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Biomedical subjects

A Baskerville

Publications and source records attributed to A Baskerville.

At least 55 records · Page 3Linked to original sources
PubMed1988

Isolation of a gastric campylobacter-like organism from the stomach of four rhesus monkeys, and identification as Campylobacter pylori.

Campylobacter-like organisms, isolated from the gastric antrum of Rhesus monkeys, were compared with Campylobacter jejuni and C. pylori. They were similar to C. pylori by light microscopy, in ultrastructural morphology, in enzymic, fatty-acid-methyl-ester, and protein-profile analysis, and in antigenic reactivity with rabbit antisera to C. jejuni and C. pylori and with C. pylori-specific monoclonal antibody. Because this natural infection of the Rhesus monkey is associated with chronic gastritis, resembling the disease in humans colonised with C. pylori, we recommend the animal as a model for the investigation of human gastritis.

Animals↗
PubMed1988

Isolation of colonial variants of Bacteroides gingivalis W50 with a reduced virulence.

The spontaneous appearance of unusual colony forms was observed during prolonged growth of Bacteroides gingivalis W50 in a chemostat. Two variants were selected for further study which could be distinguished from the parent strain by the rate and intensity of pigmentation of their colonies. For example, after anaerobic incubation for 14 days, variant W50/BR1 produced brown colonies whereas those of the parent strain were black; in contrast, variant W50/BE1 did not show signs of pigmentation until incubation had continued for 21 days. In subsequent studies in the chemostat, variant W50/BE1 bred true even after prolonged growth whereas other colony forms appeared after incubation of variant W50/BR1 for 14 days. The relatedness of W50/BR1 and W50/BE1 to the parent strain was confirmed by comparisons of the whole-cell fatty-acid profiles, the patterns of pre-formed enzymes and by the metabolic end products after growth. However, the variants did differ from the parent strain in their virulence in a mouse pathogenicity model. The parent strain killed all mice given infective doses greater than 5 x 10(8) cfu whereas W50/BR1 was much less virulent (2 out of 10 mice killed and higher infective doses needed for higher mortality rates) and W50/BE1 was avirulent at all infective doses tested.

Animals↗
PubMed1988

Naturally occurring chronic gastritis and C pylori infection in the rhesus monkey: a potential model for gastritis in man.

Histological examination of the stomachs of Rhesus monkeys at autopsy showed chronic gastritis in a high proportion of all ages. Lesions consisted of mild to heavy infiltration of the lamina propria by lymphocytes, plasma cells, and histiocytes. The antrum was most consistently affected, but lesions were also present in the fundus and pylorus. Gastric Campylobacter-like organisms (GCLO) apparently identical to human C pylori were cultured and/or detected immunohistologically in several animals. Electron microscopy showed the spiral bacteria on the epithelial surface and in gastric pits. They did not penetrate the cells but were intimately attached to the apical plasma membrane and caused loss of microvilli. Antibodies to C pylori were detected in serum of the monkeys by ELISA. The immunospecificity of this antibody response was confirmed by Western blotting techniques. A small number of cynomolgus monkeys examined had gastritis, which may also be associated with the presence of C pylori. Baboons did not have gastritis, nor was C pylori cultured from their stomachs. The study indicates that the Rhesus monkey has a naturally occurring gastritis associated with C pylori infection and may therefore be a suitable experimental animal for the human disease.

Animals↗
PubMed1988

Effects of inhaled titanium dioxide dust on the lung and on the course of experimental Legionnaires' disease.

Guinea-pigs were exposed for 14 days to an aerosol of titanium dioxide (TiO2) dust to produce macrophage blockade. Groups of the animals were later infected by aerosol with Legionella pneumophila. Histological and ultrastructural studies showed that TiO2 dust alone was inert and non-fibrogenic and even at 6 weeks induced no pathological lesions in the lungs, apart from accumulation of macrophages in interalveolar septa. The macrophage blockade by TiO2 did not alter the animals' susceptibility to Legionnaires' disease nor increase mortality. The blockade was effective in the early stages of the infection and limited multiplication of L. pneumophila in the lungs. Later blood monocytes were recruited into the lungs, where they phagocytosed Legionellae, resulting in lung counts comparable to those of TiO2-free control animals.

Animals↗
PubMed1988

Effects of polymorphonuclear leucocyte depletion on the pathogenesis of experimental Legionnaires' disease.

Guinea-pigs were depleted of circulating polymorphonuclear leucocytes (PMN) by administration of anti-polymorph serum. Groups of animals were then infected by aerosols containing different doses of Legionella pneumophila and the effects compared with those in intact infected controls. Elimination of PMN lowered the dose of L. pneumophila necessary to establish infection, increased bacterial numbers in the lungs and caused much higher mortality. It did not change the nature or extent of pulmonary lesions. The findings confirm the importance of PMN in defence of the lung against L. pneumophila infection and indicate that PMN and their enzymes are not responsible for the pulmonary lesions, which are probably caused directly by the bacteria.

Animals↗
PubMed1987

Covalent linkage of carboxypeptidase G2 to soluble dextrans--II. In vivo distribution and fate of conjugates.

The in vivo fate of the therapeutic enzyme, carboxypeptidase G2 (CPG2) in native form and covalently-linked to soluble dextrans was studied in the mouse using radiolabelled compounds. Clearance, from the blood, of all compounds tested was found to be as intact, active material, whilst excreted radiolabel was associated in all cases with low molecular weight substances. The clearance and excretion rates of native CPG2 were found to balance, but this was not so for dextran-CPG2 conjugate or CNBr-activated dextran. Tissue distribution studies demonstrated that there was little or no tissue uptake of native CPG2, whereas dextran-CPG2 conjugate, and CNBr-activated dextran were retained in the liver. Within the liver, the CPG2 component of dextran-CPG2 conjugate was degraded more rapidly than the dextran moiety. Blockade of reticulo-endothelial system (RES) led to increased half-lives of dextran CPG2 conjugate and CNBr-activated dextran, demonstrating the involvement of the RES in the clearance of these compounds. Impairment of RES activity did not affect the clearance rate of native CPG2. These results are discussed in relation to the potential use of dextran-CPG2 conjugates in cancer chemotherapy.

Animals↗
PubMed1987

Immunocytochemical demonstration of the association between Legionella pneumophila, its tissue-destructive protease, and pulmonary lesions in experimental legionnaires' disease.

Using immunocytochemical techniques at the light and electron microscope levels, Legionella pneumophila and one of its extracellular proteases were located in the lungs of guinea pigs with experimental Legionnaires' disease (LD). L. pneumophila was immunostained by several peroxidase- and gold-labelling methods for light and electron microscopy. The protease was immunolabelled in tissue fixed in Carnoy's fluid at the light microscopical level and on broth-grown organisms at the ultrastructural level. It was not labelled in either formalin- or glutaraldehyde-fixed tissue. Using double-labelling techniques, L. pneumophila and protease were located in the same section and were shown to be intimately associated with pulmonary lesions, providing strong evidence for the role of this protease in LD pneumonia.

Animals↗
PubMed1987

Experimental infection of monkeys with Leptospira interrogans serovar hardjo.

Grivet monkeys experimentally infected with two different strains of Leptospira interrogans serovar hardjo showed no signs of severe clinical disease. There were no significant macroscopic lesions in any of the tissues examined, but the organisms were demonstrated in various tissues by immunofluorescent technique and were isolated from the blood and urine of two monkeys and the kidney of one. Abraded skin was shown to be a viable route of infection in non-human primates.

Animals↗
PubMed1986

Separation of Legionella pneumophila proteases and purification of a protease which produces lesions like those of Legionnaires' disease in guinea pig lung.

Six discrete protease activities were recovered from the supernatant broth of Legionella pneumophila cultures by ion-exchange chromatography. One of these demonstrated in vitro activity against collagen, casein and gelatin. When administered into the lungs of guinea-pigs this protease elicited lesions which were pathologically similar to those seen in clinical and experimentally induced Legionnaires' disease.

Animals↗
PubMed1986

Effect of hemin on the physiology and virulence of Bacteroides gingivalis W50.

Bacteroides gingivalis W50 was grown in a chemostat under steady-state conditions at pH 7.5 +/- 0.2 and a constant growth rate of 6.9 h for periods of up to 6 weeks (146 bacterial generations) in a complex medium. Hemin was capable of limiting the growth of cells up to a concentration of approximately 0.5 micrograms/ml since higher concentrations of hemin did not increase cell yields; cells grew in the absence of exogenously added vitamin K1. Only a limited number of amino acids was metabolized during growth, but because none of these was totally depleted, the limiting nutrient under hemin excess conditions was probably a peptide. A range of fermentation products was produced under all conditions of growth; higher concentrations of cytotoxic metabolites such as propionate and butyrate were formed under hemin excess conditions, although more ammonia was released under hemin limitation. When viewed by electron microscopy, cells grown under hemin limitation appeared to be either coccobacillary or short rods and possessed few fimbriae per cell, but large numbers of extracellular vesicles could be seen both surrounding the cell surface and free in the environment. In contrast, cells grown under hemin excess conditions were more commonly coccus shaped and were more heavily fimbriated but had fewer extracellular vesicles. Marked differences were found in the susceptibility of mice to infection with cells grown under different concentrations of hemin. Cells transferred to media without any added hemin were avirulent, whereas those grown under conditions of hemin limitation (0.33 and 0.40 micrograms/ml) produced a 20 and 50% mortality in mice, respectively. In contrast cells grown under hemin excess always caused 100% mortality in mice, although this virulence was dose dependent. When virulent, the bacteria caused an extensive, spreading infection with necrosis of the skin and subcutaneous tissues. Collagen disintegration was seen histologically, implying a role for collagenase production in the pathogenicity of these bacteria.

Animals↗
PubMed1986

Pulmonary damage caused by a protease from Legionella pneumophila.

Intranasal (or intratracheal) administration of a tissue-destructive protease from Legionella pneumophila to guinea-pigs produced areas of haemorrhagic pneumonia in the lungs after 1/2 h. By 24 h there was confluent consolidation in all lobes. Histological and ultrastructural studies showed alveolar haemorrhage, vesiculation and necrosis of type I alveolar epithelium and endothelium, followed by progressive exudation of oedema fluid, fibrin, PMN and macrophages. Damage to type II cell lamellated bodies and discharge of lamellar material were significant features of the lesion. Collagenase activity was indicated by morphological degradation of collagen fibres in severely affected interalveolar septa. The pathological changes of Legionnaires' disease pneumonia can thus be reproduced experimentally by the administration of a L. pneumophila tissue-destructive protease, suggesting that production of this protease in vivo during L. pneumophila infection may play an important role in causing the pneumonia.

Animals↗
PubMed1985

Ultrastructural pathology of experimental Ebola haemorrhagic fever virus infection.

The organs of monkeys infected with Ebola haemorrhagic fever were examined by light and electron microscopy during the acute stage of the disease. The virus caused focal coagulative necrosis in the liver, spleen, kidney, lung and testis and widespread mild vascular damage. In the brain there was intense congestion, with erythrocyte 'sludging', but no inflammatory reaction. There was significant injury to the microvasculature in all organs. Virus replicated in endothelial cytoplasm causing focal necrosis, separation of tight junctions and detachment from basement membranes. These changes were associated with oedema and haemorrhage, but though contributing to the hypovolaemic shock were not sufficiently extensive to account for the severity of vascular collapse. Renal involvement was also clinically important. Some renal cellular injury was caused by direct virus invasion of glomerular endothelium and tubular epithelium, but much tubular damage was probably due to ischaemia resulting from thrombosis in the peritubular capillaries. The virus also replicated in lymphocytes and monocytes and in interstitial cells of the testis. Since particles were not found in seminiferous epithelium, the degeneration of spermatogonia and spermatocytes was probably secondary to ischaemia.

Animals↗
PubMed1985

Studies on ciprofloxacin therapy of experimental Legionnaires' disease.

The concentration of ciprofloxacin in the serum and tissues of normal guinea-pigs was monitored after intramuscular and oral administration. Significant concentrations were attained in the kidneys, but higher doses were required before serum and lung concentrations became measurable. Ciprofloxacin, given parenterally, prevented pyrexia and death of guinea-pigs infected by aerosols of Legionella pneumophila. Although it markedly reduced the number of bacteria in the lungs, it did not prevent the development of pulmonary lesions. Ciprofloxacin administered orally was not so effective in preventing death, although pyrexia was prevented and numbers of bacteria in the lungs of guinea-pigs were reduced. The low minimum inhibitory and bactericidal concentrations of ciprofloxacin against L. pneumophila together with the in vivo results observed suggest that this antibiotic could be of value in the treatment of human beings suffering from Legionnaires' disease.

Administration, Oral↗
PubMed1985

A comparison of virulence of two strains of Legionella pneumophila based on experimental aerosol infection of guinea-pigs.

Two strains of Legionella pneumophila (LP) serogroup I, of differing virulence, were examined in terms of numbers of viable organisms in tissues, pyrexia and mortality following aerosol infection. The Corby strain was the more virulent, with pyrexia and deaths of guinea-pigs 3 to 6 days after infection. This strain multiplied very rapidly in the lungs to reach a peak of 5 X 10(11) viable organisms/lung. Organisms were present in the blood, liver, spleen and kidney. The Philadelphia-1 strain (NCTC 11192) was unable to replicate in the lung and was cleared between 14 and 21 days after infection. Pyrexia was not observed. No guinea-pigs died and viable LP was not found in any organ other than the lung. Lung lavages on aerosol infected animals were performed and the virulent Corby strain was found to be mainly intracellular. The avirulent Philadelphia-1 strain was found predominantly in the extracellular location. There were approximately 10 times the number of viable virulent LP in the lung macrophage fraction than in the lung PMNL fraction. In comparison, there were approximately equal numbers of the viable avirulent strain in the macrophages and the PMNL. Experimental evidence suggests that the macrophage preferentially supports the growth of the virulent Corby strain compared with the PMNL. The avirulent strain on the other hand appears to be destroyed by both the macrophages and the PMNL.

Aerosols↗