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)

The phenotypes of infiltrating lymphocytes in liver with chronic hepatitis C, including changes associated with interferon (IFN) treatment, were characterized. Specimens obtained from 22 patients treated with IFN were examined using avidin-biotin-peroxidase immunohistochemistry. In areas of lobular and periportal inflammation, most lymphocytes were CD8+ T cells of the CD45RO+ (memory) subset. The centres of lymphoid follicles were occupied by CD20+ B cells and a few CD4+ T cells which were CD45RA+ (naive subset). Follicular centres were surrounded mainly with CD4+ T cells. CD8+ T cells, mostly CD45RO+, were scattered through the mantle zones of follicles and extended around them. No significant changes in CD45RA+ lobular infiltrates accompanied IFN treatment. On the other hand, the number of CD45RO+ lobular infiltrates decreased after IFN treatment in complete responders (P < 0.01). Moreover, there were significant correlations between CD45RO+ cell counts and serum alanine aminotransferase concentrations, CD45RO+ cell counts and the liver histologic grade and CD45RO+ cell counts and CD8+ cell counts. These results suggest that CD8+ memory T cells participate in hepatocyte injury in chronic hepatitis C, and that a decrease of CD8+ memory T cells correlates with the decreased liver inflammation with IFN treatment.
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PMID:Naive and memory T cell infiltrates in chronic hepatitis C: phenotypic changes with interferon treatment. 921 25

Characteristics of hepatitis C virus (HCV), importance of its genotypes and mutant variants "quasi-species", as well as the mechanisms of disease chronicity and tissue injuries caused by HCV have been discussed. Both a presumed direct cytopathy of the virus and the host's immune response may play a role in the pathogenesis. HCV infects not only hepatocytes but lymphoid cells, thereby modulates immune functions. A molecular minicri--that is a cross-reaction between viral and host antigens--also contributes to autoimmune phenomena developed during chronic HCV infection, in addition a genetic predisposition for autoimmunity can be involved. Until now the only accepted therapy for HCV infection is interferon, that at a standard low dose regimen, results long-term benefit only in one-fourth of treated patients. In Hungary, between 1994-1996 601 chronic hepatitis C patients have been treated: biochemical remission (ALT normalization) was found in 38% of the patients and elimination of the HCV was achieved in 25%. Several questions are to be answered concerning the optimalization of the treatment, e.g. dosage, duration of treatment, re-treatment of relapse, problem of non-responders, the role of predictors of response in the individualized therapy, usefulness of combination treatment. The original end-points and goals of therapy are sustained HCV-RNA negativity, normalization of serum GPT/ALT, and inactivity in liver histology, yet the real end-points are incidence and prevention of cirrhosis and hepatocellular carcinoma, that is the better survival. Concerning these questions, newer therapeutic experiences are discussed, including results from Hungarian researchers.
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PMID:[Chronic hepatitis C: virologic and immunologic aspects and questions of therapy]. 922 76

Recurrent hepatitis C infection after orthotopic liver transplantation (OLT) is frequent and may occur as early as a few weeks postoperatively. Early histopathological features of recurrent hepatitis C virus (HCV) infection may be modified by immunosuppressive therapy and can be difficult to differentiate from acute allograft rejection (AAR). Thus, we retrospectively compared histopathological features of liver biopsy specimens from two carefully selected patient groups: one with unequivocal recurrent hepatitis C, the other with unequivocal AAR. Index biopsy specimens obtained at the time of the appearance of liver test abnormalities after OLT and all serial liver biopsy specimens (2 to 13 per patient) were assessed under code and scored semiquantitatively for 44 histopathological variables. The index biopsy specimens from patients with recurrent HCV infection and AAR index biopsies (AAR-Ib) differed significantly (P < .05) for 11 features (10 features were statistically associated with AAR and 1 with early recurrence of HCV infection). Statistically significant features associated with AAR included bile duct injury with overlapping nuclei, lymphocytic infiltrates and necrosis, endothelialitis, portal inflammatory infiltrates containing eosinophils and polymorphonuclear leukocytes, hepatocyte mitoses, and zone 3 canalicular cholestasis. In contrast, the only statistically significant feature associated with early recurrent HCV was sinusoidal dilatation. Stepwise discriminant analysis showed that the presence of eosinophils in the portal inflammatory infiltrate, bile duct necrosis, and bile duct lymphocytic infiltrates were independently associated with AAR. However, serial biopsy specimens from patients with recurrent HCV infection showed statistically significant progression in scores for portal inflammation, portal lymphoid aggregates, and lobular inflammation. We conclude that (1) multiple histopathological features are associated with AAR; (2) early recurrent HCV infection is characterized by elevated alanine aminotransferase levels, positive HCV RNA by polymerase chain reaction (PCR), and absence of diagnostic histopathological features; and (3) serial biopsies are needed to demonstrate progression of histopathological features of recurrent hepatitis C.
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PMID:Comparison of histopathology in acute allograft rejection and recurrent hepatitis C infection after liver transplantation. 934 70

The subchronic toxicity of ISIS 2302 and ISIS 3082, phosphorothioate oligonucleotides with antisense activity against human and murine ICAM-1 mRNA, respectively, was investigated in CD-1 mice. ISIS 2302 is currently in clinical trials as an anti-inflammatory agent. Because of the differences in mRNA sequence targets between humans and mice, ISIS 2302 has no pharmacologic activity in mice. ISIS 3082 was specifically designed to inhibit murine ICAM-1 and was included in this study to evaluate the effects of prolonged ICAM-1 inhibition. The oligonucleotides were administered by bolus i.v. injection (via tail vein) every other day for 27 days (14 doses) at dose levels of 0, 0.8, 4, 20, and 100 mg/kg per injection ISIS 2302 or 20 mg/kg per injection ISIS 3082. The basic group size consisted of 10 male and 10 female mice, which were sacrificed 2 days after the last dose and an additional 5 mice per sex in vehicle control and 100 mg/kg ISIS 2302 dose groups, which remained on study for a 28-day treatment-free period. No treatment-related deaths occurred during this study, and there were no effects of either oligonucleotide on body weight gain or food consumption. The most common changes observed in this study included a mixed mononuclear cell infiltrate seen in a number of organs or tissues, splenomegaly, and lymphoid hyperplasia at dose levels of > or = 20 mg/kg ISIS 2302. In the group that received the highest dose level of ISIS 2302 (100 mg/kg), there were alterations in serum chemistry parameters that appeared to be related to perturbations in the liver, including 3- to 4-fold increases in aspartate and alanine aminotransferase and smaller changes in bilirubin, alkaline phosphatase, cholesterol, triglycerides, and albumin levels. Treatment-related effects on hematologic parameters were limited to the 100 mg/kg ISIS 2302 dose group and included slight monocytosis and thrombocytopenia. None of the effects observed appeared to be life threatening. Complete or partial reversal of all effects was evident in the remaining high-dose ISIS 2302 animals at the end of the 4-week recovery period. Comparison of the effects produced by the same dose level (20 mg/kg) of ISIS 2302 and ISIS 3082 did not reveal any differences that could be attributed to exaggerated pharmacology. In conclusion, treatment-related alterations were observed primarily at the 100 mg/kg dose level, including immune stimulation and hepatic alterations, which were partially reversed following a 4-week treatment-free period.
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PMID:Evaluation of the toxicity of ISIS 2302, a phosphorothioate oligonucleotide, in a 4-week study in CD-1 mice. 936 6

To assess the biochemical and histological characteristics of hepatitis G virus (HGV) infection, we examined four patients who were infected with HGV only (HGV group), and compared them with 16 patients infected with both HGV and hepatitis C virus (HCV; HGV + HCV group) and 18 patients infected with HCV only (HCV group). Biochemical examination showed a significantly low level of serum alanine aminotransferase (ALT) in the HGV group, and that the gamma-glutamyl transpeptidase (gamma-GTP)/ALT ratio in the same group was significantly higher than in the other two groups. Although all three patient groups had a similar degree of liver fibrosis, both the degree of periportal inflammation and total histological activity index were significantly lower in the HGV group than in the other two groups. Fibrous enlargement of the portal tract without lymphoid infiltration and thin fibrous septa was characteristically observed in the HGV group. No significant difference was found between the HGV + HCV group and HCV group. Our results suggest that biochemical and histological changes in HGV infection are very mild and quite different from those of HCV infection.
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PMID:Biochemical and histological features of hepatitis G virus infection. 973 67

The administration of concanavalin A (Con A) (0.2 mg/mouse) into mice induced significant elevation of plasma alanine aminotransferase (ALT) at 8.5 hr after Con A treatment. CD8 mRNA, which is a marker of cytotoxic T-cell, was strongly induced at 16 and 24 hr after Con A treatment. Although pretreatment with cyclosporine A (CsA) (50 and 100 mg/kg, i.p.) inhibited Con A-induced elevation of plasma ALT, it did not inhibit Con A-induced CD8 mRNA expression. Morphological study revealed lymphoid cell infiltration in the liver, but the lymphoid cells were not present at the site of hepatocyte necrosis. These results suggest that Con A-induced CD8+ T-cell infiltration has a minimal effect in the development of hepatitis.
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PMID:Effects of concanavalin A treatment on CD8 mRNA expression in mouse liver. 980 70

1. Groups of five male and five female CD-1 mice received a single intravenous injection of gadolinium chloride at dosages of 0 (saline control), 0.05, 0.1 and 0.2 mmol/ kg. All mice were necropsied 48 h post dose. 2. Plasma analysis showed increases in concentrations of lactate dehydrogenase (both sexes), aspartate aminotransferase and alanine aminotransferase (females only) in the 0.2 mmol/kg group. Cholesterol was elevated at all dosages in both sexes whilst globulin was raised in both sexes at 0.1 and 0.2 mmol/kg. 3. Histological lesions were present at all dosages and increased in severity in a dose-related fashion. The most common lesions were: mineral emboli in capillaries, accumulation of mineral in the mononuclear phagocytic system, hepatocellular necrosis, and lymphoid depletion, necrosis and mineralisation in the spleen. 4. Such observations are similar to those in rats given gadolinium chloride and should be assessed when evaluating the toxicological profile of gadolinium containing compounds being developed for nuclear magnetic resonance imaging.
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PMID:Gadolinium chloride toxicity in the mouse. 986 21

The aim of the present study was to investigate the prevalence of hepatitis G virus (HGV) and also hepatitis C virus (HCV) infections in maintenance haemodialysis patients, and to identify extrahepatic sites as HGV reservoirs. HGV RNA was detected in the serum of 6/61 (10%) patients and in the peripheral blood mononuclear cells of 2/61 (3%) patients (one of whom was serum negative). These findings suggest that lymphoid cells constitute an extrahepatic HGV reservoir. HCV RNA was detected in 7/61 (11%) patients. Five of these patients (71%) were identified as carrying HCV genotype 1b. Co-infection with HCV and HGV was detected only in one patient. Haemodialysis patients are at risk for HGV infection, by nosocomial routes or via transfusions. HGV itself does not seem to be an important cause of hepatitis since all six HGV RNA positive patients not co-infected by HCV or HBV showed normal ALT values.
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PMID:Detection of HGV in serum and peripheral blood mononuclear cells of maintenance haemodialysis patients. 1038 66

Hepatic steatosis has been reported as one of the characteristics which discriminates hepatitis C from other forms of hepatitis, besides lymphoid follicles and bile duct damage. However, it is unclear whether or not the presence of hepatitis C virus (HCV) itself is associated with the development of steatosis. The possibility that the HCV itself is directly related to the development of steatosis was examined. The intrahepatic core protein levels, as a marker of the HCV load, were correlated with the presence of steatosis in 43 patients with chronic hepatitis C. Among 43 patients studied by Western blotting, the core protein was detected in the liver in 27 (62.8%). On the other hand, hepatic steatosis was observed in 21 (48.8%) of the 43 patients. Importantly, the core protein was detectable in 19 (90.4%) of the 21 patients with steatosis, while it was detected in only 8 (36.4%) of the 22 patients without steatosis (P = 0.008). However, serum HCV-RNA levels as determined by the Amplicor monitor were not significantly different between patients with and without steatosis. Multivariate analysis showed that the serum alanine aminotransferase level (P = 0. 013), body mass index (P = 0.038), and intrahepatic HCV core protein positivity (P = 0.038) were the independent parameters best predictive of steatosis. These results indicate a close relationship between intrahepatic HCV and the development of steatosis, and suggest a possible role of the HCV itself or core protein in the pathogenesis of steatosis in human chronic hepatitis C.
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PMID:Steatosis and intrahepatic hepatitis C virus in chronic hepatitis. 1045 47

We report a patient, a 23-year-old man, who was a hepatitis B virus(HBV) carrier complicated with nephrotic syndrome. He was admitted to our hospital because of generalized edema and massive ascites. Laboratory data on admission were as follows: proteinuria 9,850 mg/day, Cr 2.7 mg/dl, BUN 73 mg/dl, albumin 1.9 g/dl, cholesterol 501 mg/dl, GOT 23 IU/l, GPT 19 IU/l, HBsAg(+), and HBeAg(222.7). Since his nephrotic symptoms were seriously complicated with renal failure, we selected steroid therapy for nephrosis preference. His renal function was improved and the urinary protein decreased immediately, but his liver function deteriorated. The renal biopsy revealed focal mesangial proliferative glomerulonephritis. Immunofluorescent examination revealed slight deposits of IgG, IgM, and C3 along the glomerular basement membrane and mesangial matrix. He was not compliant and often stopped taking the steroid therapy, thereby causing nephrosis to recur each time. After all, nephrotic symptoms have been well-controlled with cyclosporin and steroid. In spite of the seroconversion of HB virus by formation of HBe antibody, mutant HBV infection continued. The fact that liver biopsy revealed severe lymphoid infiltration at the portal area suggested chronic active hepatitis. His clinicopathologic course suggests that HBV-associated nephropathy does not always remit as there are some cases in whom hepatitis remains in an active state even after seroconversion, due to its mutant status. In these cases, the long-term prognosis of HBV nephropathy has not been defined. Further study is necessary to establish the optimal treatment for HB nephropathy in adults.
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PMID:[A case of hepatitis B virus carrier complicated with nephrotic syndrome]. 1099 20


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