Search PubMed⌕ Search

Biomedical subjects

A C Allison

Publications and source records attributed to A C Allison.

At least 145 records · Page 8Linked to original sources

Induction of specific tolerance in rabbits by kidney allografting and short periods of cyclosporin-A treatment.

A short period of daily treatment with cyclosporin A (25 mg/kg orally or 18 mg/kg by intramuscular injection) induced specific tolerance lasting more than 12 months in 60% of nephrectomised rabbits allografted with one kidney. Tolerant rabbits accepted second kidney and skin allografts from the original donor even though all immunosuppressive therapy had been withdrawn at least 70 days earlier, while third party allografts were rejected normally. These results strongly support the hypothesis that cyclosporin A induces operational tolerance to antigens in a donor-specific, not tissue-specific fashion.

Animals↗

Lysosomal enzyme secretion by macrophages during intracellular storage of particles.

Cultured mouse peritoneal macrophages containing previously endocytosed zymosan or small-fibre asbestos (but not latex or sucrose) were shown to release selectively into the medium the lysosomal hydrolase beta-N-acetylglucosaminidase. Thus macrophage lysosomal enzyem secretion was experimentally dissociated from endocytosis (as the residual external particles were washed away from the cells). The cells remained viable, and total activities of both N-acetyl-beta-D-glucosaminidase and of lactate dehydrogenase (a cytosol enzyme) rose with time. The relevance of such secretion by macrophages containing stored materials to chronic inflammatory processes is discussed.

Acetylglucosaminidase↗

Protection of mice against endotoxin-induced liver damage by anti-inflammatory drugs.

Mice were injected with Corynebacterium parvum, which induces multiple granulomas in liver and renders animals hyper-reactive to the lethal effect of bacterial lipopolysaccharide (LPS). Such animals when challenged with LPS developed also extensive liver parenchymal cell damage as estimated by elevated blood asparate transaminase levels and a hypoglycaemia. Treatment with indomethacin, hydrocortisone, dexamethasone, promethazine, metiazinic acid and (+)-catechin ameliorated the liver damage. Hydrocortisone, dexamethasone, promethazine and metiazinic acid also reduced the mortality rate in mice challenged with LPS. Diarrhoea, accompanying the LPS-induced shock, was prevented by the drugs used. Possible agents mediating the hepatotoxic and shock effects of LPS are discussed.

Animals↗

Separation of erythrocytes infected with murine malaria parasites in metrizamide gradients.

Density gradients with metrizamide, a tri-iodinated benzamido derivative of glucose, have been used to separate erythrocytes infected with 3 species of murine plasmodia. Good separations were obtained of uninfected erythrocytes from erythrocytes containing parasites in different developmental stages. With metrizamide solutions, the densities required for isopyenic separation can be obtained without hypertonicity or high viscosity, and the viability and those aspects of the metabolism of parasites and erythrocytes that we measured are not detectably modified by exposure to these solutions. This type of separation has many possible applications to biochemical and immunological investigations.

Animals↗

Increased hepatotoxicity of bacterial lipopolysaccharide in mice infected with Schistosoma mansoni.

Mice infected with Schistosoma mansoni were highly sensitive to the lethal effects of bacterial lipopolysaccharide (LPS). The hyper-reactive state of LPS coincided with the development around the parasite eggs of multiple granulomas in the liver. Elevated aspartate transaminase levels in blood and severe hypoglycaemia in LPS-challenged animals indicated extensive liver parenchymal cell damage. There was also a complete depletion of glycogen in hepatocytes of these animals. From this work and studies on other hepatitis models, it is suggested that individuals affected with granulomatous disorders may be at risk because of everyday exposure to LPS from the gut.

Animals↗

Induction of macrophage lysosomal enzyme secretion by agents acting at the plasma membrane.

Cultured mouse peritoneal macrophages were shown to secrete the lysosomal enzyme N-acetyl-glucosaminidase (N-ac-Glu) in response to IgG-Sepharose and some other non-endocytosable particles without substantial release of the cytoplasmic enzyme, lactate dehydrogenase. The interaction with IgG-Sepharose was studied in some detail, and was shown to be time- and dose-dependent, and to leave the cells viable. Ovalbumin and glycine insolubilised on Sepharose did not induce secretion. By means of several control experiments, it was demonstrated that the IgG-Sepharose exerted its effects directly on the plasma membrane. Thus, normal macrophages can secrete in response to certain agents which act solely on the plasma membrane. This mechanism of induction of secretion is probably quite distinct from those previously established, which involve secretion during phagocytosis, during intracellular storage of phagocytosed materials or during pharmacological intervention by cytochalasin B.

Acetylglucosaminidase↗

Spontaneous and induced cytotoxic properties of human adherent mononuclear cells: killing of non-sensitized and antibody-coated non-erythroid cells.

A method is described which demonstrates that human adherent mononuclear cells have a strong capacity to kill human nucleated target cells. Cytotoxicity was measured by the release of 51chromium from two established cell lines. Freshly prepared monolayers killed both non-sensitized and anti-body coated K562 and CLA-4 target cells. These spontaneous events decreased after short term culture. A second peak of cytotoxic activity was induced by activating the effector cells with endotoxin-treated serum or phytohaemagglutinin. Cytotoxicity was inhibited by silica particles. Studies with alpha-naphthyl esterase showed that 95% of freshly prepared cells and 99% of monolayers cultured for 68 h were monocytes. These studies suggest that adherent monocytes are the predominant cytotoxic effector cell although a contributing effect by the small numbers of contaminating lymphocytes can not be excluded. Evaluation of monocyte cytotoxicity should have a useful role in clinical investigation.

Antibody-Dependent Cell Cytotoxicity↗

Metrizamide density gradients for separation of different developmental stages of malarial parasites.

Density gradients with metrizamide, a tri-iodinated benzamido derivative of glucose, have been used to separate erythrocytes infected with three species of murine plasmodia. Uninfected erythrocytes separated well from erythrocytes containing parasites in different developmental stages. With metrizamide solutions, the densities required for isopyknic separation can be obtained without hypertonicity or high viscosity, and the viability and metabolism of parasites and erythrocytes are not detectably modified by exposure to these solutions. This type of separation has many possible applications to biochemical and immunological investigations.

Animals↗

Malaria infections in different strains of mice and their correlation with natural killer activity.

Different mouse strains show marked variation in susceptibility to murine malaria parasites. Of those studied, strain A mice showed the highest susceptibility, most animals dying from Plasmodium chabaudi infections. In contrast, C57Bl and CBA mice all recovered from P. chabaudi infections and were then resistant to challenge with a virulent strain of P. yoelii. BALB/c mice recovered from P. chabaudi infections but were not uniformly resistant to P. yoelii challenge. B10.A mice, which share haplotypes (H-2(a)) with strain A mice, were resistant to P. chabaudi infections. Of all the correlates of resistance, one appears to be of special interest: natural killer (NK) activity. This was high in C57Bl mice and in malaria-infected mice considerable increases in spleen cell numbers and in NK activity were observed. In contrast, strain A mice showed low NK activity and in malaria-infected animals spleen cell numbers and NK activity showed little or no increase. It is suggested that NK cells, recruited and activated by T lymphocyte-mediated immune responses to parasite antigens, recruit and activate NK cells and macrophages, and that a product of the reacting cells may produce death of parasites within circulating erythrocytes.

Animals↗