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Biomedical subjects

J B Thomas

Publications and source records attributed to J B Thomas.

At least 19 recordsLinked to original sources

Apterous is a Drosophila LIM domain gene required for the development of a subset of embryonic muscles.

The recently discovered LIM motif is found in a set of homeodomain-containing proteins thought to mediate the generation of particular cell types. Of the four LIM domain family members described to date, mec-3 and lin-11 determine cell lineages in C. elegans. Isl-1 and Xlim-1 may play similar roles in vertebrates. We have identified a Drosophila member of this class, the product of the apterous (ap) gene. During embryogenesis, ap is expressed in a small subset of fusing mesodermal precursors that give rise to 6 muscles in each abdominal hemisegment and in 5 neurons within each corresponding CNS hemisegment. Lack of ap function results in loss of ap-expressing muscles, while misexpression of ap using a heterologous promoter produces ectopic muscles.

Amino Acid Sequence

Developing interorganizational relationships in the health sector: a multicase study.

Because of the wide diversity among health care organizations, interorganizational relationships (IORs) among them are difficult to manage. This article describes three case studies that, taken together, suggest that IOR performance is related to IOR development processes. Specifically, IOR performance is related to the way managers process information to manage uncertainty and ambiguity.

Chief Executive Officers, Hospital

Cryptococcosis in seven horses.

The clinical, radiographic and post-mortem findings in 6 horses with cryptococcal pneumonia and one horse with an abdominal cryptococcal granuloma are described. In pulmonary cryptococcosis, the lesions were either diffuse and multiple, with bilateral lung involvement, or localised mainly to the dorsocaudal region of one lung. The cases of diffuse multiple cryptococcosis were thought to be associated with haematogenous spread of the fungus after gastrointestinal infection and dissemination from regional lymph nodes. The localised form of the disease was thought to have been associated with inhalation of cryptococci. In all cases of pulmonary cryptococcosis, encapsulated yeast-like organisms were demonstrated in Wright's-stained sediment of tracheal washes. In the horse with the abdominal granuloma, cryptococci were present in a fine needle aspirate sample. Isolates of Cryptococcus neoformans var gattii were recovered from 2 of the 5 horses in which cultures were attempted. In addition to a history of previous illness that may have predisposed to infection, most horses in this report had been in areas in which Eucalyptus camaldulensis, or the closely related E rudis, were growing. In humans, an epidemiological relationship between E camaldulensis and infection with C neoformans var gattii has been suggested. Cases of equine cryptococcosis carry a poor prognosis and treatment was not attempted in any of these cases.

Abdomen

Experimental copper and heliotrope intoxication in sheep: morphological changes.

Young Merino wethers were used to determine the effects of copper and heliotrope, fed together or separately, on the development of toxicity and the concentration of trace elements in the liver and kidney. In one experiment copper and heliotrope were given concurrently, in a second experiment heliotrope was fed for 12 weeks and copper administration commenced 8 weeks later. The 10 sheep fed heliotrope alone did not show signs of clinical illness but one died and was found to have severe liver damage. Eleven sheep were given copper alone and three developed the clinical signs and lesions of haemolysis. Fourteen sheep were given copper and heliotrope and 13 became ill. Of these, three developed haemolysis, eight became jaundiced and two became weak without developing jaundice. The concentrations of copper in the livers of control and heliotrope-treated sheep, were comparable. In the animals given copper alone, the concentration of copper in the liver was twice as high as that in controls and in those given heliotrope and copper, it was three times as high as in the liver of control sheep. Feeding heliotrope alone induced the histological changes of pyrrolizidine alkaloid toxicity in the liver, but this was not associated with an excessive accumulation of copper or the development of clinical illness. However, it did predispose the animals to the effects of a second toxin since giving heliotrope and copper concurrently, or giving copper subsequent to feeding heliotrope, markedly enhanced the toxicity of the two substances and caused an excessive accumulation of copper in the liver.

Animals

Hospitals as interpretation systems.

In this study of 162 hospitals, it was found that the chief executive officer's (CEO's) interpretation of strategic issues is related to the existing hospital strategy and the hospital's information processing structure. Strategy was related to interpretation in terms of the extent to which a given strategic issue was perceived as controllable or uncontrollable. Structure was related to the extent to which an issue was defined as positive or negative, was labeled as controllable or uncontrollable, and was perceived as leading to a gain or a loss. Together, strategy and structure accounted for a significant part of the variance in CEO interpretations of strategic events. The theoretical and managerial implications of these findings are discussed.

Decision Making, Organizational

Molecular genetics of neuronal development in the Drosophila embryo.

Making a functional nervous system involves the production of specific types of neurons in characteristic locations and their ability to find and synapse with appropriate target cells. By capitalizing on the advanced genetics and molecular biology of Drosophila, a rapidly growing number of genes have been identified that control these events. Studies of the expression and function of these genes in single, uniquely identified cells is possible because of the relative simplicity of the Drosophila embryonic nervous system. A class of neurogenic genes, including N, Dl, and E(spl), controls the emergence of the entire neuronal precursor population, whereas some of the segmentation genes, such as ftz and eve, control the fates of individual neurons. Later in development, genes encoding cell-surface molecules, called fasciclins, may be involved in the ability of growing neurons to recognize and elongate axons along specific pathways to reach their synaptic targets.

Animals

Generalised protothecosis in a collie dog.

A case of generalised protothecosis in a Collie dog is discussed. A long-standing history of severe colitis was the major clinical sign. Dissemination to many organs was confirmed histologically. Possible pathogenesis is discussed along with a review of the literature. The possibility of a breed disposition in Collie dogs is discussed. The organisms are ubiquitous in the environment and generalised disease suggests the possibility of immune competence.

Animals

Immunohistochemical demonstration of canine distemper virus antigen as an aid in the diagnosis of canine distemper encephalomyelitis.

Brain tissue from 33 dogs with non-suppurative encephalitis was examined for evidence of canine distemper virus (CDV) encephalitis. Sections were examined for lesions, inclusion bodies, syncytial cells and CDV antigen using a double bridge unlabelled antibody enzyme technique. Histopathological lesions considered to be typical of granulomatous meningoencephalomyelitis were found in seven dogs. They all lacked inclusion bodies, syncytial cells and CDV antigen. The remaining 26 dogs all had histopathological lesions typical of CDV encephalitis. Inclusion bodies were found in 24 dogs, four of which also had syncytial cells and CDV antigen was detected immunocytochemically in 25. One dog had no inclusion bodies or syncytial cells and was immunohistochemically negative. Syncytial cells have been found to be of limited diagnostic value for the diagnosis of CDV encephalitis. While inclusion bodies proved to be a good diagnostic criterion for the confirmation of CDV infection, the immunohistochemical demonstration of CDV antigen proved to be superior. CDV antigen was more prevalent than inclusion bodies in tissue sections and much more easily detectable.

Animals

Molecular genetics of the single-minded locus: a gene involved in the development of the Drosophila nervous system.

The embryonic neuroepithelium of Drosophila gives rise to the central nervous system. We have studied the mutant phenotype and expression of a gene, single-minded (sim), which is involved in generating a specific region of this neuroepithelium. In sim mutant embryos, a subset of neuronal and nonneuronal precursor cells lying along the midline fail to emerge with the rest of the neuroepithelium. We have identified the sim transcription unit and have shown by in situ hybridization to embryos that the sim gene is expressed specifically in the midline neuroepithelium. Both the mutant phenotype and the temporal and spatial expression of transcripts suggest that the sim gene plays a key role in the emergence of this subset of cells along the midline of the developing central nervous system.

Animals

The Drosophila single-minded gene encodes a nuclear protein with sequence similarity to the per gene product.

Mutations in the single-minded (sim) gene of Drosophila result in the loss of the precursor cells giving rise to the midline cells of the embryonic central nervous system. We have examined the structure of the sim product by sequencing a sim cDNA clone, and have also determined the subcellular localization of the protein and its developmental expression by staining embryos with an antiserum against a sim fusion protein. The results indicate that sim is a nuclear protein specifically expressed along the midline of the neuroepithelium, the same subset of cells that are missing in the mutant. No similarity is observed between sim and any known nuclear protein, but, surprisingly, it is similar to the Drosophila period (per) locus gene product, which controls the periodicity of biological rhythms.

Amino Acid Sequence

Malignant fibrous histiocytoma in a dog.

A large tumour present on the proximal tibia of a Bull Mastiff dog was diagnosed on histological appearance as a Malignant Fibrous Histiocytoma. These tumours, rarely identified in domestic animals, but well recognised in humans, are typically pleomorphic sarcomas with histiocytic and fibroblastic differentiation. Less commonly, one cell type predominates. In this case there was prominent histiocytic differentiation.

Animals

Cell recognition during neuronal development.

Insect embryos, with their relatively simple nervous systems, provide a model system with which to study the cellular and molecular mechanisms underlying cell recognition during neuronal development. Such an approach can take advantage of the accessible cells of the grasshopper embryo and the accessible genes of Drosophila. The growth cones of identified neurons express selective affinities for specific axonal surfaces; such specificities give rise to the stereotyped patterns of selective fasciculation common to both species. These and other results suggest that early in development cell lineage and cell interactions lead to the differential expression of cell recognition molecules on the surfaces of small subsets of embryonic neurons whose axons selectively fasciculate with one another. Monoclonal antibodies reveal surface molecules in the Drosophila embryo whose expression correlates with this prediction. It should now be possible to isolate the genes encoding these potential cell recognition molecules and to test their function through the use of molecular genetic approaches in Drosophila.

Animals

Duplicated neural structure in bithorax mutant Drosophila.

The bithorax complex (BX-C) of genes in Drosophila control the segmental identity of the thoracic and abdominal cuticle. In flies containing BX-C mutations causing meta- to mesothoracic transformation, the mesothoracic branching pattern of a well-studied identified neuron is faithfully duplicated in the metathoracic ganglion. Thus these mutations also cause the duplication of mesothoracic cues involved in this neuron's branching.

Abdomen

Mutations altering synaptic connectivity between identified neurons in Drosophila.

By studying the effects of mutations on a simple circuit of identified neurons in Drosophila, we have found genes whose proper functioning is necessary to produce normal synaptic connections between the neurons. These neurons comprise the giant fiber (GF) system; the GFs are command neurons activated by a light-off stimulus and evoke a stereotyped pattern of activity in the thoracic muscles producing an escape jump. Each GF monosynaptically drives a motor neuron innervating the tergotrochanteral muscle (jump muscle, TTM). Each GF also disynaptically drives the motor neurons innervating the dorsal longitudinal flight muscle (DLM) via the peripherally synapsing interneuron (PSI) (King, D. G., and R. J. Wyman (1980) J. Neurocytol. 9: 753-770; M. A. Tanouye and R. J. Wyman (1980) J. Neurophysiol. 44: 405-421). A search was made for mutations affecting these identified synapses. Fifty thousand mutagenized flies were screened for nonjumping behavior to the light-off stimulus. Fifty-seven nonjumping mutant lines were established from individuals selected in the screen. Members of the lines were then tested for abnormal GF motor output to the TTM and DLM. From these lines, four X-linked mutations (representing three complementation groups) were isolated which affect the circuit. The mutations differentially disrupt specific synapses within the GF system. One mutation, bendless, disrupts synaptic transmission between the GF and the TTM motor neuron. Another, gfA, disrupts the synaptic connections of the PSI, and a third mutation, passover, disrupts transmission in both pathways.

Animals