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)

Eight patients with metastatic hypernephroma were treated with constant infusion recombinant Interleukin-2 (rIL-2), changes in renal and hepatic function and protein levels were monitored during 2 cycles of treatment. The rIL-2 infusion caused a reversible fall in ures and a non-reversible rise in creatinine. Liver function tests (bilirubin, ALT, ALP and GGT) rose during rIL-2 treatment and had returned to pretreatment levels 3 weeks after the last day of rIL-2. There was also a reversible fall in serum protein levels during rIL-2 infusion. Although constant infusion rIL-2 ameliorated much of the severe toxicities usually seen with high-dose bolus rIL-2, the non-reversible rise in serum creatinine levels is not a previously reported feature of rIL-2 therapy.
 ...
PMID:Changes in biochemical laboratory investigation in patients treated with constant infusion recombinant interleukin-2. 177 40

The systemic administration of interleukin-2 (IL-2) can lead to significant antitumor responses in some patients with metastatic cancer in whom standard therapy has failed. A limitation of this immunotherapy is the toxicity associated with IL-2 infusion. To assess toxicity, we determined aspartate aminotransferase (AST; EC 2.6.1.1), alanine aminotransferase (ALT; EC 2.6.1.2), gamma-glutamyltransferase (GGT; EC 2.3.2.2), lactate dehydrogenase (LD; EC 1.1.1.27), alkaline phosphatase (ALP; EC 3.1.3.1), creatine kinase (CK; EC 2.7.3.2), total bilirubin (TBI), direct bilirubin (DBI), creatinine, urea nitrogen, and C-reactive protein in serum from 21 patients before and during five consecutive days of IL-2 treatment. Ten patients were followed for an additional five days after the end of IL-2 therapy. The IL-2 infusion caused liver toxicity and prerenal azotemia, as evidenced by significant increases (P less than 0.05) of all analytes except CK by day 1. There was a progressive increase in the results (except CK) for these tests until IL-2 treatment was stopped. Seven tests related to liver function (AST, ALT, GGT, LD, ALP, DBI, and TBI) showed increases, but the test results indicated significant improvement and moved toward the baseline value five days after the end of IL-2 therapy. Concentrations of creatinine and urea nitrogen in serum were normal three days after the cessation of IL-2 therapy.
 ...
PMID:Changes in laboratory results for cancer patients treated with interleukin-2. 231 Dec 9

Chronic hepatitis B virus (HBV) infection is a serious problem because of its world wide distribution and possible adverse chronic sequalae such as cirrhosis and hepatocellular carcinoma. Over the past 20 years, many antiviral or immunomodulatory agents, or both, have been used in patients with chronic HBV infection. Among immunomodulatory agents, levamisole, BCG, picibanil and interleukin-2 have been shown to be ineffective. Corticosteroid therapy is also ineffective and can cause deleterious effects in chronic HBV infection. Thymosin-alpha 1 therapy is currently in phase III clinical trial. Among antiviral agents, acyclovir, dideoxynucleosides, suramin, zidovudine and ganciclovir have been shown to be ineffective and have intolerable side effects. While adenine arabinoside (Ara-A) and its monophosphate derivative (Ara-AMP) are effective agents if the treatment course is long enough, they have been withdrawn from investigative use because of their substantial neuromuscular toxicity. Interferon-alpha may directly inhibit HBV replication and enhance hepatocyte HLA class I antigen expression with subsequent increase of T-cell mediated cytotoxicity. Randomized, controlled clinical trials have shown that 25% to 50% of adult patients with elevated alanine transaminase (ALT) levels lost HBeAg and HBV-DNA when treated with IFN-alpha at a dose of 5MU daily or 10 MU three times a week for 3 to 6 months. In view of the fact that the response rate is far from satisfactory, particularly in Asian patients, combination therapies including interferon alpha with Ara-AMP, acyclovir, didoxynucleoside or interferon-gamma have been studied. Most forms of combination therapy have been shown to be of limited effect.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Drug therapy in patients with chronic type B hepatitis]. 754 84

To evaluate whether hepatocellular protein adducts of the nonsteroidal antiinflammatory drug diclofenac could elicit a specific cell-mediated or antibody-dependent immune response that eventually results in liver cell destruction, we developed a murine ex vivo/in vitro mixed lymphocyte hepatocyte culture (MLHC) model. C57BL/6 mice were immunized either with diclofenac conjugated to keyhole limpet hemocyanin (KLH) or with KLH alone. Splenocytes from mice exhibiting hgih antidiclofenac antibody titers were isolated and co-cultured at an effector/target cell ratio of 100:1 with syngeneic murine hepatocytes preexposed to diclofenac. By 48 and 72 hours, extracellular alanine transaminase (ALT) activity had increased 6.4- and 7.6-fold, respectively, versus the 24-hour value. In contrast, there was no significant cytotoxic response after either drug treatment alone or immunization alone. Furthermore, those cellular populations capable of inducing ALT release also showed lymphocyte stimulation as determined by interleukin-2 (IL-2) receptor expression and lymphocyte proliferation analysis. The extent of cell injury was highest in the presence of lymphocytes highly enriched in T cells and was reduced by 40% in the presence of anti-MHC I antibodies. Similarly, albeit to a lesser extent, non-T cell-enriched lymphocyte fractions also induced hepatocyte injury. The addition of co-culture supernatants to hepatocytes had no effect, thus ruling out the possibility that soluble factors alone mediated the cell injury. However, supernatants from diclofenac-stimulated lymphocytes, combined with nonstimulated splenocytes, triggered an immediate (< 1 hour) cytotoxic response, suggesting antibody-dependent cell-mediated mechanisms of target cell injury. These results indicate that diclofenac-treated hepatocytes carried antigenic determinants that were recognized by T cells and non-T cells derived from diclofenac/KLH-immunized mice, resulting in cell-mediated destruction of the target hepatocytes.
 ...
PMID:Cytotoxic activity of T cells and non-T cells from diclofenac-immunized mice against cultured syngeneic hepatocytes exposed to diclofenac. 760 15

To assess the degree of immune system activation associated with addiction or hepatotropic viruses infection, we examined 60 HIV-negative heroin addicts for the presence of hepatitis B virus (HBV) infection markers, hepatitis C virus antibodies (anti-HCV), various auto-antibodies, and serum levels of soluble interleukin-2 receptors (sIL-2R). In addition, 28 anti-HCV positive patients comprising the disease control group, were also examined. Our results demonstrated a high prevalence of anti-HCV antibodies (61.7% and 90% with 1st and 2nd generation ELISA, respectively). Eighty-seven percent (87%) of the addicts positive for anti-HCV by the latter and 92.8% of the disease control patients, were also positive with 2nd generation recombinant immunoblot assay (RIBA-II). In 88.9% of anti-HCV positive addicts, antibody to C22-3 was the predominant (anti-C33c in 81.5%). Antibodies to C33c and C22-3 polypeptides were also more frequent in disease control group (92.8% and 85.7%, respectively). Anti-HCV antibodies were associated with increased transaminases (ALT or AST, P < 0.05), as well as with longer duration of addiction (P < 0.005). HBV infection markers (HBsAg, anti-HBc only and anti-HBs) were also present in the addicts (5%, 28.3% and 26.7%, respectively). Rheumatoid factors (RF) were detected in 36.7%, antinuclear antibodies (ANA) in 11.7%, antibodies (IgG and/or IgM) against cardiolipin (anti-CL) and double stranded DNA (anti-ds DNA) in 20% and 50%, respectively. RF, ANA, anti-CL and anti-dsDNA antibodies were also detected in the disease control group (32.1%, 89.3%, 28.5% and 28.5% respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Immunologic and viral markers in the circulation of anti-HIV negative heroin addicts. 768 80

A total of 107 cancer patients were treated with 148 cycles of subcutaneous (SC) immunotherapy employing interleukin-2 (rIL-2) and/or interferon-alpha (rIFN-alpha). The systemic toxicities of SC cytokine therapy were retrospectively evaluated with regard to hepatic and metabolic adverse effects, and compared to adverse effects previously reported upon high- or intermediate-dose intravenous (IV) rIL-2 therapy. Our study cohorts consisted of 15 patients who received SC rIL-2 at doses of 4.8-14.4 million IU/m2/day on 5 days per week for a total of 8 weeks, 20 patients who received rIFN-alpha 2b at 3.0-6.0 million U/m2/day thrice weekly for a total of 6 weeks, and 72 patients who were given SC rIFN-alpha 2b at 6.0 million U/m2/day thrice weekly plus SC rIL-2 at 14.4-18.0 million IU/m2/day on days 1 and 2, followed by 4.8 million IU/m2/day, 5 days per week for 6 consecutive weeks. These treatment regimens were well tolerated in the outpatient setting; no toxic deaths occurred, and none of the patients developed life-threatening toxicity. Upon SC rIL-2/rIFN-alpha combination therapy, we observed mild decreases in plasma protein and albumin levels (mean nadir +/- standard deviation, 67 +/- 5 g/L and 38.8 +/- 3.9 g/L, respectively), minor albeit significant increases in serum total bilirubin levels (mean peak +/- standard deviation, 7.8 +/- 3.1 mumol/L), serum aspartate aminotransferase (25.9 +/- 9.9 U/L), alanine aminotransferase (42.0 +/- 45.9 U/L), alkaline phosphatase (301 +/- 255 U/L), lactate dehydrogenase (230 +/- 64 U/L), gamma-glutamyl transpeptidase (147 +/- 141 U/L) activities and triacylglyceride (2.6 +/- 0.9 mmol/L) concentrations. Cholinesterase activities (mean nadir +/- standard deviation, 42.6 +/- 13.7 kU/L), and serum cholesterol levels (4.4 +/- 0.9 mmol/L) decreased upon SC rIL-2/rIFN-alpha combination therapy. These mild clinical side effects and laboratory changes were in marked contrast to a multitude of dose-limiting and life-threatening adverse reactions described upon IV rIL-2 therapy. It is concluded that low-to intermediate-dose SC rIL-2/rIFN-alpha combination therapy as used in this study, can be given in the outpatient setting with good practicability and excellent safety.
 ...
PMID:Hepatic and serologic toxicity of systemic interleukin-2 and/or interferon-alpha. Evidence of a risk-benefit advantage of subcutaneous therapy. 791 Jul 16

We have reported the efficacy of intraarterial-combined immunochemotherapy including interleukin-2 (IL-2) for unresectable hepatocellular carcinoma (HCC). To further test this therapy for prevention of intrahepatic recurrence after hepatectomy, the influence of IL-2 on liver regeneration was examined using mitotic index (MI) and the bromodeoxyuridine (BrdU) labeling index (LI) in 70% hepatectomized Donryu rats. In addition, gap junction appearance, which may change during liver regeneration, was analyzed using a monoclonal antibody (HAM8). Serum albumin, alanine transaminase, and total bilirubin (TB) levels were also evaluated. IL-2 (45,000 Japanese reference units [JRU]/d) or saline was administered continuously via the portal vein immediately after hepatectomy using an infusion pump. We also examined the influence of IL-2 on liver regeneration after hepatectomy with splenectomy. No difference in the weight of the liver, serum albumin, alanine transaminase, or TB was observed in any groups at 1, 2, or 4 days after hepatectomy. Neither IL-2 nor splenectomy influenced MI and BrdU LI at all three points. Gap junctions began to disappear after hepatectomy and reached a minimum on day 2 in all groups. Four days after hepatectomy, the density of the reappearing gap junctions was markedly lower in groups treated with IL-2 than in those receiving saline with or without splenectomy. However, the density returned to close to preoperative levels 6 days after hepatectomy in all groups. Continuous portal infusion of IL-2 transiently disturbed gap junction reappearance during liver regeneration. However, no other parameters of liver regeneration or liver functions differed. These results suggest that the liver regeneration after partial hepatectomy may be suppressed by the administration of IL-2, even though the suppression may not be harmful for overall recovery of the resected liver. However, it seems that hepatic IL-2 administration can be performed without serious complications after hepatectomy.
 ...
PMID:Influence of continuous interleukin-2 administration via the portal vein on liver regeneration following partial hepatectomy in rats. 867 80

Efficient energy utilization is essential for cell growth; in an attempt to improve the growth conditions of the rat T-lymphocyte culture model for potential use in studying the mutagenic activity of carcinogens in vitro, we have investigated the effects of phytohemagglutinin (PHA), interleukin-2 (IL-2) and 2-mercaptoethanol (2-ME) on the activities of intermediary metabolism enzymes and cell proliferation. Isolated lymphocytes were cultured in the presence and absence of PHA, IL-2, or 2-ME. The intermediary metabolism enzymes investigated were glutamate dehydrogenase, glutamate-pyruvate transaminase, malate dehydrogenase, isocitrate dehydrogenase, lactate dehydrogenase, pyruvate kinase, and fatty acid synthetase (FAS). Measurable activity of all enzymes investigated, except for FAS, was detected in PHA-stimulated cells cultured with IL-2 or 2-ME. The unstimulated lymphocytes had significantly lower enzyme activity than stimulated cells. The combination of all three agents showed increased enzyme activity. This increase in activity brought about by the combination of the three agents was not reproduced by either agent acting alone. In general, the increase in enzyme activity correlated with cell proliferation as measured by [3H]thymidine uptake in PHA-stimulated cultures containing IL-2 and/or 2-ME. The results suggest that the addition of exogenous IL-2 and 2-ME enhances metabolic function and may be beneficial in in vitro culture of rat lymphocytes.
 ...
PMID:Characterization of rat lymphocyte primary culture for the development of an in-vitro mutagenesis assay: effect of interleukin-2 and 2-mercaptoethanol on the activities of intermediary metabolism enzymes and cell proliferation. 873 77

The optimal and safer interleukin-2 (IL-2) dose for treatment of chronic hepatitis C virus (HCV) infection has been studied in 33 HCV-RNA positive patients with chronic hepatitis C. Patients were randomly allocated to receive 5 days per week during 12 weeks IL-2 doses of: 0.9 MIU (n = 10), 1.8 MIU (n = 10), or 3.6 MIU (n = 13). After 12 weeks, responder patients stopped treatment, whereas nonresponders received 12 additional weeks of IL-2 at the next higher dose: 1.8, 3.6, or 5.4 MIU. As a whole, after the first 12 weeks of IL-2 alanine aminotransferase (ALT) levels significantly decreased (P < .001) with respect to the baseline values (140 +/- 63 vs. 70 +/- 30 IU/L). At the end of treatment (24 weeks), the mean ALT level (80 +/- 50 IU/L) continued significantly lower (P < .001) than the baseline one, and 24% of patients normalized ALT levels; according to dosage, ALT normalization was: 0% for 0.9 MIU, 25% for 1.8 MIU, 5% for 3.6 MIU, and 18% for 5.4 MIU. HCV-RNA levels decreased during treatment, but in none of the patients became undetectable. All patients had a local reaction at the injection site with induration, erythema, and swelling, which was dose-related. The dose of 5.4 MIU was poorly tolerated and was reduced to 3.6 MIU in 4 of 11 patients. No changes in hematological parameters were observed. At the end of follow-up (6 months) four of eight responder patients continued with normal ALT. In conclusion, IL-2 treatment for chronic hepatitis C induced a biochemical response in 8 of 33 (24%) patients at the end of therapy while at the end of follow-up, 4 of 33 (8%) patients remained with normal ALT. The dose of 1.8 MIU is well tolerated and seems to be the most efficacious.
 ...
PMID:A pilot study of recombinant interleukin-2 for treatment of chronic hepatitis C. 936 78

A single intravenous injection of concanavalin A (Con A) induces T-cell activation-associated inflammatory injury selectively in the liver. This study investigated the strain difference in the development of Con A-induced hepatic injury. Normal C57BL/6 and BALB/c spleen cells produced comparable levels of T-cell-derived lymphokines (interferon gamma [IFN-gamma], tumor necrosis factor alpha [TNF-alpha], and interleukin-2 [IL-2]) following in vitro stimulation with Con A. A single intravenous injection of Con A to C57BL/6 mice induced the plasma levels of TNF-alpha and IL-2 comparable with or slightly higher than those observed in BALB/c mice, whereas the same treatment resulted in an apparently lower level of IFN-gamma production in C57BL/6 mice. RNA from livers of Con A-treated C57BL/6 mice exhibited lower levels of IFN-gamma mRNA than RNA of BALB/c livers. Unexpectedly, a dramatic difference in the severity of hepatic injury was observed between C57BL/6 and BALB/c. Namely, the peak alanine transaminase (ALT) level was more than 15,000 U/L and inducible as early as 8 hours after injection of 0.2 mg Con A per mouse in the C57BL/6 strain, whereas the peak was approximately 3,000 U/L and induced as late as 24 hours after Con A injection in the BALB/c strain. The increase in plasma ALT levels was limited to less than 10% by injection of anti-IFN-gamma monoclonal antibody (mAb) in both strains. The C57BL/6 strain inducing lower levels of IFN-gamma exhibited higher IFN-gamma responsiveness as exemplified by the intrahepatic expression of an IFN-gamma-inducible gene, an inducible type of nitric oxide (NO) synthase (iNOS). These results indicate that, while IFN-gamma produced in vivo by activated T cells induces hepatic injury, there exists a striking strain difference in the induction of IFN-gamma-dependent hepatic injury.
 ...
PMID:Strain difference in the induction of T-cell activation-associated, interferon gamma-dependent hepatic injury in mice. 946 51


1 2 3 4 5 Next >>