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)

In the present study, intrahepatic CD8+ lymphocyte infiltrates as well as HLA class I and CD54 (ICAM-1) antigen expression at both tissue and serum levels were evaluated in 54 untreated patients with chronic hepatitis C stratified on the basis of histological diagnosis (Chronic Persistent Hepatitis/Chronic Lobular Hepatitis -CPH/CLH- and Chronic Active Hepatitis -CAH-: 22 and 32 subjects, respectively). The relationships between soluble HLA-I (sHLA-I) and ICAM-1 (sICAM-1) serum levels and their membrane-bound counterparts, CD8+ liver infiltration and serum alanine aminotransferase (ALT) were also studied. A strong HLA-I and CD54 tissue expression, associated to the presence of CD8+ cell infiltrates in necro-inflammatory areas, and elevated sHLA-I and sICAM-1 serum amounts were observed in all patients. At the same time, no difference was found at tissue level between the two groups of patients with respect to the mean scores of HLA-I and CD54 expression, while CAH subjects displayed a significantly higher CD8 periportal and lobular reactivity in comparison to the other subset. Serological assays outlined higher values of circulating HLA-I molecules in CPH/CLH patients and higher sICAM-1 levels in the CAH group. Finally, a negative correlation was found between sHLA-I and ALT in CAH subjects while, in all patients, sICAM-1 positively correlated with both CD8 tissue infiltration and ALT. Our findings confirm the occurrence of an immune activation status during chronic hepatitis C and suggest that sHLA-I molecules might play a down-modulating role on immunoresponsiveness of these patients.
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PMID:Immunoresponsiveness in chronic hepatitis C patients: correlation between tissue and serum findings. 973 40

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

A 25-year-old man was referred because of skin rash, lymphadenopathy and anemia. Laboratory examinations revealed severe anemia (Hb, 4.8 g/dl) and elevated levels of GOT, GPT, LDH and soluble interleukin-2 receptor. Work-up studies disclosed the involvement of lymphoma cells in lymph nodes, skin, bilateral kidneys and bone marrow. Lymph node biopsy revealed diffuse proliferation of medium- to large-sized lymphoblastic cells. Bone marrow aspiration showed massive infiltration of large blastic cells with no cytoplasmic granules. The lymphoma cells in bone marrow and lymph node showed surface CD3-, cytoplasmic CD3epsilon+, CD4+, CD8-, CD56+, CD57-, CD16- and CD43 (MT-1)+ phenotype. Analyses of T cell receptor beta and gamma genes showed germ line configurations. EBER-1 was not detectable in the lymphoma cells. He was diagnosed as having blastoid natural killer (NK) cell lymphoma. In spite of several courses of combination chemotherapy, the lymphoma was progressive. He was then treated with high-dose chemotherapy and peripheral blood stem cell rescue, achieving remission which has now lasted for more than 12 months. We consider that blastoid NK cell lymphoma is an extremely aggressive subtype of CD56-positive lymphomas, and high-dose chemotherapy with peripheral blood stem cell rescue should be included for the choice of the treatment.
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PMID:High-dose chemotherapy with peripheral blood stem cell rescue in blastoid natural killer cell lymphoma. 1004 32

To investigate the roles of intrahepatic T cells in liver injury after Salmonella infection, we examined serum alanine transaminase (ALT), histopathology, and bacterial numbers in liver after infection with Salmonella choleraesuis strain 31N-1 in mice genetically lacking TCRalpha beta+, CD4(+), CD8(+), or NK1.1(+)T cells with C57BL/6 background. In control (+/+) mice, serum ALT reached a peak level by day 7 after an intraperitoneal inoculation of 2 x 10(6) CFU Salmonella choleraesuis 31N-1. In TCR-beta-/- mice, liver injury, as assessed by serum ALT level and histological examination, was significantly suppressed on day 7 after Salmonella infection but the numbers of bacteria in liver did not differ from those in normal mice, suggesting that alpha beta T cells are responsible for liver injury induced by Salmonella infection. To further determine which subsets in alpha beta T cells are important for the liver injury, we compared serum ALT level in mice genetically lacking CD4, CD8, beta2-microglobulin (beta2m, IAbeta, or Jalpha281 after Salmonella infection. In CD4(-/-) mice, serum ALT was significantly lower in comparison with control mice, but there was no difference in serum ALT levels in CD8(-/-) and IAbeta-/- mice from that in control mice. Notably, serum ALT levels and pathological lesions in liver were significantly decreased in beta2m-/- or Jalpha281(-/-) mice, which lacked in NK1.1(+) T cells bearing TCR Valpha14-Jalpha281 specific for beta2m-associated CD1d, following Salmonella infection. Taken together, it is suggested that alpha beta T cells bearing NK1.1 and CD4 may be main effector cells for liver injury after Salmonella infection.
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PMID:The roles of intrahepatic Valpha14(+) NK1.1(+) T cells for liver injury induced by Salmonella infection in mice. 1034 23

In hepatitis C virus (HCV) infection, mechanisms responsible for liver cell damage are still poorly understood and both necrosis and apoptosis may be operative. By using terminal deoxynucleotydil transferase-mediated d-UTP-biotin nick-end labeling (TUNEL) we have evaluated and quantified apoptosis in liver biopsy specimens from 61 patients with chronic hepatitis C. All patients had detectable apoptotic cells in the liver. Presence of increased apoptotic activity was confirmed in selected cases by electron microscopy and by DNA gel electrophoresis. The amount of liver cell apoptosis expressed as apoptotic index, ranged between 0.01% to 0.54% and showed a positive correlation with histological activity grading (P <.0005) and with the amount of infiltrating CD8-positive cells (P =. 01). Apoptosis did not correlate with transaminase levels or with HCV load and genotype. These results support the concept that immune-mediated apoptosis may play a role in the pathogenesis of chronic hepatitis C and indicate that this type of reaction may occur in the absence of significant alanine transaminase (ALT) elevation, thus explaining the lack of correlation between biochemical activity and liver histological damage.
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PMID:Liver cell apoptosis in chronic hepatitis C correlates with histological but not biochemical activity or serum HCV-RNA levels. 1079 92

In order to assess the relationship between human immunodeficiency virus (HIV) RNA, hepatitis C virus (HCV) RNA, CD4, CD8, and liver enzymes during combination antiretroviral therapy, these parameters were measured in 12 HIV-HCV-coinfected patients (who were naive for antiretrovirals) on the day before and 3, 7, 14, 28, 56, and 84 days after initiating the following treatments: stavudine and lamivudine in all patients, indinavir in 6 patients, and nevirapine in 6 patients. HIV RNA declined rapidly, CD4 cells increased slowly, and CD8 cells and liver enzymes were stable. HCV RNA showed a transient significant increase at days 14 and 21 (7.33+/-0.16 [mean +/- SE] and 7.29+/-0.2 log copies/mL vs. 7+/-0.2 log copies/mL at baseline; P<.05). These changes were similar in both treatment groups. A 2-fold alanine aminotransferase increase was observed in 4 of 12 patients; 4 of 4 patients showed increased HCV RNA. The relationship between HCV RNA increase and HIV RNA decrease indicates virus-virus interference. An HCV RNA increase may cause significant liver damage only in a minority of patients.
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PMID:Liver damage and kinetics of hepatitis C virus and human immunodeficiency virus replication during the early phases of combination antiretroviral treatment. 1268 26

Carbon tetrachloride (CCl(4)) is an environmental contaminant that has been detected in ambient air, seawater, surface-water and snow. The immunotoxic potential of CCl(4) was evaluated in female B6C3F1 mice. The animals were administered with CCl(4) daily for 14 days at doses of 50, 100, 500 or 1000 mg/kg body weight by gavage with corn oil as a vehicle. Exposure to CCl(4) resulted in an increase of liver weight but not the body weight and the weights of brain, spleen, lungs, thymus and kidneys. Exposure to CCl(4) produced minimal effect on differential hematological parameters; however, it produced a significant increase in serum glutamic-pyruvic transaminase (SGPT) levels in all dose groups while other serum chemistries showed sporadic increases, primarily at the dose level of 1000 mg/kg. Exposure to CCl(4) produced a decreased humoral immune response; the IgM antibody forming cell (AFC) response to sheep red blood cells (sRBC) was suppressed with the maximal decrease (45%) observed at the dose level of 1000 mg/kg. The IgM serum titer to sRBC was also reduced with a maximal decrease (54%) observed at the dose level of 500 mg/kg. Although exposure to CCl(4) had no effects on the mixed leukocyte response (MLR), cytotoxic T lymphocyte activity and natural killer (NK) cell activity, a decrease in both the absolute number and the percentage of CD4(+)CD8(-) at the dose level of 500 mg/kg was observed. The functional activity of the mononuclear phagocyte system was compromised as reflected by a decrease in the vascular clearance of (51)Cr-sRBC and a decrease in the uptake of (51)Cr-sRBC by the liver. Finally, in the two host resistance models evaluated, exposure to CCl(4) decreased host resistance to both Streptococcus pneumoniae and Listeria monocytogenes with greater susceptibility to the latter. Overall, these studies demonstrate that CCl(4) was immunosuppressive in female B6C3F1 mice.
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PMID:Carbon tetrachloride is immunosuppressive and decreases host resistance to Listeria monocytogenes and Streptococcus pneumoniae in female B6C3F1 mice. 1111 73

The impact of dengue on liver function was studied on fifty serologically confirmed dengue cases admitted to Hospital Universiti Kebangsaan Malaysia (HUKM). Twenty-five of these patients had classic dengue fever (DF) and 25 had grade 1 or 2 dengue hemorrhagic fever (DHF). There were more (60%) DHF patients with hepatomegaly compared to DF (40%) but the difference was not statistically significant. Analysis of the liver profile showed that liver dysfunction was commoner in DHF compared to DF, indicating that the degree of liver impairment may be related to the severity of DHF. Hyperbilirubinemia was noted in 3 (12%) DHF and 2 (8%) DF patients. The mean (range) serum bilirubin was higher in DHF [14.2(5-50) micromol/l] compared to DF [10.9(5-30) micromol/l)] (p > 0.05). Elevated levels of serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were observed more frequently in DHF (20 and 12 patients respectively) compared to DF (16 and 8 patients respectively). Nine (36%) DHF and 6 (24%) DF patients had concomitant elevation of ALT and ALP levels. The mean (range) serum ALT levels were 109.3(23-325) U/l in DHF and 90.8(13-352) U/l in DF (p > 0.05). The mean (range) serum ALP levels were 102.2(15-319) U/l in DHF and 93.3(34-258) U/l in DF (p > 0.05). The ALT and ALP levels were significantly higher in DHF patients with spontaneous bleeding than those without bleeding (p < 0.05) None of the patients developed fulminant hepatitis. The immunoregulatory cells, which include the T (CD3), B (CD 19), CD4, CD8, CD5 and natural killer (NK) cells were significantly lower in DHF compared to DF patients (p < 0.05). However, the reduction in these cell counts did not correlate with the liver dysfunction seen in DHF patients. In conclusion, hepatomegaly and liver dysfunction were commoner in DHF compared to DF.
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PMID:A comparison of the pattern of liver involvement in dengue hemorrhagic fever with classic dengue fever. 1112 22

Immunity to allogeneic MHC Ags is weak in rodent livers, raising questions as to the mechanisms that might control responses in this organ. Infection with an adenovirus vector reveals that T cell-mediated immunity to nonself-Ags in the liver is self-limiting. Virus-induced liver injury decreases and coincides with disappearance of virus-specific CTL, concomitant to an increase of apoptotic T cells early after infection. But whereas death in CD4 cells is independent of Fas, perforin, and TNF-alpha, that of CD8 cells requires Fas and not perforin or TNF-alpha pathways. Fas ligand is expressed on liver-infiltrating cells, pointing to death by fratricide that causes almost complete disappearance of virus-specific CTL 4 wk after infection. CTL elimination is virus dose dependent, and high doses induced high alanine aminotransferase values, elevated expression of Fas ligand on CD8 cells, and increased CD8 cell migration into the infected liver.
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PMID:Fas-mediated apoptosis causes elimination of virus-specific cytotoxic T cells in the virus-infected liver. 1120 53

The present study demonstrates that the quality of the virus-specific CD8(+) T cell responses, as detected by both enzyme-linked immunospot assay and specific MHC-peptide tetramers, changed in relation to the different disease activity in chronically hepatitis C virus-infected patients. Indeed, both the serum alanine transaminase and the hepatic flogosis levels were related directly to the frequencies of peripheral memory effector CD8(+) T cells producing IFN-gamma (Tc1), but inversely to the frequencies of those producing both IL-4 and IL-10 (Tc2). Longitudinal studies highlighted that Tc1 or Tc2 responses fluctuate in relation to the different phases of the disease in the same individual. Furthermore, the Tc1 or Tc2 phenotype correlates with tetramer-positive cells expressing either CXCR3 or CCR3, promoting differential tissue localization of these cells and the maintenance of T cell homeostasis. Finally, studies at the level of liver-infiltrating lymphocytes indicated that they produced both IFN-gamma and IL-4 with an evident bias towards the Tc1-like phenotype. Our studies suggest that the progressive fluctuation of Tc1 and Tc2 responses may play a fundamental role in maintaining a long-lasting low-level liver inflammation, and may constitute the basis for new therapeutic strategies of immune regulation.
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PMID:Virus-specific CD8(+) T cells with type 1 or type 2 cytokine profile are related to different disease activity in chronic hepatitis C virus infection. 1124 Dec 95


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