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)

An immunologic profile may be useful to predict the development of Acquired Immune Deficiency Syndrome (AIDS) in both high risk patient groups including homosexuals, hemophiliacs, Haitians, and users of illicit intravenous narcotics as well as the general population. We evaluated 76 consecutive, apparently healthy, adults with congenital bleeding disorders for serum beta-2 microglobulin concentration by competitive enzyme immunoassay, T-lymphocyte subpopulations with monoclonal antibodies and serum interferon by inhibition of vesicular stomatitis virus plaque forming units. Findings on physical examination were remarkable with 24% of the group having longstanding splenomegaly and 24% lymphadenopathy. beta-2 microglobulin levels were 3232 +/- 220 micrograms/l (mean +/- SEM) with normal controls 2134 +/- 119 micrograms/l. The ratio of Leu3a (helper/inducer) positive to Leu2a (suppressor/cytotoxic) positive T-lymphocytes was 1.33 +/- 0.1 (mean +/- SEM, median = 1.18). Normal control ratios were all greater than 1.35 with a mean +/- s.d. = 1.96 +/- 0.28. Abnormal ratios of T-lymphocyte subpopulations appeared to persist over time. Increases in beta-2 microglobulin correlated with an inverted helper/suppressor T-lymphocyte ratio, the presence of lymphadenopathy, and elevations in aspartate aminotransferase. Interferon was detected in 18% of patient sera. More frequently transfused and more severely affected patients had a higher frequency of immunologic abnormalities although abnormalities also occurred in some rarely and never transfused less severely affected patients. These studies document a high incidence of immunologic abnormalities in patients with inherited coagulation defects.
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PMID:Immunologic profiles of adults with congenital bleeding disorders. 608 22

beta-2 microglobulin levels were measured in stored serum taken at presentation from 262 patients treated with combination chemotherapy for Kiel classification high-grade lymphoma at a single centre over a 15 year period. A significant association was found between elevated levels and advanced (Ann Arbor stage III or IV) disease or hepatic infiltration, but not with other sites of extranodal involvement or bulky disease. Patients with normal levels at presentation had a 70% remission rate with treatment compared to 37% of those with elevated levels (P < 0.001). With median follow up of 6 years duration of remission was significantly greater in patients with normal beta-2 microglobulin at presentation (plateau at 70%, compared to median remission of 19 months in those with raised levels, P < 0.001). Survival overall was also better in the group with normal levels (actuarial median 9 years compared to 1 year, P < 0.001). Multivariate analyses including treatment type, age, sex, B symptoms, stage, bulk, albumin, sodium, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase and beta-2 microglobulin, placed beta-2 microglobulin among the three most influential independent variables for prediction of response rate, duration of remission and overall survival.
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PMID:Beta-2 microglobulin: a prognostic factor in diffuse aggressive non-Hodgkin's lymphomas. 847 38

To evaluate the safety, toxicity, and maximum tolerated dose (MTD) of IFN beta-1a (Rebif, Serono Laboratories, Inc.) in patients with malignant diseases unresponsive to standard therapies and to assess the pharmacodynamics and pharmacokinetics associated with IFN beta-1a administration, an open-label, single-center phase I study was designed. Thirty-four patients were enrolled and treated with IFN beta-1a. All had measurable solid neoplasms or evaluable hematological malignancies. All patients received a single i.v. bolus dose of IFN-beta-1a on day 1, followed 7 days later by daily s.c. injections for 28 consecutive days. Successive groups of three patients received increasingly higher doses (in geometric progression from 1.5 million international units (MIU)/m2 to 24 MIU/m2) until dose-limiting toxicities were noted. Pharmacokinetic and biological studies, including measurement of the activity of 2',5'-oligoadenylate synthetase (2',5'-OAS) in peripheral blood mononuclear cells and serum levels of soluble Tac (CD 25) and beta-2 microglobulin, were performed on patients who agreed to participate. i.v. and s.c. doses of IFN beta-1a up to 24 MIU/m2 were administered. The most frequent adverse events (AEs) were constitutional symptoms. Grade III AEs during i.v. dosing included fever, elevation of bilirubin, and infection unrelated to therapy. No grade IV events were seen. AEs noted during continuous s.c. therapy included fever, liver transaminase increase, albuminuria, fatigue, nausea, myalgia, and rigors. Dose-limiting toxicities were encountered during s.c. dosing at the 24-MIU/m2 and 18-MIU/m2 dose levels and included gastrointestinal toxicity, elevations of aspartate aminotransferase and alanine aminotransferase, and albuminuria. The s.c. MTD was determined to be 12 MIU/m2, although there was great variability in the individual patient's ability to tolerate IFN beta-1a. 2',5'-OAS activity, thought to be indicative of IFN activity, increased within hours after i.v. and s.c. dosing, with the level remaining persistently elevated during the s.c. daily injections. The highest peak level was attained in the 6-MIU/m2 group. There was no evidence that the increase in 2',5'-OAS activity decayed with repetitive dosing, nor was there evidence of accumulation in this pharmacodynamic marker. Serum beta-2-microglobulin levels showed a modest time- and dose-dependent increase after s.c. administration of IFN beta-1a, with the largest increase seen at the 24-MIU/m2 dose level. There were no clear dose-dependent responses noted in soluble Tac serum levels. IFN beta-1a was well-tolerated when administered by a single i.v. bolus injection at doses up to and including 24 MIU/m2. Daily s.c. injections for at least 28 days were well-tolerated at doses up to and including 12 MIU/m2, with some patients tolerating doses twice as high as this. The MTD for the i.v. route could not be clearly determined according to the guidelines of the protocol. However, i.v. bolus doses up to 24 MIU/m2 were relatively well-tolerated. For the s.c. route, the MTD was determined to be 12 MIU/m2, but there was great interpatient variability, with some patients able to tolerate higher doses.
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PMID:A phase I study of recombinant interferon-beta in patients with advanced malignant disease. 1063 30

Liver injury is an important prognostic indicator during acute pancreatitis. The aim of this study was to determine the role of Fas ligand (FasL) in hepatocyte injury. Liver parenchymal enzymes were measured in cocultures of hepatocytes and Kupffer cells treated with elastase. FasL and FasL mRNA were measured in elastase-treated Kupffer cells. Hepatocytes were treated with FasL and their viability was assessed by monotetrazolium (MTT), apoptosis by flow cytometry, as well as caspase-3 and p38-mitogen-activated protein kinase (MAPK) by immunoblotting. Elastase increased aspartate aminotransferase and lactate dehydrogenase in cocultures of hepatocyte and Kupffer cells (P<0.040). Elastase increased FasL production from Kupffer cells (P=0.02) and upregulated FasL mRNA (FasL/beta-2 microglobulin (BMG): 0.23+/-0.03 vs. 0.11+/-0.003; P=0.04). FasL increased alanine aminotransferase and lactate dehydrogenase (P<0.03) and reduced hepatocyte viability by 45% (P=0.01). FasL increased the number of dually labeled cells with AnnexinV/7AAD (P=0.03) while upregulating cleavage of caspase-3 and the phosphorylation of p38-MAPK. FasL antibody attenuated the FasL-related increase in dually labeled cells (P=0.02), the cleavage of caspase-3, and phosphorylation of p38-MAPK. Pancreatic elastase upregulates FasL within Kupffer cells. FasL induces hepatocyte injury and death and upregulates p38-MAPK and caspase-3 within hepatocytes. The ability to manipulate interactions between Kupffer cells and hepatocytes may have important therapeutic implications.
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PMID:Kupffer cell-derived Fas ligand plays a role in liver injury and hepatocyte death. 1503 92