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Biomedical subjects

A J Morgan

Publications and source records attributed to A J Morgan.

At least 73 records · Page 4Linked to original sources
PubMed1991

Salivary and serum IgA antibodies to the Epstein-Barr virus glycoprotein gp340: incidence and potential for virus neutralization.

Human antibody responses to the Epstein-Barr virus (EBV) glycoprotein gp340 have been measured using purified preparations of the native molecule as the substrate in ELISAs. This glycoprotein is the dominant component of the EBV envelope and a major target for the virus-neutralizing antibody response. Healthy virus carriers (both Caucasian and Chinese) regularly show detectable anti-gp340 IgG in serum and, unexpectedly, 21-30% of these individuals are also serum anti-gp340 IgA positive. Chinese patients with the EBV-genome-positive malignancy nasopharyngeal carcinoma (NPC) show elevated serum IgA antibodies to gp340 but, given the background of responses amongst healthy virus carriers, anti-gp340 IgA titres are a poorer diagnostic indicator of NPC than serum IgA antibodies detectable by immunofluorescence against the multicomponent EBV early antigen (EA). Salivary IgA antibody responses to gp340 are potentially important as a means of neutralizing orally-transmitted virus. We detected salivary IgA (but not IgG) to gp340 in a minority (12-19%) of healthy virus carriers and in a higher proportion (49%) of NPC patients. Even saliva samples chosen for their relatively high anti-gp340 IgA titres showed only weak neutralizing activity against transforming EBV preparations whether from B95.8 cell culture supernatant or from the throat washing of an infectious mononucleosis patient. We conclude that in healthy virus carriers, salivary IgA responses to gp340 are unlikely to provide effective local immunity against re-infection with a second EBV strain.

Adult↗
PubMed1991

Accumulation of heavy metals from polluted soils by the earthworm, Lumbricus rubellus: can laboratory exposure of 'control' worms reduce biomonitoring problems?

This paper compares the patterns of metal (Pb, Zn, Cd, Cu) accumulation in nine populations of the epigeic earthworm, Lumbricus rubellus, native on metalliferous soils, with the patterns of metal accumulation in batches of L. rubellus sampled from an uncontaminated site and maintained on the nine contaminated soils for 31 days under laboratory conditions. The primary findings were: (1) the Pb, Zn and Cd concentrations in the 'native' worms were significantly higher in most cases than in the 'introduced' worms; (2) multiple regression analyses indicated that the relationships between tissue and soil metal concentrations were similar for 'native' and 'introduced' worms; (3) high soil organic matter content reduced the bioavailability of Pb, but low pH increased Pb bioavailability. It was concluded that, although no phenotypic evidence of metal-tolerant ecotypes was obtained, the exposure of earthworms from uncontaminated soils to contaminated soils under laboratory conditions can provide meaningful integrative data concerning metal bioavailability in soils which, for biomonitoring purposes, often present formidable sampling problems.

Journal Article↗
PubMed1991

A comparison of (Pb, Cd and Zn) accumulation in terrestrial slugs maintained in microcosms: evidence for metal tolerance.

The relative tissue accumulation of Pb, Cd and Zn were compared in two populations each of two species of slugs (Arion subfuscus and Deroceras reticulatum). One population was resident at a contaminated Pb/Zn mine site, and the other population was from an uncontaminated site and was transferred for 20 days to microcosms established at the mine site. It was found that when the experiment was conducted during late spring (May), but not in late winter (February), that the Pb and Zn concentrations in the tissues of the 'transplants', were significantly higher than in the tissues of 'residents'; the Cd concentrations in the transplants, although significantly higher in the May sample than in February, did not exceed those of their 'resident' counterparts. It was postulated that: (a) Pb and Zn tolerance in slugs is phenotypically expressed by a reduction in metal accumulation; (b) Cd tolerance, if present, may be characterized by enhanced storage capacity; and (c) the presence of local metal-tolerant ecotypes is a biotic variable that may confound the relationship between dry tissue and environmental metal concentrations that forms a basis of pollution biomonitoring.

Journal Article↗
PubMed1991

Identification of two T-cell epitopes on the candidate Epstein-Barr virus vaccine glycoprotein gp340 recognized by CD4+ T-cell clones.

Current efforts to develop an Epstein-Barr virus subunit vaccine are based on the major envelope glycoprotein gp340. Given the central role of CD4+ T cells in regulating immune responses to subunit vaccine antigens, the present study has begun the work of identifying linear epitopes which are recognized by human CD4+ T cells within the 907-amino-acid sequence of gp340. A panel of gp340-specific CD4+ T-cell clones from an Epstein-Barr virus-immune donor were first assayed for their proliferative responses to a series of truncated gp340 molecules expressed from recombinant DNA vectors in rat GH3 cells, by using an autologous B lymphoblastoid cell line as a source of antigen-presenting cells. The first four T-cell clones analyzed all responded to a truncated form of gp340 which contained only the first 260 N-terminal amino acids. These clones were subsequently screened for responses to each of a panel of overlapping synthetic peptides (15-mers) corresponding to the primary amino acid sequence of the first 260 N-terminal amino acids of gp340. One clone (CG2.7) responded specifically to peptides from the region spanning amino acids 61 to 81, while three other clones (CG5.15, CG5.24, and CG5.36) responded specifically to peptides from the region spanning amino acids 163 to 183. Work with individual peptides from these regions allowed finer mapping of the T-cell epitopes and also revealed the highly dose-dependent nature of peptide-induced responses, with inhibitory effects apparent when the most antigenic peptides were present at supraoptimal concentrations. Experiments using homozygous typing B lymphoblastoid cell lines as antigen-presenting cells showed that the T-cell clones with different epitope specificities were restricted through different HLA class II antigens; clone CG2.7 recognized epitope 61-81 in the context of HLA DRw15, whereas clones CG5.15, CG5.24, and CG5.36 recognized epitope 163-183 in the context of HLA DRw11. The present protocol therefore makes a systematic analysis of CD4+ T-cell epitopes within gp340 possible; it will be necessary to screen gp340-specific T-cell clones from a variety of donors to assess the wider influence of HLA class II polymorphism upon epitope choice.

Amino Acid Sequence↗
PubMed1991

An integrated study of the morphological and gross-elemental consequences of methyl mercury intoxication in rats, with particular attention on the cerebellum.

Methylmercury accumulates in the kidney and liver of rats, but fairly selectively damages the cerebellum, resulting in the clinical symptoms of neurological ataxia after prolonged exposures. Within the cerebellum, morphological examination indicated that the small granule cells beneath the Purkinje layer are especially susceptible to the toxin, showing signs of pyknosis during the phase of locomotory disability, whilst the large Purkinje cells are relatively resistant to cytotoxic injury. Flame photometric and electron probe X-ray microanalysis (EPXMA) of digested samples of the major organs failed to detect any significant changes in the Na, K, Ca, Mg, S and P concentrations of the organs, including the cerebellum, at intervals after methylmercury administration by either gastric gavage or via the drinking water. It was suggested that if the lesion within the cerebellum is restricted, as the morphological evidence suggests, to a small cohort of functionally important granule cells, then it may be difficult to detect elemental changes within this subpopulation against the compositionally unaltered majority of cerebellar cells and their extracellular spaces. To identify and compositionally characterize the injured cells requires electron probe X-ray microanalysis of frozen sections, or fractured bulk samples. The deep-seated nature of the 'target cells' within the cerebellum presents formidable cryopreparative problems.

Animals↗
PubMed1989

Validation of a first-generation Epstein-Barr virus vaccine preparation suitable for human use.

The efficacy of a new vaccine preparation against Epstein-Barr (EB) virus was investigated in cotton-top tamarins. The vaccine consists of fast protein liquid chromatography-purified EB virus membrane antigen glycoprotein of 340 Kd (MA gp340) mixed with a synthetic muramyl dipeptide adjuvant emulsified in squalane containing a pluronic polymer; it is suitable for both scaled-up batch production and eventual administration to man. Vaccinated tamarins rapidly developed ELISA detectable high titre antibodies to MA gp340, and their sera became strongly EB virus-neutralising. After challenge with a massive 100% carcinogenic dose of EB virus, the vaccinated tamarins had a strikingly low level of circulating EB virus-carrying mononuclear cells, in contrast to a control animal, and remained entirely free of tumours. This first-generation vaccine has thus been validated in experimental animals and the way opened for a phase I human trial.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1989

The effect of lead incorporation on the elemental composition of earthworm (Annelida, Oligochaeta) chloragosome granules.

The elemental compositions of chloragosome 'granules' in the earthworm Lumbricus rubellus living in non-polluted (Dinas Powys) and heavily Pb-polluted (Wemyss) soils were determined by fully quantitative electron probe X-ray microanalysis. P, Ca, S and Zn were the major elemental components of the chloragosomes. High Pb concentrations were found in chloragosomes of Wemyss animals; Pb was not detected in chloragosomes of Dinas Powys animals. Partial correlation and regression analysis indicated that the in vivo accumulation of Pb by chloragosomes was accompanied by diminished chloragosomal Ca concentrations. Pb is bound by P-containing ligand(s) in the chloragosome matrix. The sequestration of Pb by chloragosomes results in the detoxification of the metal by accumulative immobilization.

Animals↗
PubMed1989

Zinc sequestration by earthworm (Annelida: Oligochaeta) chloragocytes. An in vivo investigation using fully quantitative electron probe X-ray micro-analysis.

The elemental compositions of chloragosome "granules" in the earthworm Lumbricus rubellus living in non-polluted and heavily Zn-polluted soils were determined by fully quantitative electron probe X-ray microanalysis. P, Ca, S and Zn were the major elemental components of the chloragosomes. The in vivo accumulation of Zn by the chloragosomes was accompanied by diminished chloragosomal Ca concentrations. Zn was apparently bound by at least two ligand pools (Pool 1 = uncharacterised; Pool 2 = P-containing ligands, binding approximately 45% and 55% of the Zn, respectively) in the "control" chloragosomes. In Zn-contaminated chloragosomes, most (approximately 70%) was bound by P-containing ligand(s) but some (less than 1%) was also bound by S-containing ligands. It is suggested that the sequestration of Zn in chloragosomes results in the detoxification of the metal by accumulative immobilisation.

Animals↗
PubMed1989

Seasonal changes in metal levels (Cu, Pb, Cd, Zn and Ca) within the grey field slug, Deroceras reticulatum, living in a highly polluted habitat.

Slugs (Deroceras reticulatum) (Muller)) were collected from a disused Pb/Zn mine site for a period encompassing 3 years. The analysis of whole body replicates, collected monthly for a period of one year, demonstrated a large variability in metal concentrations for each of the five metals (Cu, Pb, Cd, Zn and Ca) analysed. Nevertheless, a number of significant monthly differences in metal levels were found, the most regular being for Ca, and the least regular for Cu. Significant differences in metal body burdens were also found between slugs collected during the same month, but in consecutive years. The presence of such large and irregular variability greatly restricts the potential value of terrestrial slugs as biomonitors of heavy metal contamination.

Journal Article↗
PubMed1989

Epstein-Barr virus gene expression in malignant lymphomas induced by experimental virus infection of cottontop tamarins.

Inoculation of cottontop tamarins with a large dose of Epstein-Barr virus (EBV) leads to the induction of multiple EBV genome-positive lymphomas. These tumors have been characterized as oligoclonal or monoclonal large-cell malignant lymphomas that closely resemble the EBV genome-positive B-cell lymphomas that arise in human allograft recipients. The expression of latent and lytic EBV-encoded proteins was investigated in these virus-induced tamarin lymphomas and in derived cell lines. The tamarin tumors were found to express EBV nuclear antigen 1 (EBNA 1), EBNA 2, EBNA leader protein, and the latent membrane protein (LMP) as determined both by immunohistochemical staining and by immunoblotting. However, within the limits of the immunoblotting assays, no expression of the EBNA 3a protein family could be detected. Assays for lytic-cycle proteins by using both polyclonal human sera and monoclonal antibodies against viral capsid antigen, early antigen, and membrane antigen (gp340/220) showed minimal, if any, expression of these antigens in the lymphoma biopsies. In contrast, the cell lines derived from these lymphomas, even in early passage, expressed abundant levels of the lytic-cycle antigens and also expressed the EBNA 3a protein as well as EBNA 1, EBNA 2, EBNA leader protein, and LMP. This finding suggests that the virus-lymphoma cell interaction, in particular the switch to lytic cycle, is subject to some form of host control in vivo. The expression of EBNA 2 and LMP in these tamarin lymphomas strengthens their resemblance to posttransplant lymphomas in humans, since these human tumors are also EBNA 2 and LMP positive (L. S. Young, C. Alfieri, K. Hennessy, H. Evans, C. O'Hara, K. Anderson, A. Rickinson, E. Kieff, and J. I. Cohen, submitted for publication). Since both proteins are known to be important effector molecules of virus-induced B-cell growth transformation in vitro, their expression in these lymphomas constitutes the best evidence for a direct oncogenic role for EBV in vivo.

Animals↗
PubMed1988

Efficient purification of Epstein-Barr virus membrane antigen gp340 by fast protein liquid chromatography.

A rapid and efficient procedure for the isolation of Epstein-Barr (EB) virus membrane glycoprotein gp340 has been developed. The mild, two step method consisted of anion exchange chromatography of B95-8 cell membrane detergent extracts followed by further purification by gel filtration. Production of homogeneous gp340 was achieved routinely with recoveries of at least 35% from starting material. The purified molecule, when injected into mice with a synthetic muramyl dipeptide adjuvant, N-acetylmuramyl-L-threonyl-D-isoglutamine ((Thr1)MDP), elicited high titres of EB virus-neutralizing antibody.

Animals↗
PubMed1988

Recombinant vaccinia virus expressing Epstein-Barr virus glycoprotein gp340 protects cottontop tamarins against EB virus-induced malignant lymphomas.

A strong association exists between Epstein-Barr (EB) virus and two human cancers, endemic Burkitt's lymphoma and nasopharyngeal carcinoma. In addition, the virus causes infectious mononucleosis [reviewed in Epstein and Achong, 1979, 1986] and more recently has been implicated in lymphomas arising in immunosuppressed individuals [Cleary et al., 1986]. The possibility of preventing or influencing the course of these diseases by vaccination has been advocated for a number of years [Epstein, 1976], especially in the case of undifferentiated nasopharyngeal carcinoma, which is the most common tumour of men in southern China and is prevalent in other specific regions; it therefore represents a major world cancer problem [Shanmugaratnam, 1971]. Two vaccinia virus strains were employed to make recombinants expressing the gene coding for the EB virus envelope glycoprotein, gp340, and were used to vaccinate cottontop tamarins. Protection against EB-virus-induced lymphoma was obtained in animals immunized with the laboratory (WR) strain recombinant but not with those recombinants derived from the vaccine (Wyeth) strain. Circulating antibodies to EB virus gp340 were not detected in any of the immunized animals.

Animals↗
PubMed1988

Earthworms as biological monitors of cadmium, copper, lead and zinc in metalliferous soils.

Earthworms (Lumbricus rebellus and Dendrodrilus rubidus) were sampled from one uncontaminated and fifteen metal-contaminated sites. Significant positive correlations were found between the earthworm and 'total' (conc. nitric acid-extractable) soil Cd, Cu, Pb and Zn concentrations (data log1) transformed). The relationships were linear, and the accumulation patterns for both species were similar when a single metal was considered, even though there were species difference in mean metal concentrations. Generally, the earthworm Cd concentration exceeded that of the soil; by contrast, the worm Pb concentration was lower than the soil Pb concentration in all but one (acidic, low soil Ca) site. Our observations suggest that Cu and Zn accumulation may be physiologically regulated by both species. Total-soil Cd explained 82-86% of the variability (V2) in earthworm Cd concentration; 52-58% of worm Pb and worm Zn concentrations were explained by the total-soil concentrations of the respective metals. Total-soil Cu explained only 11-32% of the worm Cu concentration. The effect of soil pH, total Ca concentration, cation-exchange capacity (CEC) and organic carbon on metal accumulation by L. rubellus and D. rubidus was investigated by multiple regression analysis. Soil pH (coupled with CEC) and soil Ca had a major influence on Pb accumulation (V2 of worm Pb increased to 77-83%), and there was some evidence that Cd accumulation may be suppressed in extremely organic soils. The edaphic factors investigated had no effect on Cu or Zn accumulation by earthworms. In the context of biomonitoring, it is proposed that earthworms have a potential in a dual role: (1) as 'quantitative' monitors of total-soil metal concentrations (as shown for Cd); and (2) as estimators of 'ecologically significant' soil metal, integrating the effects of edaphic factors (as shown for Pb).

Journal Article↗