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Biomedical subjects

M R Alley

Publications and source records attributed to M R Alley.

At least 73 records · Page 4Linked to original sources

An encephalomyelopathy in related Birman kittens.

The clinical and morphological features of an encephalomyelopathy in five related Birman kittens are described. The five kittens showed hind limb paresis and ataxia which progressed to hind limb paralysis. Four of the kittens had bilateral nuclear cataracts. Histological examination revealed diffuse lesions within the brain and spinal cord, especially within the thoracolumbar spinal cord. The major changes were foci of spongy change and vacuolation along with Wallerian degeneration. All kittens were inbred and an inherited aetiology was suspected.

Journal Article↗

Polar localization of a bacterial chemoreceptor.

The bacterial chemotaxis signal transducer MCP is an integral membrane receptor protein. The chemoreceptor is localized at the flagellum-bearing pole of Caulobacter crescentus swarmer cells. Amino-terminal sequences of the MCP target the protein to the membrane while the carboxy-terminal portion of the protein is responsible for polar localization. The C. crescentus and Escherichia coli MCPs have highly conserved carboxy-terminal domains, and when an E. coli MCP is expressed in C. crescentus, it is targeted to the swarmer cell progeny. These results suggest that subcellular localization of a prokaryotic protein involves interaction of specific regions of the protein with unique cell sites that contain either localized binding proteins or a specific secretory apparatus.

Amino Acid Sequence↗

DNA sequence of the Doc retroposon in the white-one mutant of Drosophila melanogaster and of secondary insertions in the phenotypically altered derivatives white-honey and white-eosin.

We analysed the structure of the white locus of Drosophila melanogaster in a family of related white mutants. The white-one mutant has bleach white eyes, and a Doc transposable element is inserted into the promotor region of the white locus. The DNA sequence of this Doc insertion was determined, and showed it to be closely related to other Drosophila melanogaster retroposons such as the I factor and the F, G and jockey elements. There are two long open reading frames, which encode a putative nucleic acid binding protein and a putative reverse transcriptase, respectively. Two independent, partially pigmented derivatives were analysed by cloning sequences from this region. In white-honey a transposable element of the retroviral class, B104, is inserted within the Doc element. In white-eosin there is an insertion within the Doc element of a 190 bp sequence that appears to be a member of a novel family of transposable elements. This pogo element is of the same structural class as the Drosophila melanogaster P and hobo elements. These data are consistent with the hypothesis that the Doc retroposon cannot excise, and that, for the white-one mutation, flies with altered phenotypes are most often generated by the insertion of additional transposable elements.

Amino Acid Sequence↗

Experimental pneumonia in mice produced by combined administration of Bordetella parapertussis and Pasteurella haemolytica isolated from sheep.

One-hundred-and-thirty-seven, 3-week-old, Swiss mice were inoculated intranasally with Bordetella parapertussis and Pasteurella haemolytica which had been isolated from naturally occurring cases of chronic non-progressive pneumonia in sheep. The combined administration produced a significantly more severe bronchopneumonia which occurred earlier, persisted for a longer period and involved a higher percentage of mice than that which was produced with B. parapertussis or P. haemolytica alone. These findings demonstrate an additive or synergic action between the two agents or their metabolic products, and provide indirect evidence that such interaction may occur in ovine chronic non-progressive pneumonia.

Animals↗

The potential role of the ovine pharyngeal tonsil in respiratory tract immunity: a scanning and transmission electron microscopy study of its epithelium.

The mucosal epithelium of the pharyngeal tonsil was studied in 10 conventionally raised sheep by scanning and transmission electron microscopy. The surface of the tonsil was covered by two types of topographically and ultrastructurally distinct epithelium. The epithelium overlying the lymphoid follicle region (follicle-associated epithelium) was compressed by adjacent ciliated epithelium and consisted of predominantly non-ciliated cells of varying height. The majority of these cells possessed microvilli or microfolds of varying number, height and density on their surface. Small numbers of squamous cells and, occasionally, intermediate cells were also present in these areas. Ultrastructurally, the microvillous cells showed features similar to M cells which occur in other mucosal sites. They contained cytoplasmic vesicles and vacuoles and formed intercellular digital junctions. Between these cells was a heavy infiltration of lymphoid cells. Focal disintegration of the mucosal epithelium was occasionally seen. The epithelium covering non-follicle areas consisted of mainly ciliated cells interspersed with some goblet cells and squamous cells, morphologically resembling those elsewhere in the respiratory tract. These findings have provided evidence which confirms that the ovine pharyngeal tonsil is part of the respiratory tract-associated lymphoid tissue.

Animals↗

Positional information during Caulobacter cell differentiation.

The formation of two distinct daughter cells upon division of the bacterium Caulobacter crescentus is the result of asymmetry in the predivisional cell, in part due to localization of both flagellar and chemotaxis proteins to the swarmer cell pole. Recent evidence suggests that both localized transcription and protein targeting directed by specific amino acid sequence are involved in the localization.

Bacterial Proteins↗

Clearance of ovine isolates of Bordetella parapertussis from murine trachea and lungs.

Thirty-six mice were inoculated intranasally with Bordetella parapertussis organisms (isolated from sheep with chronic non-progressive pneumonia) to study their deposition and clearance in the lower respiratory tract. The deposition of the organism was greater in the trachea than in the lungs. At 48 hours after inoculation, almost 100% of organisms were cleared from the trachea but only 55% of organisms were cleared from the lungs. This result correlates well with the morphological changes seen previously in the pulmonary parenchyma and airways of mice and lambs experimentally infected with this organism.

Journal Article↗

Genetic analysis of a temporally transcribed chemotaxis gene cluster in Caulobacter crescentus.

Caulobacter crescentus performs chemotaxis by short intermittent reversals of rotation of its single polar flagellum. Tn5 insertions causing a general chemotaxis phenotype, an inability to reverse swimming direction and to form large swarm colonies, have been mapped to an 8-kb region of the C. crescentus genome. These Tn5 mutations had different effects on the methyl-accepting chemotaxis proteins (MCP), and the activities of methyltransferase and methylesterase. The Tn5 insertion mutant SC1130 had no cross-reacting MCP and had reduced levels of activity of the methyltransferase and methylesterase. Other mutants bearing Tn5 insertions retained cross-reacting MCP activity and were altered only in their methyltransferase and methylesterase activities. Using a cosmid library we isolated a clone that complemented SC1130. Complementation studies of the Tn5 mutants using derivatives of the cosmid clone showed that all the Tn5 insertions lie within a single operon that appears to encode many chemotaxis genes. The first gene in this operon was shown to encode an MCP by immuno-blot analysis of strains carrying beta-galactosidase protein fusions to portions of the operon. The promoter of this operon was located by chromosomal integration of subclones of this region and by identifying DNA fragments that were capable of expressing lacZ transcriptional fusions. The transcription of the che operon occurred at a defined time in the cell cycle, prior to cell division.

Bacterial Proteins↗

Airway inflammation in sheep with acute airway hypersensitivity to inhaled Ascaris suum.

In order to investigate the relationship between airway inflammation and the development of naturally occurring allergic airway hypersensitivity, the lower respiratory tract was studied in eighteen sheep 14 days after challenge with inhaled Ascaris suum antigen. Sheep could be classed into three groups on the basis of their response: group A (n = 6) had significant changes in both airway resistance and dynamic lung compliance; group B (n = 6) had changes in only dynamic lung compliance, and group C (n = 6) were nonresponders. The results showed that the volume density of secretory granules in lung mast cells was greater in hypersensitive sheep than in nonreacting sheep (p less than 0.01). This high volume density was due to a high numerical density of granules in the mast cells. There was, however, no significant difference between groups in the numerical density of mast cells and eosinophils, or the observed degree of degranulation of mast cells. Although lymphocytes were commonly seen within the airway epithelium and subepithelial regions, infiltration of neutrophils or aggregation of dense and nodular lymphoid tissues were not common in the airways of any sheep. There was no significant difference in the infiltration of neutrophils or the aggregation of lymphocytes and lymphoid tissue in airways between the three groups. These findings indicate that there is an inherent difference in the volume density of lung mast cell granules between hypersensitive and nonreacting sheep but that other inflammatory cells are probably not directly involved in the initial development of allergic airway hypersensitivity in this species.

Animals↗

Morphological and morphometric studies of the airways of sheep with acute airway hypersensitivity to inhaled Ascaris suum.

The airways of 12 sheep with naturally-occurring allergic airway hypersensitivity, six of which had changes in both airway resistance and dynamic lung compliance (Group A) and six of which had changes in only dynamic lung compliance (Group B), were compared quantitatively with six non-reacting sheep (Group C) in order to examine the relation between airway hypersensitivity and various morphological features thought to be related to airway hypersensitivity. Compared to the non-reacting sheep (Group C), the hypersensitive sheep (Groups A and B) had a thinner epithelium in medium bronchi and bronchioles, fewer goblet cells in bronchioles, and greater gland area at most airway levels. The differences of the gland dimensions and the types of mucosubstance between hypersensitive and non-reacting animals were more variable. No significant differences between the three groups were noted with regard to luminal occlusion or epithelial sloughing and squamous metaplasia. Although there was a positive association between epithelial thickness and goblet cell density in the small airways, the development of allergic airway hypersensitivity in sheep may occur in the absence of major morphological changes in the airway epithelium.

Animals↗

Airway hypersensitivity induced by Ascaris suum extract in New Zealand Romney sheep.

Sheep from local farms with and without previous exposure to pigs were tested for their skin and airway responses to a commercial Ascaris suum antigen. There was an immediate reaction to intradermal injection of the antigen in 90% of 101 sheep. A bronchial provocation test by aerosol of the same antigen was undertaken on 43 of the sheep with a positive skin reaction. About 70% of sheep showed an immediate airway response to the antigen as an aerosol, reflected as a significant increase in airway resistance and/or decrease of dynamic lung compliance. The mean peak airway resistance and mean lowest dynamic lung compliance were 165% above and 61% below their baselines, respectively. No significant changes were recorded when the same animals were given an aerosol of phosphate buffered saline. Similarly, no correlation was found between the degree of skin reaction and the magnitude of bronchoconstriction (p>0.05). The sheep with previous exposure to pigs showed no significant differences in airway responses to antigen challenge, although they showed significantly greater skin reactions than those without exposure to pigs. These results indicate that the majority of Romney sheep in the Manawatu have a natural skin and airway sensitivity to A. suum antigen and may therefore be used as an animal model to study human airway hypersensitivity. The origin of this sensitivity has yet to be determined.

Journal Article↗

Lafora's disease in an epileptic Basset hound.

A 6-year-old Basset hound developed a progressive central nervous system disease culminating in epileptic seizures. Histologically, Lafora bodies were found in neurones of the middle and deeper cerebral cortex and midbrain, in Purkinje cells and their processes, and in glial cells of the molecular layer of the cerebellum. Many were also observed free in the neuropil. The ultrastructural and histochemical characteristics of the bodies were similar to those described in previous human and canine cases of Lafora's disease.

Journal Article↗

Perinatal development of lymphoid tissue and its associated epithelium in the ovine pharyngeal tonsil: a morphological study.

The perinatal development of lymphoid tissue and its associated epithelium in the pharyngeal tonsil of sheep was investigated by light and electron microscopy. The lymphoid cells first appeared in the subepithelium in a scattered form at about 92 days gestation. These cells proliferated rapidly during the last trimester of gestation, and had formed many dense aggregates at the time of parturition. At birth, the epithelium overlying the aggregates was extensively infiltrated with lymphocytes and showed early transformation of follicle-associated epithelium. The lymphoid tissue and its associated epithelium did not, however, fully develop until after birth, when well-differentiated follicle-associated epithelium and lymphoid follicles with vigorous lymphopoiesis were present. In 1-2 week old lambs, these structures were ultrastructurally similar to those seen in adult sheep although their size was smaller. The results of this study suggest that the lymphoid tissue of the ovine pharyngeal tonsil and its associated epithelium are morphologically ready to cope with antigens in the extra-uterine environment at birth, but that their full development and maturation are dependent postnatal antigen stimulation.

Journal Article↗

Chondrodystrophy in calves associated with manganese deficiency.

A severe congenital chondrodystrophy in Charolais calves is described. Thirty-two calves were born on the same farm with shortened limbs and enlarged joints. Histologically, there was poor cartilage maturation with excessive amounts of rarefied cartilage matrix. There were degenerative changes in the chondrocytes and a severe reduction in the mucopolysaccharide content of all body hyaline cartilage. The cartilage matrix, when examined ultrastructurally, showed loose, disorganised fibres in a rarefied matrix, and extensive vacuolation of the chondrocytes. A low level of manganese was found in the liver of an affected calf. The pregnant cows were fed on apple pulp and corn silage, both of which are low in manganese.

Journal Article↗

Mast cells in the ovine lower respiratory tract: heterogeneity, morphology and density.

The lower respiratory tract (LRT) of 6 adult sheep was fixed in either isotonic formalin-acetic acid or neutral buffered formalin in order to study the heterogeneity, morphology and density of mast cells (MCs). Two subtypes of MCs were found, one histochemically similar to connective tissue MCs (formalin resistant) and the other similar to mucosal MCs as found in the intestine of the rat (formalin sensitive). Although both subtypes were present at all levels of the tract, formalin-sensitive MCs were significantly more abundant (p less than 0.01) at all levels, and their density increased distally from the trachea to the peripheral lung. The formalin-sensitive MCs were predominantly located in the alveolar septa and in the superficial lamina propria of airways and less frequently within the airway epithelium. The MCs in the ovine LRT were found to be morphologically heterogeneous at both the light-microscopic and electron-microscopic levels. These findings indicate that ovine respiratory tract MCs have similarity to human lung MCs, and therefore potential for use as a model for the study of human allergic disease of the respiratory system.

Animals↗

Pneumonia in mice produced by cell-free extract of cultures of Bordetella parapertussis.

A single dose of culture fluid of Bordetella parapertussis freed from cells (CFCF) given intranasally to four-week-old mice free from intercurrent respiratory disease produced a subacute bronchopneumonia, which was similar to that induced by whole cells of ovine isolates of B parapertussis, except that the lesions were less severe and less extensive. From eight hours to 17 days after inoculation, the mice exhibited marked infiltration of neutrophils and macrophages into the alveolar septa, bronchiolar and alveolar spaces, and hyperplasia of peribronchiolar and perivascular lymphoid tissue. Electron microscopy showed damage to ciliated cells, type 1 pneumocytes and alveolar macrophages. These results suggest that extracellular toxic substance(s) produced by ovine isolates of B parapertussis might be involved in the initiation and development of lesions in ovine chronic non-progressive pneumonia.

Animals↗

Respiratory tract-associated lymphoid tissue in conventionally raised sheep.

The distribution and morphological features of respiratory tract-associated lymphoid tissue was investigated in 20 clinically healthy sheep aged from 6 months to 9 years. Five different forms of lymphoid tissue were identified, but their distribution varied between regions of the respiratory tract and between individuals. Scattered lymphoid cells were the most predominant form. Dense lymphoid aggregations were frequently seen in the pharyngeal tonsil and bronchioles. They were less common in the mid-nasopharynx and about the opening of the auditory tube, occasionally seen in the anterior nasopharynx, trachea and bronchus and rarely found in the regions of the nasal conchae, nostril, nasal vestibule and epiglottis. Nodular lymphoid aggregations with morphologically distinct lympho-epithelium were seen only in the pharyngeal tonsil and opening of the auditory tube region. Small numbers of intra-epithelial lymphoid cells were always present throughout the mucosa, but intraluminal lymphocytes were observed mainly in the regions of pharyngeal tonsil, trachea, bronchi and large bronchioles. The respiratory tract-associated lymphoid tissue is less developed in sheep than in most other species studied, except perhaps cattle.

Animals↗