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)

A nonisotopic in situ hybridization (NISH) assay was used to detect hepatitis C virus (HCV) RNA. A synthetic oligonucleotide complementary to bases 252-301 of the highly conserved 5' noncoding region of the HCV genome was end-labeled by terminal deoxynucleotidyltransferase using digoxigenin-conjugated dUTP. The hybridized oligomer was revealed by an immunohistochemical reaction after incubation with an alkaline phosphatase-conjugated anti-digoxigenin antibody and subsequent amplification with a complex of alkaline phosphatase and anti-alkaline phosphatase antibodies. The intracellular distribution of HCV RNA was monitored in the livers of two chimpanzees experimentally infected with the H strain of HCV and compared with the serum alanine aminotransferase activity, serum HCV RNA, and liver histopathology. Most cells were stained in the cytoplasm as early as 2 days after inoculation, 1 and 2 days, respectively, before the appearance of viral RNA in the serum. The time course of HCV RNA replication was correlated with increases in serum alanine aminotransferase. However, neither one paralleled the appearance of liver cell necrosis nor showed any correlation with the inflammatory response. The NISH signal was not found in liver biopsy specimens taken from these two animals before inoculation with HCV, from chimpanzees with acute hepatitis type A, B, or delta, or from two animals never experimentally infected with any hepatitis agent; moreover, it disappeared when the positive specimens were predigested with RNase and it was not observed after hybridization of positive controls with a labeled oligomer unrelated to HCV RNA. Thus, detection of liver HCV RNA by NISH is a sensitive and specific method for studying HCV replication at the cellular level. Intracellular replication of HCV did not appear to be associated with histopathologic changes in the liver, although the correlation with increases of liver enzyme activity in the serum suggested possible damage to the liver cell membrane.
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PMID:Detection of intrahepatic replication of hepatitis C virus RNA by in situ hybridization and comparison with histopathology. 131 16

We immunohistochemically analyzed the expression of double-stranded RNA-dependent protein kinase (PKR) using a monoclonal antibody, 71/10. Test samples included 64 human liver biopsies and 25 liver sections of rats inoculated with diethylnitrosamine. The PKR signals in human fatty livers and normal rat livers were minimum. Scoring signal intensity from 0-4, the average scores of chronic active (14 cases) and chronic persistent (6 cases) hepatitis associated with hepatitis virus C (HCV) were 2.8 and 2.0, respectively (P = 0.038). The stained cells were significantly more abundant in the periportal than centrilobular regions for both chronic active and persistent hepatitis (P < 0.001 each). The average score of liver cirrhosis associated with HCV was 1.9. Those scores of well-, moderately, and poorly differentiated hepatocellular carcinomas associated with HCV were 3.4, 2.1, and 0.3, respectively (P < 0.001 for each pair). Those scores of well- and poorly differentiated carcinomas associated with hepatitis virus B were 2.3 and 0.0, respectively (P < 0.001). The average score of rat carcinomas induced by diethylnitrosamine was 1.9. Morphologically, nuclei of the vast majority of PKR-positive cells looked not apoptotic. The ratio of PKR-positive cells to apoptotic cells by terminal transferase-mediated dUTP nick end labeling method was approximately 20 in hepatitis, and over 100 in well-differentiated carcinoma.
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PMID:Aberrant expression of double-stranded RNA-dependent protein kinase in hepatocytes of chronic hepatitis and differentiated hepatocellular carcinoma. 976 75

The ability of PCR reagent containing dUTP/uracil-DNA glycosylase for controlling carry-over contamination of PCR products was explored. All of 204 sera taken from hepatitis patients were used for HBV DNA detection by PCR with PCR-dUTP/UDG reagent in comparison with that without dUTP/UDG. The results showed that its efficiency of controlling contamination was excellent. At least, contamination of 100 ng PCR products was got rid of. The corresponding rate of HBV DNA detection by PCR-dUTP/UDG in combination with dot hybridization using digoxin-labeled HBV probe was as high as 89.32%, higher than that (81.45%) of PCR without dUTP/UDG plus dot hybridization(P < 0.05). It suggests that PCR-dUTP/UDG method could prevent PCR products from contaminating and increase accuracy and specificity of PCR amplification.
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PMID:[Serum HBV DNA detected by polymerase chain reaction with dUTP/uracil-DNA glycosylase]. 1068 59

NFkappaB is an essential survival factor in several physiological conditions such as embryonal liver development and liver regeneration. However, NFkappaB is also a main mediator of the cellular response to a variety of extracellular stress stimuli, and it has been shown that some viral-induced host cell apoptosis appears to be dependent on NFkappaB activation. The activation of NFkappaB upon viral infection may be a rapid way of initiating an innate immune response against the viral particles. We have assessed the role of NFkB during the early phase of adenoviral hepatitis in a nude mouse model using an adenoviral vector expressing a mutant form of IkappaBalpha. Administration of a LacZ-expressing adenoviral vector induces NFkB DNA and correlates with the up-regulation of Fas (CD95) mRNA, but not FasL (CD95L) mRNA, during the early phase of adenoviral hepatitis. The rapid increase in NFkappaB DNA binding after adenoviral infection of the liver could be very effectively inhibited by IkappaBalpha. Compared with the LacZ control virus, the IkappaBalpha-expressing adenoviral vector inhibits the increase of Fas (CD95) mRNA expression, in particular in the very early phase of the hepatitis. Reporter gene experiments in hepatoma cell lines with a Fas promoter-luciferase construct indicated that the repression of Fas (CD95) mRNA by IkappaBalpha was transcriptionally mediated. The functional relevance of the NFkappaB-dependent increase in Fas (CD95) transcription was assessed by caspase 3 assays and terminal dUTP nick-end labeling tests. Compared with the control, IkappaBalpha adenoviral infection resulted in reduced caspase 3 activity during the early phase of viral hepatitis and in a prevention of liver cell apoptosis 24 h after adenoviral administration. Therefore our study demonstrates a new pro-apoptotic function of NFkappaB in Fas (CD95)-mediated apoptosis of hepatocytes. Interestingly, NFkappaB mediates liver cell apoptosis upon viral infection even in a phase where tumor necrosis factor-alpha is already induced, as shown by the time curves of tumor necrosis factor-alpha serum levels. Therefore, the pro- or anti-apoptotic role of NFkappaB appears to be more determined by the nature of the death stimulus than by the origin of the tissue.
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PMID:NFkappaB mediates apoptosis through transcriptional activation of Fas (CD95) in adenoviral hepatitis. 1069 45

To explore the expression of Fas/Fas-L in liver tissue of hepatitis gravis patients and its implication in hepatocyte apoptosis, Fas/Fas-L expression and cell apoptosis was detected by the means of inmmunohistochemistry and terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL). It was found that in the 20 patients with clinical hepatitis gravis, Fas in hepatocytes showed strong expression and Fas-L also showed intensive expression in infiltrating lymphocytes and scattering hepatocytes. The apoptosis existed in all the samples, scattering in the areas of inflammatory, necrotic area and hepatic lobule. It was suggested that the overexpression of Fas/Fas-L could cause the death of hepatocytes and thus the occurrence of hepatitis gravis. The apoptosis caused by Fas might be one of the important pathogeneses of hepatitis gravis. Among the detected samples, apoptosis and necrosis coexisted, indicating that both two types of cellular death were closely associated with the pathogenesis of hepatitis gravis.
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PMID:Study on Fas/Fas-L expression in liver tissue and hepatocyte apoptosis in patients with hepatitis gravis. 1152 12

beta-L-Thymidine (L-dT) and beta-L-2'-deoxycytidine (L-dC) are potent and highly specific inhibitors of hepatitis B virus (HBV) replication both in vivo and in vitro (50% effective concentrations, 0.19 to 0.24 microM in 2.2.15 cells). The intracellular metabolisms of L-dT and L-dC were investigated in HepG2 cells and primary cultured human hepatocytes. L-dT and L-dC were extensively phosphorylated in both cell types, with the 5'-triphosphate derivative being the predominant metabolite. In HepG2 cells, the 5'-triphosphate levels were 27.7 +/- 12.1 and 72.4 +/- 1.8 pmol/10(6) cells for L-dT and L-dC, respectively. In primary human hepatocytes, the 5'-triphosphate levels were 16.5 +/- 9.8 and 90.1 +/- 36.4 pmol/10(6) cells for L-dT and L-dC, respectively. Furthermore, a choline derivative of L-dCDP was detected at concentrations of 15.8 +/- 1.8 and 25.6 +/- 0.1 pmol/10(6) cells in human hepatocytes and HepG2 cells, respectively. In HepG2 cells exposed to L-dC, the 5'-monophosphate and 5'-triphosphate derivatives of beta-L-2'-deoxyuridine (L-dUMP and L-dUTP, respectively) were also observed, reaching intracellular concentrations of 6.7 +/- 0.4 and 18.2 +/- 1.0 pmol/10(6) cells, respectively. In human hepatocytes, L-dUMP and L-dUTP were detected at concentrations of 5.7 +/- 2.4 and 43.5 +/- 26.8 pmol/10(6) cells, respectively. It is likely that deamination of L-dCMP by deoxycytidylate deaminase leads to the formation of L-dUMP, as the parent compound, L-dC, was not a substrate for deoxycytidine deaminase. The intracellular half-lives of L-dTTP, L-dCTP, and L-dUTP were at least 15 h, with intracellular concentrations of each metabolite remaining above their respective 50% inhibitory concentrations for the woodchuck hepatitis virus DNA polymerase for as long as 24 h after removal of the drug from cell cultures. Exposure of HepG2 cells to L-dT in combination with L-dC led to concentrations of the activated metabolites similar to those achieved with either agent alone. These results suggest that the potent anti-HBV activities of L-dT and L-dC are associated with their extensive phosphorylation.
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PMID:Pharmacology of beta-L-thymidine and beta-L-2'-deoxycytidine in HepG2 cells and primary human hepatocytes: relevance to chemotherapeutic efficacy against hepatitis B virus. 1201 82

The role of apoptosis in mouse hepatitis virus (MHV) infection is still controversial. To better assess the role of apoptosis in MHV infection, we used three different biologic phenotypes of MHV to examine their differential effect on the induction of apoptosis. MHV-A59 produces acute hepatitis, meningoencephalitis, and chronic demyelination. MHV-2 causes only acute hepatitis and meningitis, whereas Penn98-1 produces acute hepatitis and meningoencephalitis without demyelination. We detected TdT-mediated dUTP nick-end labeling (TUNEL) staining in the livers and meninges of MHV-A59-, MHV-2-, and Penn98-1-infected mice. TUNEL staining in brain parenchyma was only detected in MHV-A59- and Penn98-1-infected mice. We detected apoptosis by electronmicroscopy in olfactory neurons during acute infection with MHV-A59. The kinetics and distribution of TUNEL staining correlated with the pathologic damage and colocalized with viral antigen in some cells. At 1 month, TUNEL staining was found exclusively in areas of demyelination in the spinal cord of MHV-A59-infected mice; however, it was not found in nondemyelinated mice infected with MHV-2 or Penn98-1, or in mock-infected mice. TUNEL-positive cells were identified as macrophage/microglial cells, some astrocytes, and some oligodendrocytes, by colabeling with cell-specific markers. The presence of TUNEL staining in oligodendrocytes suggests that apoptosis may play an important role in MHV-induced demyelination.
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PMID:Differential induction of apoptosis in demyelinating and nondemyelinating infection by mouse hepatitis virus. 1240 65

Recently, liver natural killer T (NKT) cells, which are specifically stimulated by alpha-galactosylceramide (alpha-GalCer), were found to play a critical role in intrahepatic immunity to several infections and certain hepatic disorders. However, the role of psychophysical stress on NKT cell-dependent liver injury induced by alpha-GalCer still remains to be elucidated. In this study, we employed inescapable electric foot shock as the mode of psychophysical stress and evaluated its effect on alpha-GalCer-induced hepatitis. Pre-exposure of 12 hours of foot shock stress before alpha-GalCer administration significantly enhanced alpha-GalCer-triggered increase in serum alanine aminotransferase levels, followed by increases in both liver caspase-3 activity and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive hepatocytes, thus indicating that the liver NKT cell-dependent apoptotic response was exacerbated by stress. Foot shock stress also significantly increased both the number of liver NKT cells and Fas expression levels on hepatocytes. Pretreatment with RU-486, a glucocorticoid (GC) receptor antagonist, completely reversed such stress-induced enhancement of the alpha-GalCer-triggered serum alanine aminotransferase and hepatocyte Fas antigen responses. In contrast, such a reversal effect was not found in the mice pretreated with naloxone, a micro-opioid receptor antagonist, which thus suggests that an elevation of endogenous GCs, but not beta-endorphin, as responsible for such stress-induced aggravation in mouse hepatitis models. In conclusion, foot shock stress-induced elevation of endogenous GCs exacerbates alpha-GalCer-initiated hepatic apoptosis through the expansion of liver NKT cells and the up-regulation of hepatocyte Fas antigen.
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PMID:Electric foot shock stress-induced exacerbation of alpha-galactosylceramide-triggered apoptosis in mouse liver. 1505 17

The hepatoprotective effects of Acanthopanax koreanum Nakai (Araliaceae) were evaluated in D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure in mouse. Preparations of Acanthopanax koreanum used were an ethanol extract, a water extract, and the ethanol-soluble and ethanol-insoluble components of the water extract of roots or stems of the plant. Mice were pretreated with various extracts by intraperitoneal injection or orally, 12 and 1 h before intraperitoneal injection of D-galactosamine and lipopolysaccharide (LPS). Intraperitoneal pretreatment with the water extract or the ethanol-insoluble component of the water extract markedly reduced the elevated levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and tumor necrosis factor-alpha (TNF-alpha), reduced the histological changes in the liver, and attenuated hepatocyte apoptosis confirmed by the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling method and DNA fragmentation assay. Oral pretreatment with the ethanol-insoluble component of the water extract also reduced serum AST, ALT, and TNF-alpha levels. The present study shows that the ethanol-insoluble component of a water extract from Acanthopanax koreanum has a protective effect against the induction of fulminant hepatitis in mice by D-galactosamine and lipopolysaccharide.
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PMID:Effect of Acanthopanax koreanum Nakai (Araliaceae) on D-galactosamine and lipopolysaccharide-induced fulminant hepatitis. 1509 51

Understanding the function of the hepatitis B virus X protein (HBx) is fundamental to elucidating the underlying mechanisms of hepatitis and hepatocarcinogenesis caused by hepatitis B virus (HBV) infection. We identified heat shock protein 60 (Hsp60) as a novel cellular target of HBx by the combination of affinity purification and mass spectrometry. Physical interaction between HBx and Hsp60 was confirmed by standard immunoprecipitation and immunoblot methods. Analysis of HBx deletion constructs showed that amino acids 88-117 of HBx were responsible for the binding to Hsp60. Confocal laser microscopy demonstrated that HBx and Hsp60 colocalized in mitochondria. Furthermore, terminal deoxynucleotidyl transferase-mediated dUTP end labeling (TUNEL) revealed that the introduction of Hsp60 into cells facilitated HBx-induced apoptosis. These findings suggest the importance of the molecular chaperon protein Hsp60 to the function of HBV viral proteins.
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PMID:Interaction of the hepatitis B virus X protein (HBx) with heat shock protein 60 enhances HBx-mediated apoptosis. 1512 Jun 23


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