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Biomedical subjects

P Hambleton

Publications and source records attributed to P Hambleton.

68 records · Page 4Linked to original sources

The pathology of untreated and antibiotic-treated experimental tularaemia in monkeys.

Grivet monkeys were infected intranasally with the virulent Schu-S4 strain of F. tularensis. One group of animals remained untreated and two other groups received a 7-day course of kanamycin therapy starting on either the third or fourth day after infection. Untreated monkeys developed pyrexia and mucopurulent oculonasal discharge and died 5--7 days after infection. All had pyogranulomatous lesions in the liver, spleen, respiratory tract and lymph nodes. Electron microscopy of liver and spleen showed phagocytosis of F. tularensis organisms by macrophages and polymorphonuclear leucocytes, but many bacteria survived phagocytosis and were released on destruction of the cells. Kanamycin therapy enabled most monkeys to survive the disease, but it did not prevent the development of persistent lesions in all animals. Caseous nodules were larger and more widespread in the organs of monkeys in which treatment was delayed until the fourth day of infection.

Animals↗

Changes in whole blood and serum components of grivet monkeys with experimental respiratory Francisella tularensis infection.

Grivet monkeys infected with virulent Francisella tularensis Strain Schu S4 showed significant early changes in serum levels of trace metals, triglycerides and activities of alkaline phosphatase, lactate dehydrogenase and alpha-hydroxybutyrate dehydrogenase. Free amino acid levels decreased slightly and there was a marked increase in the phenylalanine: tyrosine ratio. Serum lysozyme activity and seromucoid levels also increased. Kanamycin therapy produced remission of overt signs but the changes in blood constituents were less readily affected. Immunization with the live vaccine strain of F. tularensis induced transient responses similar to those resulting from Schut S4 infection. Immunized monkeys subsequently challenged with the virulent Schu S4 strain showed no clinical signs or marked changes in blood constituents.

Animals↗

Determination of antibacterial antibodies in serum by immunoradiometric assays.

When used to determine immunopurified antibacterial globulins in saline-phosphate buffer, the detection sensitivities of direct competitive and indirect immunoradiometric assays were respectively 25 and 2 ng. Normal human and rabbit sera interfered in both types of assay, markedly decreasing sensitivity and precision. Various pre-treatments of sera and modifications of reaction conditions substantially decreased interference in the competitive assay without affecting the activity of added antibody, but they had only marginal effects in the indirect assay. When serum samples taken from rabbits after vaccination with the Live Vaccine strain of Francisella tularensis were tested with the two assays and agglutination tests, newly synthesised circulating antibody was usually detected earlier by the competitive assay than by the other methods.

Animals↗

Changes in whole blood and serum components during Francisella tularensis and rabbit pox infections of rabbits.

Rabbits infected with virulent Francisella tularensis strain Schu S4 or rabbit pox virus (Utrecht strain) showed significant early changes in serum levels of trace metals, neutral fat and alkaline phosphatase activity. With F. tularensis infections a marked early leukopenia and a decrease in serum amino acids were also observed; the effect on amino acid levels was less pronounced in rabbit pox infections. In both diseases these changes preceded the appearance of acute phase globulins in the serum. Vaccination with the live vaccine strain of F. tularensis slightly increased survival times but did not delay the onset of metabolic changes in rabbits subsequently infected with the virulent Schu S4 strain.

Alkaline Phosphatase↗

Pathogenesis and pathology of respiratory tularaemia in the rabbit.

The development of pathological lesions in the organs of rabbits was examined at intervals from 1 h to 4 days after aerosol infection with Francisella tularensis. The earliest change, accumulation of polymorphonuclear leucocytes (PMN) in ulmonary alveolar ducts, occurred at 19 h. From the 2nd day multiple foci of necrosis and PMN infiltration were present in large airways and alveoli throughout the lungs and progressively increased in size. Pulmonary arteritis was a prominent feature of the infection. Areas of necrosis were present in the nasal mucosa, pharynz and trachea, and pyogranolomatous lesions consistently developed in the liver, spleen, and lymph nodes.

Animals↗

Experimental transmission of legionnaires' disease by exposure to aerosols of Legionella pneumophila.

Pyrexia and pneumonia developed in guinea-pigs after exposure to aerosols of Legionella pneumophila in a Henderson apparatus. Mortality was high 1-3 days after exposure. Histopathological changes were of an acute fibrinopurulent pneumonia, with widespread fibrin exudation and accumulation of neutrophils and macrophages in alveoli-lesions similar to those of legionella pneumonia in man. Rhesus monkeys given low doses of bacteria had slight fever and mild histological lesions in the lungs. Aerosol infection of these species offers suitable experimental models of legionnaires' disease.

Aerosols↗

Purification of bacterial exotoxins. The case of botulinum, tetanus, anthrax, pertussis and cholera toxins.

Bacterial protein toxins and their fragments have been isolated and purified for various reasons, including the development of efficient vaccines and for methods of identification of bacterial agents causing disease. This activity continues today but a new area of bacterial protein toxin research has recently emerged. Since it was shown that toxin molecules comprise several types of biological activity within their structural domains, it was suggested to use these domains (and their combinations) as biochemical tools for developing novel agents for disease imaging and and/or relieving. In this way eukaryotic cell-receptor specific fusion toxins have been developed to prevent malignancy in human. While human clinical trials of these preparations have only recently begun, the preliminary clinical findings are promising. Also fusion proteins which combine independent immunodominant epitopes from different antigens have also been developed thus opening a way for the generation of new vaccines for both human and veterinary use. Receptor binding fragments of microbial toxins when combined with other molecules may be useful in delivering these molecules into the cell. In this way novel agents may be developed with a potential for inducing specific changes at the molecular level for the correction of metabolic disorders causing human and animal diseases. Bacterial protein toxins such as anthrax, botulinum, cholera, pertussis and tetanus for which considerable progress has been achieved in structure-function analysis are promising candidates for such research. Particularly exciting appears the idea of extending this research to the cells of the nervous system, exploiting the unique specificity of the botulinum or tetanus toxin fragments which may bring long desired methods for treatment of various disorders of the nervous system. Data on functional domains of these toxins as well as methods of purification of the whole toxins and their fragments are considered in this review as they form a base for their further structure-function analysis and engineering applications.

Animals↗