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)

Eighteen heterosexual HBsAg carriers with anti-HBe- and HBV-DNA-positive chronic hepatitis B (CHB) were randomly assigned to receive human lymphoblastoid interferon (ly-IFN) at a dose of 5 MU/m2 i.m. three times a week for 6 months (ten cases) or no treatment (eight cases). All patients were followed for 24 months after IFN discontinuation and received a second liver biopsy. During the 6 months of treatment all patients had a progressive reduction of serum HBV-DNA levels, and at the end of therapy nine out of ten were HBV-DNA-negative and had normal ALT values. None of the untreated patients became persistently HBV-DNA-negative or showed significant variations of ALT levels. During the post-treatment follow-up, from 1 to 17 months after ly-IFN discontinuation, eight of the nine responders (89%) had recurrent or persistent reappearance of HBV-DNA in the serum and reactivation of the liver disease activity, with an ALT peak in four of them. On the post-trial liver biopsy seven of the eight relapsed patients showed persistence of HBcAg reactivity with no significant difference in the percentage of positive cells with respect to the pre-treatment liver specimen. Histological features improved in four treated patients, worsened in one untreated case and were unchanged in the remaining patients. These results indicate that ly-IFN shows a transient antiviral effect in the therapy of anti-HBe- and HBV-DNA-positive CHB. The 6-month treatment regimen employed in this study seems insufficient for eradicating the replicating virus from the liver cells in the majority of patients and consequently does not appear to prevent HBV reactivation after IFN discontinuation.
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PMID:Anti-HBe-positive chronic hepatitis B with HBV-DNA in the serum response to a 6-month course of lymphoblastoid interferon. 150 Jun 86

The effect of three anticancer agents, cisplatin, doxorubicin, and mitomycin, on liver regeneration after 70% partial hepatectomy in rats was investigated by total DNA content of the liver and flow cytometric analysis of hepatocyte nuclei using two-color staining of anti-bromodeoxyuridine monoclonal antibody and propidium iodide. Total DNA content of regenerating liver 7 days after hepatectomy showed significant suppression of regeneration by these agents (P less than 0.01). The inhibitory effects of the agents on the cell cycle of hepatocytes by flow cytometric analysis were (1) a delay of the peak or a decrease in the proportion of S phase nuclei and/or (2) polyploidization of the nuclei, demonstrated by accumulation of 8c and occasionally 16c nuclei, of which the DNA contents were four and eight times as much as that of diploid (2c) cell nuclei, respectively. The former (1) suggests G0 or G1 phase block, and the latter (2) G2 phase block. In terms of total DNA content of regenerating liver, the inhibitory effect was most prominent in the cisplatin-administered groups. The polyploidization of nuclei was most remarkable in the mitomycin-administered groups. Although the total DNA content recovered to the level of control at 6 weeks after hepatectomy, the polyploidization effect persisted in the drug-administered groups. These agents had no cytocidal action on proliferating hepatocytes as can be seen from the aspartate aminotransferase and alanine aminotransferase serum levels. We conclude that in a short-term observation, the anti-cancer agents significantly inhibit liver regeneration, although the inhibitory effect on DNA synthesis does not last long.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of anticancer agents on cell cycle of regenerating hepatocytes in rats. 152 46

Viral sequence and host immune response were investigated in an unusual, asymptomatic chronic hepatitis B virus carrier (human leukocyte antigen type A24, Bw61, Bw62, Bw6, DRw11, DRw52, DQw7) who was consistently nonreactive for antibody to HBc and had a normal ALT level over a 5-yr study period. The precore and core region DNA sequences of virus isolated from his serum had seven silent mutations that resulted in no changes in the amino acid sequence of the adr HBsAg subtype. He had no abnormalities in the number of peripheral blood T or B cells and no HBcAg-specific suppressor T cells. His lymphocytes proliferated in vitro in response to phytohemagglutinin, pokeweed mitogen, Staphylococcus aureus and tetanus toxoid but not to recombinant HBcAg. Unlike other HBsAg carriers and hepatitis B virus-immune individuals, his monocytes did not ingest beads coated with HBcAg. Failure to produce antibody to HBc was not due to an hepatitis B virus variant but to a selective immune system defect in this asymptomatic HBsAg carrier.
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PMID:Chronic hepatitis B virus infection in an anti-HBc-nonreactive blood donor: variant virus or defective immune response? 153 7

Spontaneous loss of HBsAg is infrequent in adult HBV carriers. Little is known about this serological change in children. In a prospective study of 420 hepatitis B virus-carrier children who were observed for 1 to 12 yr (mean = 4.3 yr), spontaneous loss of HBsAg occurred in 10 patients, with an average incidence of 0.6%/yr. The HBsAg clearance rate was significantly higher in children who had anti-HBe; children who were at an older age on entry; children whose mothers were HBsAg-; or children with severe liver histological changes detected while they were HBeAg+. Children who seroconverted from HBeAg to anti-HBe before the age of 6 or who had a peak serum ALT level above 100 IU/L were more likely to clear HBsAg. In all 10 patients who became HBsAg-, serum hepatitis B virus DNA became undetectable by both spot hybridization and the polymerase chain reaction, suggesting a complete clearance of the virus from serum. After the loss of HBsAg, the anti-HBs levels were higher in the children born to carrier mothers than in those born to noncarrier mothers. These findings suggest that chronic hepatitis B virus-carrier children rarely lose HBsAg, especially if they have been infected during the perinatal period and have mild histological changes. The poor humoral immune response to HBsAg may be a contributing factor in the establishment of carrier status during horizontal infection but may not be primarily involved in the establishment of carrier status during perinatal infection.
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PMID:Spontaneous loss of HBsAg in children with chronic hepatitis B virus infection. 154 19

Ongoing hepatitis B virus replication in the presence of antibody to HBeAg can be observed in patients with active liver disease. These forms of chronic hepatitis B have been described as having a poor prognosis. We have conducted a randomized controlled trial to assess the efficacy of lymphoblastoid interferon-alpha in 60 patients with antibody to HBeAg and hepatitis B virus DNA-positive chronic hepatitis. Patients received 5 million U/m2 interferon three times a week for 6 mo, or no treatment. Final evaluation 18 mo after randomization showed hepatitis B virus DNA negativity and ALT normalization in 53% of treated patients and in 17% of controls (p less than 0.01). The probability of sustained hepatitis B virus DNA loss was significantly higher in treated patients than in controls (p less than 0.005). Blinded histological assessment revealed improvement in 50% of treated patients compared with 33% of controls. Pretreatment hepatitis B virus DNA and aminotransferase levels and histological appearance were not predictive of response. The results of this trial indicated that marked reduction of viral replication in serum and remission of liver damage can be obtained with lymphoblastoid interferon in about 50% of patients with HBeAg antibody- and HBV DNA-positive chronic hepatitis. This rate of response is higher than that reported previously.
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PMID:A randomized controlled trial of lymphoblastoid interferon-alpha in patients with chronic hepatitis B lacking HBeAg. 155 34

Ornithine decarboxylase (ODC) activity, the rate limiting enzyme in polyamine biosynthesis, was determined after 12-O-tetradecanoylphorbol 13-acetate (TPA) administration to female Sprague-Dawley rats. The extent of induction depended on the dose, exposure, time and route of administration. The most effective dose for ODC induction by the intraperitoneal route was 40 ug TPA/kg which caused 3-5 fold ODC induction. Maximal ODC induction occurred in a narrow time band 5 hours after TPA administration. TPA had no adverse effects on hepatic DNA (measured by alkaline elution), cytochrome P-450 content and reduced glutathione content or serum alanine aminotransferase (SGPT) activity.
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PMID:Dose, time and route dependency of the induction of rat hepatic ornithine decarboxylase by 12-tetradecanoylphorbol 13-acetate. 155 24

The polymerase chain reaction (PCR) was used to investigate the presence of hepatitis B virus (HBV)-related DNA sequences in blood from three blood donors and two transfusion recipients who developed posttransfusion non-A, non-B hepatitis (NANBH). In the first case, the sole donor was positive for antibody to hepatitis B surface (HBs) and core (HBc) antigens and had elevated alanine aminotransferase (ALT) levels, while the recipient had no HBV serologic markers. Both the donor and the recipient had serologic markers of hepatitis C virus (HCV) and were found positive for HBV DNA and HCV RNA sequences by PCR. The second case involved two donors and one recipient. Serologic tests for conventional HBV markers were negative in all three individuals, but one of the donors had elevated ALT. HBV DNA sequences were detected by PCR in the serum of the recipient and of the donor with high ALT, but not in the serum of the donor with normal ALT. Anti-HCV was detected in the serum of the recipient and of the suspect donor but not in that of the donor with normal ALT. The sequences amplified in the S region and determined after cloning of PCR products for both donor-recipient pairs were indistinguishable from each other and identical to the sequence of the major HBV subtype of adw in the first case and ayw in the second case. Furthermore, for the second case, an identical single-point mutation was found in both the donor and the recipient. These data confirm the transmission of conserved HBV sequences together with HCV in posttransfusion NANBH.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transmission of serologically silent hepatitis B virus along with hepatitis C virus in two cases of posttransfusion hepatitis. 155 1

Giardia lamblia is believed to be the earliest branching derivative from the eucaryotic lineage. Genomic and cDNA clones encoding the giardia NADP-dependent glutamate dehydrogenase have been isolated and characterized. Southern hydridization using genomic DNA indicates that the gene encoding this activity is unique and single copy. Primer extension, S1 nuclease protection, and genomic and cDNA sequence analysis demonstrate that gene transcripts are initiated within a conserved AT-rich sequence element immediately preceding the ATG translation initiation codon and the short 5' untranslated region is not extended by transsplicing. The open reading frame is 1350 nucleotides in length and encodes a protein of 449 amino acids. The reading frame is not interrupted by introns and the primary transcript is probably not subjected to RNA editing. In the strictly anaerobic metabolism of giardia, NADP-dependent glutamate dehydrogenase activity participates along with alanine aminotransferase, in the cyclic dissipation of reducing equivalents (NADPH) through the conversion of pyruvate to alanine. The deduced amino acid sequence of the giardia protein exhibits substantial homology to numerous fungal and eubacterial NADP-dependent glutamate dehydrogenases. Comparisons of alignment gap positions and amino acid identities indicate that the giardia sequence is at least as similar or more similar to the eubacterial sequence than it is to the fungal sequence. This supports the hypothesis that giardia diverged very early from the eucaryotic lineage.
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PMID:Isolation and characterization of a NADP-dependent glutamate dehydrogenase gene from the primitive eucaryote Giardia lamblia. 155 91

Female Wistar rats were pretreated with I ml of carbon tetrachloride/kg of body weight or with olive oil. All the rats were given this dose of CCl4 20 or 40 days later. Liver regeneration as evaluated by 3H-thymidine incorporation into liver DNA and by the number of mitotic hepatocytes was markedly impaired in CCl4-pretreated rats when compared with olive oil-pretreated controls. DNA labelling reached only 83 and 59% and mitotic index 35 and 58% of control values, respectively, at 20-day and 40-day time intervals. The variables characteristic of liver damage did not parallel the changes in cell division. About 20% of hepatocytes were necrotic both in the CCl4-pretreated and in the control rats. The activity of serum alanine aminotransferase was higher in the CCl4-pretreated rats. Only serum aspartate aminotransferase activities were somewhat lower when compared to controls. Similarly, serum aminotransferases were much less affected by the pretreatment than the markers of regeneration when two low doses of CCl4 (0.125 ml/kg) were given to rats 20 days apart. The activities of microsomal enzymes aniline hydroxylase and pethidine demethylase were equal in control and in experimental rats 20 days after CCl4 pretreatment which indicated that the effects of CCl4 were not mediated by an overall decrease in cytochrome P-450 enzymes. In summary, a single pretreatment of rats with CCl4 induced changes in liver that lasted for 40 days and impaired liver regeneration when another dose of CCl4 was applied.
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PMID:Prolonged reduction of hepatocyte proliferative ability in rats after a single treatment with carbon tetrachloride. 157 74

AM3, a biological response modifier (BRM) of polysaccharide/protein nature, was given by the oral route to 13 patients with chronic active hepatitis B (CAHB). After 12 months of daily treatment, 8 patients cleared serum HBV-DNA and HBeAg together with ALT normalization. Immunohaematologic studies showed how time of inhibition of viral replication was related to significant decreases of CD4, CD8 and B cell blood lymphocytes. After serum viral elimination, however, a significant haematologic rebound of peripheral blood mononuclear cells (PMNC): CD3, CD4 and CD8 lymphocytes was seen. These data, suggest that the antiviral activities of AM3 may be due to its immunodulatory capacities. These promising results, together with the absence of any side effects, justify the entry to trials with a larger number of patients. Furthermore, treatment with AM3 may help to elucidate the pathophysiology of CAHB.
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PMID:Therapeutic response of chronic active hepatitis B (CAHB) to a new immunomodulator: AM3. Immunohematological effects. 159 53


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