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:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increased concentrations of neopterin have been found in conditions causing a stimulation of cellular immunity, including various malignancies. In liver diseases, serum or urinary neopterin levels have been studied in acute viral hepatitis, chronic hepatitis, fatty liver and liver cirrhosis. In the present study neopterin serum levels have been measured in 16 patients with hepatocellular carcinoma (HCC), in 32 patients with liver cirrhosis, and in 28 healthy subjects as controls. Mean values of serum neopterin were significantly increased (p < 0.01) in patients with HCC (15.89 +/- 6.34 nmol/l) when compared with those of normal subjects (4.74 +/- 2.13 nmol/l), but no difference was observed between patients with HCC (associated or not with liver cirrhosis) and patients with liver cirrhosis. Neopterin concentrations are not affected by liver cirrhosis aetiology, nor by its clinical severity, and are not correlated to the values of serum alpha-fetoprotein, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl-transferase, and gamma-globulin. The results show that there is a consistent overlap of values in patients with HCC and liver cirrhosis; macrophage activation seems to be a feature of chronic liver diseases, irrespective of HCC development.
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PMID:Serum neopterin levels in patients with hepatocellular carcinoma. 128 21

Albert (Clin Chem 1982;28:1113-9) has proposed estimation of likelihood ratios by logistic regression analysis. The usual likelihood-ratio approach for estimation of post-test probability of disease from sensitivity and specificity data of a diagnostic test has been extended by Birkett (J Clin Epidemiol 1988; 41:491-4) for situations with more than two diagnostic categories. We suggest here a combination of these ideas, demonstrating this by a re-evaluation of previously published data on the validity of neopterin as a tool for differential diagnosis between chronic non-A, non-B hepatitis and fatty liver. Analysis of neopterin data in combination with the ratio between serum concentrations of aspartate aminotransferase and of alanine aminotransferase yielded a good discrimination between three mutually exclusive diagnostic categories, namely, fatty liver and chronic persistent and chronic aggressive non-A, non-B hepatitis. The approach is flexibly applicable to situations with different pre-test probabilities. The sum of estimated post-test probabilities deviates slightly from the sum of pre-test probabilities. This deviation is a function of the coefficients obtained in logistic regression, and an analytical expression for the deviation is given. The generalized likelihood-ratio approach appears promising in complex diagnostic situations when multiple diagnostic tests are available.
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PMID:Generalized likelihood ratio concept and logistic regression analysis for multiple diagnostic categories. 249 33

Neopterin is a pyrazino-pyrimidine compound which is biosynthesized by macrophages. Increased concentrations of neopterin have been reported in conditions causing a stimulation of cellular immunity, such as viral and other infections, graft versus host disease, autoimmune disease and different malignancies. Recently, urinary neopterin levels have been found increased in patients with acute viral hepatitis and NANB chronic hepatitis. In the present study, neopterin serum levels have been measured in 23 cirrhotic patients (6 HBV related, and 17 cryptogenetic cirrhosis, 7 of them occurring in alcoholic subjects) and in 24 normal subjects. Mean values of serum neopterin were significantly increased in cirrhotics (3.92 +/- 3.28 ng/ml versus 1.24 +/- 0.51 ng/ml in controls, p less than 0.01). Serum neopterin values were not found to be significantly different in cirrhotics assessed in three different clinical classes according to Child's classification and in cirrhotics with and without serological findings of active disease. In fact, in cirrhotic patients, serum neopterin levels did not correlate with the values of serum AST, ALT, ALP, GGT and gamma-globulin. These data show that increased levels of serum neopterin occur in cirrhotic patients, but there is no relation between serum neopterin values and the activity or the clinical severity of the disease. The results are consistent with the hypothesis that activated macrophages are involved in all stages of liver cirrhosis irrespective of its aetiology.
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PMID:Serum neopterin levels in liver cirrhosis. 263 48

Poor initial graft function may increase postoperative morbidity including the risk of early allograft rejection. Various mediators, including immunostimulatory cytokines, may be released during reperfusion in relation to the extent of preservation and reperfusion injury. For this purpose, 81 patients with 85 liver transplants were monitored for cytokines, adhesion molecules, extracellular matrix (ECM) parameters, and neopterin at predefined time-points during and after transplantation. To estimate the origin of cytokine release, blood was obtained central and hepatic venously for the first 48 hr after reperfusion and subsequently from a peripheral vein. One-year patient survival was 88.9%; no relation to initial graft function was observed. Poor initial graft function failed to increase the risk for subsequent infectious complications but was associated with an increased risk of early allograft rejection. The incidence of steroid-resistant rejection was significantly increased in patients with poor initial graft function (35.7% versus 12.7% in patients with good and moderate initial graft function; P < or = 0.05). Various cytokines, adhesion molecules, and ECM parameters including sTNF-RII, sIL-2R, IL-8, IL-10, sVCAM-1, E-selectin, hyaluronic acid, sialic acid, and laminin correlated significantly with the extent of preservation and reperfusion injury. Although none of these parameters was more appropriate in determining the extent of preservation and reperfusion injury than currently established parameters (AST, ALT, and color and amount of bile production), the combined increase in these parameters may not only promote tissue repair but may also perpetuate liver allograft injury and thereby cause significant morbidity. Besides cytokines and adhesion molecules, the ECM may play a pivotal role in determining repair or ongoing tissue injury. Ongoing changes at the microvasculature and basement membrane may result in an increase of local and circulating cytokines and adhesion molecules, which increase the risk of subsequent early allograft rejection. Furthermore, the increase in sTNF-RII, E-selectin, and laminin during reperfusion was predictive of subsequent development of acute allograft rejection. These observations may be of value for further strategies to decrease reperfusion injury and prevent early allograft rejection.
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PMID:The release of cytokines, adhesion molecules, and extracellular matrix parameters during and after reperfusion in human liver transplantation. 890 Mar 13

We studied the associations of macrophage activity, T-helper cell types 1 and 2 (Th-1/Th-2) responses, and iron status in 55 patients with hepatitis C virus (HCV)-related liver disease and 28 control patients with noninfectious liver disease. Serum concentrations of soluble tumor necrosis factor receptor type II (sTNFrec 75), a macrophage activation marker, were higher in cirrhotic than in noncirrhotic patients (P<.001) regardless of their HCV status, whereas levels of neopterin, interleukin (IL)-4 and IL-10 did not differ significantly. In HCV-positive patients, sTNFrec 75 levels and transferrin saturation (TfS) correlated positively with levels of aspartate transaminase (P<.001 for sTNFrec 75 and P=.028 for TfS) and alanine transaminase (P=.003 for sTNFrec 75 and P=.039 for TfS). Increased TfS correlated significantly with both advanced liver disease and a predominant Th-2 pattern in HCV patients. Our data suggest that an association exists between macrophage activation and hepatic dysfunction, and that iron status may affect the clinical course of HCV infection by modulating Th-1/Th-2 responses in vivo.
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PMID:Associations between cellular immune effector function, iron metabolism, and disease activity in patients with chronic hepatitis C virus infection. 1051 3

CT/MRI findings, laboratory examinations and prognoses of 42 patients with acute encephalopathy (AE) (Japan Coma Scale > or = 200) were reported. 1. Findings on CT/MRI were divided into the following 7 categories: Group 1 (normal), Group 2 (CT/MRI looked normal in acute phase, but brain atrophy developed and progressed slowly by weeks or months), Group 3 (CT/MRI looked normal within a few days after the onset of AE, but cortical laminar necrosis developed at 4-5 days after the onset), Group 4 (marked brain edema developed within 2 days after the onset of AE), Group 5 (AE with symmetric thalamic lesions), Group 6 (symmetric pallidum, lesions on MRI which appeared after brain edema disappeared), and Group 7 (the brain shrinked during acute phase, which normalized on the follow up CT/MRI). 2. Serum AST elevated in approximately 50% of the patients with AE. Sixty percent of them exhibited DIC, whose prognoses were poor. Cerebrospinal fluids (CSF) neopterin (NP) and/or interleukin (IL)-6 were elevated in all the 8 patients examined. In the two cases whose serum NP and IL-6 were measured at the same time, their values in the CSF were higher than those in the serum in one case, and almost the same in the other. In a patient with a condition mimicking hemorrhagic shock and encephalopathy, serum IL-6 concentration was very high (94,000 pg/ml). 3. Mild hypothermia (around 34 degrees C) combined with methylprednisolone pulse therapy was excellently effective on AE. A 6-year-old boy exhibited tonsillar herniation at admission recovered well to be able to run. 4. Differentiation between Reye syndrome and HSE, and the pathogenesis of AE were also discussed.
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PMID:[Infection-related acute encephalopathy: CT scan/MRI finding, laboratory examination and prognosis]. 1072 91

A pilot dose-escalation study of recombinant human interleukin 12 (rhIL-12) was conducted in Japanese patients with advanced malignancies. Cohorts of three patients received escalating doses of rhIL-12 that increased from 50 to 300 ng/kg/day s.c. three times a week for 2 weeks followed by 1-week rest. The same dosage and schedule was repeated for two additional courses. Sixteen previously treated patients were registered, and 15 were evaluated. Common toxicities were fever and leukopenia; the abnormality of laboratory tests included elevations in aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, C-reactive protein, and beta2-microglobin. Dose-limiting toxicity was the grade 3 elevation of aminotransferases, and was observed in two of six patients at the 300-ng/kg dose level after the first course in one patient and after the third course in the other. Leukopenia was observed at all of the dose levels; two of six patients at 300 ng/kg experienced grade 3 leukopenia. Thus, 300 ng/kg was determined to be the maximum acceptable dose. Peak plasma levels of rhIL-12 decreased in the second courses, but the areas under the curve were almost the same in the first and second courses. Biological effects included increases of plasma levels of IFN-gamma, tumor necrosis factor-alpha, IL-6, IL-10, and neopterin. In two patients with renal cell carcinoma, complete response and partial response of metastatic tumors were observed with 50 and 300 ng/kg; the responses lasted for 5 and 3.5 months, respectively. Although immunological response to rhIL-12 varies depending on administration route and schedule and on patients' physiological conditions, the recommended dose for Phase II studies is 300 ng/kg s.c. three times a week for 2 weeks followed by 1-week rest.
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PMID:A dose-escalation and pharmacokinetic study of subcutaneously administered recombinant human interleukin 12 and its biological effects in Japanese patients with advanced malignancies. 1091 7

Liver disease is frequent in patients taking home parenteral nutrition (HPN), but its cause remains unclear. Ongoing inflammation was implicated in HPN-associated cholestasis, so we examined the relation between liver-enzyme concentrations and circulating inflammatory and immune markers in these patients. In 17 HPN patients and 10 age- and sex-matched control subjects, we examined erythrocyte sedimentation rate, blood neopterin, soluble interleukin (IL)--2 receptors, circulating tumor necrosis factor-alpha, IL-6, aspartate and alanine aminotransferases, alkaline phosphatases, and gamma-glutamyltranspeptidase (GGT) concentrations. Fourteen of 17 patients had abnormal liver function tests with an increase in alkaline phosphatases (P < 0.001), gamma-glutamyltranspeptidase (P < 0.01), and aspartate aminotransferase (P < 0.01). Alkaline phosphatases were positively correlated to erythrocyte sedimentation rate, neopterin, tumor necrosis factor-alpha, and IL-6. gamma-Glutamyltranspeptidase was positively linked to tumor necrosis factor-alpha and soluble IL-2 receptors. There was no link between aminotransferases and inflammatory parameters. Liver-enzyme concentrations were correlated to the amount of total intravenous calories and calories originating from carbohydrates but not to infused lipids (median infused lipids x kg(-1) body weight x d(-1) = 0.62 g) in contrast to recently published data. Our results confirmed that the number of infused calories contributes to liver toxicity in HPN patients and strongly suggested that sustained inflammation is probably a key factor in worsening HPN-associated cholestasis.
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PMID:Persistent inflammation and immune activation contribute to cholestasis in patients receiving home parenteral nutrition. 1136 68

The aim of this study was to determine the existence of immune activation by measuring neopterin in HBV (Hepatitis B virus) carriers with viral load (HBV DNA) less than 5 pg/ml. Forty-three subjects and 56 healthy controls were included in the study. Neopterin levels of were compared. ALT and ALP levels in one patient and AST levels in two patients were found minimally higher than upper limit, and GGT levels were within the reference range in all patients. Neopterin levels in the patient group and in the controls were 159.97+/-13.39 and 84.10+/-11.45 nmol/l, respectively (P<0.0001). The difference between the two groups was statistically significant (P<0.0001). In conclusion, the increased neopterin levels of HBV carriers might be the indicators of the effect of cellular immunity. This increase might also implicate a background inflammation based on mainly cellular immunity that exists within the liver.
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PMID:Neopterin levels in nonreplicative HBV carriers. 1224 88

Most patients with liver cancer are diagnosed when they are not suitable for resection. Although some palliative approaches can be applied to these patients, the overall survival rate remains unsatisfactory. Active hexose correlated compound (AHCC), a newly developed functional food, has been shown to act as a potent biological response modifier in in vitro experiments. Recently, AHCC was found to improve the prognosis of hepatocellular carcinoma patients following surgical treatment. We investigated whether AHCC could prolong survival and improve the prognosis of patients with advanced liver cancer. A prospective cohort study was performed with 44 patients with histologically confirmed liver cancer. All of the patients underwent supportive care. Survival time, quality of life, clinical and immunological parameters related to liver function, cellular immunity, and patient status were determined. Of the 44 patients, 34 and 10 received AHCC and placebo (control) orally, respectively. Patients in the AHCC treated-group had a significantly prolonged survival when compared to the control group by Mann-Whitney test (95% CI, p = 0.000). Quality of life in terms of mental stability, general physical health status, and ability to have normal activities were significantly improved after 3 months of AHCC treatment when tested using the Wilcoxon signed-rank test (on one-sided test, p = 0.028, 0.037, and 0.040, respectively). The apparent different clinical parameters between the two groups were the levels of albumin and percentage of lymphocytes with p-values of 0.000 and 0.026 at 1 and 2 months after treatment, respectively. Unlike the control patients, AHCC treated-patients with longer survival time had the tendency of better outcomes since the levels of AST and ALT had not increased rapidly from their baselines at follow-up. In addition, the levels of total IL-12 and neopterin were slightly increased in AHCC treated-patients. This study suggests that AHCC intake could prolong the survival and improve the prognosis of patients with advanced liver cancer and delay the gradual decline of their physiological status.
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PMID:Prognostic improvement of patients with advanced liver cancer after active hexose correlated compound (AHCC) treatment. 1691 87


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