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Biomedical subjects

P Hambleton

Publications and source records attributed to P Hambleton.

At least 55 records · Page 3Linked to original sources
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

Survival of virulent Legionella pneumophila in aerosols.

Aqueous suspensions of virulent Legionella pneumophila grown on solid medium retained virulence and aerosol survival characteristics for several months. Significant numbers of viable organisms were recovered from aerosols held at various relative humidities (r.h.) for up to 2 h. The organisms survived best at 65% r.h. and were least stable at 55% r.h. Exponential phase broth-grown organisms survived poorly in aerosols in comparison with stationary phase broth cultures or organisms grown on solid medium, suggesting that the metabolic status of Legionella pneumophila organisms may be an important factor affecting their ability to survive in aerosols and cause respiratory disease.

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↗
PubMed1982

Preparation and characterisation of homogeneous neurotoxin type A from Clostridium botulinum. Its inhibitory action on neuronal release of acetylcholine in the absence and presence of beta-bungarotoxin.

1. Large-scale production and purification of complexes between Clostridium botulinum neurotoxin and haemagglutinin have been achieved. 2. Haemagglutinin-free neurotoxic protein of the complexes was purified to high specific neurotoxicity by affinity chromatography, on p-aminophenyl beta-D-thiogalactopyranoside coupled to Sepharose 4B, followed by chromatography on DEAE-Sephacel. 3. The resultant neurotoxin was homogeneous on isoelectric focussing (pI = 6.3) and on dodecylsulphate/polyacrylamide gel electrophoresis under non-reducing conditions when its Mr was 1.4 X 10(5); after reduction two polypeptides (Mr = 9.9 and 5.5 X 10(4) were present. 4. On double-immunodiffusion gels, using antiserum against neurotoxin-haemagglutinin complex, the neurotoxin showed a single, sharp precipitin line that was immunologically distinct from a relatively non-toxic protein (Mr = 1.3 X 10(5), which co-purifies with the neurotoxin but is removed by the ion-exchange chromatography step. 5. Application of the neurotoxin to animals in vitro or in vivo produced near complete and irreversible blockade of neurotransmission. Botulinisation of rat leg muscles reduced spontaneous transmitter release; the amplitude of miniature end-plate potentials was altered from the normal 'bell-shaped" to a skewed distribution. 6. In normal muscle, a large transient increase in frequency of the miniatures was produced by beta-bungarotoxin. In contrast, with botulinised muscle the latter induced a much smaller increase in the absolute frequency; in addition, the mean amplitude was increased somewhat but the distribution remained skewed. The results show botulinisation of muscle modifies the action of beta-bungarotoxin.

Acetylcholine↗
PubMed1982

Localization of sites for 125I-labelled botulinum neurotoxin at murine neuromuscular junction and its binding to rat brain synaptosomes.

Botulinum neurotoxin, purified to homogeneity from Clostridium botulinum (Type A), was found to be highly neurotoxic (greater than 8 X 10(7) mouse LD50/mg protein). Labelling of this pure neurotoxin with 125I-iodine to high specific radioactivity was achieved without appreciable loss of biological activity. This was used to demonstrate saturable binding sites for this toxin at the neuromuscular junction, following in vivo administration into mice. A demonstrable inhibitory effect of the neurotoxin on release of acetylcholine from rat cerebrocortical synaptosomes indicates that it affects synapses in the central nervous system. Kinetic studies on the binding of 125I-labelled neurotoxin to brain synaptosomes yielded an association rate constant of 2.3 x 10(5)M-1s-1; dissociation plots were biphasic and the predominant species showed a rate constant of 1.2 X 10(-4)s-1. The saturable binding component is heat-sensitive and inactivated by trypsin. Preliminary studies showed that botulinum neurotoxin associates with plasma membrane fractions of synaptosomes and that binding does not result in any gross structural changes, at least in the majority of the toxin molecules.

Animals↗
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

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↗
PubMed1981

Some normal clinical chemistry values for cerebrospinal fluid of the rhesus monkey (Macaca mulatta).

The concentrations of many components of the cerebrospinal fluid are much lower than in serum. Values for sodium, potassium, calcium and magnesium are similar to those in other primates. Activities of alkaline phosphatase (18.7 U/1), creatine phosphokinase (9.9 U/1), glutamine oxaloacetate transaminase (13.7 U/1), glutamine pyruvate transaminase (9.2 U/1), gamma-glutamyl transpeptidase (3.1 U/1), alpha-hydroxybutyrate dehydrogenase (33.0 U/1, lactate dehydrogenase (47.2 U/1) and sorbitol dehydrogenase (3.9 U/1), and levels of zinc (1.0 mu g/dl), copper (2.6 mu g/dl), iron (35.9 mu g/dl) and triglycerides (33.2 mu g/dl) have not previously been reported for this species. Values for free amino acids, total protein, creatinine and urea nitrogen are compared with those of other primates. The use of gradient pore polyacrylamide gel electrophoresis for analysing proteins of CSF is described.

Amino Acids↗
PubMed1980

Metabolic sequelae of experimental leptospirosis in grivet monkeys.

Leptospira interrogans serovars balcanica and tarassovi both induced mild subclinical infections in grivet monkeys. The activities in serum of lactate dehydrogenase, alpha-hydroxybutyrate dehydrogenase, aspartate aminotransferase, alanine aminotransferase and creatine phosphokinase and the level of alpha 1-antichymotrypsin increased in a few days after infection. Concomitant decreases in serum iron levels were observed in some cases. These changes occurred in the absence of any observable clinical signs though there were histopathological lesions in some organs. No haematological changes or alterations in other sreum components were detected.

Alanine Transaminase↗
PubMed1980

Benign leptospirosis: the pathology of experimental infection of monkeys with Leptospira interrogans serovars balcanica and tarassovi.

Grivet monkeys experimentally infected with Leptospira interrogans serovars balcanica and tarassovi showed no clinical disease, but severe meningoencephalitis was demonstrated histologically in animals killed 26 and 33 days after infection. The meningeal and perivascular reactions were exclusively lymphocytic. Mild focal lesions of degeneration and cellular infiltration were also present in the kidneys and femoral musculature.

Animals↗
PubMed1980

Pathological features of glutaminase toxicity.

In an investigation of the toxicity of the anti-tumour enzyme glutaminase Rhesus monkeys, marmosets, rabbits and mice were given various doses of chemically modified glutaminase parenterally. The enzyme induced diarrhoea and dysentery and at all but the lowest doses caused illness which was fatal within 10 days. Pathological lesions produced were hepatic lipidosis and glycogen accumulation, and, in the primates, acute necrotizing colitis.

Animals↗
PubMed1980

Clinical biochemical aspects of glutaminase toxicity in rabbits and Rhesus monkeys.

Treatment with a chemically modified glutaminase was lethal to rabbits and Rhesus monkeys at all but the lowest doses. Changes in the serum levels of triglycerides, glucose, creatinine, urea, cholesterol and protein and in the activities of some serum enzymes were the probable result of the development of lesions in liver, kidney and intestine observed at necropsy. Treatment with unmodified glutaminase induced similar changes in rabbits but not in Rhesus monkeys.

Amino Acids↗
PubMed1979

Normal values for some whole blood and serum components of grivet monkeys (Cercopithecus aethiops).

Normal values for a number of blood components of grivet monkeys are reported. Haematological data and values for glucose, cholesterol and urea are similar to those of rhesus monkeys. Activities of alkaline phosphatase (1526 U/l), glutamine oxaloacetate transaminase (30.9 U/l), glutamine pyruvate transaminase (13.7 U/l), lactate dehydrogenase (629 U/l), alpha-hydroxybutyrate dehydrogenase (175 U/l), creatine phosphokinase (227 U/l), gamma-glutamyl transpeptidase (38.7 U/l) and sorbitol dehydrogenase (14.2 U/l), and levels of lysozyme (178 mg/dl), zinc (162 microgram/dl), copper (81.3 microgram/dl) and iron (296.5 microgram/dl) have not previously been reported for this animal. Values for serum amino acids, proteins, electrolytes, triglycerides and creatinine are compared with those of other primates.

Amino Acids↗