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)

Intravenous injection of praseodymium nitrate into female Wistar rats results in liver damage. The aim of this study is to investigate the quality of serum high density lipoprotein content as an index for the severity and time course of liver damage and regeneration following the administration of praseodymium. Serum high density lipoprotein content drastically decreases to a minimum after 24 - 48 h, returning to control values after four days. Liver degeneration is characterized by some intracellular parameters, i.e. the nuclear RNA polymerase reactions, the ribosomal protein synthesis, hepatic spermidine concentration and the activities of serum transaminases (GOT, GPT) and the sorbitdehydrogenase. From the data it is evident that the time course of serum high density lipoprotein content follows the intracellular changes closely. Liver regeneration is represented by the ornithin decarboxylase, the deoxycytidylate deaminase, the thymidine kinase activities and the hepatic putrescine content. The time course of these parameters shows that the regeneration reaches a maximum after 3 - 4 days. In the serum, high density lipoprotein content reflects this process by returning to control values. From our data we conclude that serum high density lipoprotein content after i.v. administration of praseodymium can be considered as an expression of the functional state of the liver.
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PMID:Correlation between serum high density lipoprotein content and liver function during experimental hepatic degeneration and regeneration. 18 75

Cell free extracts were prepared from E. coli CRT266 9 min after infection with T3 phages. RNA synthesis in these extracts is almost entirely due to T3 RNA polymerase. The inactivation of T3 RNA polymerase in these extracts proceeds rapidly at 42 degrees C. 90% of the activity is lost within 10 min at this temperature. Under conditions where the formation of a stable initiation complex with T3 DNA is possible, i.e., in the presence of GPT, APT, and UTP the T3 RNA polymerase becomes protected against heat inactivation losing only )0% of its activity during an exposure to 42 degrees C for 10 min. Studies on the time course of RNA synthesis have shown that reinitiation is still possible at 37 degrees C and 42 degrees C. At 44 degrees C, however, RNA synthesis stops abruptly after 3 min indicating that reinitiation does no longer take place. The elongation of already initiated T3 RNA chains is rather resistant to heat. At 44 degrees C the same elongation rates are observed as at 37 degrees C and 42 degrees C, respectively.
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PMID:[Effect of temperature on the transcription of T3 DNA b y T3-specific RNA polymerase in cell-free extracts of Escherichia coli CRT266]. 60 62

Sera from 39 out of 40 patients with chronic hepatitis C virus (HCV) infection who had been treated for 60 weeks with interferon alfa-2b proved initially HCV RNA positive by reversed transcriptase polymerase chain reaction (PCR). These patients were analysed for genotype and quantitatively for HCV RNA levels prior to treatment by using a competitive PCR method with colorimetric detection of the amplified products. HCV RNA levels were correlated to outcome of treatment, mode of acquisition, histology and HCV genotype. The median pretreatment HCV RNA level in sustained responders (n = 15) with eradication of the viremia and normalization of serum ALT levels lasting 24 weeks post treatment was significantly lower than that in the combined group of non-sustained responders (n = 9) and non-responders (n = 15), 2.52 x 10(5) vs 8.90 x 10(5) genome equivalents per ml serum, p < 0.0125, respectively. 10 out of 17 patients with HCV RNA levels lower than the median level (5.64 x 10(5) genome equivalents per ml serum) had a sustained response to interferon treatment versus only 5/22 with levels equal to or higher than the median level, p = 0.04. No significant pretreatment differences in median HCV RNA levels according to mode of acquisition, genotype, or liver histology prior to treatment were seen. It is concluded that a low pretreatment HCV RNA level seems to be indicative of a sustained response to interferon alfa-2b treatment, whereas a high level seems to be indicative of a non-sustained or non-response. In the individual patient, however, the levels varied widely irrespective of response category.
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PMID:Serum hepatitis C virus RNA levels in chronic hepatitis C--importance for outcome of interferon alfa-2b treatment. 793 25

A quantitative competitive RNA polymerase chain reaction (QC-PCR) assay was developed for measuring absolute levels of hepatitis C virus (HCV) RNA in the sera of 121 viremic persons, including 64 asymptomatic blood donors, 39 symptomatic patients referred for treatment of chronic hepatitis C, and 18 patients with end-stage liver disease referred for liver transplantation. Mean HCV RNA levels (log molecules per milliliter) were lowest among blood donors with normal alanine aminotransferase (ALT) values (5.8 +/- 1.5), higher among blood donors with elevated ALT (6.9 +/- 0.8) and clinic patients with chronic active hepatitis (6.9 +/- 0.7), and highest among patients with cirrhosis (7.1 +/- 0.8) or end-stage liver disease (7.6 +/- 1.0). High-titer viremia ( > or = 7.5 logs/mL) was more frequent among patients with end-stage liver disease (14/18; 78%) than either blood donors (10/64; P < .001) or patients with chronic active hepatitis (7/26; P < .001). Thus, 121 (94.5%) of 128 anti-HCV-positive persons were viremic. QC-PCR may be valuable for monitoring HCV infection status and selecting individuals for therapy.
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PMID:Assessment of hepatitis C virus RNA levels by quantitative competitive RNA polymerase chain reaction: high-titer viremia correlates with advanced stage of disease. 819 99

In Germany, transmission of hepatitis C virus by blood transfusion is prevented by screening the donations for anti-HCV and ALT. The specificity of the anti-HCV screening in low seroprevalence populations has been questioned. In order to evaluate this screening policy we wanted to estimate the prevalence of viremic and potentially infectious donors by the HCV-RNA polymerase chain reaction (PCR) in our donor population of southern Germany. Donors (n = 301) were divided into four subgroups according to anti-HCV status and ALT levels. HCV sequences were detected by nested PCR, using primers for the most conserved region of the viral genome. The recombinant immunoblot assay (RIBA-4) was applied to the same samples. PCR detected 4.2% HCV-RNA carriers in the subgroup anti-HCV-/ALT-; 3% in the subgroup anti-HCV-/ALT+; 19.4% in the subgroup anti-HCV+/ALT-; and 59.4% in the subgroup anti-HCV+/ALT+. It was concluded that, on the one hand, the lack of specificity of the anti-HCV ELISA gives rise to many false-positive results; on the other hand, a minority of infected donations will not be detected by the screening procedure. ALT in conjunction with anti-HCV improves the quality of screening for potentially infectious donors.
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PMID:Prevalence of HCV-RNA-positive blood donors and correlation to ELISA and RIBA status. 838 3

The significance of a positive hepatitis C virus (HCV) screening test in asymptomatic blood donors with normal or near normal aminotransferases was studied along with the usefulness of HCV RNA polymerase chain reaction (PCR) testing for predicting chronic hepatitis in these individuals. One hundred and thirty-nine volunteer blood donors who were found positive by second generation ELISA for antibodies to HCV agreed to participate in the study. Thirty-one of them were supplemental test positive, had ALT values less than twice normal, and were followed over a minimum of 12 months. Thirteen consented to percutaneous liver biopsy and also had HCV RNA determination by PCR. Ten of the 13 subjects were positive for HCV RNA by PCR. Of the nine who were positive for HCV RNA and had adequate tissue for evaluation, seven had evidence of chronic hepatitis, three with limiting plate necrosis. Lobular inflammation was similar in severity to that found in the portal region. In addition, two had periportal fibrosis, and one had bridging fibrosis. Of the three subjects who were negative for HCV RNA, only one had portal inflammation which was limited to the portal region. None of these three had lobular changes, or periportal or bridging fibrosis. Of the three normal biopsies, two were from subjects who were negative for HCV RNA. The sensitivity and specificity of HCV RNA testing for chronic hepatitis was 87.5% and 50%, respectively, yielding an overall accuracy of 75%. We conclude that asymptomatic blood donors with antibodies to HCV, normal or mildly elevated liver tests, and HCV RNA may have abnormal liver histology indicating the potential for progressive liver disease. HCV RNA testing by PCR may be clinically useful as a noninvasive means to discriminate between those with and without chronic liver disease.
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PMID:Liver histology in anti-HCV-positive persons with normal or minimally elevated aminotransferases. 858 5

Because current standard therapy of chronic hepatitis C with alpha interferon is less than ideal, numerous other approaches have been studied. Iron in the liver, particularly that found in vascular endothelial cells of portal tracts, has been associated with decreased responsiveness to alpha interferon therapy. Iron reduction alone, generally achieved by therapeutic phlebotomy, regularly has been associated with biochemical improvement (decrease in serum alanine aminotransferase), but not with virological improvement. Iron reduction has been reported to increase the therapeutic response to alpha interferon. Most studies of this combination have been conducted in patients who had not responded to interferon alone; in these patients, improved responsiveness has been observed in some, but not all studies. In patients not previously treated, iron reduction was found in a recent trial to improve the sustained biochemical and virological response rate from 5% to 29%. Hepatic iron and chronic hepatitis C increase oxidative stress in the liver and are associated with decreases in hepatic glutathione levels. In one report, administration of N-acetyl cysteine, a sulfhydryl donor, led to improved response to interferon in chronic hepatitis C. Several cytokines and immunomodulators have undergone limited study; perhaps the most promising of these is thymosin alpha-1. In one small study, amantadine was found to produce some response in patients who previously had failed to respond to interferon. Ursodiol improves serum aminotransferase levels in chronic hepatitis C but has no antiviral effect, nor has it been found to improve histologic abnormalities. The future of therapy of chronic hepatitis C will likely include measures to decrease oxidative stress and injury and multidrug combinations, including inhibitors of the hepatitis C viral protease and RNA polymerase.
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PMID:Therapy of hepatitis C: other options. 930 80

A recently discovered non-A-E hepatitis virus has been designated as hepatitis G virus (HGV) and identified as a new member of the Flaviviridae family. Infection by this virus is thought to be associated with blood-borne hepatitis and usually in the presence of hepatitis C or hepatitis B virus (HBV) infection. In this study, the presence of HGV-RNA in serum or plasma and the prevalence of antibodies against an HGV envelope protein (E2) were investigated in patients undergoing chronic hemodialysis using a sensitive reverse-transcriptase polymerase chain reaction and an enzyme-linked immunosorbent assay, respectively. HGV-RNA was detected in 19 of 112 patients investigated (17%) and anti-E2 antibodies were detected in 15 of 106 patients studied (14.2%). With the exception of two patients, the appearance of anti-E2 is associated with the clearance of serum HGV-RNA. The total prevalence of current (HGV-RNA positivity) and/or past (anti-E2 positivity) HGV infection in this patient population is thus 28.6% (32 of 112 patients were positive for serum HGV-RNA and/or anti-E2 antibodies). In apparently healthy blood donors, serum HGV-RNA was detected in four of 358 individuals (1.12%) and anti-E2 was not detected in 50 individuals investigated. From the 19 patients with serum HGV-RNA positivity, nine were coinfected with other hepatitis viruses (seven with HBV; one with HBV, hepatitis C virus [HCV], and hepatitis D virus; and one with HBV and cytomegalovirus). Thirteen of 15 patients with anti-E2 positivity (10 were positive for only anti-E2 and three were also positive for anti-HBc) had no detectable HGV-RNA. In two patients, both HGV-RNA and anti-E2 antibodies were concomitantly present (both patients were coinfected with HCV or HBV). Of the HGV-infected patients, only three who were coinfected with HBV showed elevated serum alanine aminotransferase levels. The serum HCV-RNA and/or anti-HCV were detected in five (4.5%) of 112 patients. From these findings, we conclude that there is a high prevalence of HGV infection (28.6%) compared with HCV (4.5%) in patients undergoing hemodialysis in our hospital. However, approximately 50% of patients had spontaneously lost the viremia and developed anti-HGV-E2 antibodies. We confirm that HGV infection alone is not associated with elevated serum transaminases, and the appearance of anti-HGV-E2 is usually accompanied with clearance of serum HGV-RNA. In contrast to the results of our previous study, the majority of patients infected with HGV are not coinfected with HCV, indicating that HGV is capable of independent transmission. It is likely that there is a preferential HGV acquisition in the hemodialysis unit. The clinical significance of long-term infection with HGV remains to be established.
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PMID:High prevalence of hepatitis G virus infection compared with hepatitis C virus infection in patients undergoing chronic hemodialysis. 946 14

A commercially available kit, Amplicor, was compared with a locally developed nested reverse-transcriptase (RT) PCR for qualitative detection of HCV-RNA. Sixty-one serum samples from sixty-one patients with liver disease, and 60 samples from 60 hemophiliacs without symptoms, but known to have been heavily exposed to hepatitis C virus, were investigated. There was a high degree of concordance between the two diagnostic tests (97%), the Amplicor kit being slightly more sensitive than the in-house PCR, when evaluated using serial dilutions of samples showing discrepant results. The relationship between viremia and abnormal ALT levels was studied in the two groups of patients. Among those with chronic liver disease, 8.3% of patients with viremia had normal ALT levels, whereas transaminases were normal in 20% of hemophiliacs with viremia. This points to ALT as being a poor marker of ongoing viral replication.
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PMID:Viremia in chronic hepatitis C patients evaluated by the Amplicor RT-PCR, a nested RT-PCR, and transaminase levels. 953 67

The aim of this study was to compare the short-term and long-term efficacy and safety of lymphoblastoid interferon with a recombinant interferon alfa (IFN-alpha) in a 24-week treatment course for chronic hepatitis C. One thousand seventy-one patients with chronic hepatitis C were randomized to receive lymphoblastoid IFN-alpha n1 or recombinant IFN-alpha2b at the same dosing regimen, 3 million units administered subcutaneously three times a week for 24 weeks. Hepatitis C viral (HCV) genotype (by line probe assay) was determined at baseline, and serum HCV RNA level (by quantitative reverse-transcriptase polymerase chain reaction) was measured at baseline and weeks 24, 48, and 72. Primary end points were normalization of serum alanine aminotransferase (ALT) levels at end of therapy (week 24) and sustained ALT normalization at weeks 48 and 72. Secondary end points were nondetectability of serum HCV RNA at 24, 48, and 72 weeks, and histological improvement at weeks 24 and 72. The two treatment groups were similar with respect to demographic, clinical, and histological variables (10% had cirrhosis at entry), baseline serum HCV RNA levels, and distribution of HCV genotypes. Intent-to-treat analysis showed that ALT response at end of treatment was 35.3% for IFN-alpha n1 and 37.9% for IFN-alpha2b (P = .38). Histological improvement and nondetectability of HCV RNA were also similar between the two treatment groups at the end of treatment, as were the type and frequency of reported adverse experiences. Among treatment responders, post-treatment relapse was significantly less frequent with IFN-alpha n1 than with IFN-alpha2b. Thus, sustained ALT responses (SR) to IFN-alpha n1 were significantly more frequent than SR to IFN-alpha2b (12.0% vs. 7.6% at 48 weeks, P = .02; 10.3% vs. 6.7% at 72 weeks, P = .04). SR were associated with viral loss and histological improvement, and more patients treated with IFN-alpha n1 were HCV RNA negative at week 72 compared with patients treated with IFN-alpha2b (P = .03). SR at week 72 were two- to sixfold better with other HCV genotypes relative to type 1, but the improved long-term efficacy of IFN-alpha n1 compared with IFN-alpha2b was evident for all major HCV genotypes. It is concluded that IFN-alpha n1 and IFN-alpha2b have similar end-of-treatment response rates and safety profiles but the sustained response rate is higher with IFN-alpha n1. SR to IFN-alpha treatment are associated with clearance of HCV RNA, and histological improvement was maximal in patients who exhibited sustained ALT normalization and clearance of HCV RNA.
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PMID:Lymphoblastoid interferon alfa-n1 improves the long-term response to a 6-month course of treatment in chronic hepatitis C compared with recombinant interferon alfa-2b: results of an international randomized controlled trial. Clinical Advisory Group for the Hepatitis C Comparative Study. 953 53


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