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)

One hundred and one patients were included in a double-blind controlled trial to determine whether malotilate (diisopropyl 1,3-dithiol-2-ylidene malonate) is therapeutically effective in primary biliary cirrhosis. Fifty-two patients received malotilate (500 mg three times a day) and 49 patients placebo. The mean follow-up time was 28 months (range 6-46 months). The large majority of patients did not have advanced liver disease since only ten patients were in Child-Pugh class B and none in class C, and the median bilirubin and albumin at entry were normal. Malotilate had no clear effect on pruritus. In malotilate recipients the following statistically significant biochemical changes occurred: alkaline phosphatase decreased 21%, AST 20%, ALT 40%, IgA 12% and IgM 26%. In the placebo group no significant changes occurred. Evaluation of entry and 2-year liver biopsies indicated that malotilate diminished plasma cell and lymphocytic infiltrate and piece-meal necrosis, but had no effect on liver fibrosis. There was no difference in survival or in disease progression according to Child-Pugh criteria. In six patients receiving malotilate, but in none on placebo, treatment was discontinued due to suspected side effects. All patients recovered completely. We conclude that malotilate has an immune-modulating, anti-inflammatory but not anti-fibrotic effect in primary biliary cirrhosis. The clinical relevance of the observed benefits, however, appears too slight to recommend malotilate as single drug therapy in primary biliary cirrhosis.
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PMID:The results of a randomized double blind controlled trial evaluating malotilate in primary biliary cirrhosis. A European multicentre study group. 844 37

We report the case of a young HIV seropositive patient with severe hemophilia A who presented rapid liver failure related to his chronic C hepatitis. The patient had been receiving factor VIII:C clotting factor concentrates (mean 60,000 U/year) since 1975. In 1984 alanine aminotransferase presented abnormal levels. The CD4 lymphocyte count in 1991 was normal and ultrasonographic scan showed normal liver morphology. In 1991 the patient were found to be seropositive for HCV antibodies as detected by the ELISA method and confirmed by the RIBA method. One year later, a progressive increase in policlonal gamma-globulin and a decrease in the CD4+ lymphocyte count to below 500/muL were detected in concomitance with ultrasonographic evidence of a progressive increase in the longitudinal diameters of the liver and spleen and signs of liver inhomogeneity. A significant inverse correlation was observed between the increase in the longitudinal diameter of the liver and the decline in albumin levels, and between the increase in the longitudinal diameter of the liver and the drop in platelet count. Elevated levels of ammonemia, gamma-glutamyl transpeptidase, alkaline phosphatase and IgA were detected. Moreover, decreased levels of the C4 and C3 complement fractions were documented. At this time (1994), esophagogram and esophagogastroscopy evidenced varicosities in the lower esophageal section (stage F1). The patient died in 1995 March at the age of 29 years of sudden septic shock related to Pseudomonas aeruginosa infection.
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PMID:Rapid liver failure related to chronic C hepatitis in an HIV seropositive hemophilic patient with severe immunodepression. 887 Mar 78

The serum immunoglobulin (IgG, IgM and IgA) concentrations of 52 chlorinated-exposed workers were examined and compared with those of non-exposed, age- and sex-matched individuals. At the time of testing, the exposed population had mean hexachlorobenzene (HCB) blood levels of 3.84 micrograms/dl with a range of 0.1 to 16 micrograms/dl. Increased IgG and IgM levels were found in the HCB-exposed workers (P < 0.05 and P < 0.01, respectively). Hepatic function was evaluated by serum aspartate (AST) and alanine aminotransferase (ALT) activities, as well as by bilirubin levels. IgM concentrations were positively correlated with three of the studied parameters, namely, length of exposure (r = 0.367) and the activities of both AST (r = 0.367) and ALT (r = 0.507).
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PMID:Immunoglobulin levels in workers exposed to hexachlorobenzene. 958 86

We have recently found that antibodies to total histones are common in a group of American patients with type 1 autoimmune hepatitis (AIH). In an attempt to determine the profile and clinical association of anti-histone antibody (AHA), 45 Japanese AIH patients were studied for serum isotypic reactivity with individual histones (H1, H2A, H2B, H3, H4) by enzyme-linked immunosorbent assay and western blotting. The results revealed that 40% of sera had reactivities with at least one of individual histones and that the antibodies were detected in all three classes of immunoglobulins (IgG, IgM, IgA). Immunoglobulin G type anti-H3 showed the dominant reactivity and it characterized 72% of sera with AHA. The titre of anti-H3 decreased significantly (P < 0.0075) after steroid therapy and the index of decrease for anti-H3 was correlated in individuals with that for serum aminotransferase. In general, patients with AHA showed higher serum level of alanine aminotransferase (P < 0.05), immunoglobulin G (P < 0.025), and higher frequency of A2-DR4 haplotype (53 vs 17%) than their seronegative counterparts. However, the titre of AHA was low in this disease condition and histone class-specific antibodies did not distinguish patients with distinctive clinical features, although patients with anti-H3 tended to be younger than those without AHA.
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PMID:Characterization of anti-histone antibodies in patients with type 1 autoimmune hepatitis. 964 38

Oxygen free radicals have been implicated in exercise-induced cell and tissue injury, indicating an oxidative stress. Fatigue accompanied by a number of physiological and metabolic changes is in indication of overtraining. This study aimed to examine the influence of a continuous 24-h intermittent speed driving (1 h driving/1 h stop), on the response of hormones, antioxidative factors, lipid, and enzyme levels. Seven race car drivers of national level were examined before, during, and immediately after the trial of speed driving on a test designed to check endurance to stress. The parameters measured were: testosterone (Tes), cortisol (Cor), IgM, IgA, cholesterol, HDL, billirubin, ceruloplasmin, urea, uric acid, creatine kinase, and transaminases. Stress hormone Cor declined significantly (p < 0.05), while Tes did not change significantly. Fatigue enzyme, aspartate transaminase (GOT) increased significantly (p < 0.05), while alanine transaminase (GPT) did not change and urea declined. Muscle enzyme, creatine kinase (CK) increased to sixfold (p < 0.01). IgA, IgM and lipids did not change. The primary antioxidant ceruloplasmin increased significantly (p < 0.001), while antioxidants uric acid and glucose remained unchanged. Among the factors measured, ceruloplasmin, cortisol, urea, GOT, and CK seem to give a picture of the organism's alertness and defence capabilities in conditions of stress and fatigue.
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PMID:Stress hormonal factors, fatigue, and antioxidant responses to prolonged speed driving. 967 60

We analysed the time from the date CD4+ cell counts fell below 200 x 10(6) L-1, defined as ti, to the onset of clinical AIDS, according to the 1987 Centers for Disease Control and Prevention case definition, in 129 Japanese haemophilia patients infected with HIV-1. The cumulative onset of clinical AIDS was analysed by the Kaplan-Meier method and proportional hazard model. Incorporated covariates were age of each patient at time ti, as well as CD4+ and CD8+ cell counts, serum levels of IgG, IgA, IgM, GOT and GPT at ti. The time of antiretroviral treatment initiation was also considered. The 50% AIDS-free interval after ti was 3.00 years (95% confidence interval (CI), range 0.49-5.51) and 1.71 years (95% CI, range 0.66-2.76) for the patients at CDC stage II and stage III, respectively (significantly different, P = 0.0013). Among the patients at CDC stage II at ti, higher levels of IgA were tightly associated with a shorter period from ti to onset of clinical AIDS (P < 0.0001), and relative hazard was 1.35 (95% CI, 1.11-1.64) with increase of IgA level by 1.0 g L-1. Thus there is a broad distribution in the time to onset of clinical AIDS in Japanese haemophiliacs even after CD4+ cell counts fall below 200 x 10(6) L-1. This should be taken into consideration in deciding upon the therapy and care of HIV-1 infected people.
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PMID:Analysis of clinical AIDS-free interval after CD4+ cell counts fall below 200 x 10(6) L-1 in Japanese haemophiliacs infected with HIV-1. 987 64

A 67-year-old man was admitted because of thrombocytopenia in May 1998. His white blood cell count was 4,900/microliter with 3.5% blasts. Laboratory findings were as follows: hemoglobin level, 10.1 g/dl; platelet count, 1.8 x 10(4)/microliter; ALT, 56 IU/l; LDH, 3,570 IU/l; IgG, 653 mg/dl; IgA, 64 mg/dl; IgM, 49 mg/dl; IgD, 674 mg/dl. Serum immunoelectrophoresis confirmed IgD lambda M-component. Bone marrow aspiration showed 79.2% myeloma cells expressing a mostly plasmablastic morphology. No mature plasma cells were found in the bone marrow. The patient received a continuous drip infusion of 20 mg/body cytarabine (Ara-C) and 50 mg/body etoposide (VP-16) for 7 days. No plasmablastic myeloma cells were detected, but 2.1% mature plasma cells were found in his bone marrow on day 20. On day 18 his platelet count exceeded 10.8 x 10(4)/microliter, and the serum IgD level fell to 210 mg/dl. Therapy consisting of melphalan, methylprednisolone and vincristine was started from day 23. No IgD lambda M-component was detectable by serum immunoelectrophoresis seven months after the diagnosis of multiple myeloma. The patient has been in complete remission as of April 2000.
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PMID:[Complete remission of plasmablastic IgD lambda multiple myeloma induced by continuous infusion of low-dose cytarabine and etoposide]. 1092 52

The aim of this study was to analyze the clinical impact of hepatitis C virus (HCV)-related cryoglobulinemia in patients that had received liver transplants after HCV cirrhosis. Thirty patients who had received transplants between 1990 and 1996 for HCV cirrhosis and who had a follow-up longer than 1 year were studied. Serum HCV RNA levels, HCV genotype, cryoglobulinemia, rheumatoid factor, serum C3 and C4, IgA, IgG, IgM levels, liver tests, and liver histology were studied 30 +/- 16 months post-transplant. Cryoglobulinemia was found in 9 of 30 patients (30.0%) and was symptomatic in 4 of the 9 cases (glomerulonephritis, 1 case; palpable purpura, 3 cases). Age, sex distribution, alanine aminotransferase (ALAT) activity, and Knodell score did not differ, whether cryoglobulinemia was present or not. Rheumatoid factor (209.5 +/- 70.4 IU/l vs 12.0 +/- 4.4 IU/l, P = 0.004) and IgM levels (3.2 +/- 0.5 g/l vs 1.6 +/- 0.9 g/l, P = 0.0001) were significantly higher, and C4 levels (0.16 +/- 0.16 g/l vs 0.30 +/- 0.10 g/l, P = 0.009) were significantly lower in patients with cryoglobulinemia. One patient died from cryoglobulin-related renal failure. We concluded that, after liver transplantation (LT) for HCV cirrhosis, cryoglobulinemia was frequent and often symptomatic. Cryoglobulinemia did not seem to be associated with more severe graft damage. Cryoglobulinemia-associated morbidity must be taken into account in the management of post-transplant HCV infection.
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PMID:Hepatitis C virus (HCV)-related cryoglobulinemia after liver transplantation for HCV cirrhosis. 1187 6

Endotoxins of intestinal origin are supposed to play an important role in the development of alcoholic hepatitis in man. To estimate the role of immunoglobulin response to gut-derived endotoxin in the development of alcohol-induced liver disease, serum levels of IgA and IgG against fecal endotoxin, endotoxin, and acute-phase proteins were measured in patients with different stages of alcoholic liver disease and in healthy controls. Antibodies of type IgA, but not IgG, against fecal endotoxins were significantly increased in patients with alcohol-induced liver disease. IgA antibodies against fecal endotoxin were found to be closely correlated with the plasma concentrations of alanine aminotransferase, gamma-glutamyl transferase, and C-reactive protein in patients with alcoholic liver disease. In conclusion, as IgA located in body tissue was shown to suppress the inflammatory process, enhanced production of IgA against endotoxin of intestinal origin may contribute to inactivation of this compound, thereby reducing its damaging effect on the liver.
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PMID:IgA against gut-derived endotoxins: does it contribute to suppression of hepatic inflammation in alcohol-induced liver disease? 1199 6

Hepatitis C virus (HCV) is known for its ability to establish persistent infection and cause chronic hepatitis in most infected individuals. The antibody response to HCV in HCV-circulating immune complexes (CIC) is unknown. In the present study, we have characterized distinct changes in patterns of HCV-immunoglobulin (Ig) constituents with disease category, viral mutation and clinical markers. The number of samples positive for single HCV-Ig, HCV-IgG and HCV-IgA, HCV-IgM and HCV-IgA, HCV-IgM and HCV-IgG, HCV-IgM, HCV-IgG and HCV-IgA in 47 samples tested were 8 (17%), 1 (2.1%), 9 (19.1%), 4 (8.5%) and 17 (36.2%), respectively. The occurrence of HCV-IgM and HCV-IgA in combination of two isotypes of HCV-Ig became predominant. These results show that defective IgG in HCV-CIC may contribute to long-term viremia. Further analysis indicated that the frequency of HCV RNA/IgA-CIC in the abnormal aspartic aminotransferase (AST) group was significantly higher than that of the normal AST group, and HCV RNA/IgA-CIC frequency in the abnormal alanine aminotransferase (ALT) group was slightly higher than that in the normal ALT group. IgA complexes may reflect the damage degree of liver function during the course of HCV infection. We also found that there were more mutations in supernatant than in other constituents from single-strand conformation polymorphism (SSCP) analysis. Our results suggest that Ig-complexed virions and free virions may have different biological consequences, with the latter being elusive to immunological elimination. The findings in this study may provide some new insights into antibody response to HCV.
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PMID:Analysis of HCV-immunoglobulin isotype complexes provide new insights into antibody response to HCV. 1210 Apr 76


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