number of positive hepatocytes and the extent of liver cell necrosis. The distribution patterns of HBsAg were distinctive in each type of chronic hepatitis and in acute hepatitis. Homogeneous full cytoplasmic fluorescence, distributed diffusely in the whole liver lobule, was observed in chronic persistent hepatitis and in cirrhosis with little activity whereas peripheral liver cell membrane and/or peripheral cytoplasmic fluorescence associated with cytoplasmic positivity in a smaller number of hepatocytes was a characteristic finding in chronic aggressive hepatitis, active cirrhosis, and acute hepatitis with possible transition to chronicity. Focal cytoplasmic fluorescence was observed in acute hepatitis and a group of biopsies in chronic hepatitis in which HBsAg was detected in the liver but no antigen was detectable in the serum. The results show that the different patterns of distribution of HBsAg in the liver biopsy are helpful for the histological diagnosis of different types of HBAg positive viral hepatitis and are consistent with the hypothesis of the role of specific immune response in the pathogenesis of type B viral hepatitis.

Acute Disease↗

Differential distribution of hepatitis B surface antigen and hepatitis B core antigen in the liver of hepatitis B patients.

One hundred liver biopsies from 100 patients with clinical presumptive diagnosis of hepatitis were examined by immunofluorescence for the presence of hepatitis B surface antigen (HBSAg) and hepatitis B core antigen (HBcAg). Of the 60 HBsAg-positive livers, 51 were diagnosed as chronic hepatitis on histological grounds, 6 as acute hepatitis, and 3 as "near-normal liver." From the 60 tissue-positive cases, 3 subjects were HBsAg seronegative. HBcAg was detected in 44 livers, all of which also had HBcAg in the localized in the cytoplasm and the membranes of the hepatocytes, and HBcAg in the nuclei and in 4 cases also in the cytoplasm. Predominant HBsAg expression in the cytoplasm was observed in near-normal liver, chronic persistent hepatitis, and cirrhosis with little activity. This correlated with the amount of ground glass hepatocytes in the biopsies. HBcAg and membrane-localized HBsAg were minimal in those conditions. HBcAg was most prevalent in patients with chronic aggressive hepatitis and active cirrhosis treated with immunosuppressive drugs, whereas the amounts of HBsAg and HBcAg in nontreated patients of those two groups and in acute hepatitis with signs of transition to chronicity were almost equal. HBsAg expression in liver cell membranes was most prominent in active forms of chronic hepatitis (chronic aggressive hepatitis and in active cirrhosis) and in acute hepatitis with signs of transition to chronicity. This observation correlated in the presence of HBcAg in the biopsies of those patients. In acute hepatitis both HBsAg and HBcAg were detected rarely and no membrane expression of HBsAg was observed. The over-all results show a significant relationship between the different degrees of accumulation of HBsAg and HBcAg in the liver and the various histological types of hepatitis and further suggest an interplay of both hepatitis B virus and host immune response in the development and pathogenesis of hepatitis B.

Acute Disease↗