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 hepatitis C virus (HCV) is an RNA virus without apparent cytopathic effects, and hepatocellular damage in chronic infection is generally believed to be immune-mediated by cytotoxic T lymphocytes. Activated T cells release the soluble form of the
interleukin-2
(
IL-2
) receptor (sIL-2R) and its concentration is correlated with the degree of lymphocyte activation. We measured sIL-2R in 69 subjects: 24 healthy repeat blood donors (group I), 17 HCV carriers without liver damage (group II) and 28 patients with HCV-related chronic active hepatitis (group III). There was no significant difference between sIL-2R levels in patients of group I (36.5 +/- 14.6 U ml-1) and group II (46.8 +/- 17.4 U ml-1), and the levels for both of these groups were significantly lower than those observed in the patients with active HCV, group III (176.9 +/- 59.5 U ml-1). Hence, among HCV-infected subjects (HCV RNA positive) with persistently normal
alanine aminotransferase
(
ALT
) levels, the plasma levels of sIL-2R are normal, but, in patients (HCV RNA positive) with HCV-related chronic active hepatitis there are increased plasma levels of sIL-2R. We conclude that in HCV infection high levels of sIL-2R are related to activity of the disease rather than to virus replication. In patients with HCV-related chronic liver disease, the sIL-2R concentration may be a useful marker of disease activity.
...
PMID:In subjects with antibody to hepatitis C virus a high serum level of interleukin-2 soluble receptor suggests activity of liver disease. 957 34
Treatment of mice with concanavalin A (Con A) induced
interleukin-2
(
IL-2
) mRNA expression in the liver, which might be a result of Con A-induced T-cell activation. Pretreatment with cyclosporine A (CsA) (50 mg/kg, i.p.) or dexamethasone (DEX) (2.5 mg/kg, i.p.) inhibited the Con A-induced liver injury, as assessed by the plasma
alanine aminotransferase
level, by 85% and 95%, respectively. CsA inhibited the Con A-induced
IL-2
mRNA expression completely, whereas DEX only partially inhibited it. Thus CsA seems to prevent Con A-induced hepatitis mainly by inhibiting T-cell activation. In the case of DEX, rather than by inhibiting Con A-induced T-cell activation, it may prevent Con A-induced hepatitis through other means.
...
PMID:Effects of immunosuppressants on concanavalin A-induced interleukin-2 mRNA expression in mouse liver. 971 75
The effect of Kupffer cell depression on concanavalin A (Con A)-induced cytokine mRNA expression in the liver was studied. Gadolinium chloride (GdCl3) is a commonly used Kupffer cell inhibitor. GdCl3 (40 mg/kg, i.p.) was injected into each mouse, and 24 hr later, Con A (0.2 mg/mouse) was administered. Plasma was obtained at 24 hr after Con A treatment for
alanine aminotransferase
(
ALT
) measurement. GdCl3 treatment inhibited Con A-induced elevation of
ALT
. However, it did not inhibit Con A-induced
interleukin-2
or tumor necrosis factor-alpha mRNA expression. The present results suggest that Kupffer cells are not responsible for Con A-induced cytokine expression in the liver.
...
PMID:Effect of gadolinium chloride treatment on concanavalin A-induced cytokine mRNA expression in mouse liver. 980 71
To test whether (HCV) persistence is related to interferon (IFN) hyporesponsiveness, peripheral blood monuclear cells from 29 patients and 11 controls were studied for MxA protein expression. In vitro, only IFN-alpha (P<.001) and
interleukin-2
(P<.05) induced MxA protein expression above unstimulated levels. Forty patients were treated with IFN-alpha2b. Patients showed higher basal levels of MxA protein (P<.02) and 2',5'-oligoadenylate synthase (2-5A) activity (P<.05) than controls. During therapy, MxA protein levels (P<.001) and 2-5A activity (P<.05) increased; after 1 month, MxA levels remained high, whereas 2-5A activity declined to initial levels. Increases in MxA were inversely correlated with decreases in serum
alanine aminotransferase
levels, and MxA induction was greater among virological responders. Thus, the IFN system seems to be activated in chronic HCV infection, but HCV appears to modulate these two components of the IFN system differentially. These results suggest that an inefficient response may contribute to virus persistence and affect the therapeutic outcome.
...
PMID:In vivo and in vitro induction of MxA protein in peripheral blood mononuclear cells from patients chronically infected with hepatitis C virus. 1039 38
To study the effects of three kinds of treatment: Zhuling polysaccharides combined with hepatitis B vaccine (group I), LAK cells, induced by
interleukin-2
(
IL-2
) in vitro, transfusion therapy, (group II), bacille Calmette-Guerin (BCG) combined with persatin (group III) in chronic hepatitis B and the mechanism of their effects, we observed 286 patients with chronic hepatitis B, diagnosed according to the criteria made by The 6th National Meeting for Viral Hepatitis and Substantiated by the results of liver biopsy. The patients were divided into 3 treatment groups randomly, with interferon 3 MIU, thrice a week and 10% glucose 500 ml (i.v.) dripping everyday as two different control groups. The
ALT
recovery rates in group I, II, III were 64%, 35% and 57%, respectively. At the end of the treatment, the HBeAg and HBV DNA clearence rates in group I, II, III were 43% and 44%, 34% and 30%, 57% and 61%, respectively. After one year of follow up, the HBeAg and HBV DNA clearence rates in group I, II, III were 59%, 58%, 61% and 55%, 70%, 60%, respectively. The effects of these kinds of treatment were similar to these of interferon. We also injected Zhuling polysaccharides combined with hepatitis B vaccine, Zhuling polysaccharides alone and normal saline as control to DHBV vertical transmission duck. It was shown that serum DHBV DNA was cleared and the results were also proved by liver histologic change in the two treatment groups. According to these data, it is suggested that the three kinds of treatment for hepatitis B could restore the
ALT
level, suppress the replication of HBV and improve the liver histologic change. Their effects were similar to those of interferon.
...
PMID:[A study on the effects of three kinds of treatment in chronic hepatitis B]. 1043 79
Aminoguanidine is an inhibitor of the inducible form of nitric oxide synthase (iNOS). In the present study, the effect of aminoguanidine on concanavalin A-induced hepatitis was examined. Treatment of mice with concanavalin A (10 mg/kg, i.v.) induced interferon-gamma and iNOS mRNA expression in the liver before the elevation of plasma
alanine aminotransferase
activity. Immunohistochemical study showed the induction of iNOS protein expression in the area of necrosis. Aminoguanidine (1, 3 and 10 mg/kg, i.p.) inhibited the concanavalin A-induced elevation of
alanine aminotransferase
activity. Aminoguanidine (10 mg/kg, i.p.) did not inhibit concanavalin A-induced
interleukin-2
, interferon-gamma, tumor necrosis factor-alpha or iNOS mRNA expression in the liver. The plasma nitrite/nitrate level was elevated at 6 and 24 h after concanavalin A treatment. The elevation of nitrite/nitrate was inhibited by aminoguanidine (10 mg/kg, i.p.). From these results, we conclude that nitric oxide formed by iNOS may be involved in the development of concanavalin A-induced hepatitis.
...
PMID:Aminoguanidine prevents concanavalin A-induced hepatitis in mice. 1082 65
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.
...
PMID:T-Cell immune activation in children with vertically transmitted hepatitis C virus infection. 1139 12
Agroclavine is a natural, clavine type of ergot alkaloid with D1 dopamine and a-adrenoceptor agonistic properties. We showed previously that in vitro agroclavine enhances natural killer (NK) cell activity, increases
interleukin-2
and interferon-gamma production and prolongs the survival time of tumor-bearing mice. The aim of this study was 1) to test the effect of agroclavine on NK activity in vivo, and 2) to assess the potential toxicity of high doses of agroclavine on cardiac and liver functions using creatine kinase MB (CKMB) and
alanine aminotransferase
(
ALT
) as biochemical markers in normal and stressed animals. The effect of stress was studied because we examined promising anticancer properties of agroclavine and malignant diseases are supposed to be a potent stressful event for patients. In our experiments 3-month-old male rats of the Wistar-Kyoto strain were used. Agroclavine was injected intraperitoneally (0.5 mg/kg or 0.05 mg/kg) 30 min before stress (four hours' restraint and immersion in 23 degrees C water). The animals were killed 30 min after stress, blood was collected and the spleen was removed. Non-stressed animals treated with agroclavine were killed 5 h after the drug administration. The results confirmed our previous in vitro results and showed that also in vivo agroclavine increases NK cell activity under non-stress conditions. Agroclavine only slightly increased CKMB and had no influence on
ALT
in non-stressed animals. These promising results are limited by the fact that agroclavine (0.5 mg/kg) diminished NK cell activity and significantly increased
ALT
and CKMB under stress conditions.
...
PMID:Effect of agroclavine on NK activity in vivo under normal and stress conditions in rats. 1170 56
To evaluate therapeutic immunostimulation nine chronic hepatitis B patients received six monthly intradermal vaccinations with HBsAg in combination with daily lamivudine. Another five patients received six doses of the vaccine and daily lamivudine together with daily
Interleukin-2
(
IL-2
) s.c. within 3 months in an open-labeled trial. Clinical efficacy was assessed by
alanine transaminase
levels and HBV serology. The induction of specific T and B cell responses was analyzed serially by 3H-thymidine uptake, ELISA and ELISPOT assays. After the therapy was stopped, seven of nine vaccine/lamivudine and two of five vaccine/lamivudine/
IL-2
recipients did not have detectable HBV DNA. Four complete responders cleared the virus and had normalized
ALT
levels, however, one of these patients showed transient disease reactivation followed by spontaneous viral clearance and normal
ALT
five months later. Low frequencies of anti-HBs producing B cells and HBV specific T helper cells secreting predominantly interferon-gamma were induced by i.d. vaccine therapy. The ELISPOT technique demonstrated transient induction of HBV peptide specific cytotoxic T cells in seven HLA-A2 positive chronic HBV carriers. The preliminary data from this study demonstrate that the HBV surface antigen vaccine in combination with antiviral or immunomodulating drugs induced antiviral immune responses and consequently viral elimination may be achieved in patients with unfavorable prognosis.
...
PMID:Clinical and immunological efficacy of intradermal vaccine plus lamivudine with or without interleukin-2 in patients with chronic hepatitis B. 1185 21
Hepatitis C virus (HCV) is remarkably efficient in establishing persistent infection, possibly mediated by an impaired immune response to HCV infection. There is compelling evidence that HCV can infect immune cells, such as macrophages, B cells, and T cells. It has been previously reported that HCV core, the first protein expressed during the early phase of viral infection, contains the immunomodulatory function of suppressing host immune responses. This altered function of immune cells caused by HCV infection may explain the ineffective immune response to HCV. To further characterize the immunomodulatory role of HCV core in vivo, we generated transgenic (TG) mice by directing the expression of core protein to T lymphocytes by using the CD2 promoter. T-lymphocyte responses, including the production of gamma interferon and
interleukin-2
, were significantly diminished in these mice compared to their non-TG littermates. The inhibition of T-lymphocyte responsiveness may be due to the increased susceptibility of peripheral T lymphocytes to Fas-mediated apoptosis. Surprisingly, significant lymphocyte infiltration was observed in the portal tracts of livers isolated from core TG mice, associated with increasing serum
alanine aminotransferase
levels. Moreover, no intrahepatic lymphocytes or liver damage was found in non-TG littermates and core TG mice bred to Fas-deficient lpr mice. These results suggest that HCV core drives liver injury by increasing Fas-mediated apoptosis and liver infiltration of peripheral T cells.
...
PMID:Hepatitis C virus core protein leads to immune suppression and liver damage in a transgenic murine model. 1218 17
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