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)

Groups of BALB/c mice were treated with a sub-lethal dose (60 micrograms) of staphylococcal enterotoxin B (SEB) intraperitoneally and were sacrificed at 2, 5, 8, or 10 h post-injection. Organ, blood plasma and lymph node samples from these mice were analyzed. Plasma levels of urea, creatinine and alanine aminotransferase were significantly raised above normal by 5 h post-injection. However, alkaline phosphatase levels showed an erratic increase after toxin administration and, after administration of 10-40 microgramS SEB per mouse, were consistently at least 30% below normal levels at 24 h post-injection. Weight change was also monitored but found to be inconsistent. Lung, spleen and kidney samples appeared normal on histopathological examination, but liver samples showed minor polymorph infiltration and congestion. TNF-alpha, and IL-1 alpha levels in the plasma were raised by 8 h to picogram levels per ml of plasma, whereas IFN-gamma and IL-2 were raised by 2 h to nanogram levels per ml of plasma. Lymph node cells taken from mice treated with toxin were given a secondary stimulation with toxin in vitro. Although the response of the cells was lower than normal on assay at four days, a time response curve showed a peak in cell responsiveness to secondary stimulation with toxin at three days. These data indicate that biochemical markers and cytokine levels are affected by the administration of SEB to mice and may be used as indicators of toxicity.
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PMID:Staphylococcal enterotoxin B toxicity in BALB/c mice: effect on T-cells, plasma cytokine levels and biochemical markers. 764 Jun 77

The authors established a new experimental model of fulminant hepatic failure (FHF) with prolonged hepatocellular necrosis and impaired liver regeneration, and evaluated the immunological mechanisms related to the impaired liver regeneration in this model. A novel lipid A analogue, FS-112, was injected intravenously into male Balb/c mice, followed by a 70% partial hepatectomy 2 days later. Serum levels of T.Bil. and ALT rose 7 days after the partial hepatectomy, as compared with controls. In mice pretreated with FS-112, labeling indices of both BrdU and PCNA 36 hrs after the partial hepatectomy were significantly lower than those in the controls. Splenic lymphocytes harvested from the FHF mice 1-5 days after the partial hepatectomy showed a cytotoxic activity against regenerating hepatocytes with a peak effect on day 5. Cytotoxic activity against YAC-1 cells was also found up to 5 days after the partial hepatectomy, and resembled that directed against the regenerating hepatocytes. On the 5th day of FS-112 administration, there was a marked rise in the production of IFN-gamma from splenocytes. When FK-506, an immunosuppressive agent, was given intracutaneously daily for 7 days, serum levels of T.Bil. and ALT significantly decreased, as compared with controls. Furthermore, the PCNA-labeling index 36 hrs after the partial hepatectomy was enhanced by the administration with FK-506 in the FHF mice. These results strongly suggest that the NK cells activated by IFN-gamma may be involved in killing the regenerating liver cells, and thus play a role in the pathogenesis of the impaired liver regeneration in FHF.2+ recovery from the impaired liver regeneration in FHF.
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PMID:Natural killer cell may impair liver regeneration in fulminant hepatic failure. 768 19

This study was carried out to test the hypothesis that, in chronic hepatitis (CH), inflammatory processes, including viral replication, host immune response, and hepatocyte destruction, are regulated by a cytokine network in the liver. Expression of the mRNA of the cytokines IL1-beta, IL2, IL4, IL5, IL6, TNF-alpha, and IFN-gamma, the lymphocyte markers CD4 and CD8, and the HLA class I molecule, beta 2-microglobulin (B2MG) in the liver tissue of 20 CH(C) cases and 9 CH(B) patients was investigated by the reverse transcription polymerase chain reaction (RT-PCR) method. TNF-alpha, CD4, and B2MG mRNA were detected in 100% of cases of in both CH(B) and CH(C). The expression rates of IL1-beta, IL2, IL4, IFN-gamma, and CD8 mRNA were 80%, 40%, 25%, 40%, and 80% in CH(C) and 88.9%, 44.5%, 30%, 55.6%, and 100% in CH(B). IL6 mRNA was detected only in CH(B), in 22.2% of cases, IL5 mRNA was not detected in either CH(B) or CH(C). IL2, IL4, and IFN-gamma mRNA were expressed significantly more frequently in patients who had high serum ALT and a high histological activity index (HAI) score. There was no difference in cytokine expression between CH(B) and CH(C), except in IL6, suggesting the existence of a common immunopathogenesis for CH(B) and CH(C). In chronic viral hepatitis, IL1-beta and TNF-alpha appear to play a major role in immune responses and IL2, IL4, and IFN-gamma seem to be associated with increased cytotoxic T cell response.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression rate of cytokine mRNA in the liver of chronic hepatitis C: comparison with chronic hepatitis B. 771 13

To investigate the hypothesis that Th1 phenotype cytokines are associated with the increasing activity of hepatitis and Th2 phenotype cytokines with decreasing activity in the liver of chronic viral hepatitis, expressions of the mRNA of the cytokines IL-2, IFN-gamma and IL-4 in the liver of 23 patients with chronic hepatitis B were investigated by reverse transcription polymerase chain reaction. Patients were divided into three groups according to the phase of acute exacerbation of hepatitis as increasing (n = 9), decreasing (n = 8), and stable phase (n = 6). Both IL-2 and IFN-gamma mRNA were preferentially expressed in increasing phase than in decreasing phase (P < 0.01, P < 0.05, respectively) and associated with the high serum alanine aminotransferase (ALT) level. On the other hand, IL-4 mRNA was detected in decreasing phase with significant frequency compared with increasing phase (P < 0.05). However, expression of IL-4 mRNA was not associated with serum ALT level. Our results suggest that Th1 phenotype cytokines up-regulate and Th2 phenotype cytokines down-regulate the liver inflammation of chronic viral hepatitis.
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PMID:The expression of IL-2, IL-4 and interferon-gamma (IFN-gamma) mRNA using liver biopsies at different phases of acute exacerbation of chronic hepatitis B. 777 54

The roles of neutrophil Mac-1 (CD11b/18) adhesion molecule, TNF-alpha and IFN-gamma in hepatic warm ischemia-reperfusion injury (IRI) were investigated with a newly established mouse model. Blood supply to the left lateral and the median lobe of the liver was interrupted with an atraumatic clip for 50 minutes. From 1 hour to 24 hours after reperfusion, TNF-alpha in the ischemic liver tissue was detected. IFN-gamma was not detected in ischemic liver tissue and blood. Pretreatment with anti-mouse Mac-1 monoclonal antibody (mAb) diminished the plasma GPT level, area of necrosis, and number of myeloperoxidase positive cells in ischemic liver lobe at 24 hours after reperfusion. Pretreatment with anti-mouse TNF-alpha or anti-mouse IFN-gamma mAb did not affected any parameters. From these results, Mac-1 was considered to play an important role in a hepatic warm IRI. However, TNF-alpha and IFN-gamma were not considered to play a pivotal role in the pathogenesis of the injury and in the regulation of the neutrophils adhesion via Mac-1.
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PMID:[Roles of Mac-1, endogenous TNF-alpha, and IFN-gamma in pathogenesis of hepatic warm ischemia-reperfusion injury]. 854 78

T lymphocytes and immunoregulatory cytokines may be important in the host response to hepatitis C virus (HCV) infection. T-helper type 1 (Th1) cytokines (interleukin [IL]-2, interferon gamma [IFN-gamma]) are required for host antiviral immune responses, including cytotoxic T-cell generation and natural killer cell activation, while T-helper type 2 (Th2) cytokines (IL-4,IL-10) can inhibit the development of these effector mechanisms. In this study, the serum levels of Th1 and Th2 cytokines in patients (n = 23) infected with HCV were measured and compared with biochemical (alanine transaminase [ALT]) and viral (HCV RNA) indicators of infection. Serial cytokine levels were measured in a subset of 11 patients at 1 and 12 weeks during and at 1 week after interferon alfa (IFN-alpha) therapy (n = 33 samples). Levels of circulating IL-2, IL-4, IL-10, and IFN-gamma were significantly elevated in HCV patients versus normal controls (128 vs. 25 pg/mL, 3,045 vs. 29 pg/mL, 2,949 vs. 18 pg/mL, and 307 vs. 24 pg/mL respectively; P < .01). Treatment with IFN-alpha decreased the levels of IL-4 (321 +/- 224 pg/mL), and IL-10 (1,011 +/- 344 pg/mL), which paralleled a decrease in HCV RNA (114 +/- 27 vs. 25 +/- 20 Eq/ml X 10(5), pre- vs. post-IFN-alpha [12 weeks];P <.05). These findings indicate that an activated T-cell response, as manifest by increased circulating immunoregulatory cytokines, is present in patients with HCV liver disease. Furthermore, treatment with HCV liver disease. Furthermore, treatment with IFN-alpha diminishes the Th2 cytokine response. Thus, modulation of T-cell function and cytokine production may be one mechanism whereby IFN-alpha therapy results in reduced viral burden.
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PMID:Immunoregulatory cytokines in chronic hepatitis C virus infection: pre- and posttreatment with interferon alfa. 870 83

1. This study investigates the effects of the non-selective ETA/ETB receptor antagonist, SB 209670, on systemic haemodynamics, renal function, liver function, acid-base balance and survival in a rat model of endotoxic shock. 2. Injection of E. coli lipopolysaccharide (LPS, 10 mg kg-1, i.v.) resulted in increases in the serum levels of tumour necrosis factor-alpha (TNF-alpha, maximum 60 min after LPS), endothelin-1, (ET-1; maximum 120 min after LPS), and interferon-gamma (IFN-gamma, maximum 180 min after LPS). 3. Injection of LPS also resulted in a fall in blood pressure from 113 +/- 3 mmHg (time = 0) to 84 +/- 4 mmHg at 360 min (n = 15) as well as a hyporeactivity to the vasoconstrictor responses elicited by noradrenaline (NA, 1 microgram kg-1, i.v.). Pretreatment of rats with a continuous infusion of SB 209670 (3 mg kg-1, i.v. bolus + 100 micrograms kg-1, i.v. infusion commencing 15 min prior to LPS) significantly augmented the hypotension as well as the vascular hyporeactivity to NA caused by endotoxaemia. 4. Pretreatment of LPS-rats with SB 209670 (3 mg kg-1, i.v. bolus given 15 min prior to LPS) or infusion of SB 209670 (bolus dose and infusion as above) resulted in a reduction in 6 h-survival from 71% (control) to 30% and 13%, respectively. 5. Endotoxaemia for 4 h resulted in rises in the serum levels of urea and creatinine (indicators of renal failure), but not in the serum levels of bilirubin, GPT and GOT (indicators of liver dysfunction and/or hepatocellular injury). Pretreatment of LPS-rats with SB 209670 (3 mg kg-1, i.v. bolus 15 min prior to LPS) significantly augmented the serum levels of creatinine, bilirubin, GPT and GOT caused by endotoxin. In addition, endotoxaemia caused, within 15 min, an acute metabolic acidosis (falls in pH, HCO3- and base excess) which was compensated by hyperventilation (fall in PaCO2). Pretreatment of LPS-rats with SB 209670 (3 mg kg-1, i.v. bolus) significantly augmented the metabolic acidosis caused by LPS. 6. Thus, the non-selective ETA/ETB receptor antagonist, SB 209670, augments the degree of (i) hypotension, (ii) vascular hyporeactivity to noradrenaline, (iii) renal dysfunction and (iv) metabolic acidosis caused by endotoxin in the anaesthetized rat. In contrast to rats treated with LPS alone, LPS-rats treated with SB 209670 exhibited liver dysfunction and hepatocellular injury. We propose that the release of endogenous ET-1 serves to maintain blood pressure and subsequently organ perfusion in septic shock.
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PMID:Effects of the endothelin receptor antagonist, SB 209670, on circulatory failure and organ injury in endotoxic shock in the anaesthetized rat. 873 96

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.
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PMID:Strain difference in the induction of T-cell activation-associated, interferon gamma-dependent hepatic injury in mice. 946 51

We studied whether the infection with a blood-stage murine malaria lethal Plasmodium berghei NK65 induces IL-12 production, and if so, how the IL-12 production is involved in the protection or pathogenesis. The infection of C57BL/6 mice enhanced mRNA expression of IL-12 p40 and also IFN-gamma, IL-4, and IL-10 in both spleen and liver during the early course of the infection. It also enhanced the mRNA expression of TNF-alpha, Fas ligand, and cytokine-inducible nitric oxide synthase. Increased IL-12 p40 production was also observed in the culture supernatant of spleen cells and in sera of infected mice. In addition, the infection caused massive liver injury with elevated serum glutamic-oxaloacetic transaminase and serum glutamic-pyruvic transaminase activities and body weight loss. Treatment of these infected mice with neutralizing mAb against IL-12 prolonged the survival and diminished the liver injury with reduced elevation of serum serum glutamic-oxaloacetic transaminase and serum glutamic-pyruvic transaminase activities and decreased body weight loss. However, the anti-IL-12 treatment did not affect parasitemia, and all these mice eventually died. Similar results were obtained when infected mice were treated with neutralizing mAb against IFN-gamma. Moreover, anti-IL-12 treatment greatly reduced the secretion and mRNA expression of IFN-gamma in both spleen and liver. These results suggest that the lethal P. berghei NK65 infection induces IL-12 production and that the IL-12 is involved in the pathogenesis of liver injury via IFN-gamma production rather than the protection.
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PMID:A pathogenic role of IL-12 in blood-stage murine malaria lethal strain Plasmodium berghei NK65 infection. 960 53

Interleukin (IL)-12 plays an essential role in host defense against infectious diseases. Serum IL-12 concentration and blood mononuclear cell production with or without specific interferon (IFN)-gamma priming were investigated in 65 chronic hepatitis C virus (HCV) patients and 25 healthy donors. HCV patients had higher serum IL-12 levels (P = .004) and produced higher amounts after IFN-gamma priming (P < .001) than donors. A subset of patients did not produce IL-12: They had lower serum levels (P = .032) and showed signs of liver piecemeal necrosis less frequently (P = .011). Patients with greater liver necroinflammatory activity produced more IL-12 than patients with minimal or mild activity and donors (P < .01). During IFN-alpha therapy for 16 HCV patients, individuals with end-of-treatment alanine aminotransferase normalization and clearance of viremia had higher serum levels and produced more IL-12 than those who did not (P < .05). These results suggest a role for IL-12 in the immunopathogenesis and outcome of HCV infection.
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PMID:Induction of interleukin-12 production in chronic hepatitis C virus infection correlates with the hepatocellular damage. 965 48


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