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Biomedical subjects

A J Morgan

Publications and source records attributed to A J Morgan.

At least 91 records · Page 5Linked to original sources
PubMed1988

Calcium-lead interactions involving earthworms. Part 2: the effect of accumulated lead on endogenous calcium in Lumbricus rubellus.

The calcium and lead burdens of tissue fractions of Lumbricus rubellus were quantified in 'native' animals from acidic and calcareous disused lead mines, and from control ('naive') animals exposed to lead-polluted soils under laboratory conditions. Most of the body burden of lead was accumulated within the posterior alimentary canal, and significant positive correlations were generally found between the calcium and lead burdens in this tissue fraction, which were evident in both the naturally and laboratory lead-exposed animals. The calcium:lead correlation is probably due to a proliferation of the calcium-rich, lead-sequestering chloragosome granules, and may thus be regarded as a specific tissue response to cellular lead incursion. No calcium-lead relationship was recorded in the rest (largely composed of the body wall) fraction of earthworms inhabiting the lead-polluted sites. However, a concomitant increase in calcium and lead in this tissue fraction of the laboratory lead-exposed control animals was noted. It is concluded that in naturally lead-exposed earthworms, the cells of this tissue fraction may be relatively resistant to the toxic effects of the metal. By contrast, it is apparent that a non-specific cytotoxic response by the cells of the rest of 'naive' animals occurs, as demonstrated by the concurrent increase in its calcium and lead burdens. These results suggest that a tolerance mechanism to lead, perhaps with a genetic basis, may exist in earthworms naturally exposed to lead.

Journal Article↗
PubMed1988

Calcium-lead interactions involving earthworms. Part 1: The effect of exogenous calcium on lead accumulation by earthworms under field and laboratory conditions.

Earthworms (Lumbricus rubellus and Dendrodrilus rubidus) were collected from several acidic and calcareous abandoned ferrous metalliferous mine sites. Tissue lead concentrations were substantially lower than the total soil lead concentrations, except at one site (Cwmystwyth) where the tissue lead concentrations of both species were approximately 5 to 10 times higher than that of the soil. Soil lead was the major factor in determining the tissue lead concentration, although it was demonstrated that both soil pH and soil calcium concentration could markedly increase the % variance in tissue lead concentration. These findings help explain the apparent anomaly in tissue lead concentrations of earthworms from Cwmystwyth, where the soil is acidic and has exceptionally low calcium concentrations. Soil-liming experiments provided supportive evidence that soil pH, coupled with soil calcium, influences lead accumulation by earthworms, but a filter paper feeding experiment provided unequivocal evidence that soil calcium concentration alone can influence lead accumulation by earthworms. It is concluded that, although lead accumulation by earthworms is influenced by both physico-chemical and biochemical mechanisms, the latter over-rides the former, i.e. soil calcium is more important factor in determining the accumulation of lead earthworms than is soil pH.

Journal Article↗
PubMed1988

Prevention of Epstein-Barr (EB) virus-induced lymphoma in cottontop tamarins by vaccination with the EB virus envelope glycoprotein gp340 incorporated into immune-stimulating complexes.

Experimental induction of malignant lymphomas can be achieved in the cottontop tamarin by inoculation with Epstein-Barr (EB) virus. This system provides an animal model for assessing the efficacy of vaccine protection against the virus which is intended to reduce the incidence of human tumours associated with EB virus infection, namely endemic Burkitt's lymphoma and undifferentiated nasopharyngeal carcinoma. Cottontop tamarins have been vaccinated with the major envelope glycoprotein of EB virus, gp340, incorporated into immune-stimulating complexes (iscoms) and were thereby protected against a 100% lymphomagenic dose of virus. The gp340 iscoms are highly immunogenic, requiring only a few micrograms of immunogen to induce protective immunity and thus would be a strong candidate for further development as an EB virus vaccine for use in man.

Adjuvants, Immunologic↗
PubMed1988

Demonstration in vitro of cell mediated immunity to Epstein-Barr virus in cotton-top tamarins.

In the course of developing an effective Epstein-Barr (EB) virus vaccine, the immune responses in cotton-top tamarins to a tumourigenic dose of EB virus were studied. Cell mediated responses were measured using a tissue culture 'growth inhibition' assay where peripheral blood lymphocytes were tested for their ability to inhibit the outgrowth of autologous EB virus transformed lymphoblastoid cells. This system has previously been recognized as a very sensitive assay for detecting cell-mediated responses to EB virus in man. Using this assay no cell-mediated immunity was detected up to the time of death in two tamarins following injection with a tumourigenic dose of EB virus. However, two other animals which had recovered from tumours induced by a first dose of EB virus 18 months previously when subsequently re-stimulated with a second tumourigenic dose did exhibit cell-mediated responses. These latter animals remained healthy following the re-challenge and did not show evidence of EB virus-induced disease.

Animals↗
PubMed1987

Varicella-zoster virus as a live vector for the expression of foreign genes.

The previous demonstration of the efficacy and tolerability of the Oka strain of varicella-zoster virus (VZV) in clinical trials involving vaccination of both normal and immunocompromised individuals has laid the foundation for its use in preventing chickenpox. In this context, VZV could be useful as a vector for vaccinating against other infectious agents as well. As an initial application, a live recombinant VZV expressing Epstein-Barr virus (EBV) membrane glycoproteins (gp350/220) was generated by inserting a gene fusion of the VZV gpI promoter and hydrophobic leader-encoding sequence with the gp350/220 coding sequence into the thymidine kinase (TK) gene of VZV (Oka). Insertion of the foreign DNA into the thymidine kinase gene was demonstrated by Southern blot analysis and the ability of the recombinant virus to replicate in the presence of bromodeoxyuridine. RNA splicing, glycosylation, and plasma membrane presentation of gp350/220 in cells infected with the recombinant virus were similar to those seen in EBV-infected cells. In addition, the expression of VZV-specific glycoproteins was unaltered by the concomitant expression of this large foreign glycoprotein. Thus, VZV can be used as a live viral vector for active immunization against EBV and other pathogens.

Cell Line↗
PubMed1985

Individual tumors of multifocal EB virus-induced malignant lymphomas in tamarins arise from different B-cell clones.

Cotton-top tamarins were inoculated with sufficient Epstein-Barr virus to induce multiple tumors in each animal within 14 to 21 days. The tumors consisted of large-cell lymphomas that contained multiple copies of the Epstein-Barr virus genome and generated Epstein-Barr virus-carrying cell lines showing no detectable consistent chromosomal abnormality. Hybridization of tumor DNA with immunoglobulin gene probes revealed that each lymphoma was oligo- or monoclonal in origin and that individual tumors from the same animal arose from different B-cell clones. Thus the virus induced multiple transformation events in tamarins in vivo to cause malignant tumors resembling the Epstein-Barr virus-associated lymphomas of patients with organ transplants.

Animals↗
PubMed1985

Large-scale purification of Epstein-Barr virus membrane antigen gp340 with a monoclonal antibody immunoabsorbent.

A purification method has been elaborated to isolate Epstein-Barr (EB) virus membrane antigen, gp340, in milligram amounts. The gp340 was prepared from detergent extracts of B95-8 cells by affinity chromatography with a monoclonal antibody immunoabsorbent. Bound material was eluted and the eluate, consisting of 50% gp340, was then fractionated by gel filtration. The final gp340 product was antigenically active and 95% pure. The purification method was found to be rapid and reproducible with no loss of the ability of the immunoabsorbent to retain gp340 after repeated elution. The procedure provides suitable material to permit the detailed structural analysis of gp340 necessary for both vaccine design and for the investigation of the role of gp340 in immunity to EB virus infection.

Antibodies, Monoclonal↗
PubMed1984

Comparative immunogenicity studies on Epstein-Barr virus membrane antigen (MA) gp340 with novel adjuvants in mice, rabbits, and cotton-top tamarins.

The effectiveness of immunisation of mice, rabbits, and cotton-top tamarins with small amounts of EB virus MA glycoprotein gp340 , incorporated into artificial liposomes, has been compared using various routes of injection with or without additional adjuvants. Liposomes containing gp340 gave specific high titre antibodies after i.p. or i.v. administration, and the addition of lipid A to the liposomes resulted in a significant enhancement of the response. Antibodies generated by the above procedure were virus neutralising and bound gp340 specifically. These findings indicate an advantageous approach for use with a prototype vaccine for the prevention of EB virus infection.

Adjuvants, Immunologic↗
PubMed1984

A structural investigation of the Epstein-Barr (EB) virus membrane antigen glycoprotein, gp340.

Epstein-Barr (EB) virus membrane antigen (MA) glycoprotein (gp340) purified by a molecular weight-based technique has been subjected to biochemical analysis. Following treatment with glycosidases or tunicamycin during synthesis, the carbohydrate moiety was found to be made up of both O-linked and N-linked types and to constitute about 50% of the molecular mass. Digestion studies with neuraminidase and oligosaccharidase have indicated that the molecule is heavily sialated with most of the sialic acid located on the O-linked sugars. The high carbohydrate content of gp340 appears to confer resistance to proteolysis; thus, V8 protease was only effective at concentrations above 1 mg/ml when three large fragments of mol. wt. 330K, 190K and 160K were generated. Removal of sialic acid before V8 protease digestion did not alter this pattern nor affect the antigenicity of the digestion fragments. Antigenicity of the intact molecule was likewise unaffected by removal of sialic acid nor were the O-linked and N-linked carbohydrate moieties essential for this property. The binding of virus-neutralizing human sera and monoclonal antibody by gp340 from which either O-linked or N-linked sugars had been removed seems to indicate that the sites on the molecule that generate the neutralizing antibodies are present in the protein component. The significance of these results is discussed in relation to the development of a subunit vaccine against EB virus.

Animals↗
PubMed1983

Purification and properties of the gp340 component of Epstein-Barr virus membrane antigen in an immunogenic form.

Preparative SDS-polyacrylamide gel electrophoresis has been used in the purification of the gp340 component of Epstein-Barr (EB) virus-determined membrane antigen (MA), in tractable quantities, from the B95-8 marmoset lymphoblastoid cell line. Successful renaturation of the purified molecule was achieved. This procedure gave a 50-fold increase in the recovery of antigen compared to conventional techniques. The data suggest that the antigenic sites recognized by human sera containing antibodies to MA are largely confined to the protein portion of the molecule. An eightfold improvement in the yield of gp340 was obtained when B95-8 cells were cultured in the presence of 12-O-tetradecanoyl-phorbol-13-acetate. Gel filtration studies indicate that the major polypeptide components of MA are not associated in detergent solution. Immunization of rabbits with purified and renatured gp340 resulted in the generation of high-titre antisera which were specific for gp340, demonstrating that antigen prepared by this procedure is suitable for further evaluation as an experimental vaccine against EB virus infection.

Animals↗
PubMed1983

Oral ketamine.

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Bandages↗
PubMed1983

The electron microprobe analysis of sprayed microdroplets of solubilized biological tissues: a useful preliminary to localization studies.

The TEM-EDS bulk-tissue analysis procedure described involves: (1) low-temperature oxygen-plasma ashing of soft tissue specimens weighing greater than 20 micrograms in aluminum-foil crucibles; (2) the solubilization of the ash in 5 microliter 0.5N HNO3 containing a known quantity of cobalt as an internal, non-interfering reference element; (3) the spraying of the solubilized ash from glass microcapillary tubes onto thin carbon-collodion films mounted on titanium grids; (4) EDS analysis of individual microdroplets approximately 3 micron in diameter; (5) the quantitation of elemental concentrations from the element: cobalt intensity ratio by the "ratio model" technique. This technique was assessed and found to yield linear curves (greater than or equal to 0.999) for elements in 'artificial tissue' standards (concentration range = 5 - 340 mM kg-1 dry weight). The overall reproducibility of the technique is therefore quite good (e.g. error of 4.7% for P and K in 25 analyses) within the range of concentrations expected for most of the major biological elements encountered in vertebrate and invertebrate soft tissues. Absolute accuracy can be improved with quantitative procedures that account for peak-overlapping and escape peak contributions etc., so that the ultimate MDL for sodium may well be of the order of 1 mM kg-1 dry weight. The usefulness of the technique for the provision of basic biochemical information (especially in invertebrate systems which have received but meagre attention) is illustrated: (a) by comparing the calcium content of male and female blood-flukes (Schistosoma mansoni) in mixed-sex and unisexual laboratory infections; and (b) by determining the changes induced by daily injections of the drug Astiban on the element composition of female Schistosoma. We conclude that the technique can represent a useful multi-element detection facility which offers certain pertinent advantages over alternative microchemical techniques, such as atomic absorption spectrophotometry.

Animals↗
PubMed1982

The elemental composition of the chloragosomes of two earthworm species (Lumbricus terrestris and Allolobophora longa) determined by electron probe X-ray microanalysis of freeze-dried cryosections.

The elemental composition of the chloragosomes of the two earth-worm species, one with complex highly active Ca-secreting calciferous glands (L. terrestris) and the other with non-secretory glands (A. longa), was determined by the electron probe X-ray microanalysis of unfixed freeze-dried cryosections. The predominant constituents of the chloragosomes of both species were P, Ca, Zn and S, with lesser quantities of K, Cl and Fe. The most striking species differences in chloragosomal chemistry were the higher concentrations (expressed as relative mass fractions) of P(x 2.1), Ca(x 1.5), and Zn(x 2.3) in L. terrestris, and the much higher S(x 19.6) in A. longa. These differences were discussed in relation to the general ecophysiology of the two species, and more specifically in relation to heavy metal uptake and binding.

Animals↗