Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

EBV serological tests have been used for many years as accessory diagnostic predictors of nasopharyngeal carcinoma (NPC). To increase the sensitivity and specificity of the NPC detection rate, a novel enzyme-linked immunosorbent assay (ELISA) was established using a bacterially-expressed GST-EBNA-1 protein, containing the EBNA-1 sequence cloned from an NPC patient. Serum samples were collected from age- and gender-matched patients with NPC, community control subjects and hospital control patients and tested using this ELISA. The positivity rates were 78.7% (247/314) in NPC, 11.5% (28/244) in hospital controls and 3.8% (10/263) in the community control group. These serum samples were also tested for IgA anti-VCA antibodies and their ability to neutralize EBV DNase and the sensitivities of the anti-VCA antibody and DNase-neutralization tests also were analyzed. The optimum combination is VCA plus EBNA-1, which can identify 92.5% (287/310) of NPC patients, and shows a specificity of 92.7% (242/261) for normal individuals.
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PMID:Use of bacterially expressed EBNA-1 protein cloned from a nasopharyngeal carcinoma (NPC) biopsy as a screening test for NPC patients. 1128 69

Schistosomiasis, the second major parasitic disease in the world after malaria, affects 200 million people. Vaccine strategies represent an essential component of the control of this chronic debilitating disease where the deposition of millions of eggs in the tissues is the main cause of pathology. Research developed in our laboratory over the last 20 years has led to the identification of novel effector mechanisms, pointing for the first time to the protective role of Th2 responses and of IgE antibodies now supported by seven studies in human populations. The identification and molecular cloning of a target antigen, a glutathione S-transferase (GST), has made it possible to demonstrate its vaccine potential in several animal species (rodents, cattle, primates) and to establish consistently the capacity of vaccination to reduce female worm fecundity and egg viability through the production of neutralizing antibodies (IgA and IgG). Following promising preclinical studies, clinical trials (phase I and II) have been undertaken using Schistosoma haematobium GST, Sh28GST. High titers of neutralizing antibodies were produced (IgG3 and IgA) together with Th2 cytokines, consistently with the concepts developed from experimental models. With these results we are on the way towards a feasible approach of vaccine development against a major human parasitic disease.
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PMID:Vaccine strategies against schistosomiasis: from concepts to clinical trials. 1130 14

Linear IgA disease (LAD) is an autoimmune subepidermal blistering skin disease characterized by the linear deposition of IgA at the dermoepidermal junction. Serum from patients with LAD most commonly contains autoantibodies that are directed against the hemidesmosomal transmembrane glycoprotein BP180 (type XVII collagen). Various antigenic sites on the extracellular domain of this anchoring filament protein have been shown to be targeted by autoantibodies in different autoimmune bullous skin diseases, including bullous pemphigoid and cicatricial pemphigoid (CP). However, little is known about epitopes on BP180 recognized by autoantibodies in LAD. In this study, we used three recombinant GST fusion proteins, together roughly covering the entire BP180 ectodomain, to characterize the autoimmune response in serum from patients with LAD. Interestingly, we found both IgA and IgG reactivity to all three portions of the BP180 ectodomain. The strongest reactivity was observed with the C-terminal portion of BP180. This is also the major region recognized by autoantibodies in patients with CP. This finding correlates with the observation that there may be significant overlap of the clinical and immunopathological findings in LAD and CP.
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PMID:Mapping of epitopes on the BP180 ectodomain targeted by IgA and IgG autoantibodies in patients with the lamina lucida-type of linear IgA disease. 1135 23

To produce a water-soluble form of microsomal P450 2B4, fusion proteins with glutathione-S-transpherase were genetically engineered. Specific proteolitic sites recognized by Factor Xa and Thrombin have been introduced into N-terminus of P450 2B4 (46-49), lacking signal anchor sequence (2-27). It was supposed that proteolysis at this site could give the possibility to produce protein lacking hydrophobic N-terminus sequence (1-49). However, it was shown that given region in P450 2B4 his resistant against specific proteinase action. Positive result has been obtained at specific proteolysis with IgA endoproteinase, recognizing the native sequence PPGP (31-34) in P450 2B4. Thus, at first time truncated form of cytochrome 2B4, lacking its 33 N-terminal amino acid residues has been created. It was found that the expression of genetically engineered variants of GST-2B4 in Escherichia coli is accompanied by tight complex formation with molecular chaperones GroEL and DnaK. Dissociation of the complex occurred after proteolysis in: linker sequence (position 6-7) between C-terminal part of GST domain and N-terminal part of 2B4, and also before N-terminal methionine 2B4 and at position 33-34 (2B4). These results suggest the possibility that interaction with a GroEL/DnaK molecular chaperones may be requirement for correct folding of eukaryotic cytochrome 2B4 during its biosynthesis in E. coli.
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PMID:[Association of cytochrome P450 2B4 with molecular chaperones in heterological expression in E coli]. 1155 14

Deoxynivalenol (DON) and nivalenol (NIV) are toxic Fusarium secondary trichothecene metabolites that often co-occur regularly in cereal grains. These compounds were compared for their toxicity towards C57BL/6 mice on several parameters including alteration in plasma biochemistry, immune system reactivity and hepatic drug metabolism capacity. Mice received individual or combined oral doses of each toxin: 0.071 or 0.355 mg/kg of body weight, administrated three days a week for 4 weeks. Food consumption was altered by the single administration of 0.355 mg/kg of NIV, although no noticeable change of body and organ weights or liver protein contents was detected. NIV administration did cause also significant changes in total CO2 and uric acid concentrations in plasma. Individual toxin exposures led to increases in plasma IgA without no detectable change in the ex vivo production of cytokine by splenocytes. The liver ethoxyresorufin O-deealkylase, pentoxyresorufin O-depenthylase and glutathione S-transferase activities were increased in concert with cytochrome P4501a and P4502b subfamily expression. Administration of combinations of DON and NIV resulted in responses similar to that observed using individual doses of each toxin. However, depending on the ratio of toxin doses and biochemical parameters, some responses could be also additive (plasma IgA and hepatic DCNB conjugation) or synergistic (plasma uric acid).
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PMID:Individual and combined effects of low oral doses of deoxynivalenol and nivalenol in mice. 1637 17

The effects of hexachlorocyclohexane (HCH) on growth performance and immune and oxidative stress in growing/finishing pigs were studied. Seventy-two pigs, with equal numbers of barrows and gilts, of the same genotype (Duroc x Landrace x Large White), were randomly assigned to three groups receiving the same basal diet, exposed to 0, 0.4 and 0.8 mg/kg technical HCH, respectively, for 90 days. Six pigs from each group were randomly picked out and slaughtered on a finishing feeding trial. The result showed that addition of HCH did not affect the growth performance significantly but increased the weight of kidney and thymus significantly. Total serum IgG and IgM were elevated significantly, but there were no significant differences in serum IgA, C3 and C4 among the groups. Addition of HCH to feedstuff reduced superoxide dismutase (SOD), glutathione S-transferase (GST), glutathione reductase (GR) and glutathione peroxidase (GSH-Px) activities in liver, reduced serum catalase (CAT) activity, and increased serum malondialehyde (MDA). Moreover, the activities of serum alanine aminotransferase and alkaline phosphatase were increased significantly. Addition of 0.4 mg/kg or 0.8 mg/kg HCH did not affect the growth performance but affected the immune and antioxidant potential.
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PMID:Effect of HCH contamination of diet on the growth performance and immune and antioxidant ability in growing/finishing pigs. 1683 6

Helicobacter pylori has to counteract acidity during colonization in the stomach. The most important region for the enzymic activity of H. pylori urease, consisting of 138 aa (ureB138), was determined by a comparison of the homology of amino acid sequences, and a structural analysis, between urease of H. pylori and various other species. This region was expressed in Escherichia coli as a fusion protein with glutathione S-transferase (GST), which was cleaved by PreScission protease between the GST moiety and ureB138. The ureB138 protein was then purified by gel filtration. The polyclonal antibody (pAb) induced by immunization with the purified ureB138 could suppress urease activity by about 50 %, while the pAb against the H. pylori urease did not show any inhibitory effect at all. Immunohistochemical analysis indicated that the ureB138-specific pAb specifically recognized the H. pylori infecting human gastric tissues. The effects of vaccination of recombinant ureB138 against infection by this organism were also examined. Specific IgG and IgA antibodies against H. pylori urease were induced in the serum of mice immunized with ureB138. A reduction in the number of colonizing H. pylori was observed in mice treated with ureB138 compared to ones treated with BSA and infection control mice. In the protected mice, severe gastritis characterized by marked infiltration of mononuclear cells was noted compared with the gastritis observed in unprotected mice. Immunohistochemical staining for IgA in gastric mucosa showed that the number of mice positively stained with IgA was significantly higher in ureB138-vaccinated mice than in non-vaccinated mice. This indicates that local IgA antibody and severe post-immunization gastritis correlate well with the protection of mice against H. pylori infection.
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PMID:Effects of vaccination by a recombinant antigen ureB138 (a segment of the beta-subunit of urease) against Helicobacter pylori infection. 1751 Feb 73

Initiation of protein synthesis in bacteria relies on the presence of three translation initiation factors, of which translation initiation factor IF1 is the smallest having a molecular weight of only 8.2kDa. In addition to its function in this highly dynamic process, the essential IF1 protein also functions as an RNA chaperone. Despite extensive research, the exact function of IF1 in translation initiation has not yet been determined, and the research in the function of the factor has in some areas been impeded by the lack of monoclonal antibodies specific for this protein. Several attempts to induce immune response in mice with wild-type IF1 for the production of antibodies have failed. We have now succeeded in producing monoclonal antibodies specific for IF1 by applying a new immunization strategy involving an antigen combination of IF1 coupled to glutathione S-transferase (GST) and a recombinant dimer of IF1. This resulted in the generation of 6 IgG, 2 IgM, and 1 IgA anti-IF1 antibodies, which can be used in ELISA screening and Western immunoblots. We also provide a mapping of the functional epitopes of the generated anti-IF1 monoclonal antibodies by screening the antibodies for binding to IF1 proteins mutated at single amino acid positions.
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PMID:Production and epitope characterization of mAbs specific for translation factor IF1. 1793 21

Serological tests for Epstein-Barr virus (EBV) have been used for many years as diagnostic predictors of nasopharyngeal carcinoma. It has been shown previously that the conventional immunofluorescence assay has a limited diagnostic value, especially in young patients from North African area. In the search for more reliable immunoglobulin (Ig) G or IgA antibody markers for the diagnosis of nasopharyngeal carcinoma, immunoblot analysis was performed using a full spectrum of EBV proteins. Sera were collected from 108 patients with nasopharyngeal carcinoma and three control groups composed of 18 patients with lymphoma, 18 other patients with autoimmune diseases and 55 healthy EBV carriers. It was observed that the IgA Epstein-Barr nuclear antigen 1 (EBNA1), IgA early antigen (EA)-p138 and IgG EA-p138 antibodies represent the most specific anti-EBV responses in either young or older patients with nasopharyngeal carcinoma which yield higher positive rates compared to the three control groups. Since the IgA EBNA1 response showed the highest sensitivity value for the detection of nasopharyngeal carcinoma, a novel enzyme-linked immunosorbent assay (ELISA) was established using a GST-EBNA1 protein expressed in bacteria, containing the P-threonine EBNA1 subtype cloned from DNA EBV sequence of C15 xenograft cells. Detection rates were 85.7% and 94.9% in young and older patients with nasopharyngeal carcinoma respectively, while only 3.6%, 11.1%, and 16.6% in healthy EBV carriers, patients with lymphoma and patients with autoimmune diseases, respectively. Thus, IgA EBNA1 ELISA may be useful for early diagnosis and mass screening of nasopharyngeal carcinoma in Tunisia even in young patients.
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PMID:IgA antibodies against the Epstein-Barr nuclear antigen1 as a valuable biomarker for the diagnosis of nasopharyngeal carcinoma in Tunisian patients. 1955 36

One of the promising approaches in mucosal immunization relies on live recombinant vaccine carriers. In this study, we used a six-extracellular protease-deficient Bacillus subtilis strain WB600 to express Schistosoma japonicum 26 kDa glutathione S-transferase (GST). Western blot, immunofluorescence, and flow cytometry analyses were used to identify SjGST expression on spore surface. SjGST recombinant spores were used for oral vaccination in mice and were shown to generate mucosal and systemic response. Both SjGST-specific secretory IgA in feces and IgG in serum augmented significantly on day 33 after oral administration. It seemed that surface display of recombinant S. japonicum SjGST on B. subtilis WB600 spores showed good immunogenicity, and B. subtilis spores could be used as potential mucosal delivery vehicles to provide more effective vaccination strategies for parasite prevention and control in the future.
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PMID:Immunogenicity of self-adjuvanticity oral vaccine candidate based on use of Bacillus subtilis spore displaying Schistosoma japonicum 26 KDa GST protein. 1975 53


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