Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Plasma levels of prothrombin fragment F 1 + 2 (PTF) and thrombin-antithrombin III complex (TAT) were assayed in 86 cases of disseminated intravascular coagulation (DIC). A significant elevation of both parameters was observed in most cases of DIC, which suggested that the in vivo generation of thrombin is highly accelerated by the cleavage of the prothrombin molecule by factor Xa. On the contrary, no significant elevation of plasma levels of PTF was observed in cases of DIC with severe hepatic failure or fulminant hepatitis in spite of significant elevation of TAT. Plasma levels of PTF were directly proportional to those of TAT in 86 cases of DIC as a whole (r = 0.682, p < 0.001). The measurement of both parameters was considered to be useful to estimate the hemostatic activation in DIC.
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PMID:Changes in plasma levels of prothrombin fragment F 1 + 2 in cases of disseminated intravascular coagulation. 848 Apr 81

Activation of the immune coagulation system has been implicated in the pathogenesis of liver injury following infection of inbred mice with murine hepatitis virus strain 3 (MHV-3). Following MHV-3 infection, macrophages isolated from MHV-3-susceptible and -semisusceptible inbred strains of mice express increased procoagulant activity (PCA), whereas macrophages from resistant strains express no increase in PCA over basal levels. The PCA induced by MHV-3 is a prothrombinase, encoded by the gene Fgl-2, which encodes a fibrinogen-like protein (musfiblp). In this study, MHV-3-resistant A/J mice treated with methylprednisolone prior to infection with MHV-3 developed elevated levels of alanine aminotransferase in serum and died within 10 days of infection, with histological findings of fulminant hepatitis. In vitro, macrophages isolated from A/J mice and pretreated with methylprednisolone produced a marked increase in functional PCA following infection with MHV-3. The PCA was shown to be a prothrombinase by its ability to cleave 125I-prothrombin. Northern blot analysis of RNA transcripts from these macrophages demonstrated increased transcription of the Fgl-2 gene relative to that in macrophages which had not been pretreated with methylprednisolone prior to MHV-3 infection. Methylprednisolone pretreatment of MHV-3-infected macrophages stabilized the Fgl-2 mRNA. Thus, loss of resistance to MHV-3 secondary to methylprednisolone therapy is associated with increased transcription and stability of Fgl-2 mRNA resulting in expression of the Fgl-2 gene product, musfiblp. These results provide further insight into mechanisms of PCA regulation in response to MHV-3 infection in inbred strains of mice.
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PMID:Loss of resistance to murine hepatitis virus strain 3 infection after treatment with corticosteroids is associated with induction of macrophage procoagulant activity. 867 49

Coagulation assays, including platelet counts, antithrombin III, fibrinogen, fibrinogen degradation product levels, prothrombin (PT), activated partial thromboplastin (APTT) and activated clotting times (ACT), were performed on 20 healthy juvenile northern elephant seals (Mirounga angustirostris) stranded along the central California coastline from 15 March to 15 April 1994, to establish baseline parameters for this species. Elephant seals appear to have relatively short ACT, PT, and APTT times, while fibrinogen, platelet and antithrombin III levels are similar to domestic species. Based on these mean values in healthy animals, disseminated intravascular coagulation (DIC) was diagnosed in an elephant seal with low plasma fibrinogen and extended ACT, PT and APTT times; this animal had hemorrhages, mixed bacterial suppurative interstitial pneumonia with verminous arteritis, epicarditis, hepatitis and enterocolitis.
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PMID:Baseline coagulation assay values for northern elephant seals (Mirounga angustirostris), and disseminated intravascular coagulation in this species. 882 84

BALB/cJ mice die of fulminant hepatitis within 7 days of exposure to murine hepatitis virus strain 3 (MHV-3) whereas A/J mice are fully resistant to the lethal effects of MHV-3 infection. Previous studies have implicated macrophage activation with production of a unique macrophage prothrombinase (PCA) and lymphocyte cytokine secretion in the pathogenesis of MHV-3 susceptibility and have demonstrated that immunosuppression induces susceptibility in resistant mice. This study was undertaken to determine whether macrophages, derived from resistant A/J mice and treated in vitro with methylprednisolone sodium succinate (MP), elaborated PCA following MHV-3 exposure and whether therapy with MP altered resistance of A/J mice to MHV-3 infection in vivo. Macrophages, incubated with MP in vitro, expressed dose dependent increases in PCA following infection with MHV-3. No induction of PCA occurred in macrophages treated with MHV-3 or MP alone. Analysis of mRNA transcripts for mouse fibrinogen like protein (musfiblp), the MHV-3 specific prothrombinase, in macrophages which were incubated with MP prior to exposure to MHV-3 demonstrated significantly increased mRNA levels as compared to macrophages not incubated with MP prior to MHV-3 exposure. In vivo, A/J mice treated for 3 days with 500 mg/kg/day of MP prior to infection with MHV-3 demonstrated extensive hepatocyte necrosis and fibrin deposition in hepatic sinusoids on histological examination of liver tissue, elevated serum transaminases and 100% mortality within 10 days of infection. These results therefore provide further support for the role of increased PCA in the pathogenesis of MHV-3 related liver necrosis.
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PMID:Treatment of resistant A/J mice with methylprednisolone (MP) results in loss of resistance to murine hepatitis strain 3 (MHV-3) and induction of macrophage procoagulant activity (PCA). 883 May 51

Activation of the immune coagulation system has been implicated in the pathogenesis of fulminant liver failure caused by murine hepatitis virus strain 3 (MHV-3). The recent discovery of the fgl2 gene, which encodes for MHV-3-induced prothrombinase (fgl2 prothrombinase), allows for fundamental studies to determine the molecular basis for fulminant liver failure. Transcription of the fgl2 gene and translation of the protein it encodes were examined in the liver and other organs of susceptible mice following MHV-3 infection. No constitutive expression of the fgl2 gene or the fgl2 prothrombinase was detected. Within 12 to 24 h of MHV-3 infection, however, fgl2 gene transcripts were detected in large amounts in the liver, spleen, and lungs, all of which are rich in reticuloendothelial cells, but were only focally present in small amounts in the kidney and brain. There was sequential detection of fgl2 prothrombinase in the liver, where it was localized specifically to the endothelium of intrahepatic veins and hepatic sinusoids; this was allowed by fibrin deposition, which resulted in confluent hepatocellular necrosis. These results provide further evidence for the role of the selective expression of this novel fgl2 prothrombinase in the pathogenesis of MHV-3-induced fulminant liver failure.
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PMID:Fulminant hepatic failure in murine hepatitis virus strain 3 infection: tissue-specific expression of a novel fgl2 prothrombinase. 937 81

Ribavirin, a synthetic guanosine analogue, possesses a broad spectrum of activity against DNA and RNA viruses. It has been previously shown to attenuate the course of fulminant hepatitis in mice produced by murine hepatitis virus strain 3. We therefore studied the effects of ribavirin on murine hepatitis virus strain 3 replication, macrophage production of proinflammatory mediators including TNF, IL-1, and the procoagulant activity (PCA), fgl2 prothrombinase; and Th1/Th2 cytokine production. Although ribavirin had inhibitory effects on viral replication (<1 log), even at high concentrations complete eradication of the virus was not seen. In contrast, at physiologic concentrations (up to 500 microg/ml), ribavirin markedly reduced viral-induced parameters of macrophage activation. With ribavirin treatment, the concentrations of PCA, TNF-alpha and IL-1beta all decreased to basal concentrations: PCA from 941 +/- 80 to 34 +/- 11 mU/10(6) cells; TNF-alpha from 10.73 +/- 2.15 to 2.74 +/- 0.93 ng/ml; and IL-1beta from 155.91 +/- 22.62 to 5.74 +/- 0.70 pg/ml. The inhibitory effects of ribavirin were at the level of gene transcription as evidenced by Northern analysis. Both in vitro and in vivo, ribavirin inhibited the production of IL-4 by Th2 cells, whereas it did not diminish the production of IFN-gamma in Th1 cells. In contrast, ribavirin had no inhibitory effect on TNF-alpha and IL-1beta production in LPS-stimulated macrophages. These results suggest that the beneficial effects of ribavirin are mediated by inhibition of induction of macrophage proinflammatory cytokines and Th2 cytokines while preserving Th1 cytokines.
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PMID:Ribavirin inhibits viral-induced macrophage production of TNF, IL-1, the procoagulant fgl2 prothrombinase and preserves Th1 cytokine production but inhibits Th2 cytokine response. 953 10

We report a patient with clinical, biochemical and immunological indices suggestive of autoimmune hepatitis with marked transaminasaemia, raised immunoglobulins and positive anti-nuclear and anti-smooth muscle antibodies. A coagulation screen revealed a transient, markedly increased, activated, partial thromboplastin time and a normal prothrombin time, with elevated levels of anticardiolipin antibodies and the presence of lupus anticoagulant, indicating the presence of antiphospholipid antibodies. Subsequent histology confirmed moderate hepatitis with piecemeal necrosis and fibrosis. Appropriate autoimmune therapy was commenced. This presentation illustrates the rare association of anti-phospholipid antibodies with autoimmune chronic active hepatitis presenting with a temporarily abnormal coagulation screen.
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PMID:Autoimmune chronic active hepatitis associated with the presence of antiphospholipid antibodies. 958 93

Infection with mouse hepatitis virus strain 3 (MHV-3) results in lethal fulminant hepatic necrosis in fully susceptible BALB/c mice compared to the minimal disease observed in resistant strain A/J mice. Macrophages play a central role in the pathogenesis of MHV-3-induced hepatitis. In the present study we have shown that MHV-3 infection of macrophages induces these cells to undergo apoptosis. Three methods to detect apoptosis were applied: flow cytometry analysis of nuclear DNA content, fluorescence microscopic visualization of apoptotic cells labeled by the TUNEL assay, and gel electrophoresis to detect DNA laddering. Apoptosis in A/J and BALB/c macrophages was first detected at 8 h postinfection (p.i.) and reached a maximum by 12 h p.i. The degree of MHV-3-induced apoptosis was much greater in A/J-derived macrophages than in BALB/c-derived cells. Apoptosis was inversely correlated with the development of typical MHV cytopathology, namely syncytia formation. Infected macrophages from A/J mice did not form synctia in contrast to the extensive synctia formation observed in BALB/c-derived macrophages. In MHV-3-infected BALB/c macrophage cultures, apoptotic cells were not incorporated into syncytia. Apoptosis was also inversely correlated with the expression of MHV-3-induced fgl2 prothrombinase in macrophages. These results add the murine coronavirus MHV-3 to the list of RNA-containing viruses capable of inducing apoptosis.
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PMID:Coronavirus MHV-3-induced apoptosis in macrophages. 977 Apr 18

Murine Hepatitis Virus Strain 3 (MHV-3) produces fulminant hepatitis with 80-90% mortality in Balb/cJ mice. Previous studies in our laboratory have shown that peritoneal macrophages from MHV-3 infected mice produce a procoagulant (PCA) which has the ability to cleave prothrombin to thrombin (prothrombinase) encoded by the gene fgl2 located on chromosome 5. PCA accounts for sinusoidal thrombosis and hepatic necrosis and the necrosis and mortality can be prevented by treatment of animals with a monoclonal antibody to PCA. These present studies were designed to examine the expression of this gene (mRNA by Northern analysis and in situ hybridization) and the gene product PCA (immunochemistry) in tissues recovered from MHV-3 infected Balb/cJ mice in an attempt to explain the liver specific nature of MHV-3 disease. Fgl2 gene expression was detected as early as 8 hours after MHV-3 infection which persisted to 48 hours in the liver, spleen and lungs whereas no gene expression was seen in the brain or kidneys despite the fact that equivalent viral titers were detected in all tissues at all times. In the liver, fgl2 gene expression was confined to endothelial and Kupffer cells with no expression in hepatocytes. Immunochemistry localized the PCA protein to Kupffer cells and endothelial cells and necrotic foci within the liver. No PCA protein was detected by immunochemistry in any other tissues at any time during the course of MHV-3 infection. These results explain the liver specific nature (fulminant hepatitis) of MHV-3 infection and provides further evidence for the role of PCA in the pathogenesis of fulminant hepatitis. MHV-3 induces selective transcription of the gene fgl2 and only hepatic reticuloendothelial cells produce functional protein (PCA) which is known to account for fulminant hepatic failure produced by MHV-3.
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PMID:Expression of the fgl2 and its protein product (prothrombinase) in tissues during murine hepatitis virus strain-3 (MHV-3) infection. 978 36

In the present study we have investigated the possibility that strain specific differences in the induction of apoptosis in macrophages could play a role in the resistance of strain A/J mice to MHV-3 induced hepatitis. MHV-3 infected macrophages from Balb/c and A/J mice were analyzed at various time points after infection. Apoptosis in A/J macrophages could be detected at 8 h post infection and increased significantly by 12 h, when almost 50-70% of the infected cells were undergoing apoptosis. In Balb/c macrophages, apoptotic changes were less pronounced and were observed in only 5-10% of the cells. MHV-3 induced apoptosis was inversely correlated with the ability of this virus to induce expression of fgl-2 prothrombinase protein and syncytia formation. Infected macrophages from A/J mice did not express fgl-2 protein and did not form syncytia. In contrast, infection of Balb/c derived macrophages resulted in fgl-2 expression and extensive syncytia formation. These data fit a model in which apoptosis of virally infected cells is a protective response which eliminates cells whose survival might be harmful for the whole organism.
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PMID:The pattern of induction of apoptosis during infection with MHV-3 correlates with strain variation in resistance and susceptibility to lethal hepatitis. 978 37


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