Biomedical subjects

A Baskerville

Publications and source records attributed to A Baskerville.

At least 73 records · Page 4Linked to original sources

PubMed1985

Pathophysiology of shock and hemorrhage in a fulminating viral infection (Ebola).

Eleven rhesus monkeys were monitored intensively during experimental infection with Ebola virus. Prominent neutrophilia with left shift and lymphopenia were the earliest abnormalities and were statistically significant by day 4 (P less than .02 and P less than .01, respectively). By day 4 falls in platelet counts were not statistically significant, whereas in vitro platelet aggregation was markedly depressed, progressing rapidly to complete failure by the time of maximum illness. Intraplatelet protein studies suggested this event was the result of in vivo activation and degranulation. Coagulation cascade defects were mainly in the intrinsic system and were surprisingly mild, with no evidence of selective consumption or production deficit of factor VII or VIII. When the possibility of indirectly mediated damage to endothelium possibly by a nonspecific immune response was examined, weight loss was less severe in drug-treated monkeys, and all had detectable plasma prostacyclin metabolites, but there was no improvement in survival.

Animals↗

PubMed1985

Clinical chemical responses to experimental airborne legionellosis in the guinea-pig.

Legionella pneumophila infection of guinea-pigs by the aerosol route with either of two strains, one (serogroup I) giving an acute the other (serogroup 3) giving a protracted illness, induced a pyrexia and similar pneumonic lesions. With both strains there was a bacteraemia with early decreases in serum iron and zinc and increases in serum copper concentrations. Marked changes in other serum components were evident only in those animals which had protracted illness (serogroup 3-infected animals). These included transient increases in aminotransferase, creatine kinase and sorbitol dehydrogenase activities and triglyceride levels, together with gradual decreases in alkaline phosphatase and leucine aminopeptidase activities. Serum lysozyme activity and acute-phase protein synthesis increased, as did the ratio of phenylalanine to tyrosine. The findings confirm the relevance of the aerosol-infected guinea-pig model for the investigation of the disease processes and evaluation of therapeutic measures for use in man.

Acute-Phase Proteins↗

PubMed1985

Protection against intranasal infection of mice with Bordetella pertussis.

Mice have been infected by intranasal instillation of Bordetella pertussis and the infection monitored by determining numbers of bacteria isolated from the lungs. Outer membrane proteins, filamentous hemagglutinin, toxoided-lymphocytosis promoting factor and agglutinogens (fimbriae) actively protect mice against intranasal infection and antibodies of the antigens neutralize infectivity. The neutralization of infection by agglutinins is serospecific. In general, antigens that actively protect mice against intracerebral infections also protect against intranasal infections but some antigens, such as filamentous hemagglutinin and agglutinogens, protect only against intranasal infections. The intranasal protective potency of antigens can be enhanced by including low levels of active lymphocytosis promoting factor in the preparations. The relevance of the intranasal test to the potency testing of pertussis vaccines is discussed.

Animals↗

PubMed1985

Non-specific protection against pulmonary Legionella pneumophila infection in guinea-pigs immunized and challenged with mycobacteria.

Experiments were designed to test the ability of the non-specific efferent limb of cell mediated immunity (CMI) to protect guinea-pigs against a lethal L. pneumophila challenge. A secondary CMI response was generated in the lungs of guinea-pigs using an established protocol which consisted of intraperitoneal infection with Mycobacterium bovis BCG followed by intravenous infection with Mycobacterium tuberculosis H37Ra. The animals were challenged with L. pneumophila (100 LD50) by the aerosol route 3, 6 or 10 days after the H37Ra infection, and pyrexia and survival were monitored. Lungs were taken from animals killed at intervals for histology and enumeration of viable L. pneumophila. Normal guinea-pigs and others infected with either BCG or H37Ra alone were challenged with L. pneumophila as controls. Of the animals which received both BCG and H37Ra, all those challenged 3 days after H37Ra survived but this level of protection fell progressively in groups challenged 6 or 10 days after H37Ra. None of the control animals survived. Mycobacterial lung lesions were granulomatous and were readily distinguished from the acute exudative Legionella lesions. The protected animals showed evidence of a more substantial anti-mycobacterial CMI response and a delay in the development of Legionella lesions. The numbers of L. pneumophila present in the lungs indicated that protection did not result from early elimination of the Legionella challenge. The bacterial counts together with the histopathology suggest that the L. pneumophila was more effectively contained in the protected animals so that exudative damage was reduced.

Animals↗

PubMed1984

Undifferentiated carcinoma of the nasal tissues in the common marmoset.

The occurrence of undifferentiated carcinoma of the nasal tissues in 3 adult marmosets is described. The tumours appeared to arise from the respiratory epithelium of the turbinate bones and nasal septum. They were poorly differentiated, invaded the paranasal sinuses and hard palate and metastasized to the lungs or liver.

Animals↗

PubMed1984

Herpes simplex virus genital infection of the female guinea pig as a model for the evaluation of an experimental vaccine.

Substantial protection against herpes simplex type 2 (HSV 2) infection of the female guinea pig genital tract was provided by immunization with an experimental HSV 2 vaccine prepared from the plasma membranes of infected MRC-5 cells. Protection was evaluated in terms of the modification of histopathological lesions and clinical signs and in changes in viral replication and serological responses in vaccinated and control animals.

Animals↗

PubMed1983

Histopathology of experimental Legionnaires' disease in guinea pigs, rhesus monkeys and marmosets.

Guinea pigs, rhesus monkeys and marmosets were infected with L. pneumophila in small particle aerosols. Fever and acute fibrinopurulent pneumonia resulted. The lesions involved distal lung tissue only, spreading from terminal and respiratory bronchioles and producing heavy infiltration of alveoli by polymorphs and macrophages and widespread exudation of oedema fluid and fibrin. Lesions were not found in extra-pulmonary sites.

Animals↗

PubMed1983

Ultrastructure of pulmonary alveoli and macrophages in experimental Legionnaires' disease.

Guinea pigs, rhesus monkeys and marmosets infected with Legionella pneumophila in small particle aerosols developed an acute fibrinopurulent bronchopneumonia. Changes from 24 hr included exudation into alveoli of protein-rich, often fibrinous fluid and many polymorphonuclear leucocytes (PMN) and macrophages. Damage to alveolar capillary endothelium consisted of widespread cytoplasmic swelling and vesiculation, but necrosis of endothelium and the associated alveolar epithelium was focal and less common. Phagocytosis of L. pneumophila organisms was predominantly by macrophages, but the bacteria were also seen in PMN. Free organisms were present in alveoli and capillary lumina at all stages of the infection but were not observed in lung parenchymal cells. Some infected macrophages and PMN became necrotic and lysed to release intact bacteria. In all species of experimental animal, intracytoplasmic aggregations of granular material, believed to be glycogen, were seen frequently in macrophages and PMN which had phagocytosed L. pneumophila. These deposits of glycogen may reflect either an increased energy demand by the host cell or an interference with its carbohydrate metabolism.

Animals↗

PubMed1983

Biochemical and pathological changes in experimental phycomycosis.

Intravenous inoculation of rabbits with spores of Absidia corymbifera strain V.73/8 produced acute phycomycosis and death within 2 to 10 days. Cultural and microscopical examination showed that fungal infection was widespread and involved most organ systems but with particularly extensive lesions developing in the kidneys. The progress of the infection was associated with a raised leucocyte count, an increasing erythrocyte sedimentation rate and significant changes in serum biochemistry. The latter included a decrease in serum iron, zinc, alkaline phosphatase and gamma-glutamyl transpeptidase concentrations but an increase in the synthesis of acute phase proteins and in the phenylalanine:tyrosine ratio and in serum concentrations of copper, magnesium, potassium, lactate dehydrogenase and triglycerides. The serum urea concentration increased substantially during the terminal phase of infection.

Alkaline Phosphatase↗

PubMed1983

Antibiotic therapy of experimental airborne Legionnaires' disease.

The efficacy of erythromycin, gentamicin and rifampicin has been compared in the treatment of experimental airborne Legionnaires' disease in guinea-pigs. Evaluation was based on survival of animals after 1LD50 or 10LD50 infection, on numbers of Legionella pneumophila in the lungs and on the extent of histopathological lesions. All three drugs were effective in increasing survival in 1LD50 infections, but only rifampicin gave any protection against 10LD50 infection. Rifampicin was the most effective agent in eliminating viable L. pneumophila from the lungs and also in preventing pulmonary lesions.

Aerosols↗

PubMed1983

Aerosol infection of animals with strains of Legionella pneumophila of different virulence: comparison with intraperitoneal and intranasal routes of infection.

Infection of guinea-pigs by intranasal (i.n.) instillation of 10(9) viable organisms of two newly isolated strains of Legionella pneumophila (74/81, serogroup 1; 166/81, serogroup 3) did not induce disease, but 10(4) organisms administered as a small particle aerosol (less than 5 microns diameter) produced a fatal widespread broncho-pneumonia within 3 days. Milder illness and less extensive bronchopneumonia were also produced in rhesus monkeys and marmosets by one of these two strains (74/81). Mice were resistant to induction of disease by aerosols of both these two strains, though organisms did persist in the lungs for at least 4 days. Both of these L. pneumophila strains were pathogenic for guinea-pigs by aerosol infection over a wide range of doses but the serogroup 1 type strain (NCTC 11192) was not. There was no mortality after infection of guinea-pigs by intranasal instillation of any of these strains but all proved to be fatal after intraperitoneal (i.p.) injection of large doses. Guinea-pigs, rhesus monkeys and marmosets exposed to aerosol infection with L. pneumophila provide relevant models for studying the pathogenesis of Legionnaires' disease.

Aerosols↗

PubMed1983

Pathogenesis and immune response of vaccinated and unvaccinated rhesus monkeys to tick-borne encephalitis virus.

The rhesus monkey was used as a model for diseases caused by viruses of the tick-borne encephalitis virus complex to study the efficacy and safety of a commercial killed vaccine. Animals infected intravenously developed a subclinical infection with no histopathological lesions but with transient clinical chemical changes that included elevated transaminase, dehydrogenase, and creatine kinase activities and that declined as an immune response developed. The immune response was detected as neutralizing antibody in serum and serum antibody to several viral proteins. Antibodies to viral envelope protein and two other infected cell-specific polypeptides were also detected. Intranasal infection resulted in a disease resembling that in humans, except that no pyrexia was observed. Clinical chemical changes similar to those in intravenously infected monkeys developed, but most animals died before an immune response was mounted. Using this model, we have demonstrated that a commercial vaccine protects animals against a wild-type virus isolate and that it elicits an effective immune reaction without any evidence of an immune enhancement phenomenon or adverse side effects as judged by clinical observation, clinical chemistry, and histopathology.

Animals↗

PubMed1983

An outbreak of Bordetella bronchiseptica pneumonia in a colony of common marmosets (Callithrix jacchus).

An outbreak of Bordetella bronchiseptica pneumonia occurred in a breeding colony of common marmosets (Callithrix jacchus). 16 animals, all except one under 12 months of age, died suddenly. Extensive lesions of pneumonia and pleurisy were found at necropsy and B. bronchiseptica was isolated from the nasopharynx, trachea and lungs. Older animals had only a mild rhinitis. Colonization of the nasal mucosa occurred in 71 of 156 marmosets.

Animals↗

PubMed1983

Studies on protective immunity to aerosol challenge with Legionella pneumophila.

Guinea pigs exposed to 1, 2 or 3 sub-lethal aerosol infections with L. pneumophila developed ELISA serum antibodies after each infection, but were not protected against a lethal aerosol challenge. They died earlier than untreated control animals, though with the same acute exudative bronchopneumonia. Lung bacterial counts were lower in the immunized animals. The extent of pulmonary lesions increased with each successive sublethal infection and lymphoid cell infiltration was prominent after the second. Animals immunized with serotype-specific antigen developed serum antibodies, but were also not protected against lethal aerosol challenge and died earlier than controls.

Aerosols↗

PubMed1982

Pathological and biochemical features of Legionella pneumophila infection in guinea-pigs.

The main pathological feature of experimental legionellosis produced by the intraperitoneal inoculation of guinea-pigs was a fibrinopurulent peritonitis, especially over the liver and spleen. Foci of necrosis were present in these organs from the second to seventh day after infection. Early biochemical changes in the serum included significant decreases in the concentration of zinc and iron, and increases in copper and triglycerides. Phenylalanine to tyrosine ratios increased strikingly, but free amino acid decreased slightly. The total protein concentration did not change, but acute-phase proteins increased. Serum lysozyme activity increased as leucocytosis developed but fell during the subsequent leucopenia. In the later stages of the disease the activity of alkaline phosphatase, gamma-glutamyl transpeptidase, and creatine kinase decreased; that of dehydrogenases and transaminase increased.

Amino Acids↗

PubMed1982

A study of chronic pneumonia in a guineapig colony with enzootic Bordetella bronchiseptica infection.

Three types of lesion were present in the lungs of guineapigs with chronic pneumonia - pulmonary interstitial fibrosis, perivascular lymphoid hyperplasia and foreign body granulomas. Bordetella bronchiseptica was present in the nasopharynx, trachea and lungs of a high proportion of animals from 4 weeks old, and antibodies to this organism were also found. Animals removed at 4 days old and reared in isolation from the main colony and free from B. bronchiseptica developed similar lung lesions, so that B. bronchiseptica appeared to have no causative role in these forms of chronic pneumonia.

Animals↗

PubMed1982

Ultrastructural studies of chronic pneumonia in guineapigs.

Pulmonary interstitial fibrosis commenced as focal proliferation of fibroblasts and accumulation of macrophages in interalveolar septa and was followed by deposition of excess collagen. Epithelium of airways and alveoli remained normal. Perivascular nodules of lymphoid tissues which developed in the lungs of many older animals had a high mitotic rate, but the lymphocytes were morphologically normal. Micro-organisms were not observed in the lungs of any animal.

Animals↗

PubMed1982

Experimental Brucella abortus infection in the horse: observations during the three months following inoculation.

Five mares, one stallion and a colt foal were inoculated intraconjunctivally with Brucella abortus strain 544. No clinical signs of disease developed except mild pyrexia. Intermittent bacteraemia was detected in the mares but not in the stallion or foal. Antibodies to B abortus became detectable from the second week after inoculation. Titres in the serum agglutination and complement fixation tests declined substantially after six to eight weeks but reactions to the Coombs antiglobulin, 2-mercaptoethanol and immunodiffusion tests were maintained. No consistent changes in biochemical or haematological values were observed. Post mortem examination of the foal disclosed granulomatous lesions in the lungs, liver, testes and metatarsophalangeal synovial membranes. B abortus identical with strain 544 was recovered from lymphoid and other tissues.

Animals↗