Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

X-linked hyper-immunoglobulin M (IgM) syndrome (XHIGM) is a rare genetic primary immunodeficiency disease caused by mutations of the CD40 ligand (CD40L) gene with normal or elevated levels of IgM and markedly decreased serum IgG, IgA, and IgE. Liver disease may occur as a clinical manifestation in XHIGM. This complication appears to increase with age. We report an 18-year-old male patient who had recurrent episodes of acalculous cholecystitis (AC) and sclerosing cholangitis (SC). The diagnosis of XHIGM was confirmed by the finding of CD40L expression < 1% of normal and a tyrosine 169 asparaginase (t526a) mutation in exon 5 (the tumor necrosis factor domain) of the CD40L gene. The patient had direct hyperbilirubinemia (direct bilirubin 5.5 mg/dL, total bilirubin 8.7 mg/dL), cholestasis (alkaline phosphatase 1133 U/L, gamma-glutamyl transferase 1019 U/L) and elevated transaminases (aspartate aminotransferase 70 U/L, alanine aminotransferase 101 U/L). Findings on abdominal ultrasound and abdominal computed tomography were compatible with AC. After the fourth episode of cholecystitis, cholecystectomy and liver biopsy were performed. Operative cholangiography revealed poor opacification of the hepatic duct and proximal common bile duct; the upstream intrahepatic bile ducts were not visualized. The biopsy specimen showed marked fibrosis of the portal areas. Enterococcus species was cultured from the bile. Children or adolescents with recurrent AC and SC should be evaluated for an underlying immunodeficiency syndrome such as XHIGM.
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PMID:Recurrent acalculous cholecystitis and sclerosing cholangitis in a patient with X-linked hyper-immunoglobulin M syndrome. 1603 32

Lead (Pb) increases lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-alpha), nitric oxide (NO), lipid peroxidation (LPO), and liver damage. In this study, we investigated the role of protein kinase C (PKC) and p42/44 mitogen-activated protein kinase (MAPK) and the causal relationships between TNF-alpha, NO, and LPO in Pb-increased LPS-induced liver damage in rats. Treatment with PKC and p42/44 MAPK inhibitors significantly reduced Pb + LPS-induced NO, TNF-alpha, LPO, and liver damage, which was revealed by elevated serum levels of aspartate aminotransferase and alanine aminotransferase. Pb + LPS coexposure significantly increased phosphorylation of p42/44 MAPK and TNF-alpha expression in peripheral blood cells; however, exposure to Pb + LPS did not induce TNF-alpha, NO, or LPO production and p42/44 MAPK activation in the liver. Pentoxifylline, a TNF-alpha inhibitor, also reduced liver damage but did not alter NO or LPO in Pb + LPS-treated rats. Thus, Pb increased LPS-induced liver damage through PKC and p42/44 MAPK modulation of TNF-alpha and oxidative stress, but modulation of TNF-alpha did not affect NO or LPO in rats.
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PMID:Modulation of tumor necrosis factor-alpha and oxidative stress through protein kinase C and P42/44 mitogen-activated protein kinase in lead increases lipopolysaccharide-induced liver damage in rats. 1604 92

Fumonisin B1 (FB1), a mycotoxin from Fusarium verticillioides, disrupts sphingolipid metabolism by inhibiting ceramide synthase leading to modulation of cytokines including tumor necrosis factor (TNF) alpha. Current study investigated the effect of interrupting TNFalpha signaling, known to be involved in FB1 hepatotoxicity. Male C57BL/6N mice were injected intravenously once with anti-TNFalpha antibodies or treated with pentoxifylline at 150 mg/kg intraperitoneally twice a day for 5 days to inhibit TNFalpha production before and during subcutaneous injection of 2.25mg FB1/kg daily for 5 days; mice were sampled one day after the last treatment. Results showed that both anti-TNFalpha antibodies and pentoxifylline did not prevent FB1 hepatotoxicity; the latter was somewhat augmented, indicated by increases in circulating alanine aminotransferase and aspartate aminotransferase, and incidence of apoptotic hepatocytes. Anti-TNFalpha antibodies did not alter FB1-induced accumulation of free sphingoid bases or expression of TNFalpha in liver following the FB1 treatment. Pentoxifylline significantly reduced accumulation of free sphinganine and expression of TNFalpha. Neither anti-TNFalpha antibodies nor pentoxifylline altered FB1-induced expression of interleukin-12, interferongamma, lymphotoxinbeta, and c-myc. Expression of c-myc, an inducer of cell death, increased after interference with TNFalpha signaling. These findings suggest a dual role of TNFalpha signaling activation in FB1 hepatotoxicity.
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PMID:Inhibition of tumor necrosis factor alpha signaling by anti-tumor necrosis factor alpha antibodies and pentoxifylline is unable to prevent fumonisin hepatotoxicity in mice. 1605 85

Moderate alcohol consumption is associated with increased insulin sensitivity and a reduced risk for type 2 diabetes. An important endogenous mediator of insulin sensitivity is adiponectin (AN), an adipokine that displays numerous antiatherogenic, antidiabetogenic and antiinflammatory effects. Recently, acute increase in alcohol consumption has been shown to be associated with increase in plasma adiponectin and, concomitantly, insulin sensitivity. Whether chronic alcohol consumption predicts an increase in plasma AN and whether this is independent of adiposity, markers of liver dysfunction, and plasma adipokines such as tumor necrosis factor (TNF)-alpha is not known. We, therefore, investigated these relationships in 75 men who were diagnosed with liver steatosis using ultrasound/liver biopsy. We examined 75 men, who were diagnosed for having liver steatosis (ultrasound/liver biopsy). Each filled in a questionnaire on alcohol intake. Subjects were divided into two subgroups according to alcohol history and CDT concentrations--drinkers and non-drinkers. All individuals were examined for serum concentrations of AN, glucose, triglycerides, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and glutamate transferase (GMT) activity; carbohydrate-deficient transferrin (CDT%) a marker of chronic alcohol consumption, insulin and TNF-alpha. The Quicki insulin sensitivity index was calculated. Forty-eight individuals were found to be moderate drinkers and 27 subjects non-drinkers. Moderate drinkers had significantly higher concentrations of AN (13.8 +/- 3,7 versus 9.1 +/- 5.4 mg/l, means +/- SD, p = 0.012) compared with non-drinkers, independent of adiposity. Plasma AN concentrations in the whole group were positively correlated with TNF-alpha concentrations (r = 0.6; p = 0.0001), CDT (r = 0.26; p = 0.0084), AST/ALT index (r = 0.3, p = 0.009), AST (r = 0.29; p = 0.011) and GMT (r = 0.29; p = 0.011) and negatively with BMI (r = -0.48; p = 0.0002) and glycemia (r = -0.22; p = 0.049). The positive associations of AN with TNF-alpha (0.8; p = 0.001), CDT (0.55; p = 0.017), AST/ALT index (0.55; p = 0.019) and the negative correlation with glycemia (-0.35; p = 0.0158) were independent of BMI. Stratified according to alcohol intake, in moderate drinkers, a positive correlation was found between AN and TNF-alpha concentrations (r = 0.6, p = 0.0001, AST/ALT index (r = 0.34, p = 0.0295) whereas in non-drinkers no such correlations were found. The concentration of AN and BMI displayed a negative correlation in both drinker and nondrinker patients (r = -0.42, p = 0.01 and -0.61; p = 0.012, respectively). We concluded that plasma AN is higher in moderate drinkers compared to non-drinkers, even after correction for BMI. Drinkers suffering from liver steatosis were found to have a positive correlation between AN concentrations, laboratory markers of liver disease and TNF-alpha. Such correlation was absent in non-drinkers suffering from liver steatosis. This suggests that alcohol may modulate the inhibitory effect of TNF-alpha on AN production, and thus, increase its plasma concentrations.
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PMID:High adiponectin and TNF-alpha levels in moderate drinkers suffering from liver steatosis: comparison with non drinkers suffering from similar hepatopathy. 1617 Mar 95

To clarify the laboratory characteristics and deduce the pathogenesis of acute encephalopathy associated with multiple organ dysfunctions in Japan. We measured cytokine levels [tumor necrosis factor alpha (TNF-alpha), soluble tumor necrosis factor-receptor 1 (sTNF-R1), and interleukin-6 (IL-6)] in serum and cerebrospinal fluid (CSF) as well as general laboratory examinations in 27 patients with acute encephalopathy. Urea nitrogen (UN), creatinine (Cr), aspartate aminotransferase (AST), lactic dehydrogenase (LDH), and C-reactive protein (CRP) levels in blood, and CSF protein levels at the initial stage were significantly higher in patients with an unfavorable outcome. TNF-alpha, sTNF-R1, and IL-6 levels at the initial stage were higher in the serum than in the CSF of patients with acute encephalopathy. Serum cytokine levels correlated well with patient outcome. The high CSF protein level and the high UN, Cr, AST, LDH, and CRP levels in the blood represent the severity of vascular leakage through the blood-brain barrier and multiple organ dysfunctions, respectively, and thus suggest an unfavorable prognosis. The high serum inflammatory cytokine levels at the initial stage and the good correlation of those levels with the outcome suggest that intravascular inflammation has a significant role in vascular leakage and multiple organ dysfunctions in acute encephalopathy.
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PMID:Laboratory characteristics of acute encephalopathy with multiple organ dysfunctions. 1619 4

The potential use of hydrophilic cyclodextrins (CyDs) as an inhibitor for lipopolysaccharide (LPS) was examined. Of the five CyDs used in this study, dimethylacetyl-beta-cyclodextrin (DMA7-beta-CyD) had greater inhibitory activity than other CyDs against the production of nitric oxide (NO) and various proinflammatory cytokines including tumor necrosis factor-alpha (TNF-alpha) in murine macrophages stimulated with two serotypes of LPS and lipid A. The inhibitory effect of DMA7-beta-CyD on NO production was also observed in macrophages stimulated with lipoteichoic acid (LTA), but not peptidoglycan (PGN), polyinosinic-polycytidylic acid (poly I:C) or CpG oligonucleotide (CpG-ODN). Several studies have suggested that the inhibitory effects of DMA7-beta-CyD could be ascribed to the interaction with LPS. Simultaneous administration of DMA7-beta-CyD not only intraperitoneally but also intravenously and intraperitoneal injection of aqueous solution containing LPS and d-galactosamine in murine endotoxin shock model suppressed fatality. Also, DMA7-beta-CyD decreased blood level of TNF-alpha as well as serum levels of aspartate transaminase (AST) and alanine transaminase (ALT) in mice. In conclusion, DMA7-beta-CyD may have promise as a new therapeutic agent for endotoxin shock induced by LPS.
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PMID:Inhibitory effects of dimethylacetyl-beta-cyclodextrin on lipopolysaccharide-induced macrophage activation and endotoxin shock in mice. 1621 16

Patients with rheumatoid arthritis have subnormal vitamin B6 status, both quantitatively and functionally. Abnormal vitamin B6 status in rheumatoid arthritis has been associated with spontaneous tumor necrosis factor (TNF)-alpha production and markers of inflammation, including C-reactive protein and erythrocyte sedimentation rate. Impaired vitamin B6 status could be a result of inflammation, and these patients may have higher demand for vitamin B6. The aim of this study was to determine if daily supplementation with 50 mg of pyridoxine for 30 days can correct the static and/or the functional abnormalities of vitamin B6 status seen in patients with rheumatoid arthritis, and further investigate if pyridoxine supplementation has any effects on the pro-inflammatory cytokine TNF-alpha or IL-6 production of arthritis. This was a double-blinded, placebo-controlled study involving patients with rheumatoid arthritis with plasma pyridoxal 5'-phosphate below the 25th percentile of the Framingham Heart Cohort Study. Vitamin B6 status was assessed via plasma and erythrocyte pyridoxal 5'-phosphate concentrations, the erythrocyte aspartate aminotransferase activity coefficient (alphaEAST), net homocysteine increase in response to a methionine load test (DeltatHcy), and 24 h urinary xanthurenic acid (XA) excretion in response to a tryptophan load test. Urinary 4-pyridoxic acid (4-PA) was measured to examine the impact of pyridoxine treatment on vitamin B6 excretion in these patients. Pro-inflammatory cytokine (TNF-alpha and IL-6) production, C-reactive protein levels and the erythrocyte sedimentation rate before and after supplementation were also examined. Pyridoxine supplementation significantly improved plasma and erythrocyte pyridoxal 5'-phosphate concentrations, erythrocyte alphaEAST, urinary 4-PA, and XA excretion. These improvements were apparent regardless of baseline B6 levels. Pyridoxine supplementation also showed a trend (p < 0.09) towards a reduction in post-methionine load DeltatHcy. Supplementation did not affect pro-inflammatory cytokine production. Although pyridoxine supplementation did not suppress pro-inflammatory cytokine production in patients with rheumatoid arthritis, the suboptimal vitamin B6 status seen in rheumatoid arthritis can be corrected by 50 mg pyridoxine supplementation for 30 days. Data from the present study suggest that patients with rheumatoid arthritis may have higher requirements for vitamin B6 than those in a normal healthy population.
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PMID:Pyridoxine supplementation corrects vitamin B6 deficiency but does not improve inflammation in patients with rheumatoid arthritis. 1627 93

This study was designed to determine the possible protective effect of Ginkgo biloba extract (EGb) against oxidative organ damage distant from the original burn wound. Under brief ether anesthesia, the shaved dorsum of the rats was exposed to 90 degrees C (burn group) or 25 degrees C (control group) water bath for 10 seconds. EGb (50 mg/kg/day) or saline was administered intraperitoneally immediately and at 12 hours after the burn injury. Rats were decapitated 24 hours after burn injury and tissue samples from the liver and kidney were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity, and collagen contents. Formation of reactive oxygen species in the tissue samples was monitored by the chemiluminescence technique. Tissues also were examined microscopically. Blood urea nitrogen, creatinine, alanine aminotransferase, and aspartate aminotransferase levels and tumor necrosis factor- and lactate dehydrogenase activity were assayed in serum samples. Severe skin scald injury (30% TBSA) caused a significant decrease in GSH levels and significant increases in MDA levels, MPO activity, and collagen content of hepatic and renal tissues. Treatment of rats with EGb significantly increased the GSH level and decreased the MDA level, MPO activity, and collagen contents. Similarly, serum alanine aminotransferase, aspartate aminotransferase, and blood urea nitrogen levels, as well as lactate dehydrogenase and tumor necrosis factor-, were increased in the burn group as compared with the control group. However, treatment with EGb reversed all these biochemical indices, as well as histopathological alterations that were induced by thermal trauma. Our results show that thermal trauma-induced oxidative damage in hepatic and renal tissues is protected by the administration of EGb, with its antioxidant effects. Therefore, its therapeutic role as a "tissue injury-limiting agent" must be further elucidated in oxidant-induced tissue damage.
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PMID:Ginkgo biloba extract improves oxidative organ damage in a rat model of thermal trauma. 1627 67

Sugar cane extract (SCE) has been shown to have an immunostimulating effect in chickens. This study evaluated the effect of SCE on Salmonella Abortusequi lipopolysaccharide (LPS)-induced lethal shock in d-galactosamine (GalN)-sensitized mice. Mice were administered intraperitoneally SCE (500 mg/kg) or phosphate buffered saline before or after injection of LPS and GalN. All the mice injected with LPS and GalN (control group) died of histopathologically congestive and hemorrhagic hepatic insufficiency within 24 h, showing significantly increased activities of plasma aspartate aminotransferase (AST; 380 IU/mL) and alanine aminotransferase (ALT; 130 IU/mL). Pretreatment of mice with SCE at 3 h before challenge with LPS and GalN (SCE treated group) resulted in significantly improved survival rates (92.3%) and a decrease in liver injury. These surviving mice in the SCE treated group showed no changes in the mean levels of plasma AST (60 IU/mL) and ALT (18 IU/mL). However, the level of tumor necrosis factor-alpha in the SCE treated group was not significantly different when compared with that in the control group challenged with LPS and GalN. These results suggest that SCE has protective effects on LPS-induced mortality in this mouse model.
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PMID:Protective effects of sugar cane extract on endotoxic shock in mice. 1661 63

Changes in the serum proteome were identified during early, fulminant, and recovery phases of liver injury from acetaminophen in the rat. Male F344 rats received a single, noninjury dose or a high, injury-producing dose of acetaminophen for evaluation at 6 to 120 h. Two-dimensional gel electrophoresis of immunodepleted serum separated approximately 800 stained proteins per sample from which differentially expressed proteins were identified by mass spectrometry. Serum alanine aminotransferase/aspartate aminotransferase levels and histopathology revealed the greatest liver damage at 24 and 48 h after high-dose acetaminophen corresponding to the time of greatest serum protein alterations. After 24 h, 68 serum proteins were significantly altered of which 23 proteins were increased by >5-fold and 20 proteins were newly present compared with controls. Only minimal changes in serum proteins were noted at the low dose without any histopathology. Of the 54 total protein isoforms identified by mass spectrometry, gene ontology processes for 38 unique serum proteins revealed involvement of acute phase response, coagulation, protein degradation, intermediary metabolism, and various carrier proteins. Elevated serum tumor necrosis factor-alpha from 24 to 48 h suggested a mild inflammatory response accompanied by increased antioxidant capability demonstrated by increased serum catalase activity. Antibody array and enzyme-linked immunosorbent assay analyses also showed elevation in the chemokine monocyte chemoattractant protein-1 and the metalloprotease inhibitor tissue inhibitor of metalloproteinases-1 during this same period of liver injury. This study demonstrates that serum proteome alterations probably reflect both liver damage and a concerted, complex response of the body for organ repair and recovery during acute hepatic injury.
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PMID:Alterations in the rat serum proteome during liver injury from acetaminophen exposure. 1668 75


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