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)

Infection of cultures of peritoneal macrophages with both lactate dehydrogenase-elevating virus (LDV) and mouse hepatitis virus (MHV) resulted in the formation of pseudotype virions containing LDV RNA which productively infected cells that are resistant to infection by intact LDV virions but not to infection by MHV. These cells were mouse L-2 and 3T3-17Cl-1 cells as well as residual peritoneal macrophages from persistently LDV-infected mice. Productive LDV infection of these cells via pseudotype virions was inhibited by antibodies to the MHV spike protein or to the MHV receptor, indicating that LDV RNA entered the cells via particles containing the MHV envelope. Simultaneous exposure of L-2 cells to both LDV and MHV resulted in infection by MHV but not by LDV. The results indicate that an internal block to LDV replication is not the cause of the LDV nonpermissiveness of many cell types, including the majority of the macrophages in an adult mouse. Instead, LDV permissiveness is restricted to a subpopulation of mouse macrophages because only these cells possess a surface component that acts as an LDV receptor.
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PMID:Pseudotype virions formed between mouse hepatitis virus and lactate dehydrogenase-elevating virus (LDV) mediate LDV replication in cells resistant to infection by LDV virions. 776 83

The reactive hemophagocytic syndrome may mimic acute hepatitis, as we report here. It should be considered when hepatitis is accompanied by high fever, progressive cytopenias, and weight loss, with or without adenopathy and striking lactate dehydrogenase elevation. Bone marrow, lymph node, or liver biopsy are necessary to confirm the diagnosis. Recognition is important, because the syndrome has multiple potential causes amenable to therapy. Preliminary reports suggest that high-dose corticosteroid therapy is useful in suppressing cytokine-stimulated fever and hemophagocytosis, whatever the underlying cause.
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PMID:Reactive hemophagocytic syndrome simulating acute hepatitis. A case due to hepatic peripheral T-cell lymphoma. 780 36

Interleukin-12 is a lymphokine that triggers gamma interferon secretion by various cells and differentiation of T-helper lymphocytes towards the Th1 subtype. Since viruses are potent inducers of gamma interferon production and elicit immune responses most probably mediated by Th1 cells, like B-cell immunoglobulin G2a secretion, we analyzed interleukin-12 message expression after infection of mice with lactate dehydrogenase-elevating virus, mouse hepatitis virus, and mouse adenovirus. Our results indicated that the message for the p40 component of interleukin-12 was transiently increased shortly after infection. Interleukin-12 was expressed mainly by macrophages. Therefore, production of interleukin-12 might constitute the initial event that would determine the subsequent characteristics of the immune response elicited by viral infections.
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PMID:Interleukin-12 gene expression after viral infection in the mouse. 785 41

Ketoconazole (KT) and fluconazole (FLU) are azole antifungal agents with a broad spectrum of activity against both superficial and systemic mycoses. KT is also an anticancer agent in the treatment of advanced prostate cancer. In many clinical and retrospective studies, KT has been reported to cause liver damage, i.e. chemical hepatitis. Histologic analysis of KT induced hepatotoxicity shows massive centrilobular necrosis in which the hepatotoxicity was not thought to be mediated through an immunoallergic mechanism. According to the medical literature, the pattern of hepatic injury appears to be primarily of the hepatocellular type. Because of the documented reports of KT and FLU hepatotoxicity, a cytotoxicity comparison of KT and FLU was implemented. The objective of this comparison was to evaluate the cytotoxicity of these azoles such that future mechanistic investigations of hepatotoxicity could be performed. The relative hepatotoxicity of KT and FLU was evaluated using primary cultures of postnatal rat hepatocytes. Cytotoxicity was evaluated by measuring the leakage of the cytosolic enzyme, lactate dehydrogenase (LDH), into the medium; by assessing mitochondrial reduction of 3-(4,5-dimethythiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT); by assessing lysosomal uptake of neutral red (NR); and by gross morphology (phase contrast microscopy). The cultures were exposed to various concentrations of KT (56-188 microM) for 0.5-4 h and to various concentrations of FLU (50 microM to 1.0 mM) for 0.5-6 h. There was a significant increase (P < 0.05) in LDH leakage and a large decrease in MTT reduction and lysosomal uptake of NR at 4 h for KT. One millimolar FLU had minimal effects on the LDH leakage and MTT reduction. These results demonstrate that KT is a more potent cytotoxicant than FLU; and its toxicity was expressed in a dose- and time-dependent manner.
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PMID:Comparison of ketoconazole- and fluconazole-induced hepatotoxicity in a primary culture system of rat hepatocytes. 788 87

Acute hepatocellular injury, whether due to viral hepatitis, hepatic ischemia, or drug hepatotoxicity, results in elevated levels of serum aminotransferases (AST and ALT). Serum lactate dehydrogenase (LD) is reported to be markedly elevated in ischemic hepatitis. Thus, comparisons of the degree of elevation of serum levels of LD, ALT, and AST may be helpful in the differential diagnosis of acute liver injury. To study this, we reviewed serum enzyme patterns early in the course of acute liver injury in patients with acute viral hepatitis A and B (n = 51), ischemic hepatitis (n = 20), and acetaminophen injury (n = 26). All patients had serum ALT and/or AST at least five times the upper limit of normal. For a given ALT and AST level, LD was higher in ischemic hepatitis and acetaminophen injury than in viral hepatitis. The mean ALT/LD ratio for acute viral hepatitis was 4.65, for ischemic hepatitis 0.87, and for acetaminophen injury 1.46. Mean ALT/LD ratio for viral hepatitis was significantly higher (p < 0.0001) than for the other two groups combined. An ALT/LD ratio of 1.5 differentiated acute viral hepatitis from ischemic hepatitis and acetaminophen injury with a sensitivity of 94% and a specificity of 84%.
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PMID:Serum lactic dehydrogenase in the differential diagnosis of acute hepatocellular injury. 796 56

The hepatotoxicity of flutamide, an antiandrogen that produces hepatitis in some human recipients, was studied in isolated rat hepatocytes. Flutamide (1 mM) led to the covalent binding of reactive electrophilic metabolites to male rat hepatocyte proteins. It decreased the reduced glutathione (GSH)/glutathione disulfide ratio and total protein thiols. This was associated with an early increase in phosphorylase a activity (a Ca(++)-dependent enzyme) and a decrease in cytoskeleton-associated protein thiols, the formation of plasma membrane blebs, the release of lactate dehydrogenase (LDH) and a loss of cell viability. Both covalent binding and LDH release were decreased by piperonyl butoxide (an inhibitor of cytochrome P450) and increased by dexamethasone pretreatment (which induces cytochrome P450 3A). The toxicity was increased by beta-naphthoflavone (which induces cytochrome P450 1A). Hepatocytes from female rats (which lack cytochrome P450 3A2) exhibited lower covalent binding and lower LDH release. The addition of cystine (a GSH precursor) increased hepatocellular GSH and decreased LDH release in male hepatocytes. The administration of a diet deficient in sulfur-containing amino acids had the opposite effects; it produced toxicity with 100 microM flutamide. Flutamide (50 microM) markedly inhibited respiration (mainly at the level of complex I) in isolated male rat liver mitochondria and flutamide (1 mM) decreased ATP levels in isolated male rat hepatocytes. It was concluded that flutamide is toxic to rat hepatocytes as a result of the cytochrome P450 (3A and also 1A)-mediated formation of electrophilic metabolites, whose damaging effects are further aggravated by the inhibitory effect of flutamide on mitochondrial respiration and ATP formation.
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PMID:Toxicity of the antiandrogen flutamide in isolated rat hepatocytes. 801 83

The clinical and laboratory characteristics of 201 cases of measles and its associations with complications were analyzed during an outbreak of this disease in Mexico City. The complications were hepatitis (45%), bacterial pneumonia (17%), oral candidiasis (13%), upper gastrointestinal tract hemorrhage (13%), epistaxis (8%), encephalitis (4%), subcutaneous emphysema (2%), and hypocalcemic tetany (1%). In a subgroup of 20 consecutive patients hypocalcemia was found in 14 cases (70%), associated with high levels of calcitonin in three cases. An increased lactate dehydrogenase (LDH) was observed in 83% of the patients, showing a significant association with the occurrence of complications (p = 0.04) especially in the patients with values of LDH above 750 IU/mL (odds ratio of 6.4). Two patients died (1% mortality). The young patients with measles can develop serious complications, and an increased level of LDH may be a prognostic indicative of these complications.
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PMID:[Measles in the young adult. Clinical features of 201 cases]. 805 46

Different biological materials were tested for murine viral contamination by using the mouse/rat antibody production test. Of 297 tumors examined, 75 (25.3%) were contaminated. Considerable differences in the contamination rate became evident when transplantable tumors from in vitro and from in vivo passages were compared. Of 186 tumors that had been propagated in animals, 36.6% were positive, whereas only 7 of 111 (6.3%) tumors propagated in vitro were contaminated. The highest rate of contamination was detected in mouse tumors. Testing of 135 specimens of mouse origin revealed 46.7% were contaminated, and 57 (70.4%) of 81 samples propagated in mice were positive for murine viruses. Moreover, 6.7% of 90 human tumors that had been passaged in athymic nude mice and 3.5% of 57 rat tumors were positive. Lymphocytic choriomeningitis virus was detected in 4 of 14 hamster tumors. The most frequent contaminant was lactic dehydrogenase elevating virus followed by reovirus 3, lymphocytic choriomeningitis virus, minute virus of mice, mouse hepatitis virus, rat coronaviruses, Kilham rat virus, and Mycoplasma pulmonis. Contamination with reovirus 3 and minute virus of mice was found in 4 (3.7%) of 109 cell lines tested, and 2 of 60 monoclonal antibody preparations or hybridoma cells contained lactic dehydrogenase virus. Contamination with two pathogens was detected in four mouse tumors and in one cell line.
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PMID:Contamination of transplantable tumors, cell lines, and monoclonal antibodies with rodent viruses. 823 Oct 85

We produced hepatitis in guinea pigs by immunization with acetaldehyde adducts and ethanol treatment. Human hemoglobin-acetaldehyde adducts were prepared without any reducing agents and affinity purified with polyclonal antibodies against acetaldehyde adducts. Female guinea pigs were immunized with the adducts and were simultaneously given ethanol for 40 days. These treatments induced hepatic necrosis with infiltration of mononuclear cells in the hepatic lobules. The formation of the lymphoid follicle was also observed in severe cases. These changes were accompanied by the elevation of serum AST and lactic dehydrogenase activities and titers of circulating antibodies against acetaldehyde adducts. By contrast, the combination of ethanol and immunization with unmodified hemoglobin produced only fatty change of the liver, and animals immunized with the adducts alone had minimal inflammatory changes of the liver. Peripheral blood lymphocytes obtained from the animals with hepatitis were shown to be stimulated by acetaldehyde adducts to a significantly greater degree than those from control animals who received nothing, ethanol alone or ethanol and unmodified hemoglobin. These results suggest that the immune response to acetaldehyde adducts may be involved, at least partly, in the pathogenesis of inflammation observed in alcoholic liver disease.
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PMID:Experimental hepatitis induced by ethanol after immunization with acetaldehyde adducts. 842 34

To evaluate the clinical applications of serum thymidine kinase (TK) activity, we compared the results obtained with this parameter with those of other liver function tests in 27 patients with acute viral hepatitis and 16 normal controls. In those in the acute stage, the serum TK activity increased significantly to 55.5 +/- 66.5 U/L. There was no significant correlation between serum TK activity and findings for serum albumin, bilirubin, alkaline phosphatase or r-glutamyl transpeptidase. However, it did correlate significantly well with the serum activity of aspartate aminotransferase (AST) (r = 0.621, P < 0.01), alanine aminotransferase (ALT) (r = 0.551, P < 0.01), and lactate dehydrogenase (LDH) (r = 0.620, P < 0.01). Serum TK activity reached higher than 70 U/L in 8 of 11 patients with hepatitis A; however, no patients with the other types of hepatitis reached such a high level. During the recovery stage, the serum TK activity decreased significantly to 5.9 +/- 1.7 U/L (P < 0.01), and did not correlate with AST, ALT, LDH or other conventional liver function parameters. The data suggest that an elevation of serum TK in patients with acute viral hepatitis results from hepatocellular damage. A marked elevation of serum TK activity may thus provide a marker for acute hepatitis A infection.
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PMID:Elevated serum thymidine kinase activity in patients with acute viral hepatitis. 844 Apr 24


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