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C Agius

Publications and source records attributed to C Agius.

10 recordsLinked to original sources
PubMed2004

Characterization of two outer membrane protein antigens of Porphyromonas gingivalis that are protective in a murine lesion model.

Porphyromonas gingivalis is a key periodontal pathogen that has been implicated in the aetiology of chronic adult periodontitis. The aim of this study was to characterize two potential vaccine candidates (PG32 and PG33) identified from a previous genomic sequence analysis. Gene knockout studies suggested that these proteins play an important role in bacterial growth and are transcriptionally linked. Analysis of 14 laboratory and clinical isolates of P. gingivalis found that in all strains, both genes were present with a high level of conservation and that the two proteins were also expressed in vitro. Truncated recombinant PG32 and PG33 proteins were produced in Escherichia coli in an attempt to increase the solubility of the proteins while retaining their native conformation. While most of the truncated proteins remained insoluble, two truncated proteins showed good solubility and high levels of protection in the P. gingivalis murine lesion model and may be considered as potential vaccine candidates for further testing in models of human periodontal disease.

Amino Acid Sequence↗
PubMed2003

Melano-macrophage centres and their role in fish pathology.

Melano-macrophage centres, also known as macrophage aggregates, are distinctive groupings of pigment-containing cells within the tissues of heterothermic vertebrates. In fish they are normally located in the stroma of the haemopoietic tissue of the spleen and the kidney, although in amphibians and reptiles, and some fish, they are also found in the liver. They may also develop in association with chronic inflammatory lesions elsewhere in the body and during ovarian atresia. In higher teleosts, they often exist as complex discrete centres, containing lymphocytes and macrophages, and may be primitive analogues of the germinal centres of lymph nodes. Melano-macrophage centres usually contain a variety of pigments, including melanins, and these increase in range and volume in older fish or in the presence of cachectic disease. Melano-macrophage centres act as focal depositories for resistant intracellular bacteria, from which chronic infections may develop. Iron capture and storage in haemolytic diseases appears to be a primary function, but antigen trapping and presentation to lymphocytes, sequestration of products of cellular degradation and potentially toxic tissue materials, such as melanins, free radicals and catabolic breakdown products are among other functions that have been ascribed. Recent work suggests that they are a site of primary melanogenesis rather than mere storage. Melano-macrophage centres increase in size or frequency in conditions of environmental stress and have been suggested as reliable biomarkers for water quality in terms of both deoxygenation and iatragenic chemical pollution.

Animals↗
PubMed2001

Identification of vaccine candidate antigens from a genomic analysis of Porphyromonas gingivalis.

Porphyromonas gingivalis is a key periodontal pathogen which has been implicated in the etiology of chronic adult periodontitis. Our aim was to develop a protein based vaccine for the prevention and or treatment of this disease. We used a whole genome sequencing approach to identify potential vaccine candidates. From a genomic sequence, we selected 120 genes using a series of bioinformatics methods. The selected genes were cloned for expression in Escherichia coli and screened with P. gingivalis antisera before purification and testing in an animal model. Two of these recombinant proteins (PG32 and PG33) demonstrated significant protection in the animal model, while a number were reactive with various antisera. This process allows the rapid identification of vaccine candidates from genomic data.

Amino Acid Sequence↗
PubMed1995

Synthetic peptides representing sequences within gp41 of HIV as immunogens for murine T- and B-cell responses.

Within the gp41 glycoprotein of the human immunodeficiency virus type 1 (HIV-1) there is a relatively conserved region which appears accessible to the immune system during the course of HIV infection and is recognised by antibody from virtually all patients with AIDS. This region has also been shown to function as a target for human T cells. We have examined synthetic peptides spanning this sequence, between residues 572 and 604, with a view to evaluating their potential as immunogens. Peptides 572GIKQLQARILAVERYLKDQQ591 and 579RILAVERYLKDQQLLGGIWGCSGK601 were good immunogens in two different strains of mice while peptide 576LQARILAVERYLKDQQ591 was an inferior immunogen, and peptide 593LGIWGCSGKLIC604 was non-immunogenic unless coupled to a carrier protein. For both antibody and T cell responses it was apparent that sequences that could function as determinants within one peptide could not do so in the context of a different peptide immunogen. It follows that by judicious choice of immunogen sequence it may be possible to direct the immune response towards a desired fine specificity. Unwanted responses by CD4+ T cells isolated from certain peptide-primed animals were also observed. These T cells showed an unusual reactivity in that they were incapable of recognising their determinant AVERYLKDQQ if it was extended at the C-terminal end with the native sequence and as such would not be expected to recognise the native molecule unless processing created the identical C-terminus.

Amino Acid Sequence↗
PubMed1985

Effect of streptozotocin on the glutathione S-transferases of mouse liver cytosol.

Streptozotocin (STZ) increased the activity of mouse hepatic glutathione (GSH) S-transferases assayed with 1-chloro-2,4-dinitrobenzene. Nicotinamide administered prior to STZ prevented the hyperglycemia indicative of STZ-induced diabetes, but had no effect on the increase in GSH S-transferase activity caused by the drug. Another diabetogenic agent, alloxan, did not alter GSH S-transferase activity. Thus, streptozotocin may be increasing GSH S-transferase activity directly, and not as a result of the diabetic state the drug induces. Two transferases were characterized from mouse liver cytosol. One was a homodimer with a subunit molecular weight of about 28,000 and a pI of about 8.2. The other was also a homodimer with a subunit molecular weight of about 27,500 and a pI of about 9.2. The pI 8.2 GSH S-transferase was induced by STZ, while the pI 9.2 transferase was decreased by the drug. At least one other transferase appeared to be induced by STZ. Two other nitroso compounds, chlorozotocin and diethylnitrosamine, also increased GSH S-transferase activity, suggesting that this effect may be nitroso related.

Animals↗
PubMed1982

Identification of a glucocorticoid receptor in the human leukemia cell line K562.

The binding of [3H]dexamethasone to the cytosol fraction prepared from the human leukemia cell line K562 was studied with a competitive binding assay. Specific, saturable binding was identified by incubating cytosol with increasing concentrations of [3H]dexamethasone in the presence and absence of nonlabeled dexamethasone. A Scatchard plot of the data was linear, suggesting the presence of a single class of binding sites with KD = 2.49 +/- 0.23 x 10(-8)M. The binding sites appear to be protein in nature, since specific binding was reduced by treatment of the cytosol with trypsin, pronase, and heat; neither DNase nor RNase affected the binding. Binding was also reduced in the absence of alpha-thioglycerol and in the presence of p-chloromercuribenzoate and N-ethylamaleimide, suggesting that optimal binding activity requires reduced sulfhydryl groups. The binding site appears to be specific for glucocorticoids as evaluated in competition studies. Finally, glucocorticoids were found to inhibit the clonal growth of K562 cells in vitro, suggesting a potential role for glucocorticoid binding sites in the modulation of K562 cell proliferation.

Animals↗