Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three patients, one with cryptogenic cirrhosis, one with active chronic hepatitis and one with neonatal hepatitis, were found to have corneal pigmentation rings indistinguishable from early Kayser-Fleischer rings on slit lamp examination. They did not have the clinical features of Wilson's disease and their serum copper and ceruloplasmin concentrations were normal. Urinary copper excretion rates and hepatic concentrations were only slightly raised but were below the range found in symptomatic Wilson's disease. It is concluded that the Kayser-Fleischer ring would no longer be considered as pathognomonic of Wilson's disease.
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PMID:Kayser-Fleischer-like rings in patients without Wilson's disease. 55 26

Kayser-Fleischer rings are pigmented corneal rings at the limbus of the cornea in Descemet's membrane that have been deemed pathognomonic of Wilson's disease. However, we have observed four exceptions in patients with non-Wilsonian liver disease. Three patients had primary biliary cirrhosis and one patient had chronic aggressive hepatitis with cirrhosis. Pigmented corneal rings were seen only by slit-lamp examination. Hepatic, serum, and urinary copper and serum ceruloplasmin levels were significantly elevated in the patients with primary biliary cirrhosis. Radiocopper (64Cu or 67Cu) studies in patients with primary biliary cirrhosis showed plasma disappearance curves which allowed a clear distinction from Wilson's disease in that all three patients with primary biliary cirrhosis showed a secondary rise in radiocopper that presumably represented copper incorporation into ceruloplasmin. In one patient, in whom 64Cu in ceruloplasmin was studied specifically, incorporation was found to be normal.
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PMID:Pigmented corneal rings in non-Wilsonian liver disease. 84 86

The serum non-caeruloplasmin copper concentrations were measured in normal subjects and patients with various types of liver disease by a sensitive direct method involving complexing the copper and measurement by atomic absorption spectrophotometry. In normal subjects the mean concentration (+/- S.D.) was 10.1 +/- 1.6 mug/100 ml, males having a slightly higher value (10.7 +/- 1.3 mug/100 ml) than females (9.2 +/- 1.8 mug/100 ml). In patients with various non-hepatic diseases concentrations were raised (15.8 +/- 8.9 mug/100 ml), as also in hepatitis (14.7 +/- 4.3 mug/100 ml), cholestasis (16.1 +/- 6.4 mug/100 ml) and cirrhosis (16.3 +/- 8.7 mug/100 ml). Heterozygotes for Wilson's disease and patients treated for Wilson's disease had concentrations (12.9 +/- 5.9 and 9.8 +/- 3.7 mug/100 ml, respectively) which did not differ significantly from normal whereas untreated patients had very significantly raised concentrations (22.9 +/- 4.5 mug/100 ml). Direct measurement of serum non-caeruloplasmin copper is more accurate than indirect measurement and may help in assessing the effect of treatment but it is concluded that measurement of this fraction of serum copper will not enable Wilson's disease to be differentiated from other forms of liver disease.
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PMID:Direct measurement of serum non-caeruloplasmin copper in liver disease. 127 46

In 25 patients with chronic renal failure, treated with haemodialysis (13 patients with chronic non-A, non-B hepatitis, and 12 cases without evidence of hepatocellular damage), and in 20 healthy persons, blood serum concentrations were determined of prealbumin, ceruloplasmin, alpha 2-macroglobulin, and haptoglobin. It was found that the concentrations of these proteins in both subgroups of patients were not significantly different. The concentration of prealbumin was higher, and that of alpha 2-macroglobulin and haptoglobin was significantly lower in comparison with healthy subjects.
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PMID:[Concentration of prealbumin, ceruloplasmin, alpha-macroglobulin and haptoglobin in blood serum of patients with chronic non-A, non-B hepatitis treated with hemodialysis for chronic renal failure]. 128 60

The concentration of copper in the livers of Long-Evans rats with cinnamon-like coat color (LEC), in which hepatitis and then hepatomas develop spontaneously, was recently found to be abnormally high. Therefore, we examined the copper concentrations in the livers of LEC F1 backcrosses (LEC F1 x LEC) to determine the linkage of copper accumulation with development of hepatitis. Consistent with a previously reported ratio of rats with hepatitis to rats without hepatitis of about 1:1, hepatitis developed in 14 of 30 F1 backcrosses. The copper concentrations in the livers of all LEC F1 backcrosses with hepatitis were abnormally high and comparable to those of LEC rats. In contrast, the concentrations in all backcrosses without hepatitis were similar to those in normal Long-Evans with agouti coat color or Brown-Norway rats. Copper accumulation was shown to be closely linked with the development of hepatitis in LEC rats and appeared to be a possible cause of hepatitis. The concentrations of copper in the livers of Fischer 344 rats after carbon tetrachloride treatment were in the range for normal liver, indicating that a high copper concentration in the liver is specific to LEC rats and not a specific characteristic of hepatitis. Furthermore, we found that the size and level of ceruloplasmin mRNA in the livers of LEC rats were the same as those in LEA rats and that the size and level of ceruloplasmin polypeptide in their livers and plasma were almost the same as those in LEA rats. Therefore, these results suggest that the copper accumulation is not due to alteration of expression or to gross alteration of the ceruloplasmin gene.
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PMID:Genetic linkage between copper accumulation and hepatitis/hepatoma development in LEC rats. 131 58

The Long-Evans Cinnamon rat is a mutant strain that contracts hereditary hepatitis and, eventually, spontaneous hepatocellular carcinoma. Because we found a corresponding gross copper accumulation in the liver of the rats, we examined whether the development of hepatitis in our rat system could be prevented by administration of D-penicillamine. D-Penicillamine is a copper-chelating agent and one of the drugs effective for human Wilson's disease, in which abnormal copper metabolism is also observed. The results show that D-penicillamine treatment inhibited the elevation of serum transaminases, suppressed abnormal histological changes in the liver and completely prevented the onset of hepatitis in the Long-Evans Cinnamon rats. We further found that the copper concentration in the liver and serum copper and ceruloplasmin levels were decreased, whereas the urinary copper level was increased in the D-penicillamine-treated Long-Evans Cinnamon rats. These findings demonstrate that the pathogenesis of hereditary hepatitis in Long-Evans Cinnamon rats is due to abnormal copper accumulation in the liver.
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PMID:D-penicillamine prevents the development of hepatitis in Long-Evans Cinnamon rats with abnormal copper metabolism. 137 Jan 62

The Cu concentration was about 40 and 60 times higher in the liver in Long-Evans with a cinnamon-like coat color (LEC) rats aged 80 days (without hepatitis) and 130 days (with hepatitis), respectively than in the liver in Fischer rats. Most hepatic Cu was recovered in the cytosol fraction. Furthermore, about 96% and 84% of the cytosolic Cu was found in the metallothionein region on a Sephadex G-75 column in LEC rats aged 80 and 130 days, respectively. The hepatic metallothionein concentration was about 130 to 140 times higher in LEC rats than in Fischer rats when the concentration was expressed as metallothionein-bound Cu. Three forms of Cu-metallothionein were isolated by DEAE-cartridge. Although the concentration of hepatic Cu-metallothionein and its composition of polymorphic form were not changed greatly in hepatitis phase (in the 130-day-old LEC rats), activities of serum enzymes, aspartate aminotransferase (GOT) and alanine aminotransferase (GPT) were increased significantly. The LEC rat showed a significantly low concentration of biliary Cu and markedly low activity of ceruloplasmin (as ferroxidase). Serum Cu showed a low concentration in the 80-day-old LEC rats, but recovered to the control level in the 130-day-old LEC rats. The abnormal accumulation of Cu may be due to the inherent reduction of excretion of Cu into the bile and blood. Such deposition may be a trigger for the onset of the spontaneous hepatitis occurring at 90-120 days after birth and for the onset of hepatoma later.
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PMID:Excessive accumulation of hepatic copper in LEC rats aged 80 days without hepatitis and 130 days with hepatitis. 144 42

The copper concentrations in organs of developing Long-Evans Cinnamon (LEC) rats (2 d to 13 mo) were measured to elucidate the pathogenesis of their hereditary hepatitis. Hepatic copper contents of LEC rats were significantly higher than those of control rats (26 to 92 times higher). The subcellular distribution of hepatic copper indicated that the nuclear and large granular fractions had been saturated and the cytosol fraction contained about 70% of all the hepatic copper in LEC rats. The serum concentrations of copper and ceruloplasmin were significantly lower than those of control rats from the 4th wk (10-12% and 5-19%, respectively). Copper contents in kidney of LEC rats did not exhibit an increase over those of control rats until 12 wk, but then increased to nearly 40 times higher during fulminant hepatic failure. Accumulation of copper was not detected in the brain or small intestines of LEC rats until 13 mo. The hepatic copper concentration, its subcellular distribution, and serum copper concentration of F1 rats (LEC x Long-Evans Agouti) exhibited the same levels as those of Long-Evans Agouti rats. In addition to their similarity concerning inheritance of autosomal recessive means and clinical course, we found causality relating copper accumulation to the pathogenesis of the disease. We propose that LEC rats will be the most promising animal model for the study of Wilson's disease.
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PMID:Inherited copper toxicity in Long-Evans cinnamon rats exhibiting spontaneous hepatitis: a model of Wilson's disease. 156 Oct 10

The components of the blood antioxidant systems (superoxide dismutase, catalase, ceruloplasmin, glutathione system) take a direct part in the molecular mechanisms of the body adaptation under conditions of viral hepatitis infection. The peculiarity of the mechanisms by which lipid peroxidation is regulated in different grades of hepatitis is of a role in the disease pathogenesis and underlies the prediction of the course of hepatitis.
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PMID:[The importance of the antioxidant protection systems of the blood in adaptation to the infectious process in viral hepatitis B]. 181 63

A new mutant developing spontaneous hepatitis and hepatocellular carcinoma has been discovered among Long Evans rats. Hepatitis appears suddenly in the mutant, Long Evans Cinnamon (LEC) rats, three to four months after birth. Characteristic clinical signs of the hepatitis are jaundice, bilirubinuria, subcutaneous bleeding and loss of body weight. The affected rats showed a high mortality and histological changes with focal necrosis of hepatocytes and infiltration of a few inflammatory cells. Genetic studies indicate that a single autosomal recessive gene is responsible for the hepatitis. Long-surviving rats show chronic hepatitis, and subsequently develop hepatocellular carcinoma at one and a half years of age. We recently found an abnormal copper accumulation in the liver of LEC rats prior to development of the hepatitis. Copper concentration in the liver is over 40 times more than that of normal Long Evans Agouti (LEA) rats, whereas the serum ceruloplasmin and copper levels are lower. An excess of toxic-form copper, free copper, will cause DNA damage in the presence of free radicals and oxygen radicals. Such DNA damage by the radicals is considered to be responsible for hepatic necrosis and hepatocellular carcinoma in LEC rats.
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PMID:Hepatocarcinogenesis in the LEC rat with hereditary hepatitis. 184 50


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