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)

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

A 28-year-old male was admitted to our hospital because of hepatosplenomegaly and granular lymphocytosis. His peripheral leukocyte count was 3,000/microliters with 43% of granular lymphocytes (GL). These GLs were immunologically phenotyped as CD2+CD3-CD4-CD8-CD16+CD56+HLA-DR+ and were found that TcR genes coding beta and gamma chains were not rearranged. Chromosomal analysis of his GLs stimulated with IL-2 showed 47 XY, +8. This patient was diagnosed as a granular lymphocyte leukemia of natural killer cell type. Blood chemistry showed elevation of serum GOT, GPT and LDH values. The fever persisted until administration of prednisolone was initiated. But 40 days after, high fever appeared again and the liver and spleen were extremely enlarged. Combined chemotherapy was then started but resulted in no effects. He died of hepatic failure on the 77th day from admission. 47 XY, +8, that has been reported in acute non-lymphocytic leukemia and myelodysplastic syndrome, may be related to the pathogenesis in some cases of granular lymphocyte leukemia.
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PMID:[Granular lymphocyte leukemia of natural killer cell type; association with 47 XY, +8 by interleukin 2 (IL-2)-stimulated chromosomal analysis]. 225 62

From 8 Department of Veterans Affairs Medical Centers, 296 patients with varying degrees of alcoholic liver disease were tested for hepatitis C (HCV) infection using an EIA and RIBA 2. A high frequency of positive response was observed with 13.9% reactive to both and an additional 4.4% positive only to RIBA 2 (total 18.3%). An evaluation of known risk factors (injection drug use and prior blood transfusions) failed to account for the mode of transmission in 42.6% of the HCV+ patients. The clinical severity of the liver disease and degree of liver pathology were nearly identical in HCV+ vs. HCV- patients. However, the process was accelerated in the HCV+ patients occurring at a 12.8% younger age (p < 0.0001) with a 43% increase in ALT (p = 0.05). The most striking differences were observed in immune parameters. In peripheral blood, total lymphocyte counts were increased 20% (p = 0.01) accompanied by a 56% increase in B cells (p = 0.01) and a 35% elevation of IgG levels (p = 0.0001) in HCV+ patients. T cell changes consisted of a 50% increase in CD8 cells (p = 0.047). However, lymphocyte infiltration into liver was not significantly different (HCV+ vs. HCV-) for any of the subsets studied (CD4, CD8, B cells, NK cells). The combined presence of HCV and alcohol injury did not significantly increase mortality but did significantly increase the number of hospitalizations from 2.4 to 4.0 per year (p = 0.0005).
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PMID:Relevance of anti-HCV reactivity in patients with alcoholic hepatitis. VA cooperative Study Group #275. 768 17

This study was carried out to test the hypothesis that, in chronic hepatitis (CH), inflammatory processes, including viral replication, host immune response, and hepatocyte destruction, are regulated by a cytokine network in the liver. Expression of the mRNA of the cytokines IL1-beta, IL2, IL4, IL5, IL6, TNF-alpha, and IFN-gamma, the lymphocyte markers CD4 and CD8, and the HLA class I molecule, beta 2-microglobulin (B2MG) in the liver tissue of 20 CH(C) cases and 9 CH(B) patients was investigated by the reverse transcription polymerase chain reaction (RT-PCR) method. TNF-alpha, CD4, and B2MG mRNA were detected in 100% of cases of in both CH(B) and CH(C). The expression rates of IL1-beta, IL2, IL4, IFN-gamma, and CD8 mRNA were 80%, 40%, 25%, 40%, and 80% in CH(C) and 88.9%, 44.5%, 30%, 55.6%, and 100% in CH(B). IL6 mRNA was detected only in CH(B), in 22.2% of cases, IL5 mRNA was not detected in either CH(B) or CH(C). IL2, IL4, and IFN-gamma mRNA were expressed significantly more frequently in patients who had high serum ALT and a high histological activity index (HAI) score. There was no difference in cytokine expression between CH(B) and CH(C), except in IL6, suggesting the existence of a common immunopathogenesis for CH(B) and CH(C). In chronic viral hepatitis, IL1-beta and TNF-alpha appear to play a major role in immune responses and IL2, IL4, and IFN-gamma seem to be associated with increased cytotoxic T cell response.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression rate of cytokine mRNA in the liver of chronic hepatitis C: comparison with chronic hepatitis B. 771 13

Acute infectious mononucleosis (IM) is a lymphoproliferative disease caused by the Epstein-Barr virus (EBV) infection. It has been reported that soluble T cell antigens are released from cells in response to T cell activation. In the present study, we investigated whether soluble antigen levels of CD2, CD4 and CD8 in serum increase during acute IM. Soluble CD2, CD4 and CD8 levels in serum were measured by a sandwich enzyme immunoassay. In addition, peripheral blood T cell subsets were analyzed by single and two color flow-cytometric analyses in IM. Patients with IM had increased levels of soluble CD2, CD4 and CD8 in serum samples obtained during acute stages. We found a positive correlation between serum levels of soluble CD8 and absolute counts of HLA-DR+CD8+T cells during acute IM. In addition, the correlation between soluble CD8 levels and serum GOT or GPT levels was shown to be positive during acute IM. Our findings suggest that the soluble antigen levels of CD2, CD4 and CD8, in particular CD8, in serum are an important immunologic parameter for determining the activation of T cells during acute IM.
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PMID:[Serum soluble CD2, CD4 and CD8 levels in infectious mononucleosis]. 790 99

The blood levels of soluble CD8 (sCD8) and soluble CD4 (sCD4) were measured in patients with various liver diseases, and their significance was studied. The levels of sCD8 were significantly higher in patients with chronic active hepatitis (CAH), autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), acute hepatitis (AH), fulminant hepatitis (FH) and liver cirrhosis (LC) as compared with the normal controls (NC), and correlated positively with those of GPT (r = 0.67, p < 0.001). In addition, a comparison of the exacerbation of CAH with remission showed that the sCD8 levels were significantly higher in the former. On the other hand, there was no significant rise in the level of sCD4 in patients with any liver disease, except FH, no definite relationship between sCD4 and sGPT, and no consistant tendency in sCD4 levels between exacerbation and remission. The reason for an insignificant elevation of the sCD4 level is the fact that in hepatitis the CD8-positive cells, which are cytotoxic T cells, are directly involved in hepatocyte damage; therefore the CD8-positive cells are predominantly activated, while the activity of the CD4-positive cells is considered to be lower. Instead of determining the number of CD4-positive cells and CD8-positive cells in the mononuclear cells of peripheral blood, serum sCD4 and sCD8 levels can be measured simply and inexpensively. Thus, these levels may be useful immune markers.
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PMID:Serum levels of soluble CD4 and CD8 in patients with chronic viral hepatitis. 795 75

Millions of people have been exposed to silicones because of the widespread use in consumer products such as cosmetics and toiletries, food products, household products and paints. Silicones have wide use in medical practice, including lubricants in tubing and syringes, and as implantable devices. The most prevalent silicone in medical use is polydimethylsiloxane. This study was undertaken to determine the subchronic immunotoxicologic potential of the principal constituents of breast implants: silicone fluid, silicone gel and silicone elastomer. An alternative covering for devices containing silicone gels, polyurethane, was also included in the study. Silicone fluid and gel were injected subcutaneously into female B6C3F1 mice (1 ml/mouse) and 6 mm disks of silicone elastomer or polyurethane were implanted subcutaneously. There were no treatment-related deaths or overt signs of toxicity. None of the tested materials had notable effects on body or organ weights, erythrocytes or leukocytes in the blood, blood chemistries such as alanine aminotransferase, urea nitrogen, glucose, albumin or total protein. The cellularity of the bone marrow and responses to CSF-GM and CSF-M were normal. The tested silicones did not alter the distribution of B cells and T cells in the spleen, but polyurethane perturbed the distribution of CD4+CD8+ and CD4-CD8- T cells. The antibody response to sheep erythrocytes was not markedly altered, nor were proliferative responses to concanavalin A, phytohemagglutinin, lipopolysaccharide or allogeneic cells. Reticuloendothelial function was normal, but polyurethane evoked an enhanced phagocytosis of Covaspheres by adherent peritoneal cells. Natural killer cell activity and serum complement were not altered. All silicone materials afforded modest protection to a challenge with Listeria monocytogenes that killed 40 to 58% of control mice. Host resistance to Streptococcus pneumoniae or the B16F10 tumor was not affected by any of the treatments. There is a pattern indicative of some perturbation of T cell differentiation in mice implanted with a polyurethane disk.
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PMID:Subchronic 10 day immunotoxicity of polydimethylsiloxane (silicone) fluid, gel and elastomer and polyurethane disks in female B6C3F1 mice. 798 83

Serum levels and production of soluble CD8 and soluble CD4 antigens by peripheral blood mononuclear cells were determined in patients with alcoholic cirrhosis and acute or chronic viral hepatitis. Patients with chronic viral hepatitis had significantly increased soluble CD8 serum levels (n = 18; 734 +/- 143 U/ml) (mean +/- SD) compared to healthy controls (n = 80; 312 +/- 141 U/ml; p < 0.001) and patients with alcoholic cirrhosis (n = 12; 505 +/- 256 U/ml; p = 0.006), whose soluble CD8 concentrations were also higher than controls (p < 0.001). In contrast, soluble CD4 antigen serum levels were similar in all groups. In addition, patients with chronic hepatitis showed an increased production of soluble CD8, but not soluble CD4, after mitogenic stimulation of their peripheral blood mononuclear cells compared to controls or patients with alcoholic cirrhosis. Patients with acute viral hepatitis, studied within the first 2 weeks after onset of jaundice, showed markedly elevated serum concentrations of soluble CD8 (n = 4; 807 +/- 379 U/ml; p < 0.001 vs. controls), but not soluble CD4. In addition, nine patients with chronic hepatitis C were studied during and after treatment with alpha interferon. Soluble CD8 serum concentrations of six treatment responders were not found to be different from the low levels seen in controls, whereas three non-responders had increased soluble CD8 levels which were similar to levels in untreated patients with chronic hepatitis C. After interferon-alpha therapy ended, a significant elevation of soluble CD8 serum concentrations was observed in four relapsing patients, which paralleled the serum ALT increase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Soluble CD8 and soluble CD4 antigens in viral hepatitis and alcoholic cirrhosis. 800 6

To confirm the positive results of a preliminary trial, 26 patients with mixed cryoglobulinaemia were enrolled in a controlled, randomised, crossover trial with interferon alfa-2b. A significant improvement was seen in the purpura score and alanine aminotransferase activities during six months' treatment, and was associated with a significant decrease in cryocrit and a returning to normal of the lymphocyte CD4/CD8 ratio (in eight of nine patients). No significant variations were seen during the six month period without interferon. Only six patients withdrew from treatment, three because of side effects and three because of poor compliance.
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PMID:Interferon alfa-2b in mixed cryoglobulinaemia: a controlled crossover trial. 831 85

A 24-year-old man was admitted to our hospital for further examination of pleural effusion. On physical examination, he had a temperature of 39 degrees C, the pharynx was painful and liver and spleen were enlarged. The leukocyte count was 5,700/microliters (atypical lymphocyte 6%). The serum LDH, GOT, GPT, ALP and gamma-GTP levels were elevated, and antibodies to Epstein-Barr viral capsid, early, and nuclear antigens were diagnostic of a primary Epstein-Barr virus infection. The CD4/CD8 ratio of peripheral blood lymphocyte was decreased to 0.2. The pleural effusion was exudate, and infiltration of mononuclear cells was noted. The CD4/CD8 ratio of lymphocytes in the effusion also was decreased to 1.1. The result of pleural biopsy showed a perivascular infiltration of mononuclear cells and immunological stain showed that the infiltrated cells were dominantly T-lymphocytes (about 90%). These findings suggested that the pathogenesis of pleural effusion in infectious mononucleosis was a pleulitis due to the infiltration of T-lymphocytes. Pleural effusion is known as a rare complication of infectious mononucleosis.
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PMID:[Infections mononucleosis with pleural effusion]. 882 84


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