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)

Concentrations of the enzymes alanine aminotransferase (ALT) and alkaline phosphatase (AP) were determined in blood samples from 626 randomly selected clinically healthy dobermann. ALT levels greater than three times the normal upper value were detected in 55 dogs. These dogs were selected for further investigation; the owners of 23 of the dogs allowed a liver biopsy to be performed. Histopathological examination revealed various degrees of hepatitis and excessive amounts of copper in 21 of the dogs. These cases, referred to as subclinical dobermann hepatitis (DH), were selected for a follow-up investigation in which the clinical signs and serum parameters (ALT, AP and bilirubin) were studied for a period of three to 48 months. Serum parameters of those with subclinical DH were compared with blood samples collected from 22 dogs with clinical DH. Individual dogs showed great variation in the levels of ALT and AP between consecutive serum samples. These enzyme levels never, however, fell to the normal range. During the subclinical stage no statistically significant (P > 0.05) change occurred in the concentrations of ALT or AP. When dogs with subclinical DH were compared with dogs with clinical DH, there was no statistically significant (P > 0.05) difference in ALT levels, whereas AP concentrations were significantly (P < 0.001) higher among clinically affected dogs. Elevated levels of bilirubin were detected almost exclusively in dogs with clinical DH. After the onset of clinical signs there was a decrease in the ALT levels and an increase in AP concentrations as the disease progressed, but the changes were not statistically significant (P > 0.05).
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PMID:Subclinical versus clinical hepatitis in the dobermann: evaluation of changes in blood parameters. 891 40

Wilson's disease (WD) is an inherited disorder of copper metabolism, characterized by copper accumulation in different organs. The clinical presentation of WD is variable: juvenile cirrhosis, with or without neurological symptoms, fulminant hepatitis, acute intravascular hemolysis or late onset with neurological or psychiatric symptoms. The histological picture, the histochemical stains and the ultrastructural findings of the liver are variable in WD. The recent cloning of the WD gene and the report of several mutations (at least 25) of the WD gene suggest the hypothesis that the clinical and pathological variability of this disease is related to a genetic polymorphism. These data may explain why the diagnosis of WD is often extremely difficult for the pathologist, since histochemical stains for copper may be highly variable or negative, despite increased levels of tissue copper concentrations. The most important pathological data are: 1) the evaluation of liver architecture, relevant in the staging of liver disease in three stages; 2) histochemistry for copper, which is variable and needs the use of multiple methods: Timm's method is probably the most useful one, since it shows copper deposits even in the first stage of WD, when liver changes are often reversible; 3) the determination of copper concentration may be crucial in WD diagnosis; copper levels exceeding 250 ug/g of dry tissue are considered diagnostic for the disease; 4) transmission electron microscopy shows, mainly in youngsters, mitochondrial changes considered typical of WD; the ultrastructural picture may be diagnostic for WD in cases with not specific histology and negative histochemical stains; 5) scanning electron microscopy after osmic maceration may be a new useful tool in the study of this liver disease: this technique may give both panoramic and high-power enlargements and allows the localization in the acinar zones of the intracellular hepatocytic changes. Finally, only the optimal approach to liver biopsy, obtaining the highest number of histological, histochemical, quantitative and ultrastructural data, may allow the pathologist to an early diagnosis of WD.
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PMID:[The role of the pathologist in the diagnosis and monitoring of Wilson's disease]. 892 44

Liver tissue from 17 West Highland White Terriers (WHWTs) with cirrhosis, subacute bridging necrosis, hepatitis, or massive necrosis were examined for the presence, composition, and distribution of inflammatory foci. Copper analysis was performed on the specimens. The foci of inflammation and necrosis composed a significant part of the lesion in 15 of the samples. The foci were of two types. One, characteristic of idiopathic chronic active hepatitis, consisted of one or two apoptotic hepatocytes attended by lymphocytes and plasma cells. These foci were found primarily in the vicinity of the portal tracts, not associated with centrolobular copper-laden hepatocytes. The other type of focus was characteristic of copper toxicosis. These foci were larger and composed of debris-filled macrophages, lymphocytes, plasma cells, and scattered neutrophils, and on occasion apoptotic hepatocytes were found at the periphery. These foci were always found around the central vein among the copper-laden hepatocytes. Such foci were found only in dogs with copper concentration > 2,000 parts/million on a dry weight basis. These morphologic studies show that clinical liver disease in WHWTs is caused by more than one etiologic agent. Among 17 WHWTs with clinical liver disease, two had copper toxicosis, five had idiopathic chronic active hepatitis, and 10 had hepatic disease of undetermined type.
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PMID:The relationship between hepatic copper content and morphologic changes in the liver of West Highland White Terriers. 895 24

The morphological and morphometric characteristics of peroxisomes in normal human liver and the peroxisomal alterations in the liver of patients with acquired or congenital non-peroxisomal diseases are reviewed. Secondary peroxisomal changes are observed in steatosis, hepatitis and cirrhosis induced by various agents (viruses, alcohol, drugs, etc.), in cholestasis, in hepatomas, in extra-hepatic cancer with or without liver metastasis, in extrahepatic inflammatory processes, in metabolic disorders affecting metabolism of carbohydrates, lipids and lipoproteins, glycoproteins, amino acids, bilirubin or copper, and in altered thyroid hormone levels. They are recognized as a proliferation of peroxisomes (increased in number and to a lesser extent in surface density and volume density) often accompanied by a minor reduction in size (at most to 68% of the mean diameter in control livers) but very rarely by an increase in mean peroxisomal diameter, and as proliferation-related changes in shape (tails, gastruloid cisternae, funnel-like constrictions, elongation, protrusions) in at least a few of the peroxisomes. These secondary alterations of the peroxisomes are clearly distinguishable from the primary changes in peroxisomes observed in the liver of patients with congenital peroxisomal disorders.
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PMID:Secondary alterations of human hepatocellular peroxisomes. 905 51

This study was conducted to determine serum levels of trace metals in young adult patients in the early icteric phase of acute hepatitis B virus infection. There were 15 patients (10 males, 5 females) and 15 healthy volunteers (11 males, 4 females). The age distribution of both groups ranged from 15-40 years and were comparable [mean (SD) = 28(6) vs 31(7) years; p = 0.12]. Compared to the healthy controls, the patients had significantly decreased serum zinc but elevated serum copper levels [means (SD) of zinc = 118(22) vs 97(20) micrograms/dl, p = 0.012; and of copper = 82(15) vs 135(40) micrograms/dl, p < 0.001]. The overall serum levels of calcium, magnesium and phosphorus in the studied patients were within normal ranges. Serum zinc concentrations of these patients correlated with albumin (r = 0.69, p = 0.005) and their serum calcium correlated with alkaline phosphatase (r = 0.61, p = 0.015). These results demonstrate that alterations of zinc and copper metabolism occur early during the acute icteric phase of uncomplicated hepatitis. These changes may be of pathophysiological significance in acute hepatitis, in particular in patients with pre-existing zinc deficiency.
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PMID:Serum trace metal levels in patients with acute hepatitis B. 918 56

The aims of this study were to characterize the histological changes observed in 34 accessioned cases of canine chronic hepatitis and to correlate these changes with the clinical pathological data. Cases of chronic hepatitis were subdivided into 6 categories: chronic active hepatitis (10/34), chronic persistent hepatitis (7/32), chronic cholestatic hepatitis (6/34), fibrosing hepatitis with cirrhosis (3/34), chronic cholangiohepatitis (3/34), and miscellaneous secondary hepatitis (5/34). Iron accumulation was a consistent finding in all livers examined. Although all cases of chronic hepatitis had elevated liver enzymes, no correlation was detected between biochemical parameters and the severity of morphologic changes. Similarly, no correlation was detected between rhodanine staining for copper and morphologic or biochemical indicators of cholestasis. However, presence of copper correlated well with reticulo-fibrosis (r = 0.8) and bile duct hyperplasia, suggesting that changes in the hemodynamics of the hepatic acini due to fibrosis could influence storage of copper.
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PMID:Chronic hepatitis: a retrospective study in 34 dogs. 918 2

The Long-Evans Cinnamon (LEC) rat has abnormal intrahepatic copper accumulation and spontaneously develops hepatocellular carcinomas following hereditary hepatitis. The hepatocellular carcinomas are very similar to human well-differentiated hepatocellular carcinoma in histopathological features and on MR images. Copper is believed to be one of the causes of hyperintensity of hepatocellular carcinomas compared to surrounding non-cancerous tissues on T1-weighted MR image. Eight LEC rats were studied by MR imaging. We measured copper concentrations from the hepatocellular carcinomas and surrounding non-cancerous liver tissues. Signal intensity of hepatocellular carcinomas without cystic areas was iso- to slightly hyperintense relative to surrounding non-cancerous tissues on T1-weighted images. Histopathologically, most of the tumors resembled human highly or well-differentiated hepatocellular carcinomas. Copper concentrations of the hepatocellular carcinomas were lower than the surrounding non-cancerous liver tissues. Copper may not be the cause of increased signal intensity typically observed on T1-weighted images of hepatocellular carcinomas.
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PMID:Copper concentration in hyperintense hepatocellular carcinomas of Long-Evans cinnamon rats on T1-weighted images. 928 8

Etheno adducts in DNA are formed from the carcinogens vinyl chloride and urethane, and also from products of lipid peroxidation (LPO), such as trans-4-hydroxy-2-nonenal. Using an ultrasensitive detection method, the formation of etheno-DNA adducts in the liver was demonstrated in LEC rats (a strain with hereditary abnormal copper metabolism) that develop hepatitis and hepatocellular carcinoma. Wilson's disease and primary haemochromatosis are human genetic disorders that cause copper or iron accumulation resulting in a high risk for primary liver cancers. Levels of etheno adducts were also significantly elevated in the liver of these patients. In a group of male and female volunteers kept on a controlled diet, the effect of dietary fatty acid composition on the endogenous formation of lipid peroxidation-derived DNA adducts was determined in DNA from white blood cells. Dietary omega-6-polyunsaturated fatty acids greatly increased LPO-derived etheno-DNA adducts in vivo, in females. Thus, exocyclic DNA adducts are promising biomarkers for elucidating the effect of dietary fat intake, oxidative stress and protective dietary antioxidants on endogenous DNA damage and thus may provide a possible mechanistic link with elevated risk for diet-related cancers.
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PMID:Etheno-DNA base adducts as tools in human cancer aetiology and chemoprevention. 949 54

The hepatic concentrations of copper, zinc, magnesium, calcium, and selenium were measured in LEC rats, which develop a spontaneous form of hepatitis at 3-4 months of age, and compared to trace metal concentrations in the LEA rat, its asymptomatic congenic strain. Consistent with results found by other groups, copper was found to accumulate within the liver of LEC rats to levels more than 50 times those measured in LEA rats. In addition, liver selenium concentration in LEC rats was found to be around 50% of that in LEA rats. The enzyme activity, and RNA for the selenium dependent enzyme, glutathione peroxidase, was also found to be reduced in LEC rat liver. These results indicate that hepatic selenium in the LEC rat is depleted and that, as a result of this, the capacity to protect cells from copper-induced free-radical damage is reduced.
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PMID:The LEC rat possesses reduced hepatic selenium, contributing to the severity of spontaneous hepatitis and sensitivity to carcinogenesis. 951 49

We have studied the DNA binding activities of transcription factors in the liver of Long-Evans Cinnamon (LEC) rats, an animal model of Wilson's disease. Owing to a genetic defect, this strain of rats accumulates excessive copper in the liver and develops severe hepatitis and hepatocellular carcinoma. We found that the DNA binding activity of the serum response factor (SRF) was higher in the liver of LEC rats (approximately 2-fold) than in that of Wistar rats. There was a close correlation between the intensity of the activity and the concentrations of copper in the nuclear protein. The DNA binding activity of Sp1, on the other hand, showed similar levels in both LEC and Wistar rats. SRF may play an important role in the development of hepatocellular carcinoma in LEC rats by mediating the proto-oncogene c-fos induction. We suggest that the copper in nuclear protein may be involved in the activation of SRF.
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PMID:Activation of serum response factor in the liver of Long-Evans Cinnamon (LEC) rat. 957 Mar 63


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