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)

Livers from 128 captive woodchucks (Marmota monax) that were negative for serological markers of woodchuck hepatitis virus (WHV) were examined grossly and histologically. Livers from 19 additional seronegative woodchucks were examined only grossly. The most common finding (61% of histological specimens) was mononuclear cells in portal areas. Moderate to severe portal infiltrates in association with similar scattered mononuclear cell aggregates and extramedullary hematopoiesis, were present in woodchucks that had extrahepatic inflammatory lesions. We concluded that these changes represent a response to a variety of chronic infections and are not specific for WHV infection. Other findings included parasitic granulomas, focal and diffuse lipidosis, bile duct proliferation, lesions secondary to cardiovascular compromise, and vasculitis. Two woodchucks had neoplastic lesions.
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PMID:Hepatic lesions in woodchucks (Marmota monax) seronegative for woodchuck hepatitis virus. 206 50

Conditions necessary for establishment of a graft, posttransplant supportive care and complications, and lymphohematopoietic reconstitution after bone marrow transplantation were evaluated in 7 cats. Donor-recipient pairs were selected on the basis of low mutual reactivity in one-way mixed lymphocyte reactions. Before transplantation, cats were given marrow ablative (7 Gray) total-body gamma irradiation. Cyclosporine A was administered to cat 7, which was given marrow from an unrelated donor. Rapid hematologic recovery was attained in 5 of 5 (cats 1 to 5) sibling bone marrow recipients and 1 (cat 7; cyclosporine A-treated) of 2 recipients from unrelated donors. Lymphocyte recovery was prolonged, requiring up to 100 days to attain reference concentrations. Lymphocyte blastogenic responses were below reference range in 2 of 3 cats (cats 1 and 3) examined approximately 1 to 3 months after transplantation. Serum IgG concentrations determined 1 to 6 months after transplantation were within reference range in cats 1 to 5 which were given sibling bone marrow. Fatal infections did not develop in cats that had established grafts. Antimicrobial-responsive fevers did develop, but were generally detected only when granulocyte counts were low (less than 1 x 10(9) cells/L). Clinical signs of disease in the immediate posttransplant period consisted of hepatic lipidosis (fatal) in cat 4, hepatitis (mild graft-vs-host disease) in cat 3, and immune-mediated hemolytic anemia and thrombocytopenia in cat 7. Cats with hepatitis and immune-mediated disease responded to immunosuppressive therapy.
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PMID:Clinical and lymphohematologic responses after bone marrow transplantation in sibling and unrelated donor-recipient pairs of cats. 214 32

The objective of this investigation was to characterize the acute and short- and long-term toxic potency of orally administered 1,2-dichloropropane (DCP). In the acute and short-term studies, male rats of 250-300 g were gavaged with 0, 100, 250, 500, or 1000 mg DCP/kg in corn oil once daily for up to 10 consecutive days. Although ingestion of DCP caused body weight loss and CNS depression, few other toxic effects were manifest 24 hr after a single dose of the chemical. Morphological changes were limited to liver centrilobular cells in 500 and 1000 mg/kg rats. Similarly, elevated activity of some serum enzymes occurred only at these two highest dose levels. Hepatic nonprotein sulfhydryl (NPS) levels were decreased and renal NPS levels increased at 24 hr. In the short-term study resistance developed to DCP hepatotoxicity over the 10 consecutive days of exposure, as reflected by progressively lower serum enzyme levels and by decreases in the severity and incidence of toxic hepatitis and periportal vacuolization. Nucleolar enlargement in hepatocytes, however, was observed at all dosage levels at 5 and 10 days. There were a number of manifestations of hemolytic anemia, including erythrophagocytosis in the liver, splenic hemosiderosis and hyperplasia of erythropoietic elements of the red pulp, renal tubular cell hemosiderosis, and hyperbilirubinemia. Urinalyses and histopathology revealed no evidence of nephrotoxicity. In the long-term study, male rats initially weighing 180-200 g were gavaged five times weekly for up to 13 weeks with 0, 100, 250, 500, or 750 mg DCP/kg. As over one-half the 750 mg/kg group died within 10 days, the survivors were sacrificed. Histopathological changes in the 750 mg/kg animals included mild hepatitis and splenic hemosiderosis, as well as adrenal medullary vacuolization and cortical lipidosis, testicular degeneration and a reduction in sperm, and increased number of degenerate spermatogonia in the epididymis in some members of the group. Similar testicular and epididymal degenerative change also were observed in some 500 mg/kg animals after 13 weeks of dosing. There was a progressive increase in the number of deaths in the 500 mg/kg group, such that more than 50% were dead by 13 weeks. No deaths occurred in the 100 or 250 mg/kg groups. The DCP dosage regimen also produced a dose-dependent decrease in body weight gain. DCP exhibited very limited hepatotoxic potential and no apparent nephrotoxic potential in the long-term study. Slight elevations in serum ornithine-carbamyltransferase activity, periportal vacuolization, and active fibroplasia in the liver were seen in the 500 mg/kg animals.
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PMID:Oral toxicity of 1,2-dichloropropane: acute, short-term, and long-term studies in rats. 274 74

Drugs are exogenous substances often requiring metabolic transformation to be therapeutically effective. This occurs primarily in the liver, the most important metabolic organ and a structure able to adapt to this burden. Should its adaptive potential be exceeded, damage can occur, affecting principally the liver parenchyma. Such damage manifests itself as disturbed secretory function and as reversible or irreversible structural alteration of the liver cells. The constellation of toxic-degenerative lesions is referred to as hepatosis (toxic hepatosis, toxic hepatopathy). A variety of patterns of damage (lipidosis, necrosis, cholestasis etc.) occur alone or in combination. Depending on the severity and extent of these alterations a secondary inflammatory reaction may result. These changes are manifest as cellular infiltration and proliferation with formation of reticulo-histiocytic nodules or minifocal epitheloid cell reactions and non-caseous epitheloid cell granulomas. The eosinophilic component is striking. In the face of continued toxic exposures, changes resembling those of chronic aggressive hepatitis may develop following the acute changes. Other drug-related liver damage may present as vascular lesions the afferent or efferent venous systems as well as in the sinusoids (i.e. peliosis hepatis, Budd-Chiari syndrome). Moreover there may be neoplastic alterations such as focal nodular hyperplasia or liver cell adenomas. Pathognomonic histologic criteria for drug-induced liver damage have as yet to be recognized, particularly in the case of facultative toxins. Morphologic indications can only suggest that a prior pharmaceutical agent was the likely cause of the damage. Histologic changes must however be viewed in the context of the medical history, clinical and laboratory findings, as well as results of other studies before the conclusion is drawn that the observed liver changes represent drug-induced injury.
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PMID:[Morphological reaction patterns of the liver induced by drugs]. 383 9

Physical examination, clinical laboratory testing, and medical imaging are effective in establishing the presence of liver disease; however, they infrequently establish a definitive diagnosis. Morphologic evaluation of liver tissue is generally accepted as a valuable diagnostic tool in establishing a diagnosis in liver disease. Clinicians have several options for obtaining specimens for morphologic evaluation, including surgically obtained wedge biopsies, percutaneous core biopsies, and fine-needle aspiration specimens. Surgical and core biopsy procedures require anesthesia or sedation and have a substantial risk of bleeding complications. Fine-needle aspiration usually does not require sedation and is rarely associated with hemorrhage; thus, it is frequently chosen for animals that are poor anesthetic risks or have coagulopathies. Diseases like malignant lymphoma, hepatic lipidosis, and suppurative hepatitis are readily diagnosed cytologically, whereas hepatocellular adenomas, hyperplastic nodules, fibrosis, and chronic inflammation are more difficult to identify cytologically.
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PMID:Liver cytology. 1246 95

Medical records from 39 cats with hepatic disease, examined at the Veterinary Medical Teaching Hospital, University of Florida, between 1987 and 1992 were retrospectively evaluated for alterations in red blood cell (RBC) morphology. Diagnoses included: hepatic lipidosis, neoplasia, cholangiohepatitis, hepatitis/hepatopathy, systemic histoplasmosis, and portocaval shunt. A total of 56 laboratory data sets were studied which included complete blood counts and serum chemistry results. Stained blood smears were evaluated from 51 of the data sets. Twenty-two cats (56%) were determined to have poikilocytosis on the basis of blood smear evaluation. Eleven (28%) cats had moderate to marked poikilocytosis (2+ to 4+). Acanthocytes accounted for 62.6 -/+ 22.1% of morphologically abnormal RBC and were observed in blood smears from 100% of cats with poikilocytosis. Elliptocytes (ovalocytes) comprised 19.5 -/+ 15.8% of poikilocytes and were found in smears from 82% of cats with poikilocytosis. Keratocytes (7.0 -/+ 6.8%), schistocytes (3.6 -/+ 4.4%), and blister cells (2.6 -/+ 6.4%) were present in lower numbers and in fewer cats. Serum total cholesterol values were significantly greater (p < 0.05) in cats with moderate to marked alterations in RBC morphology. Cats with hepatic lipidosis were significantly (p < 0.04) more likely to have poikilocytosis than cats with other types of hepatic disease.
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PMID:Red cell morphologic alterations in cats with hepatic disease. 1266 32

This article describes the gross, histopathologic, and ultrastructural findings of the livers of cetaceans stranded on the coast of the Canary Islands between 1992 and 2000. A total of 135 cetaceans were included in the study, among which 25 were common dolphins (Delphinus delphis), 23 Atlantic spotted dolphins (Stenella frontalis), 19 striped dolphins (Stenella coeruleoalba), and 15 other species of dolphins and whales. The most common lesion observed in these animals was a nonspecific chronic reactive hepatitis (47/135), followed by hyaline intracytoplasmic inclusions in hepatocytes (33/135). Parasitic cholangitis was detected in 8/135 animals, whereas hepatic lipidosis was presented in 7/135 animals. The ultrastructure of hyaline hepatocytic cytoplasmic inclusions is described, and possible causes of these inclusions are discussed.
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PMID:Hepatic lesions in cetaceans stranded in the Canary Islands. 1501 28

Microarray technology continues to gain increased acceptance in the drug development process, particularly at the stage of toxicology and safety assessment. In the current study, microarrays were used to investigate gene expression changes associated with hepatotoxicity, the most commonly reported clinical liability with pharmaceutical agents. Acetaminophen, methotrexate, methapyrilene, furan and phenytoin were used as benchmark compounds capable of inducing specific but different types of hepatotoxicity. The goal of the work was to define gene expression profiles capable of distinguishing the different subtypes of hepatotoxicity. Sprague-Dawley rats were orally dosed with acetaminophen (single dose, 4500 mg/kg for 6, 24 and 72 h), methotrexate (1mg/kg per day for 1, 7 and 14 days), methapyrilene (100mg/kg per day for 3 and 7 days), furan (40 mg/kg per day for 1, 3, 7 and 14 days) or phenytoin (300 mg/kg per day for 14 days). Hepatic gene expression was assessed using toxicology-specific gene arrays containing 684 target genes or expressed sequence tags (ESTs). Principal component analysis (PCA) of gene expression data was able to provide a clear distinction of each compound, suggesting that gene expression data can be used to discern different hepatotoxic agents and toxicity endpoints. Gene expression data were applied to the multiplicity-adjusted permutation test and significantly changed genes were categorized and correlated to hepatotoxic endpoints. Repression of enzymes involved in lipid oxidation (acyl-CoA dehydrogenase, medium chain, enoyl CoA hydratase, very long-chain acyl-CoA synthetase) were associated with microvesicular lipidosis. Likewise, subsets of genes associated with hepatotocellular necrosis, inflammation, hepatitis, bile duct hyperplasia and fibrosis have been identified. The current study illustrates that expression profiling can be used to: (1) distinguish different hepatotoxic endpoints; (2) predict the development of toxic endpoints; and (3) develop hypotheses regarding mechanisms of toxicity.
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PMID:Gene expression profiling reveals multiple toxicity endpoints induced by hepatotoxicants. 1512 Sep 68

From 1994 to 2002, tissues from 61 prairie dogs were submitted to Northwest ZooPath for histopathology. Of these, 12 (20%) had hepatocellular carcinoma (HCC). Three were pets submitted from private veterinary practices. The others were submitted from zoos in the United States. All were adults, ranging from young adult to 7 years of age, with average age of 5.1 years. The most common clinical signs were weight loss, lethargy, palpable abdominal mass, and respiratory difficulty. All tumors were well-differentiated HCCs in which four histologic patterns were recognized. The trabecular pattern was predominant in nine tumors, and the pseudoglandular pattern was predominant in two tumors. The pelioid pattern was also represented in eight tumors. A papillary pattern was present in one case. In seven cases vacuolar change resembling lipidosis was present in the neoplastic hepatocytes of both primary and metastatic tumors. Anaplasia was mild to moderate in most tumors, but a marked degree of anaplasia was noted in the metastatic foci of the case with papillary differentiation. Metastasis to lung was noted in five cases. One of these also had metastasis to the spleen, and another had metastasis to heart and mediastinum. In two cases there was concurrent hepatitis and in two cases, cirrhosis. All tumors and nonneoplastic liver stained negatively for woodchuck hepatitis virus surface and core antigens, and orcein and Victoria blue positive staining of hepatocytes typical of hepadnavirus infection in humans and woodchucks was not present. HCC is apparently common in captive prairie dogs. The hepatic neoplasia observed in prairie dogs was similar to that associated with hepadnaviral infection in humans, woodchucks, and ground squirrels, but no direct evidence of hepadnaviral infection was detected. The rate of metastasis in captive prairie dogs was higher than that reported in woodchucks.
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PMID:Hepatocellular carcinoma in black-tailed prairie dogs (Cynomys ludivicianus): tumor morphology and immunohistochemistry for hepadnavirus core and surface antigens. 1523 35

The diagnosis of drug-induced liver injury (DILI) is a challenging problem, often confounded by incomplete clinical information and the difficulty of eliciting exposure to herbal products, over-the-counter agents and toxins. The task is further rendered difficult on biopsy, as drugs can mimic all the patterns found in primary liver disease. Acute hepatitis, with or without cholestasis, is the most common histological pattern of DILI, and drugs such as acetaminophen are the leading causes of acute liver failure. Most cases of DILI resolve on discontinuation of the drug, but recovery can take months or rarely the disease can progress despite drug withdrawal. Drugs such as methotrexate can lead to chronic hepatitis and cirrhosis, while others such as minocycline, nitrofurantoin and methyldopa are implicated in autoimmune hepatitis. Prolonged cholestasis and ductopenia resembling primary chronic biliary disease can occur. Drug-induced steatohepatitis is also an uncommon pattern, but is well described with drugs such as amiodarone and irinotecan. In the presence of risk factors such as obesity and diabetes, some drugs such as tamoxifen, oestrogens and nifedipine can precipitate or exacerbate steatohepatitis. Other observed patterns include granulomatous hepatitis, vascular injury (eg, sinusoidal obstruction syndrome), Ito cell lipidosis and neoplasms (eg, adenomas).
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PMID:Histological patterns in drug-induced liver disease. 1947 52


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