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:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infection with hepatitis C virus (HCV) was analyzed by an enzyme-linked immunosorbent assay based on recombinant viral proteins encoded by regions of the putative viral core, NS3, NS4 and NS5, which were expressed in E. coli. Results showed that 106 of 124 cases (85.5%) of non-A, non-B chronic hepatitis and 43 of 45 cases (95.5%) of hepatocellular carcinoma, negative for HBV marker, were positive for antibodies against at least one of these viral proteins. One of 87 healthy individuals with normal alanine aminotransferase activity was positive for antibody against only the viral core, but was negative for HCV RNA. The serum of one patient with chronic hepatitis was positive for one of these proteins, but negative for HCV RNA. These findings in combination with results on detection of HCV RNA in the sera of patients with non-A, non-B chronic hepatitis indicated that 105 of 124 cases (84.6%) were positive for HCV infection. Sera that were negative for HCV antibodies against all these proteins were also negative for HCV RNA assayed by reverse transcription followed by the polymerase chain reaction. Screening of HCV infection by detecting viral antibodies in circulating blood using all these viral proteins is useful for reducing the number of ambiguous results in screening for viral infection. Thus, this assay system may be useful diagnostic purposes.
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PMID:Serodiagnostic assay of hepatitis C virus infection using viral proteins expressed in Escherichia coli. 131 40

Serial serum samples from cardiac patients with a history of chronic or resolved post-transfusion non-A, non-B hepatitis were analyzed by a combination of cDNA synthesis and the polymerase chain reaction (cDNA/PCR) to amplify HCV RNA. Analysis of sera drawn after the acute hepatitis episode from 8 of the patients who had an acute, resolving HCV infection showed no detectable levels of HCV RNA when primers from the NS3 region were used. Evaluation of these sera with primers from the 5'-untranslated (5'-UT) region revealed that one patient was positive for HCV RNA. Further analysis of serial serum samples available from two of these patients indicated that a resolved infection was associated with a disappearance of detectable HCV RNA after a peak level during the acute phase of the disease. In contrast, post-acute samples from 4 of 6 patients with symptomatic acute HCV infection evolving to chronicity were positive for HCV RNA using primers from the NS3 region, however, upon retesting with primers from the 5'-UT region, all 6 patients were found to be positive. Analysis of serial serum samples from 2 of these patients showed the persistence of HCV RNA in 70% of the samples. These two patients were subsequently treated with interferon alpha-2b. One patient resolved his disease and normalized his aminotransferase level during treatment and thereafter, while the other relapsed upon cessation of treatment. In these two patients, normalization of ALT levels was consistent with the absence of HCV RNA while relapse of disease was confirmed by the reappearance of detectable levels of HCV RNA. These results indicate the utility of HCV RNA as a marker for persisting HCV viremia and in differentiating patients with ongoing active HCV infection from those with an acute resolving disease.
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PMID:Detection of hepatitis C viral RNA by the polymerase chain reaction in serum of patients with post-transfusion non-A, non-B hepatitis. 131 77

Since detection of hepatitis C virus RNA by the polymerase chain reaction (PCR) showed that there existed anti-C100-3 (anti-HCV) antibody negative patients infected with HCV, we attempted to find out whether there were any clinical or viral genomic differences between the anti-HCV antibody positive and negative groups. One hundred and fifty-nine patients with chronic liver diseases with hepatitis C virus RNA in their sera were selected. Anti-HCV antibody was tested for anti-C100-3 antibody by an enzyme linked immunosorbent assay. The incidence of anti-HCV antibody was 129/159. The concentration of serum gamma-globulin, the titier of ZTT, and the positive rate of the PCR with the primers of the NS3/4 region (NS3/4PCR) were significantly higher in the anti-HCV antibody positive group than in the negative group. However, the other data such as alanine aminotransferase activity or past history were not significantly different. Nucleotide sequence of the cDNA fragments of NS3/4 region amplified by the PCR did not differ significantly between isolates from anti-HCV antibody positive and negative sera. The sequences observed in the present study did not differ significantly from those reported previously. Although there remains the possibility that the variation of viral genomic sequences may cause the absence of anti-HCV antibody, these results suggested that the individual clinical backgrounds or immunoreactivity of the patients might influence the antibody development.
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PMID:Anti-C100-3 antibody status, viral genomic sequences, and clinical features in chronic hepatitic patients with hepatitis C virus RNA in sera. 133 24

We tested serial serum samples for hepatitis C virus RNA from patients undergoing treatment for chronic hepatitis C with interferon-alpha using an assay that combined reverse transcription and polymerase chain reaction. The subjects studied were 20 patients with chronic hepatitis who had serum antibody to hepatitis C virus (anti-C100-3). Before therapy, hepatitis C virus RNA was detected in 18 (90%) and 20 (100%) patients using primer sets derived from the NS3 region or the 5'-noncoding region of hepatitis C virus, respectively. Hepatitis C virus RNA became undetectable in all patients whose ALT level fell into the normal range during therapy. However, hepatitis C virus RNA reappeared in all patients whose ALT levels rose again after therapy, usually before the relapse. In patients whose ALT levels did not become normal, hepatitis C virus RNA did not disappear during therapy. Thus therapy with interferon-alpha appears to be beneficial in chronic hepatitis C because of its suppressive effects on hepatitis C virus replication. Detection of hepatitis C virus RNA in serum is useful for evaluating the antiviral effect of interferon.
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PMID:Detection of hepatitis C virus RNA in serum of patients with chronic hepatitis C treated with interferon-alpha. 137 Jan 61

Liver enzyme levels, viral RNA, and the immune response against both structural and nonstructural hepatitis C virus (HCV) proteins have been studied in experimentally infected chimpanzees in order to further understand the natural history of HCV infection. An ELISA for measuring both IgG and IgM responses to core (c22), 33c (NS3), and c100 (NS4) was employed. The IgG response rates were 5/8 for core, and 8/8 for both 33c and c100. Utilizing this antigen combination, at least one antibody response is measureable at, or within 3 weeks of, the major ALT peak. Although no individual antibody response is universally associated with initial detection of seroconversion, the combination of all three recombinant proteins measures seroconversion an average of 54 days earlier than with c100 alone, in 6/8 of the animals. IgM responses were measureable in 5/8 of the chimpanzees, were of shorter duration, and usually arose concomitantly with IgG responses. IgM appears to be a good indicator of primary infection since neither boosting nor recrudescence of disease during the chronic phase of disease elicited a secondary IgM response. Viral RNA can be measured 4-7 days (average = 9 days) postinfection with the period preceding the ALT peak being characterized by several PCR positive segments interrupted by periods in which no viral RNA can be measured. Following the ALT peak, chronically infected animals with recurring ALT elevations are generally PCR positive with intercedent PCR negative periods. Those animals that appear to have biochemically resolved disease generally have PCR negative profiles, although they still may periodically exhibit PCR positive sera. This indicates that with the recent advent of new screening techniques, a more stringent definition of HCV resolution will be required.
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PMID:Temporal relationships of hepatitis C virus RNA and antibody responses following experimental infection of chimpanzees. 137 38

The localization of hepatitis C virus-infected hepatocytes in the human liver remains unclear despite the development of a serological assay for the antibody to hepatitis C virus. We studied their localization immunohistochemically with monoclonal antibodies to core, envelope and NS3 antigens of hepatitis C virus. We examined 48 liver biopsy samples from C100-3 antibody-positive patients with chronic liver disease (chronic persistent hepatitis, 5 cases; chronic active hepatitis, 41 cases; cirrhosis, 2 cases) and 12 liver biopsy samples from C100-3 antibody-negative patients with chronic liver disease (type B chronic hepatitis, 8 cases; alcoholic liver disease, 4 cases). In the C100-3 antibody-positive group, positive immunostaining for core antigen, envelope antigen and NS3 antigen was found in 23% (11 of 48), 24% (11 of 45) and 24% (11 of 46), respectively. Negative results were obtained in the C100-3 antibody-negative group. Hepatocytes with positive staining were scattered in the lobules, and they were found in the same regions irrespective of whether the antibody to core antigen, to envelope antigen or to NS3 antigen was used. Each positive cell was strongly stained in the cytoplasm; these decorations disappeared after absorption of the primary antibody with purified antigen. mean ALT levels in the patients with positive immunostaining for core, envelope or NS3 antigen (174.8 +/- 105.7 U/L) tended to be higher than in those with negative immunostaining (142.0 +/- 93.8 U/L). On histological evaluation of liver specimens with a scoring system of the histological activity index, intralobular inflammation and fibrosis had higher scores for samples with positive rather than negative immunostaining (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunohistochemical detection of hepatitis C virus-infected hepatocytes in chronic liver disease with monoclonal antibodies to core, envelope and NS3 regions of the hepatitis C virus genome. 137 9

We estimated HCV RNA in serum of 20 patients with chronic hepatitis C during interferon therapy using a combination assay of reverse transcription and polymerase chain reaction (RT-PCR). RNA was extracted from 200 microliters of serum. The primers were chosen from the NS3 region of prototype HCV RNA sequence. After 40 cycles of PCR, the products were analyzed by Southern hybridization. HCV RNA was detected in 18 of 20 (90%) patients before therapy. In cases with improvement of serum GPT level, HCV RNA became undetectable at 4 weeks of the therapy. However, HCV RNA reappeared within 4 weeks after the therapy in cases with relapse. In the no response group, HCV RNA did not disappear during the therapy. Interferon therapy is beneficial in improvement of viremia of HCV, and the detection of HCV RNA in serum is useful to evaluate the antiviral effect of interferon.
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PMID:[Detection of hepatitis C virus RNA in serum during treatment of chronic hepatitis C with interferon alpha]. 165 18

The use of quantitative assays for hepatitis C virus specific antibodies (anti-HCV) as a prognostic marker was evaluated in 31 patients with chronic hepatitis C treated with interferon (IFN). Changes in titers of serum HCV-RNA and anti-HCV antibodies; anti-C11 (anti-core), anti-C100 (anti-NS3), and anti-C7 (anti-NS3) were investigated. Recombinant IFN-alpha 2a was administered and the patients were followed for more than 1 year. The patients were classified into three groups according to their responses to IFN: 11 sustained responders with continuous normalizations of serum alanine aminotransferase (ALT) levels; 14 transient responders with transient decreases in ALT; and six nonresponders who had no changes in ALT levels. Ten of 11 sustained responders had a continuous decrease in anti-C11 titers after completion of treatment, decreasing to less than half of pretreatment titers. No patients in the other two groups had a continuous decrease in anti-C11 titers. Although sustained responders had decreases in anti-C100 and anti-C7 titers after IFN therapy, these titers also decreased in some patients in the other two groups. HCV-RNA was not detected in the sera of 10 of 11 sustained responders following IFN therapy. In contrast, while 9 of 10 transient and non-responders had a decrease or disappearance of HCV-RNA at the completion of therapy, they had increased levels thereafter. These results indicate that anti-HCV-core (anti-C11) titers most closely reflect the status of HCV replication. A quantitative assay for anti-HCV-core antibody can be used as a predictive marker of remission in IFN-treated patients with chronic hepatitis C.
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PMID:Changes in antibody titers to hepatitis C virus following interferon therapy for chronic infection. 751 50

In a series of 6 multitransfused, immunocompromised patients, the diagnosis of posttransfusion hepatitis C was based upon the analysis of long-term follow-up serum samples. The HCV RNA was detected by a nested PCR assay using primers located in the 5' noncoding region (5'NCR), and anti-HCV antibodies were assayed with third-generation tests. The interval between the first rise in alanine aminotransferase and seroconversion varied from less than 5 months to more than 38 months. Five out of 6 patients seroconverted after 14 months or later. In most cases, the anti-NS3 and anti-NS4 antibodies appeared first. In such patients, the etiology of chronic liver disease may thus be overlooked for 1 or more years, a definitive diagnosis requiring the detection of HCV RNA.
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PMID:Anti-HCV seroconversion in multitransfused and immunocompromised patients. A long-term longitudinal study. 753 42

The prevalence of hepatitis C virus (HCV) in Libya has been investigated by seeking evidence of HCV infection in 266 healthy Libyan subjects (147 females, 119 males; age range 1-78 years), 76 of whom were registered blood donors. None had any history of blood transfusions, surgery, homosexuality, drug misuse or other risk factor for viral hepatitis. Sera from all subjects were tested for anti-HCV antibodies by enzyme-linked immunosorbent assay against synthetic structural and non-structural HCV peptides from the HCV core, envelope, NS1, NS3/NS4 and NS5 regions. Eighteen (6.8%), all of whom were seronegative for hepatitis B surface antigen (HBsAg), were found to be anti-HCV positive (including 5 blood donors). The patterns of reactivity against the individual peptides varied between subjects as follows: core (14 subjects), envelope (11), NS1 (9), NS3/NS4 (10), and NS5 (6). Fourteen of the 18 had elevated serum aminotransferase activities (AST/ALT) but so also did 9 other subjects who were seronegative for both HBsAg and anti-HCV. Twelve of the 18 anti-HCV positive subjects, including 3 of the 5 anti-HCV positive blood donors, had circulating HCV RNA detected by the polymerase chain reaction. HCV RNA was also detected in 3 of the 9 anti-HCV negative cases with elevated AST/ALT. The finding that 21 (7.9%) of the 266 subjects had evidence of HCV infection indicates that there is a very high frequency of 'community-acquired' HCV in the normal Libyan population, and this has major implications for blood transfusion in that country.
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PMID:High prevalence of hepatitis C virus in the normal Libyan population. 797 63


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