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: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The TEAG rosette test was not devised as an immediate diagnostic indicator, but in order to detect gross differences over a period of time between the lymphocytes of patients with conditions where immune complexes may be formed, and those of normal people. In summary these results indicate that:- 1. Percentage TEAG rosettes were highly significantly increased in patients with SLE, active chronic hepatitis and carcinoma of lung compared with normal controls, when the tests were performed on suspensions, containing over 90% lymphocytes, separated from peripheral blood. 2. Estimates of mean B lymphocytes plus blood monocytes in the separated suspensions, as measured by EAC rosettes (and peroxidase and differential counts for monocytes) are exceeded by TEAG-rosetting cells in the patients tested. 3. Tests on patients with chronic autoimmune conditions (e.g. ACH and SLE) do not show a highly significant difference from normal controls with respect to mean total cells forming E-rosettes. 4. It may be speculated that some TEAG rosettes are formed by T-cells which could have immune complexes or autologous anti-lymphocyte globulin on their surface and that such a condition may account for the depressed T-cell function found in these conditions.
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PMID:Lymphocyte surface-attached immunoglobulins in some clinical conditions. 108 63

Thirty-five patients with active chronic hepatitis B (ACH-B) were evaluated. They were in stable replicative phase (HBeAg +; DNA polymerase and ALT stable in two determinations at least one month apart) and had not been infected by delta virus or HIV-1. Thirty-four patients were heterosexual and no patient was a drug abuser except one. The 23 initial cases were followed up for 15 months without therapy. The subsequent 12 cases were treated with maximal doses of 2.5 megaunits/m2 of lymphoblastoid alpha interferon (IFN-L) daily for two weeks and three times a week during 10 more weeks. While in the controls only two cases (8.69%) lost the DNA-polymerase activity and HBeAg, 5 treated patients (41.66%; p less than 0.05) developed seroconversion to nonreplicative phase. No patient from the control series lost the HBsAg; however, this happened in 2 treated patients (16.66%). These results show that IFN-L is effective in heterosexual patients with ACH-B in replicative phase without delta virus or HIV-I co-infection.
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PMID:[Treatment of chronic hepatitis B with lymphoblastoid alpha interferon]. 261 34

The possible immunological mechanisms involved in the progression from acute type B hepatitis to chronic hepatitis can be summarised as follows: following replication of the virus in the hepatocyte nucleus, the surface coat is added and the virus released from the hepatocyte. T cells recognise the foreign viral antigen on the surface of the liver cells and mount a T cell mediated reaction against infected hepatocytes. They also stimulate B cells to produce antibody to LSP, the ensuing antibody-dependent cell-mediated K cell reaction against normal liver membrane antigens contributing to the hepatocyte necrosis. Released virus stimulates anti-viral antibody production which complexes with the virus, the complex being removed by the reticuloendothelial system. With the removal of virus there is no longer any T cell reaction against the virus or helper effect for anti-LSP production and this, together with a normally functioning suppressor T cell system, leads to cessation of liver cell necrosis and recovery from the episode of acute hepatitis. In HBsAg-positive ACH as a result of a quantitative or qualitative defect in the production of antibody to Dane particles there is a failure to clear the virus, with reinfection of further hepatocytes and continuation of both mechanisms of immunological liver cell damage. In patients progressing to HBsAg-negative ACH, however, anti-viral antibody production is adequate and the virus is cleared. In this group of patients the defect probably lies in suppressor T cell function, which is unable to switch off the autoimmune reaction against LSP. The increased frequency of histocompatibility antigens HLA A1 and B8 and the associated high levels of autoantibodies and anti-viral antibodies suggests that this defect may be genetically inherited.
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PMID:Pathogenesis of active chronic hepatitis. 644 63

Certain conjugated biliary acids (total pool - choliglycine - sulpholytic choliglycine) and the following haematochemical parameters: total bilirubin and its direct quota, alkaline phosphatase, albumin, prothrombin activity, gamma globulin, oxalacetic and pyruvic transaminase were radioimmunologically (RIA) studied in 115 subjects. Subjects were divided into the following subgroups: --20 normal controls; --20 cases of persistent chronic hepatitis; --20 cases of active chronic hepatitis; --15 cases of A.C.H. with cirrhosis; --20 cases of cirrhosis without direct hyperbilirubinaemia; --20 cases of cirrhosis with direct hyperbilirubinaemia. Each case was assigned to its particular group on the basis of the histological report on each patient. The following observations were drawn from the results obtained: --there is a progressive increase in above normal biliary acid rate in proportion to the gravity of the liver pathology; --choliglycine especially and to a lesser extent the total pool increased sufficiently to distinguish between normal and hepatopathic subjects (PCH and ACH) and also between PCH and ACH patients; --the combination of cirrhosis and ACH causes a significant increase in total pool and chliglycine over levels noted in ACH alone; --in contrast no difference is found between the levels of these acids in inactive (or minimally active) cirrhosis and ACH with cirrhosis; --gamma globulin, oxalacetic and pyruvic transaminase levels were found to have substantially the same diagnostic significance as choliglycine in the early stages of liver diseases. Significant correlations were also encountered between total conjugated biliary acid pool and choliglycine (not in the group with cirrhosis without direct hyperbilirubinaemia) and between total pool and choliglycine with haematochemical cholestasis test results (alkaline phosphatase and total and direct bilirubin) the latter only in the two cirrhotics groups. In conclusion, choliglycine was found to be the most sensitive of the biliary acids routinely measured by RIA and is valuable in clinical practice not as a substitute for the main liver tests but as an extremely useful and sensitive addition to them. In clinical practice, its use is recommended in the diagnosis and monitoring of healthy subjects at risk and those with chronic liver conditions (PCH, ACH, ACH + C).
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PMID:[Clinico-diagnostic significance of the determination of bile acids in chronic liver diseases]. 671 31

Following a short review of the viruses underlying viral hepatitis and those which, as a secondary factory in the clinical picture, may cause fleeting liver damge, the subdivision of chronic hepatitis conditions on histopathological bases is described. Particular attention is paid to pathogenesis, with a study of the elimination of B virus, correlated to particular histopathological types. A series of 27 PCH and 49 ACH cases is reported. Of special significance was the observation of 14 ACH out of 17 biopsied drug addicts. The therapeutic problem of chronic hepatitis is then tackled.
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PMID:[Chronic hepatitis caused by B virus (HBV)]. 737 13

The intrahepatic accumulation of the c-myc protooncogene product was observed on immunofluorescence in each of six patients with chronic hepatitis delta virus infection who exhibited the hepatitis D antigen in their livers. The c-myc product was stained in the same nuclei that contained the hepatitis D antigen. C-myc was not observed in acute hepatitis D or in cases of chronic hepatitis delta virus infection without expression of the hepatitis D antigen. The protooncogene product was detected in only 1 of 32 viral and nonviral liver disorders unrelated to hepatitis delta virus. To confirm these observations, we transfected HBsAg-positive (PCL/PRF/5) and HBsAg-negative (HepG2) transformed liver cell lines with a plasmid containing a hepatitis delta virus cDNA trimer under the control of the SV40 early enhancer/promoter sequences. Whereas baseline c-myc expression was barely detectable in mock-transfected PLC/PRF/5 or HepG2 cells, strong c-myc nuclear fluorescence was observed when these same cells were transfected with the hepatitis D antigen expression vector. Similar results were obtained after infection of HeLa cells with a recombinant vaccinia virus expressing the hepatitis D antigen. Detection of c-myc mRNA sequences by means of in situ hybridization suggested that the c-myc product accumulation was not due to increased amounts of its mRNA. The c-myc protein accumulates selectively in the livers of patients with chronic hepatitis delta virus infection and in the same nuclei that contain the hepatitis D antigen. The expression of c-myc in hepatitis D antigen-containing cells does not require the presence of hepatitis B virus infection.
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PMID:Expression of the c-myc protooncogene product in cells infected with the hepatitis delta virus. 752 69

Autoantibodies against non organ-specific may be induced by IFN treatment in HCV liver chronic disease. In order to assess this issue and its clinical significance, 44 patients with chronic hepatitis C (anti HCV and RNA-HCV +) treated with IFN were evaluated. In 13 patients (29.5%) the following autoantibodies were detected during the treatment: AAML (5), AAN (9), ALK-M (4). Only in the A-LKM + patients there was a slight increase in aminotransferases with a reappearance of the viremia. Moreover 2 of these patients showed a flare of their liver disease without systemic findings. During the follow up (28) months one of the patients normalized the aminotransferases with clearance of serum HCV RNA. There were no statistical differences in the sustained response rate between patients with (2/13) or without (4/31) autoantibodies. The development of AAN, AAML and ALKM at low titer during IFN treatment in CH-C is without clinical relevance. However, ALKM detection is occasionally associated with the "breakthrough" phenomenon with HCV eradication, suggesting an immuno-modulatory activity of IFN.
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PMID:[Prevalence and clinical significance of autoantibodies in chronic hepatitis C treated with interferon alfa]. 757 7

To identify environmental, viral, and genetic factors that may influence the risk of developing hepatocellular carcinoma (HCC), large prospective studies are being conducted in Haimen City, China and Senegal, and a case-control study of genetic variation in the detoxification of aflatoxin-B1 was carried out in Shanghai, China. Analysis of 78 HCCs that have occurred among 51,020 men enrolled in a large prospective study in Haimen City, China showed a strong association of HCC with chronic hepatitis B virus (HBV) infection. There were also significant associations of HCC risk with occupation (farming), history of a clinical episode of hepatitis in adulthood, and a family history of HCC. Study of 52 HCC cases and 116 controls for genetic polymorphisms and HCC risk showed a significant association with epoxide hydrolase (EPHX) mutant alleles (1/2, 2/2) and a borderline association with homozygous deletion of the glutathione-S-transferase mu (GSTM1) gene. There was a multiplicative interaction of these polymorphisms with chronic HBV infection such that HBsAg-positive persons who were GSTM1 null and were EPHX 1/2 or 2/2 had 135 times the risk of HCC as HBsAg-negative persons with the wild type genotypes for GSTM1 and EPHX. The risk of HCC is not uniform among persons with chronic HBV or HCV infections. Studies of genetic, viral, and environmental interactions may permit identification of those individuals at highest risk within groups at increased risk of HCC. Prevention strategies could then be targeted at those individuals.
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PMID:Molecular and genetic epidemiology of hepatocellular carcinoma: studies in China and Senegal. 887 9

IFN-gamma (interferon-gamma) modulates IFN-alpha therapy in chronic hepatitis C infection; however, the underlying mechanism remains unclear. Here we demonstrate that long-term (3-6 days) but not short-term (up to 1 day) IFN-gamma treatment of human hepatoma Hep3B cells attenuates IFN-alpha activation of STAT1 (signal transducers and activators of transcription factor 1), STAT2 and STAT3, but enhances IFN-gamma and interleukin 6 activation of STATs. Prolonged exposure to IFN-gamma also significantly induces STAT1 protein expression without affecting STAT2, STAT3 and ERK (extracellular-signal-regulated kinase) 1/2 protein expression. To determine the role of STAT1 protein overexpression in regulation of IFN-alpha signalling, Hep3B cells were stably transfected with wild-type STAT1. Overexpression of STAT1 via stable transfection enhances IFN-gamma activation of STAT1, but surprisingly attenuates IFN-alpha activation of STAT1, STAT2 and STAT3 without affecting Janus kinase activation. This STAT1-mediated inhibition does not require STAT1 tyrosine phosphorylation because overexpression of dominant-negative STAT1 with a mutation on tyrosine residue 701 also blocks IFN-alpha activation of STAT1, STAT2 and STAT3. Moreover, overexpression of STAT1 blocks IFN-alpha-activated STAT2 translocation from IFN-alpha receptor 2 to IFN-alpha receptor 1, a critical step in IFN-alpha signalling activation. Finally, significantly higher levels of STAT1 protein expression, which is probably induced by IFN-gamma, are detected in the majority of hepatitis C virus-infected livers compared with healthy controls. In conclusion, long-term IFN-gamma treatment inhibits IFN-alpha-activated signals most probably, at least in part, through the induction of STAT1 protein expression, which could partly contribute to IFN-alpha treatment failure in hepatitis C patients.
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PMID:Interferon-gamma inhibits interferon-alpha signalling in hepatic cells: evidence for the involvement of STAT1 induction and hyperexpression of STAT1 in chronic hepatitis C. 1469 Apr 54

Beta-catenin is upregulated in many human cancers and considered to be an oncogene. Hepatocellular carcinoma (HCC) is one of the most prevalent human malignancies, and individuals who are chronic hepatitis B virus (HBV) carriers have a greater than 100-fold increased relative risk of developing HCC. Here we report a mechanism by which HBV-X protein (HBX) upregulates beta-catenin. Erk, which is activated by HBX, associates with GSK-3beta through a docking motif ((291)FKFP) of GSK-3beta and phosphorylates GSK-3beta at the (43)Thr residue, which primes GSK-3beta for its subsequent phosphorylation at Ser9 by p90RSK, resulting in inactivation of GSK-3beta and upregulation of beta-catenin. This pathway is a general signal, as it was also observed in cell lines in which Erk-primed inactivation of GSK-3beta was regulated by IGF-1, TGF-beta, and receptor tyrosine kinase HER2, and is further supported by immunohistochemical staining in different human tumors, including cancers of the liver, breast, kidney, and stomach.
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PMID:Erk associates with and primes GSK-3beta for its inactivation resulting in upregulation of beta-catenin. 1603 86


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