Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the role of interleukin 1 alpha (IL 1 alpha) in the pathogenesis of chronic liver disease. IL 1 alpha production by peripheral blood monocytes was measured with a specific, sensitive double-antibody radioimmunoassay. When monocytes were cultured for two days with bacterial lipopolysaccharide (LPS), IL 1 alpha production in asymptomatic hepatitis B virus carrier (ASC) and patients with chronic active hepatitis (CAH) was equivalent to that of controls (168 +/- 31 U/ml, mena +/- SD), while IL 1 alpha levels generated by monocytes from liver cirrhosis (LC) (117 +/- 45 U/ml, p less than 0.01) were significantly lower than controls. When normal monocytes were cultured together with LPS and IFN gamma, mena IL 1 alpha production was 297 +/- 56 U/ml. IL 1 alpha production in ASC did not differ from controls. On the other hand, IL 1 alpha production in patients with CAH (241 +/- 58 U/ml, p less than 0.05) and LC (189 +/- 70 U/ml, p less than 0.01) were significantly diminished in comparison with controls although there was considerable overlap. Serial study demonstrated that IL 1 alpha production rose significantly during acute deterioration of illness with marked rise in serum alanine aminotransferase. The addition of sera to normal monocytes cultures resulted in significantly enhanced suppression (p less than 0.05) for IL 1 alpha production in comparison with that of control sera. These findings indicate that decreased monocyte function and serum inhibitor(s) for IL 1 alpha production could contribute to the pathogenesis of chronic liver disease.
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PMID:Interleukin 1 alpha production by peripheral blood monocytes from patients with chronic liver disease and effect of sera on interleukin 1 alpha production. 314 31

Murine IFN(gamma) and human IFN(alpha)-AD:Bgl were compared over a limited dose range and after single and multiple dosing for their effect on male mouse liver oxidative and conjugative drug metabolizing enzymes. Both IFNs depressed the microsomal cytochrome P-450 concentration but did not alter cytosolic glutathione S-transferase nor microsomal UDP-glucuronosyltransferase activity. Both IFNs showed some slight hepatotoxicity (elevated serum ALT), alpha AD:Bgl more than gamma, especially after multiple dosing. While the IFNs did not produce significant increases in liver weight, they did increase the yield of microsomal protein. The increased endoplasmic reticulum may compensate for the decreased cytochrome P-450 concentration and so account for the lack of observed effect of the IFNs on hexobarbital sleep times in vivo. Overall, the minimal effects of murine gamma-IFN on the mouse liver were no different than those of human alpha AD:Bgl.
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PMID:Effect of murine gamma-interferon on the mouse liver and its drug-metabolizing enzymes: comparison with human hybrid alpha-interferon. 392 33

Seven children with chronic active hepatitis (CAH) and one child with persistently abnormal results of liver function test due to hepatitis B virus (HBV) infection were treated with human leukocyte interferon (Hu-alpha-IFN). Five of them were positive for eAg and two of the three who were measured for DNA polymerase (DNAP) activity in sera showed moderate elevations of its levels. Hu-alpha-IFN was injected intramuscularly daily or once weekly at doses of 0.05-1 X 10(6) IU. The total dose per patient varied from 10.5-54 X 10(6) IU. After administration of Hu-alpha-IFN, rapid loss of eAg was observed in two of the five eAg patients, and DNAP activity reverted to normal ranges in the two patients with moderate elevations of its levels. One of the patients who lost eAg has retained normal serum glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase levels for more than 2 years after therapy with Hu-alpha-IFN. Serial hepatic biopsies were performed in only one patient. In the second biopsy, 3 months after therapy with Hu-alpha-IFN, infiltration of inflammatory cells in the portal region was improved compared with earlier findings. Immediate and/or prolonged adverse side effects were not observed during or after administration of Hu-alpha-IFN. For the present, we propose these six conditions for use of Hu-alpha-IFN in children with HBV infection. Children should: (a) be more than 1 year old; (b) have abnormal liver function for more than 6 months; (c) have a liver biopsy demonstrating CAH; (d) have moderate elevation of DNAP activity; (e) be eAg positive; and (f) be unresponsive to other treatments.
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PMID:Therapeutic effects of human leukocyte interferon on chronic active hepatitis B in children. 398 64

A clinical Phase I study of recombinant human interferon alpha A (Ro 22-8181) was performed in patients with malignant tumors; twenty of them received an American product and seven others a domestic product. Both products were administered in single intramuscularly injected doses of 18, 36, 50, 75 and 100 X 10(6)U. Main side effects included fever and influenza-like symptoms (headache, chill/shivering, general fatigue, lumbago), and digestive symptoms (anorexia, nausea/vomiting). Numbness of fingers or limbs and somnolence were also observed in higher dose groups, but these symptoms all disappeared on the day of administration or by the 3rd day after administration. Abnormal laboratory findings included leukopenia, granulocytopenia, lymphocytopenia, thrombocytopenia and increased GOT/GPT/LDH, but these returned to normal by the 10th day after administration. The peak blood concentration was correlated with the dose, falling to the base line 72 hr after administration. The American product and the domestic product were nearly comparable in the type and incidence of their side effects, and also produced generally comparable blood concentrations. Furthermore, increased anti-IFN-alpha antibody titer was not observed in any of the patients; and the Prick Test proved negative in all of them. No significant changes were observed in any immunological parameters, either.
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PMID:[Phase I study of recombinant human interferon alpha A (Ro 22-8181) in patients with malignant tumors]. 400 81

Four patients with glioblastoma and one patient with astrocytoma (grade III) were treated with recombinant IFN ( rIFN -alpha A, Ro 22-8181) and the effect of IFN on clinical symptoms, CT findings and side effects of IFN were studied. Neurological symptoms were improved in one patient, stable in one patient and worsened in three patients. In all cases, there was no remarkable change of CT findings but in one case a slight decrease in tumor size was recognized. With regards to IFN side effects general malaise, anorexia, fever, nausea and vomiting were observed clinically, decrease of leukocytes, platelets, erythrocytes, hematocrit, hemoglobin and increase of GOT, GPT, LDH, AL-P were noted in the laboratory findings. These symptoms and change in laboratory findings were not serious, and they recovered spontaneously during or after IFN therapy. In one patient, an increase in IFN neutralizing antibody titer was detected. Since the biological activity of IFN may be diminished and anti-tumor effect cannot be expected in such a patient, the appearance of IFN neutralizing antibody may indicate an important problem in IFN therapy.
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PMID:[rInterferon-alpha A (Ro 22-8181) therapy for patients with malignant brain tumors]. 632 84

Sixty C3H/He male mice were divided into 6 groups (10 mice per group). Control mice (group I) received three injections of PBS and drinking water. Mice of group II were injected with PBS but drinking water was substituted by ethanol solutions with increasing concentration of ethanol (w/v): 6% during the first week of experiment, 10% during the second and 20% during the third week. Group III received three intraperitoneal injections of CCl4 (1 ml of CCl4 per 1 kg of body weight) and water for drinking. Group IV was treated with CCl4 as group III, but drinking water was substituted by ethanol solutions with increasing concentrations as in the group II. Samples of blood, liver and spleen were taken 24 h after the third acute CCl4 intoxication. Group IIIa and IVa were treated as group III and IV, respectively, but samples of blood and organs were taken a week after the last CCl4 injection. A typical increase in serum ALT and necrosis of hepatocytes as confirmed by the histological examination, was observed 24 h after CCl4 injections (group III and IV). A week later (group IIIa and IVa) regenerative changes in the liver and a significant decrease in ALT serum activity was observed. Acute CCl4 intoxication (group III) significantly decreased IFN production in liver and spleen cells isolated 24 h after the last CCl4 injection. Combined CCl4 and ethanol administration affected very strongly IFN production (group IV).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of carbon tetrachloride intoxication and ethanol ingestion on interferon production in mice. 748 75

Chronic coinfection with the hepatitis B (HBV) and hepatitis delta (HDV) viruses is known to cause severe liver disease, but the importance of coinfection with hepatitis C virus (HCV) and HBV has not been well documented. In the present study, the clinical and pathological severity of liver disease among patients with hepatitis resulting from multiple viruses was examined and an open trial of the efficacy of interferon-alpha 2b (IFN-alpha) treatment was conducted. Nineteen patients with chronic HBV and HCV infection and 17 with HBV, HCV and HDV infection were studied; 12 in each group underwent liver biopsy. For each coinfected patient, two patients infected with HCV alone were selected as controls, and these were matched for age and risk factor and were estimated to have been infected for a similar duration. Coinfection with HBV and HCV or HBV, HCV and HDV was associated with more severe liver disease than HCV alone (P < 0.01); total Scheuer score, portal and lobular inflammation and fibrosis were all worse in coinfected subjects. Eight patients with chronic HBV and HCV were treated with recombinant IFN-alpha 2b [3 million units (MU), thrice weekly for 6 months]. Liver function tests normalized in two patients and one lost hepatitis B surface antigen (HBsAg). Seven patients with hepatitis B, C and delta coinfection were treated with the same regimen and only one normalized serum alanine aminotransferase (ALT) during (and after) treatment. It is concluded that coinfection with multiple hepatitis viruses is associated with histologically more severe liver disease than HCV alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Coinfection with hepatitis B and C or B, C and delta viruses results in severe chronic liver disease and responds poorly to interferon-alpha treatment. 749 93

The efficacy and tolerability of 12-month treatment with titrated doses of recombinant interferon-alpha 2a (IFN-alpha 2a) in chronic hepatitis C were studied in 67 consecutively recruited patients randomly assigned either to a starting dose of IFN-alpha 2a 6 MU, subsequently adjusted to the serum alanine aminotransferase (ALT) response (n = 35), or to no therapy (n = 32; controls). End-of-treatment ALT levels were normal and hepatitis C virus (HCV) RNA was negative by nested polymerase chain reaction (PCR) in 17 (49%) treated patients compared to none of the controls (P < 0.001). During the 12 months after stopping treatment the number of patients who remained in remission was eight (23%) and one respectively (4%) (P = 0.031). Follow-up liver biopsy showed reduced hepatic inflammation in 80% of treated patients and in 29% of controls (P < 0.001). The eight sustained responders and 27 non-responders or relapsers received similar mean total doses of IFN (565 MU vs 545 MU) and had a similar incidence of anti-IFN neutralizing antibodys (13% vs 19%). Absence of cirrhosis was the only independent pretreatment parameter that predicted a sustained response. In conclusion, a mean cumulative dose of IFN 549 MU, titrated over 12 months, was well tolerated, and resulted in the long-term clearance of HCV RNA and normal ALT levels in 23% of patients.
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PMID:Long-term titrated recombinant interferon-alpha 2a in chronic hepatitis C: a randomized controlled trial. 749

To estimate the relationship between genomic change in the E2/NS1 region and clinical feature, we made a pairwise comparison in the nucleotide and deduced amino acid sequences for multiple recombinant clones of the E2/NS1 region, which derived from blood samples taken from four patients (three treated by IFN) at different stages. Sequence heterogeneities among the clones were generally high but they appeared to be significantly lowered after cessation of therapy. Our results showed, through IFN therapy, a few clones were selected and survived, although many clones disappeared. After discontinuation of the drug, three patients became carrier state, normal ALT levels with viremia. Evolution of defective viruses was seen in most of the cases. These features of HCV genome suggest that the virus could circulate as an extremely heterogeneous population including defective virus, and that this heterogeneity lend itself to selection pressures including interferon therapy and host immune response.
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PMID:[Genomic changes in the E2/NS1 region of HCV before and after IFN therapy in relation to clinical course]. 752 10

The indication and the evaluation of IFN treatment for chronic hepatitis type C has been discussed. Good response to IFN depend on the level of HCV RNA just before the treatment. The patients who has low level of HCV RNA (less than 1 Meq/ml by DNA probe assay) could be able to estimate the response more than 80%. On the contrary, it is less than 10% for the patients with high level of HCV RNA. The evaluation of IFN treatment for chronic hepatitis were divided into 3 groups. Cure was defined as the continuous normalization of serum ALT and disappearance of HCV RNA during 12 month or more after the treatment. Partial response was defined as continuous normalization of ALT level but positive for HCV RNA. The others were defined as non responder. First and second group should be evaluated for the IFN treatment. Final purpose for IFN treatment should be prevent to develop liver cirrhosis or hepatocellular carcinoma.
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PMID:[The indication and the evaluation of IFN treatment of chronic hepatitis C]. 752 17


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