Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Structural and nonstructural regions of the HCV-encoded polyprotein have been expressed in recombinant yeast, bacteria, or insect cells and used to capture and measure reactive antibodies circulating in different individuals. The putative nucleocapsid protein (C) and nonstructural proteins 3-5 (NS3-NS5) were found to contain the most immunodominant epitopes. The NS3, NS4, and C regions were expressed in yeast in the form of a fused, chimeric polyprotein (C25) and a capture assay for reactive antibody was developed. This anti-C25 assay detects all previously identified HCV-seropositive cases and provides a substantially more sensitive diagnostic for both acute and chronic HCV infections than the current anti-C100-3 (NS4) assay. Anti-C25 was detected more frequently than anti-C100-3 in chronic, transfusion-associated non-A, non-B hepatitis patients from the United States (95% vs. 71%) and Japan (98% vs. 82%), in cryptogenic cirrhosis patients from the United States (62% vs. 28%), and in hepatitis B surface antigen-negative cases of hepatocellular carcinoma from Japan (83% vs. 63%). These data indicate that HCV has a greater role in these liver diseases than was previously thought. In volunteer United States blood donors sampled following the introduction of anti-C100-3 screening, the prevalence of anti-C25 and anti-C100-3 was 0.5% and 0.08%, respectively.
 ...
PMID:Diagnosis of hepatitis C virus (HCV) infection using an immunodominant chimeric polyprotein to capture circulating antibodies: reevaluation of the role of HCV in liver disease. 127 66

Hepatocytes from mouse liver with experimental post-toxic cirrhosis (received by means of 10-12 inhalations with CCl4) were fused with serum-deprived (0.2%) resting NIH 3T3 mouse fibroblasts to elucidate mechanisms of liver stroma cells proliferation at cirrhosis. After fusion, nuclei of fibroblasts in such heterokaryons were found to enter into S-period without any exogenous stimulation of cell proliferation (in the medium with low content of serum). The obtained data allow us to suggest that hepatocytes from mouse liver with experimental post-toxic cirrhosis can produce and secrete into the medium (blood) factor (s) capable of stimulating the mesenchymal origin cell proliferation.
 ...
PMID:[Hepatocytes from the liver of mice with experimental post-toxic cirrhosis stimulate in heterokaryons DNA synthesis in the nuclei of resting fibroblasts of the NIH 373 line]. 174 83

In three patients with histologically proven liver cirrhosis, a large number of small, low-intensity nodule(SLIN)s was clearly seen on gradient echo(GRE) images which are sensitive to field inhomogeneity. A histological study revealed that the SLINs corresponded to the regenerating nodules, laden with iron, of liver cirrhosis. As TE was prolonged, the SLINs increased in size in all three cases and fused with each other in one of three cases on GRE images. This phenomenon suggests that the magnetic susceptibility effect due to iron included in the regenerating nodules is the cause for the regenerating nodules shown as SLINs on GRE images, and that one SLIN does not always correspond to one regenerating nodule. We conclude that GRE images should be considered important for diagnosis of regenerating nodules in liver cirrhosis.
 ...
PMID:[Siderotic regenerating nodules in liver cirrhosis--evaluation by gradient echo (FLASH) imaging 1.5T]. 260 6

We have established a human-human hybridoma producing a monoclonal antibody against a tumor-associated carbohydrate-specific antigen, Hanganutziu-Deicher (HD) antigen. Human spleen lymphocytes from a patient with esophageal varices complicated with liver cirrhosis were cultured in serum-free medium and co-stimulated with both anti-human mu-chain antibodies and supernatants of concanavalin A-stimulated human spleen cell culture (ConA sup). The activated lymphocytes were subsequently primed in vitro with particulate HD3 antigen and fused with a parent hybrid myeloma cell line, KR-12. A hybridoma, 1F43E31G7 produced anti-HD human monoclonal antibody (IgM lambda). This monoclonal antibody reacted strongly with N-glycolylneuraminyl alpha 2-3 lactosylceramide (HD3) and slightly with N-glycolylneuraminyl alpha 2-3 lactoneotetraosylceramide (HD5), but did not react with N-glycolylneuraminyl alpha 2-3 lactoneohexaosylceramide (HD7), N-acetylneuraminyl alpha 2-3 lactosylceramide (GM3) and other derivatives of HD3 prepared by chemical modification of the sialic acid residue of HD3, which indicates that the monoclonal antibody is directed precisely toward the terminal sialic acid and whole structure of HD3.
 ...
PMID:Establishment of a human monoclonal antibody to Hanganutziu-Deicher antigen as a tumor-associated carbohydrate antigen. 314 5

Putative hepatitis C virus E2 protein was applied for detection of anti-E2 antibody in patients with type C hepatitis. The Putative E2 sequence was expressed in E. coli and approximately 38 KDa hepatitis C E2 protein fused with 42 KDa maltose binding protein was obtained. The HCV E2 antibody was detected in 2 of 7 acute hepatitis cases, in 8 of 12 chronic persistent hepatitis, in 17 of 25 chronic active hepatitis, and in 2 of 4 cirrhosis. It was not detected in 10 normal subjects. Anti-E2 antibody became undetectable after successful interferon treatment in patients with type C hepatitis. The High detection rate of E2 antibody in chronic hepatitis C and disappearance of the antibody after the interferon treatment indicate that the E2 antibody is related to viral replication and is unlikely to be a neutralizing antibody.
 ...
PMID:High detection rate of hepatitis C virus E2 antibody in patients with type C hepatitis. 768 7

Changes in the synthesis of type I collagen, a major extracellular matrix component in skin and bones, are associated with both normal growth or repair processes and with several pathological conditions such as lung fibrosis and liver cirrhosis. The expression of the alpha 1(I) collagen gene is regulated by transcriptional and post-transcriptional mechanisms. Regulation at both these levels are usually utilised when extensive changes occur in collagen synthesis. We constructed plasmids carrying the whole or partially deleted 3'-UTR sequences of the alpha 1(I) collagen gene, fused to two hGH exons and to the promoter of the alpha 1(I) collagen gene. A control plasmid contained the 3'-UTR of the hGH gene. In transient transfections into Rat-1 fibroblasts, no significant differences between plasmids were found, which suggests that although 3'-end of the gene has been shown in previous studies to contain DNaseI hypersensitive sites and to bind sequence-specific nuclear proteins it does not seem to function as a transcriptional regulator. This was further supported by the finding that TGF-beta treatment induced a 2.5-fold expression of hGH mRNA from plasmids containing collagen promoter and either hGH or alpha 1(I) collagen 3'-UTR. In stable transfections, mRNAs using the first polyadenylation site were not as stable as those transcribed from the endogenous alpha 1(I) collagen gene. We suggest that the 3'-UTR alone may not be sufficient to determine the stability of the shorter alpha 1(I) collagen mRNA species.
 ...
PMID:Effect of the 3'-untranslated region on the expression levels and mRNA stability of alpha 1(I) collagen gene. 787 3

By administering an excessive amount of iodized oil via the hepatic artery, anticancer drugs in the iodized oil flow into the portal vein through the arterioportal communication. This phenomenon permits chemotherapy against extracapsular infiltration by a hepatocellular carcinoma (HCC) nourished by the portal blood flow. From May 1983 through July 1992, 240 cases of HCC underwent transcatheter arterioportal chemoembolization (TAPCE) with more than 5 ml of iodized oil (mean, 15 ml) in our hospital. In all, 32 patients survived for more than 3 years, and the factors favoring the efficacy of TAPCE therapy were investigated. Doxorubicin (mean, 46 mg) was given to 31 patients and 20 mg mitomycin C was given to 1 patient. The patients included one Stage 1 case, 13 Stage 2 cases, 17 Stage 3 cases, and one Stage 4 case. The mean tumor size was 5.0 cm, and portal invasion was suggested in 8 cases by angiography. The tumors were divided into 5 types: 13 cases of the single nodular type (SN), 7 cases of the single nodular type with proliferation (SN-P), 3 cases of the multinodular fused type (MN-F), 5 cases of the multinodular type (MN), and 4 cases of the massive type. A complication of liver dysfunction was detected in 14 cases, and half of them were Child's class C. In all, 7 patients underwent hepatectomy and 6 received percutaneous ethanol injection after TAPCE. The treated area of TAPCE was classified as segmental, lobar, or total. Segmental and lobar administration of TAPCE yielded statistically effective results, and their tumor response rate was 86%. All of the MN-F and massive types showed a good tumor response. The incidence of intrahepatic distant metastasis was higher in the localized TAPCE group than in the total TAPCE group. Segmental and lobar TAPCE should be applied for localized infiltrating HCCs, even in cases associated with liver cirrhosis, but these methods have a limited capacity to prevent distant intrahepatic metastasis.
 ...
PMID:Effective cases of transcatheter arterioportal chemoembolization with high-dose iodized oil for hepatocellular carcinoma. 813 86

Pancreatitis-associated protein I (PAP I) is a secretory protein first described as an acute phase reactant during acute pancreatitis. Recently, induction of the PAP I gene was also described in liver during hepatocarcinogenesis. To investigate the molecular mechanisms of this induction, we used constructs carrying progressive deletions of the PAP I promoter fused to the CAT gene. We showed that the silencer conferring tissue specificity on the PAP I gene was inactive in hepatoma cells. Then, in an vitro transcription system, we compared the transcription capacity of nuclear extracts from normal liver and HepG2 cells on constructs containing the silencer. The results confirmed that a trans-acting factor interacting with the PAP I silencer was present in liver cells and absent from hepatoma cells. On the other hand, immunohistochemistry showed that PAP I was expressed in a limited number of transformed hepatocytes. It was concluded that expression of PAP I in hepatocarcinoma occurred through inactivation of its silencer element and was not concomitant in all malignant cells. On that basis, we assayed PAP I in serum from patients with chronic hepatitis, liver cirrhosis or hepatocarcinoma. PAP I levels were normal in chronic active or persistent hepatitis, significantly higher in cirrhosis and strongly elevated in hepatocarcinoma. Because those clinical entities often develop in that sequence, serum PAP I appeared as a potential marker of hepatocarcinoma development.
 ...
PMID:Mechanism of PAP I gene induction during hepatocarcinogenesis: clinical implications. 895 91

Hepatitis C virus (HCV), a major etiologic agent of transfusion associated hepatitis, is a positive, single-stranded RNA virus and is also known to be implicated in liver cirrhosis and hepatocellular carcinoma. Nonstructural protein 5A (NS5A) of HCV contains acidic and proline-rich amino acids in its carboxy-terminal half. These structural features resemble eukaryotic transcription activators. In this report, we show that NS5A functions as a potent transcriptional activator when fused to the yeast (Saccharomyces cerevisiae) GAL4 DNA-binding domain (1-147). The potential transcriptional activator maps to the C-terminal half of NS5A in the yeast cell. Therefore, our data provides the first evidence that NS5A may modulate host cell function at the transcriptional level.
 ...
PMID:Hepatitis C virus nonstructural protein 5A contains potential transcriptional activator domains. 938 55

To evaluate the clinical feasibility of the antibody titer against a chimeric polypeptide (named Core 518), in which a domain of Core and NS3 of hepatitis C virus (HCV) was fused, ELISA was performed in a total of 76 serum samples. Each serum was serially diluted using two-fold dilution method with distilled water into 10 concentrations. They were all positive for second generation anti-HCV assay (HCV EIA II; Abbott Laboratories). Genotyping RT-PCR, quantitative competitive RT-PCR, and RIBA (Lucky Confirm; LG Biotech) were also assayed. Anti-Core 518 antibody was detected in x 12800 or higher dilutions of sera from 35 of 43 chronic hepatitis C (81.4%) and nine of 16 hepatocellular carcinoma sera (56.3%), one of four cirrhosis (25%), 0 of four acute hepatitis C, and one of nine healthy isolated anti-HCV-positive subjects (p=0.0000). The anti-Core 518 antibody titers were well correlated with the presence of HCV RNA in serum (p=0.002). The anti-Core 518 antibody titers decreased significantly in nine of ten responders to IFN-alpha treatment. Monitoring anti-Core 518 titers may be helpful not only for differentiating the status of HCV infection among patients with various type C viral liver diseases, but also for predicting responses to IFN-alpha treatment.
 ...
PMID:Monitoring antibody titers to recombinant Core-NS3 fusion polypeptide is useful for evaluating hepatitis C virus infection and responses to interferon-alpha therapy. 1033 62


1 2 Next >>