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Biomedical subjects

L C Cork

Publications and source records attributed to L C Cork.

At least 91 records · Page 5Linked to original sources
PubMed1984

Synaptic neurochemical alterations associated with neuronal degeneration in an inherited cerebellar ataxia of Gordon Setters.

Canine Inherited Ataxia (CIA) is an autosomal recessive cerebellar disease of Gordon Setters associated with degeneration of Purkinje and granule cells. To define specific biochemical correlates of neuronal loss, synaptic neurochemical parameters were measured in three cerebellar regions (vermis, "pars intermedia," and hemisphere) at early and late stages of this disease. At one and a half years of age, affected dogs showed the most severe lesions in the "pars intermedia," with a 39% decrease in the number of Purkinje cells and a 29% decrease in granule cells. Neurochemical measurements demonstrated decreased [3H]muscimol binding and elevations in norepinephrine concentration (248% above control) and [3H]glutamate receptor binding (118% above control). At five years of age, reduction of Purkinje cells in the three cerebellar regions ranged from 65 to 91% while loss of granule cells was between 13 and 53%. [3H]Muscimol binding remained low throughout the cerebellum (38 to 59% of control) and norepinephrine concentration and [3H]glutamate binding were markedly reduced from the levels observed at one and a half years. Glutamate decarboxylase activity, [3H]QNB binding and GABA concentration were relatively unaffected. Our results indicate that neurochemical parameters associated with cerebellar neuronal systems demonstrate specific alterations in a chronic degenerative disorder. This study also indicates the importance of evaluating neurochemical measurements with regard to both spared and degenerating neuronal systems and emphasizes the role of compensatory neurochemical alterations in cerebellar degenerative disorders.

Animals↗
PubMed1984

Pneumococcal-induced pulmonary leukostasis and hemodynamic changes: role of complement and granulocytes.

In the present study we investigated the cardiopulmonary dysfunction caused by systemic pneumococcal (PNC) disease. We studied the hemodynamic and hematologic effects of intravascular challenge with nonviable PNC in normal, granulocyte-depleted, and genetically C3-deficient dogs. In normal dogs PNC administration caused a decrease in cardiac output (CO) of 58% (p less than 0.001), an increase in pulmonary vascular resistance (PVR) of 151% (p less than 0.02), and an increase in systemic vascular resistance (SVR) of 72% (p less than 0.02). The PNC challenge also caused significant decreases in both circulating granulocytes (-73%; p less than 0.02) and platelets (-58%; p less than 0.02). Histologic examination revealed granulocyte plugging within small pulmonary vessels. PNC challenge in granulocyte-depleted and C3-deficient dogs resulted in hemodynamic and hematologic changes that were not significantly different from those seen in normal PNC-challenged animals. Infusion of PNC-activated plasma resulted in hematologic changes that were not significantly different from those seen in PNC-challenged animals. Infusion of plasma treated with ethylenediamenetetraacetic acid (EDTA) prior to PNC incubation induced the same hematologic alterations but the hemodynamic response was less pronounced. To control for PNC constituents not removed by centrifugation and filtration, saline was incubated with PNC. After the PNC was removed, infusion of the saline induced no significant hemodynamic changes, although profound granulocytopenia occurred. We conclude that an intact complement system, but not normal numbers of circulating granulocytes, is essential to PNC-induced hemodynamic changes. PNC generates a plasma factor in vitro that does not require an intact complement system or cellular machinery to induce granulocytopenia without hemodynamic effect.

Animals↗
PubMed1983

Immunocytochemical identification of cholinergic neurons in the monkey central nervous system using monoclonal antibodies against choline acetyltransferase.

A monoclonal antibody directed against rat brain choline acetyltransferase (ChAT) was used to stain cholinergic nerve cells within the brain and spinal cord of macaques. ChAT immunoreactivity was seen in motor neurons of the brainstem and spinal cord, in large neurons of the striatum, and in large neurons in the basal forebrain (medial septum--diagonal band--nucleus basalis complex); each of these groups of neurons is believed to be cholinergic. The ability to visualize cholinergic neurons in the nervous system of primates provides a new approach to the study of cholinergic systems in health and disease.

Animals↗
PubMed1983

Cytoskeletal disorganization induced by local application of beta, beta'-iminodipropionitrile and 2,5-hexanedione.

Beta, beta'-Iminodipropionitrile and 2,5-hexanedione are neurotoxins that produce neurofilamentous axonal swellings. The swellings produced experimentally with these agents are similar in structure but different in distribution. Neither the relationships between these agents nor the mechanisms of action are known. In this study local effects on nerve fibers were compared following injection of beta, beta'-iminodipropionitrile and 2,5-hexanedione beneath the perineurium of rat sciatic nerves. Soon after injection, 2,5-hexanedione reproduced the distinctive cytoskeletal disorganization previously described with beta, beta'-iminodipropionitrile: microtubules collected into a central channel, with neurofilaments segregated in a surrounding subaxolemmal ring. Later, the beta, beta'-iminodipropionitrile-injected nerves developed local neurofilaments accumulations, reproducing the neurofilamentous axonal swellings characteristic of systemic intoxication with these agents. The results indicate that both these agents have direct local effects on the axonal cytoskeleton and probably are similar in mechanism of action. Both these agents appear to segregate neurofilaments from the rest of the axonal cytoskeleton. This segregation may prevent the normal proximal-to-distal transport of neurofilaments, resulting in the formation of neurofilamentous axonal swellings.

Animals↗
PubMed1983

Canine neuroaxonal dystrophy.

Canine neuroaxonal dystrophy, a newly recognized familial disorder in Rottweiler dogs, is characterized by progressive sensory ataxia. Two of four dogs studied clinically were autopsied and the cerebellum was mildly atrophic. Massive numbers of axonal spheroids were present in many regions of the neuraxis but were most prominent in the dorsal horn of the spinal cord and the nuclei gracilis and cuneatus. Ultrastructurally, spheroids appeared to be swellings of distal axons which were filled with accumulations of smooth membrane-bound vesicles, membranous lamellae, dense bodies, and other organelles. Neuropathological changes were similar to those identified in human neuroaxonal dystrophy.

Animals↗
PubMed1982

Cholinergic innervation in neuritic plaques.

Although several studies of Alzheimer's disease suggest that the frequency of neuritic plaques in the cerebral cortex is correlated with the severity of dementia and with reduction in presynaptic cholinergic markers in the cortex, the relationship between cholinergic cortical innervation and the pathogenesis of plaques is unknown. The hypothesis was tested that the neurites in the plaque consist, in part, of presynaptic cholinergic axons, many of which arise from neurons in the basal forebrain. This hypothesis was tested by analyzing the character and distribution of plaques in monkeys, aged 4 to 31 years, with staining for acetylcholin-esterase and also with Congo red and silver stains. Immature and mature plaques were rich in acetylcholinesterase. As the plaques matured, the amount of amyloid increased, and the number of neurites and the activity of acetylcholinesterase decreased. End-stage amyloid-rich plaques lacked acetylcholinesterase. These observations indicate that changes in cortical cholinergic innervation are an important feature in the pathogenesis and evolution of the neuritic plaque.

Acetylcholinesterase↗
PubMed1982

Slow virus replication: the role of macrophages in the persistence and expression of visna viruses of sheep and goats.

Lentiviruses of sheep and goats cause slowly progressive diseases of the central nervous system (visna), lungs (maedi) and joints (arthritis) in their natural hosts. However, the virus target cell(s) in these diseases are still unknown. In this report, using laboratory-adapted Icelandic visna virus and several field strains recently obtained from sheep and goats with natural disease in the U.S.A., we show that macrophages became persistently infected when inoculated in culture. Furthermore, macrophages were an invariable source of virus from experimentally and naturally infected animals. Virus-producing macrophages developed minimal cytopathic changes and virus assembly occurred mainly intracellularly, accumulating in cytoplasmic vacuoles. In contrast to macrophages, sheep choroid plexus fibroblasts developed syncytial cytopathic changes after inoculation and virus maturation occurred at the cell surfaces. Replication of the Icelandic virus was highly productive in this system but that of the field viruses was very inefficient. In some cases these agents failed to replicate in the fibroblasts and no cytopathic effect occurred. This block in the field virus replication was, however, overcome when infected nonproducer fibroblasts were co-cultivated with macrophages. In these cases, virus production with attendant cytopathic effect in the fibroblasts required the continuous presence of macrophages because the cells reverted to a non-productive state when separated from macrophages and became productive again when subcultures were added to new macrophages. The roles of the macrophage as a virus target cell and virus inducer in the virus-macrophage-fibroblast interactions are discussed with inferences to the well-known phenomenon of restricted virus replication in infected animals and the immunopathological aspects of the diseases.

Animals↗
PubMed1982

Pathology of motor neurons in accelerated hereditary canine spinal muscular atrophy.

Hereditary canine spinal muscular atrophy is a dominantly inherited lower motor neuron disease with three phenotypic variants: accelerated, intermediate, and chronic. Pups with the accelerated disease develop weakness by 1.5 months and are quadriparetic by 3 months. The motor neurons of selected brainstem nuclei and ventral horn of the spinal cord are characterized by chromatolysis and by neurofibrillary abnormalities in perikarya, dendrites, and, most strikingly, proximal axons. Dendrites and axons are segmentally enlarged by accumulations of maloriented fascicles of neurofilaments; the axonal swelling usually involve internodes and are delimited by the initial segment or nodes of Ranvier. The disorganized neurofilaments appear to entrap mitochondria and other particular organelles. We have hypothesized that the neurofibrillary changes in this genetic disorder in dogs is associated with an abnormality of the cytoskeletal constituents of motor neurons. Hereditary canine spinal muscular atrophy shows features in common with human motor neuron disease.

Animals↗
PubMed1982

Intoxication with beta, beta' -iminodipropionitrile: a model of optic disc swelling.

Human and experimental pathologic studies have suggested that optic disc swelling is due to enlargement of axons in the optic nerve head. Beta, beta' -Iminodipropionitrile (IDPN), a toxin known to produce neurofibrillary swellings in proximal portions of motor and sensory axons, was used to induce axonal lesions in the visual system of guinea pigs and dogs. Funduscopic examination showed progressive optic disc swelling. The axonal swellings, containing maloriented skeins of neurofilaments, appeared initially in the lateral portions of the optic disc; eventually, the majority of axons in the optic disc and in the retinal nerve fiber layer were enlarged. The swellings developed proximal to the level of Bruch's membrane. In addition, myelinated axons in the optic disc and retinal nerve fiber layer developed swellings proximal to the first heminode, demarcating the junction between the unmyelinated/myelinated segments. The retinal ganglion cells remained normal, and there was little axonal degeneration in the distal optic nerve. When beta, beta' -iminodipropionitrile was discontinued, the axonal swellings gradually disappeared.

Animals↗
PubMed1981

Clinical features of inherited cerebellar degeneration in Gordon setters.

We evaluated a kindred of Gordon Setters affected with inherited ataxia. Six adults and 4 pups clinically affected by the disease were examined. Pathologic studies were performed on a 3-year-old affected female dog and on a 2-month-old pup born to affected parents. The dogs were normal at birth; the 1st signs of neurologic dysfunction (wide-based stance and hypermetria) appeared between 6 and 10 months of age. As the disease progressed, increased tone of the extensor musculature, truncal ataxia, and nystagmus were noted. The disease had a slowly progressive course. The pathologic abnormalities were limited to the cortex of the cerebellum. There was atrophy with loss of Purkinje cells and granule cells affecting predominantly the vermis and paravermian regions of lobules IV, V, and VI. The study of the pedigree and our observations of the progeny of 2 affected dogs indicated that the mode of inheritance of this ataxia is compatible with an autosomal recessive trait.

Animals↗
PubMed1981

Genetically determined deficiency of the third component of complement in the dog.

A genetically determined deficiency of the third component of complement (C3) has been identified in a colony of Brittany spaniels. Immunochemical methods show no detectable C3 in the serum of the affected dogs, and there is no evidence of an inhibitor of C3 in the serum. The C3 deficiency appears to be transmitted as an autosomal recessive trait.

Animals↗
PubMed1981

Canine inherited ataxia.

A previously unrecognized canine disorder consists of familial cortical cerebellar degeneration with many characteristics that are similar to inherited ataxias in humans. The disease occurs in Gordon setters and appears to be inherited as an autosomal recessive trait. The dogs appear normal during the first 6 months of life, but between 6 and 12 months of age they develop a broad-based gait and dysmetria, followed by truncal ataxia. Nystagmus occurs late. The disorder is slowly and insidiously progressive. Neuropathological examination shows atrophy of the cerebellar cortex, particularly the pars intermedia. There is loss of Purkinje and granule cells, more severe in older dogs. Other parts of the neuraxis appear normal. These pathological changes resemble those of the familial human cerebellar cortical atrophies.

Animals↗
PubMed1980

Chronic arthritis in goats caused by a retrovirus.

A virus was isolated from an adult goat with chronic arthritis and shown to belong to the retrovirus group by electron microscopy and biochemical methods. Inoculation of the virus into cesarean-derived specific-pathogen-free goats' kids produced arthritic lesions similar to those in the spontaneous disease. Vrus was reisolated from the experimentally induced lesions.

Animals↗
PubMed1980

Biological characterization of the virus causing leukoencephalitis and arthritis in goats.

This study describes the biological properties of a strain of virus isolated from tissues of a goat with leukoencephalomyelitis-arthritis. The agent is a retrovirus, having a virion-associated reverse transcriptase enzyme and an antigenic determinant(s) which cross-reacts with the p30 of visna-maedi viruses. Morphogenesis of the virus is also similar to visna virus in terms of virus assembly and the multinucleated giant cell formation which accompanies replication of the latter virus. Despite its cytopathogenic property the goat agent was not lytic in goat cell culture, causing instead a productive infection which persisted through multiple subcultures of the cells. The virus replicated incompletely in sheep cell cultures but could be rescued from the latter, weeks after inoculation, by co-cultivation with goat cells. Our data suggest that this strain of goat leukoencephalitis virus is a variant of the ovine retroviruses with a host range limited to the goat.

Animal Diseases↗