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

---

Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The percentage of lymphocyte subsets from the peripheral blood of healthy adults and hepatitis B surface antigen (HBsAg) carriers were analyzed by flow cytometry. The five lymphocyte subsets studied were:- T (CD3) cells, B (CD19) cells, CD4 cells, CD8 cells, Natural Killer (CD3- CD16+/CD56+) cells (NK cells) and the CD4/CD8 ratio. The percentage (mean +/- SD) for the five lymphocyte subsets from the healthy adults were (67.5 +/- 8.5)%, (12.4 +/- 4.5)%, (35.5 +/- 7.8)%, (36.8 +/- 8.5)%, (17.9 +/- 8.1)% and 1.1 +/- 0.6, respectively. HBsAg carriers positive for HBV-DNA had a lower CD4/CD8 ratio than the healthy population (P = 0.030). The percentage of CD8 cells in HBsAg carriers increased significantly (r = 0.28; P = 0.019) with an increase in ALT levels but the values remained within normal range. The percentage of NK cells and CD4/CD8 ratio in HBsAg carriers positive for anti-HBe were higher than HBsAg carriers negative for anti-HBe (92% of which are HBeAg positive) (P = 0.045 and P = 0.035, respectively). The CD4/CD8 ratio in HBsAg carriers negative for anti-HBe (92% positive for HBeAg) was also lower than in the healthy population (P = 0.042). HBsAg carriers positive for HBV-DNA, HBeAg and raised ALT levels had a lower CD4/ CD8 ratio than did the healthy population. The lower ratio was due to an increase in the percentage of CD8 cells. This suggests an activated immune response triggered by the infection in an attempt to clear the virus. HBsAg carriers with normal ALT levels and who are negative for HBV-DNA may be in a state of tolerance.
...
PMID:The cellular immune status of HBsAg-positive carriers in Malaysia. 898 Jul 96

Concanavalin A (Con A) can induce an immune-mediated hepatitis. Since direct evidence of immune mechanism for this hepatitis is lacking, we employed adoptive transfer to study the mechanism of Con A-induced hepatitis. Intravenous administration of Con A (20 mg/kg) to Balb/c mice was accompanied by elevations of serum alanine aminotransferase (ALT) levels and midzonal necrosis with lymphocyte infiltration in the liver. None of the Balb/c nu/nu mice showed biochemical or pathologic hepatic abnormalities with the same dose of Con A. In the area of midzonal necrosis, CD4-positive T lymphocytes appeared at 24 hr after injection, and then both CD4-positive and CD8-positive T lymphocytes were found at the margin of zonal necrosis at 48 hr. Pretreatment with carrageenan, a potent inhibitor of macrophages, prevented these biochemical and pathologic changes. Mononuclear cells infiltrating in the liver of Balb/c mice 24 hr after priming with Con A were harvested and injected into Balb/c nu/nu mice injected with Con A 24 hr previously. Serum ALT levels elevated and the same pathologic changes observed in Con A-treated Balb/c mice were observed. These changes were not observed when the splenic cells from Con A-treated Balb/c mice were transferred to Con A-treated nude mice. These results suggest that Con A-induced hepatic injury is mediated by macrophages and T lymphocytes sensitized by Con A or its metabolites.
...
PMID:Midzonal necrosis of the liver after concanavalin A-injection. 911 63

1. This study was performed to test the hypothesis that the exercise-induced increase in circulating cytokine levels is associated with muscle damage. Nine healthy young male subjects performed two high-intensity bicycle exercise trials separated by two weeks. The first trial consisted of 30 min of normal bicycle exercise (concentric exercise), whereas the second consisted of 30 min of braking with reversed revolution (eccentric exercise). The work loads were chosen to give the same increases in heart rate and catecholamine levels in the blood during each trial. 2. Significant increases (P < 0.05) in plasma concentration of creatine kinase (CK), aspartate aminotransferase and alanine aminotransferase were observed only after the eccentric exercise. Furthermore, the level of interleukin-6 (IL-6) in serum increased significantly after the eccentric exercise and was significantly correlated to CK concentration in the following days, whereas no significant changes were found after the concentric exercise. 3. The total concentration of lymphocytes increased significantly (P < 0.05) as a result of eccentric compared with concentric exercise. This was mainly due to a significantly more pronounced recruitment of natural killer (NK) cells and CD8 positive cells (CD8+ cells) during the eccentric trial. However, no significant differences between the two types of work were found in regard to the circulating concentration of monocytes. The concentration of neutrophils was only significantly increased 2 h after the concentric exercise. 4. The finding that high-intensity eccentric exercise caused a more pronounced increase in the plasma level of IL-6, compared with concentric exercise, supports the hypothesis that the post-exercise cytokine production is related to skeletal muscle damage. The fact that no differences between eccentric and concentric exercise were found in the recruitment of most blood mononuclear cell subsets to the blood supports the hypothesis that the exercise-induced increase in plasma catecholamines is a major determinant of the mobilization of these cells into the blood. However, as eccentric exercise caused a more pronounced increase in the concentration of NK cells and CD8+ cells, factors involved in muscle damage may also contribute to the recruitment of these cells.
...
PMID:Exercise-induced increase in serum interleukin-6 in humans is related to muscle damage. 913 Jan 76

Soluble HLA-class I and CD8 molecules were determined by sandwich ELISA in patients with viral-induced hepatic disorders. As a whole, the patients with hepatic disorders (acute hepatitis: AH; chronic hepatitis: CH; liver cirrhosis: LC; hepatocellular carcinoma: HCC) showed higher sHLA-class I and sCD8 levels than normal controls (P < 0.001). AH patients had the highest sHLA-class I levels (mean, 3513 +/- 2112 ng/ml), followed by CH (2896 +/- 1290 ng/ml), LC (2293 +/- 1266 ng/ml), and HCC (2221 +/- 1212 ng/ml) sCD8 levels wer highest in AH, followed by HCC, LC, and CH, in that order. Among histologically defined C virus-positive patients, sHLA-I levels were higher in those with chronic active hepatitis (CAH) 2A (3802 +/- 1124 ng/ml) than in those with chronic persistent hepatitis (CPH; 2200 +/- 711 ng/ml; P < 0.01), the levels then decreased as the disease progressed (CAH2B, 3564 +/- 1783 ng/ml, LC, 2376 +/- 1265 ng/ml). In contrast, sCD8 values showed little difference among the disorders. sHLA-class I levels showed a positive correlation with sCD8 values both in whole patients and in patients with AH (P < 0.01), but no correlation was shown, in any patients, with biochemical parameters such as GPT and GOT. These findings, taken together, suggest that hepatic destruction is not the only cause of sHLA-class I production, but that sHLA-class I levels, together with sCD8 levels, may reflect immunological activity in hepatic disorders.
...
PMID:Serum concentrations of soluble HLA-class I and CD8 forms in patients with viral hepatic disorders. 921 47

The success of orthotopic liver transplantation is dependent on multiple factors including MHC tissue compatibility and ischemic/reperfusion injury. Ischemic/reperfusion (I/R) injury in the liver occurs in a biphasic pattern consisting of both acute phase (oxygen free radical mediated) and subacute phase (neutrophil-mediated) damage. Although numerous studies have given insights into the process of neutrophil recruitment after I/R injury to the liver, the exact mechanism that initiates this subacute response remains undefined. Using a T cell-deficient mouse model, we present data that suggests that T-lymphocytes are key mediators of subacute neutrophil inflammatory responses in the liver after ischemia and reperfusion. To this end, using a partial lobar liver ischemia model, we compared the extent of reperfusion injury between immune competent BALB/c and athymic nu/nu mice. Studies evaluating the extent of liver damage as measured by serum transaminases (GPT) demonstrate similar acute (3-6 h) post-I/R responses in these two mouse models. In contrast, the subacute phase (16-20 h) of liver injury, as measured by both serum GPT levels and percent hepatocellular necrosis, was dramatically reduced in T cell-deficient mice as compared with those with an intact immune system. This reduction in liver injury seen in nu/nu mice was associated with a 10-fold reduction in hepatic neutrophil infiltration. Adoptive transfer of T cell-enriched splenocytes from immune competent mice was capable of reconstituting the neutrophil-mediated subacute inflammatory response within T cell-deficient nu/nu mice. Furthermore, in vivo antibody depletion of CD4(+) T-lymphocytes in immune competent mice resulted in a reduction of subacute phase injury and inflammation as measured by serum GPT levels and neutrophil infiltration. In contrast, depletion of CD8(+) T-lymphocytes had no effect on these indexes of subacute inflammation. Kinetic analysis of T cell infiltration in the livers of BALB/c mice demonstrated a fivefold increase in the number of hepatic CD4(+) T-lymphocytes within the first hour of reperfusion with no significant change in the number of CD8(+) T-lymphocytes. In summary, these results implicate CD4(+) T-lymphocytes as key regulators in initiating I/R-induced inflammatory responses in the liver. Such findings have implications for therapy directed at the early events in this inflammatory cascade that may prove useful in liver transplantation.
...
PMID:CD4(+) T-lymphocytes mediate ischemia/reperfusion-induced inflammatory responses in mouse liver. 921 4

We examined the relationship between the changes of serum soluble CD8 (sCD8) and soluble interleukin-2 receptor (sIL-2R) levels and effectiveness of interferon (IFN) in patients with chronic hepatitis (CH) C. Changes in sCD8 levels were parallel with fluctuations of alanine aminotransferase (ALT) in CH patients during IFN treatment but decreases of sCD8 levels were slower than those of ALT. In IFN effective and ALT decreased patients sCD8 levels is also decreased. sIL-2R levels was increased transiently during administration of IFN in most cases. It was suggested that decrease in sCD8 levels is indicative of the effectiveness of IFN therapy.
...
PMID:[Serum soluble CD8 and soluble interleukin-2-receptor levels during interferon therapy in chronic hepatitis C]. 936 80

The impact of human immunodeficiency virus (HIV) protease inhibitors on hepatitis C (HCV) viremia was assessed in 19 patients infected with both HIV and HCV. HIV and HCV RNA levels were measured before and during treatment with protease inhibitors. Before treatment, mean levels of HCV RNA were 5.3 log for HCV RNA and 5.0 log for HIV RNA. CD4 lymphocyte counts were 63/mm3. After 6 weeks of treatment, a mean reduction of 2.1 log10 in HIV RNA (P < .001) and a mean (+/-SE) increase of 73 (+/-21) CD4 and 296 (+/-70) CD8 cells were observed (P < .05). In contrast, both HCV viremia (+0.4 log +/- 0.1) and alanine aminotransferase increased (P < .04). HCV RNA levels returned to baseline after 17 and 32 weeks of treatment. Thus, potent anti-HIV regimens with protease inhibitors may temporarily worsen HCV status despite improvement of HIV parameters.
...
PMID:Impact of treatment with human immunodeficiency virus (HIV) protease inhibitors on hepatitis C viremia in patients coinfected with HIV. 1039 89

Conditional gene expression has greatly facilitated the examination of the functions of particular gene products. Using the Cre/loxP system, we developed efficient conditional transgene activation of hepatitis C virus (HCV) cDNA (nucleotides 294-3435) in transgenic mice. Efficient recombination was observed in transgenic mouse liver upon intravenous administration of adenovirus that expresses Cre DNA recombinase. After transgene activation, most hepatocytes were stained with anti-core polyclonal antibody, and 21-, 37-, and 64-kDa proteins were detected by Western blot analysis in liver lysates using anti-core, E1, and E2 monoclonal antibodies, respectively. Serum core protein was detected in transgenic mice 7 days after transgene activation with concurrent increases in serum alanine aminotransferase levels. Subsequently, an anti-core antibody response was detected 14 days after infection. Furthermore, a CD4 and CD8 positive cell depletion assay normalized both the serum alanine aminotransferase increases and pathological changes in the liver. These results suggest that HCV proteins are not directly cytopathic and that the host immune response plays a pivotal role in HCV infection. Thus, this HCV cDNA transgenic mouse provides a powerful tool with which to investigate the immune responses and pathogenesis of HCV infection.
...
PMID:Efficient conditional transgene expression in hepatitis C virus cDNA transgenic mice mediated by the Cre/loxP system. 953 87

The kinetics of lymphocyte function associated antigen 1 (LFA-1) expression on spleen cells (SPC) and liver non-parenchymal cells (NPC), and intercellular adhesion molecule 1 (ICAM-1) expression on hepatocytes (HC) was examined in acute liver injury mice induced by a DTH reaction to picryl chloride (PCl). The peak expression of LFA-1 on SPC was seen at 6 hr after eliciting liver injury, and then that of LFA-1 on NPC and ICAM-1 on HC appeared at 12 hr. Thereafter, the serum ALT elevation reached to a peak at 18 hr. A splenectomy before the PCl elicitation significantly reduced the ALT elevation. Both SPC and NPC from liver injury mice induced a remarkable release of ALT from HC in vitro, in parallel with their LFA-1 expression. The pre-treatment of NPC or SPC with anti-LFA-1 mAb, irrespective of the presence of complement, completely blocked the ALT release. Also, when HC was prebound with anti-ICAM-1 mAb, neither NPC nor SPC showed a cytotoxicity against the HC. Furthermore, the treatment of NPC with either anti-Thy1.2 or anti-CD4 mAb in the presence but not absence of complement, showed a complete abolishment of ALT release. Anti-CD8 mAb plus complement also tended to inhibit ALT release. The twofold increase in CD4+ LFA-1+ and mild increase in CD8+ LFA-1+ populations were also confirmed in NPC at 12 hr. These results suggest that PCl elicitation in liver may trigger an increased expression of LFA-1 on SPC and NPC and ICAM-1 on HC. LFA-1/ICAM-1 interaction between liver-infiltrating NPC, mainly including CD4+ and CD8+ T cells, and HC may be an essential step for the hepatocyte damage in PCl-DTH liver injury.
...
PMID:LEA-1/ICAM-1 interaction is essentially involved in the pathogenesis of delayed-type hypersensitivity-induced liver injury to picryl chloride. 956 70

Propagermanium is an organic germanium compound with immunopotentiating activity. We examined the hepatoprotective effect of propagermanium and its mechanism in an experimental animal model of acute liver injury induced with Corynebacterium parvum (C. parvum) and lipopolysaccharide (LPS) injection. Oral pretreatment with propagermanium decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity in a dose-dependent manner. Significant attenuation of ALT and AST activity was obtained at a dose of 3 mg/kg. Administration of propagermanium also inhibited the infiltration of mononuclear cells into the liver of mice induced by C. parvum/LPS. Immunohistochemical examination revealed infiltration of the liver by CD4-, CD8-, CD11b- and Gr-1-positive cells. Propagermanium prevented CD4- and CD11b-positive cells from infiltrating the liver. In this animal model, blood cytokine levels increased rapidly after LPS injection, causing severe hepatitis. Notably, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) are important mediators of the progress of liver injury. We demonstrated that propagermanium reduced IFN-gamma production by 53% at a dose of 3 mg/kg and also significantly inhibited the production of interleukin-12 (IL-12). These results indicate that propagermanium inhibits cell infiltration in the liver and cytokine production, and improves massive liver injury in C. parvum/LPS mice.
...
PMID:Hepatoprotective effect of propagermanium on Corynebacterium parvum and lipopolysaccharide-induced liver injury in mice. 971 10


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---