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 studied immune function in Belgian haemophiliacs treated with Factor VIII from volunteer donors. No patient had clinical evidence of immune deficiency. We found a decrease in T-helper cells (p less than 0.0005), in the ratio of T-helper over T-cytotoxic/suppressor cells (1.72 +/- 0.47 versus 2.24 +/- 0.82 in controls, p less than 0.005) and in lymphocyte responsiveness to mitogens (p less than 0.05). These findings could not be linked to the amount of F VIII received over the last year, the time since last F VIII administration, circulating immune complexes (54% positive patients, 7% positive controls, p less than 0.005), increased ALT levels, antibodies to cytomegalo -virus (85% of the patients, 45% of the controls, p less than 0.005), antibodies to Epstein-Barr virus, nor to the presence of HLA-DR 5 which was found in 56% of the haemophiliacs (20% of the overall Belgian population, p less than 0.005). Either F VIII induces long lasting immunological alterations unrelated to AIDS, or haemophilia is itself associated with such changes.
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PMID:Immunological alterations in haemophiliacs treated with lyophilized Factor VIII cryoprecipitate from volunteer donors. 642 83

Inflammation of the bile ducts was studied in liver biopsies from patients with chronic hepatitis C to determine whether the frequency of inflamed bile ducts changes with therapy and correlates with other histological variables and expression of class I and II MHC antigens on ductal epithelium. Twenty patients treated at UMMC between 1991 and 1994 underwent needle biopsies of the liver before and after therapy with interferon alpha 2B (IFN). A complete response to therapy was defined as a return to normal serum alanine aminotransferase levels occurring and persisting during therapy. The number of inflamed bile ducts/total ducts (%IBDs), presence of piecemeal necrosis and lymphoid aggregates, and grade of inflammation were assessed in each high-power field in all areas with bile ducts. The frequencies of these variables were compared in cirrhotics and non-cirrhotics and in patients with complete or incomplete responses to IFN. Frozen sections of biopsies from 5 patients were immunostained using antibodies to HLA-DR and B-2 microglobulin, and positive staining was noted on bile ducts. Before therapy, the %IBD was slightly greater in patients with cirrhosis. After IFN, both %IBD and serum alkaline phosphatase levels decreased in non-cirrhotics who responded to IFN. The change in frequency of IBD with IFN paralleled the changes in the other histological features. No correlation was noted between bile duct inflammation and expression of class I and II antigens. The conclusion is that inflammation of the bile ducts occurs frequently in chronic hepatitis C, correlates with other features of inflammation in the triads, and decreases in response to IFN therapy.
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PMID:Effect of interferon therapy on bile duct inflammation in hepatitis C. 876 34

The aims of this prospective study were to assess the frequency of serological markers of autoimmunity and cryoglobulins in renal transplant (RT) patients presenting with chronic hepatitis C, and to correlate them with serum alanine aminotransferase (ALT) levels, hepatitis C virus (HCV) genotypes and viremia, and HLA-DR phenotypes. Three groups of patients were studied: group I comprised 74 HCV + ve RT patients; group II, 33 HCV-ve RT patients, and group III, 13 HCV-ve/hepatitis B virus (HBV)-positive RT patients. The three groups did not differ significantly according to their mean age, sex ratio and baseline immunosuppression. Serum specimens of these patients were tested for complement (hemolytic activity (CH50), C3, C4 and properdin factor B (PFB) components, rheumatoid factor (RF), immunoglobulin patterns, circulating immune complexes, and autoantibodies including antinuclear (ANA), anti-smooth muscle (ASMA), antimitochondrial, antithyroid microsomal (ATM), antithyroglobulin (ATG) and anti-LKM1 autoantibodies. We also looked for the presence of cryoglobulins in groups I and III. Cryoglobulinemia of type II was present in 2 patients of group I (2.7%) which was associated in 1 case with de novo membranoproliferative glomerulonephritis but was not found in any of the patients of group III. RF (> 40U/ml) were more frequently observed in groups I (55.4%) and III (46%) than in group II (20.6%), although the difference was not statistically significant (p = 0.06). Oligoclonal or monoclonal serum immunoglobulin patterns were present in 16.2% of the patients in group I, 15.4% in group III and only 3.3% in group II (p = 0.07). There was no significant difference between the prevalence of at least one autoantibody in the three groups (ranging from 38.5 to 50%), and neither was the frequency of ANA (23-36.6%), even at a high titer i.e. above 1:320, or ASMA (13.5-23%) significantly different. Conversely, tissue-specific autoantibodies, i.e. ATM, ATG and anti-LKM1, were only observed in HCV+ve patients. CH50, C3, C4 and PFB levels were significantly lower in group I than in group II, although values below the normal ranges were observed only for CH50 and C3 and were mostly found in the HCV+ve RT patients. Circulating immune complexes detected by nephelometry were at similar levels in the three groups, within the normal ranges. The occurrence of at least one autoantibody and/or the presence of RF > 40 U/ml did not correlate with either serum ALT levels or a given HLA-DR phenotype in any of the three groups, nor did they correlate with HCV genotype or HCV viremia in group I. In conclusion, this study shows that contrary to HCV+ve immunocompetent patients, HCV+ve RT patients rarely present with cryoglobulinemia and have the same frequency of non-organ-specific autoantibodies as HCV-ve RT patients. Conversely, antithyroid autoantibodies are only observed in the former group. Finally, serological markers of autoimmunity are not related to serum ALT levels, HLA-DR phenotype, HCV viremia or HCV genotype in HCV+ve RT patients.
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PMID:Serological markers of autoimmunity in renal transplant patients with chronic hepatitis C. 948 39

The objective was to evaluate the rationale for liver needle biopsy versus blood liver functional tests in monitoring the incidence of hepatotoxicity in Egyptian rheumatoid arthritic patients treated with gold compounds. Forty patients (12 males, 28 females) were randomly selected out of 258 Egyptian rheumatoid arthritic patients treated with sodium auro-thiomalate during the past 4 years. The minimum duration of treatment was 40 weeks. The methods used were firstly, liver function tests (serum glutamic-oxaloacetic transaminase, serum glutamic-pyruvic transaminase, total serum bilirubin and total serum albumin) before, weekly during and after administration of sodium auro-thiomalate. Secondly, a needle liver biopsy was conducted by using the tru-cut needle. Then liver histology was graded according to Roenigk for grading liver toxicity. Viral hepatitis markers (hepatitis B surface antigen, anti-hepatitis C virus were done for monitoring viral hepatitis. Finally, the liver tissue contents of heavy metals were counted in the cases that showed grade IIIB histological changes. The results showed that none of the studied cases developed any clinically significant liver disease during the course of chrysotherapy. Blood liver function tests were of normal value throughout the course of drug administration. According to Roenigk grading, 20 patients (50%) showed grade I liver changes, and the other 20 patients showed liver changes of grades II and III (four grade II, eight grade IIIA, and another eight grade IIIB). None of the patients showed grade IV liver changes. It was concluded that blood liver tests are not the most sensitive methods to detect hepatotoxicity in gold-receiving Egyptian rheumatoid arthritic patients. Needle liver biopsy is not superior in detecting liver toxicity, compared with routine laboratory liver function tests, because of its complications. Rheumatoid arthritic patients with a potential risk of clinically significant liver disease should not be exposed to the risk of gold salt therapy. Pretreatment HLA-DR genetic typing may be a good detector for rheumatoid arthritic patients with potential risk of hepatotoxicity.
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PMID:Liver toxicity profile in gold-treated Egyptian rheumatoid arthritis patients. 960 32

Hantaviruses cause an important human illness, HFRS. Blood samples from 22 HFRS-positive, six seronegative patients and 15 healthy controls were examined in 1995, during the largest HFRS epidemic in Croatia. Results of double- and triple-colour immunofluorescence analysis showed an increased percentage of cytotoxic T cells (CD3+CD8+) in seropositive patients compared with seronegatives and healthy controls. The majority of seropositive HFRS patients expressed activation and memory antigens on T and B lymphocytes. The percentage of CD23+ and CD21+ B lymphocytes was lower in seropositive patients. HFRS patients had elevated levels of sCD23 and five had elevated total IgE. The increased expression of both early and late T cell activation antigens, e.g. CD25, CD71 and HLA-DR, memory cells and sCD23 positively correlated with biochemical parameters (AST, ALT, urea, alpha2-globulin) during the acute phase of HFRS. The phenotypic changes observed, especially early and late T cell activation markers, as well as memory cells, could be useful parameters in the evaluation of HFRS course, and prognostic factors of HFRS severity. Additional attention should be paid to liver involvement in the pathogenesis of HFRS.
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PMID:Role of peripheral blood mononuclear cell (PBMC) phenotype changes in the pathogenesis of haemorrhagic fever with renal syndrome (HFRS). 993 61

The serum concentrations of soluble HLA-DR antigens (sDR) were monitored in 40 patients with chronic hepatitis C (CHC) who received interferon treatment. The expression of HLA-class II antigens in liver tissues was also studied by immunohistochemistry. The sDR levels in patients with chronic hepatitis C were significantly higher than those in healthy subjects (416+/-236 [mean +/- S.D.] ng/ml vs. 286+/-163 ng/ml) (P<0.05). There was no correlation between the sDR levels and serum alanine aminotransferase levels, suggesting that sDR do not reflect the extent of liver necrosis. Although there was no difference in pretreatment sDR levels between interferon complete responders and non-responders, sDR significantly declined in complete responders, while they did not in non-responders. The hepatic expression of HLA-DR antigens was observed in dendritic cells, lymphocytes and Kupffer cells in portal area, while in Kupffer cells and endothelial cells in central acinus. These expression significantly decreased in complete responders. From these results, sDR, reflecting the hepatic expression of HLA-DR antigens, could be a predictive marker of response to inteferon treatment.
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PMID:The serum soluble HLA-DR antigens as a predictive marker of the response to interferon-alpha treatment in patients with chronic hepatitis C. 1136 9

Little is known concerning the clinical features, the histological outcome, and the effects on the maturation of immune system of children with vertically-transmitted hepatitis C virus (HCV) infection. Specifically, no data are available on the peripheral distribution of T-cell subsets. The frequency of naive and memory cells, activated T cells, and cytokine-producing T cells was analyzed in nine HCV-infected children born to HCV-positive mothers. In HCV-infected children, the distribution of naive and memory cells was not significantly altered in the CD4 subset whereas within the CD8 subset, an increase of memory and a decrease of naive cells was observed. The frequency of HLA-DR-positive and Fas-positive T cells was increased in HCV-infected children in both CD4 and CD8 subsets. The distribution of Fas-expressing T cells was directly related to that of HLA-DR cells and inversely related to the frequency of naive T cells. In regard with cytokine production we found increased levels of both CD4 and CD8 interferon-gamma (IFN-gamma)-producing cells whereas no difference in the percentage of interleukin-2 (IL-2)-producing T cells was observed. No meaningful correlation was observed between individual T cell subsets and ALT levels or HCV viral load. In conclusion, our results indicate an increased T-cell activation and a shift to a T(H)1 pattern of cytokine production in children with vertically transmitted HCV infection. The cause of this kind of immune response could reside in the persistent antigenic stimulation by chronic HCV infection.
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PMID:T-Cell immune activation in children with vertically transmitted hepatitis C virus infection. 1139 12

We analyzed the prevalence and longitudinal fluctuation of hepatitis B virus (HBV)-specific CD8 T cells in chronic HBV infection using an HLA-A2-HBc18-27 tetramer. Thirty-five HLA-A2-positive patients with chronic HBV infection were divided into 17 HBe antigen (HBeAg)-positive and 18 anti-HBe antibody (anti-HBe)-positive patients. Five HLA-A2-positive normal subjects, five HLA-A2-negative patients with chronic HBV infection, and two HLA-A2-positive patients with acute HBV infection were included as controls. HBc18-27-specific CD8 T cells (c18-27-CD8Ts) were detected at a significantly higher prevalence in patients with anti-HBe (6/18) than in those with HBeAg (1/17), and their frequency reached 0.28% of the total CD8 T cells. The prevalence was significantly higher in patients with HBV DNA below 4.0 log genome equivalents (LGE)/ml (5/12) than in those with HBV DNA above 4.0 LGE/ml (2/23). The frequency of c18-27-CD8Ts was consistently higher in liver-infiltrating lymphocytes, ranging from 0.18 to 1.28%, than in autologous peripheral blood lymphocytes. Longitudinal analysis of patients with acute flare-up demonstrated that the elevation of alanine aminotransferase (ALT) was intimately associated with the expansion of c18-27-CD8Ts. Phenotypic analysis revealed that most c18-27-CD8Ts during acute flare-up expressed HLA-DR and CCR5, while those during low-ALT periods showed low expression. Furthermore, most liver-infiltrating c18-27-CD8Ts were positive for HLA-DR and CCR5, suggesting selective recruitment of activated c18-27-CD8Ts into the liver. In conclusion. HBV-specific CD8 T cells play an important role in the suppression of virus replication, and acute flare-up is associated with the expansion and activation of HBV-specific memory cells.
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PMID:HBcAg-specific CD8 T cells play an important role in virus suppression, and acute flare-up is associated with the expansion of activated memory T cells. 1279 44

Osteopontin, a crucial factor for Th1 immune response, is expressed in stellate cells and macrophages activated in injured liver. To clarify the role of osteopontin in inflammatory changes in the liver, we attempted to establish transgenic mice expressing osteopontin in hepatocytes. Mouse osteopontin cDNA, cloned from concanavalin-A-stimulated spleen cells in C57BL/6 mice, was constructed into the vector containing serum amyloid-P component promoter. This construction was microinjected into fertilized eggs of C57BL/6 mice, and 4 lines of the transgenic mice were obtained. Western blotting and immunohistochemistry revealed that osteopontin was expressed in hepatocytes, but not in non-parenchymal cells, in the transgenic mice. The mean osteopontin concentrations in the liver and plasma in the mice were 13 and 2.6 times higher than those in negative littermates. Antinuclear antibody was positive in the plasma in 50% of the transgenic mice. In the transgenic mice later than 12 weeks of age, mononuclear cell infiltration in the liver developed, and these cells were positive for CD8 and HLA-DR. Plasma ALT activity was increased with focal necrosis in hepatic lobules in the transgenic mice later than 24 weeks of age. The transgenic mice expressing osteopontin in hepatocytes may be useful as a model of autoimmune hepatitis.
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PMID:Transgenic mice expressing osteopontin in hepatocytes as a model of autoimmune hepatitis. 1504 55

Chronic evolution of acute hepatitis C (aHC) occurs in more than 80% of patients but can frequently be prevented by early treatment with interferon (IFN)-alpha. Plasmacytoid dendritic cells (pDCs) are the major endogenous IFN-alpha producers, but their role in aHC is unknown. In this study, frequency, phenotype, and pDC function were analyzed in 13 patients with aHC and 32 patients with chronic hepatitis C (cHC) compared with 20 healthy controls, 33 sustained responders to antiviral treatment, 14 patients with acute hepatitis B (aHB), and 21 patients with nonviral inflammatory disease. In aHC, pDCs in the peripheral blood were significantly reduced compared with healthy controls (median, 0.1% vs. 0.36%, P < .0005) and were inversely correlated to alanine aminotransferase levels (r = -0.823; P < .005). Circulating pDCs in aHC were immature, as determined via reduced expression of HLA-DR and CCR7, and produced little amounts of IFN-alpha (median, 3.5 pg/50,000 peripheral blood mononuclear cells [PBMCs] vs. 498.4 pg/50,000 PBMCs in healthy controls; P < .0005). Less pronounced changes were present in cHC (median, 0.17%, 28.0 pg/50,000 PBMCs IFN-alpha, respectively). However, a significantly reduced frequency and IFN-alpha production was also found in self-limited aHB (median 0.1%, 8.6 pg/50,000 PBMCs) and in patients with nonviral inflammatory disease (median 0.19%, 7.5 pg/50,000 PBMCs). In conclusion, in aHC frequency and IFN-alpha-producing capacity of peripheral blood pDCs are dramatically reduced and inversely correlated with the degree of liver inflammation. In cHC there is incomplete recovery of pDC function, which, however, could be solely due to the chronic inflammatory state.
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PMID:Plasmacytoid dendritic cells in acute and chronic hepatitis C virus infection. 1572 47


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