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Biomedical subjects

L C Cork

Publications and source records attributed to L C Cork.

At least 73 records · Page 4Linked to original sources
PubMed1986

Genetic analysis of an inherited deficiency of the third component of complement in Brittany spaniel dogs.

Genetically determined C3 deficiency in Brittany spaniel dogs shares a number of biochemical and clinical characteristics with the human disorder. In humans, the gene for C3 deficiency is a null gene that is allelic to the structural gene for C3 and is not linked to the major histocompatibility locus. The current study used allotype analysis of canine C3 in order to demonstrate that the gene for C3 deficiency in these dogs is also a null gene allelic to the structural gene for C3. In addition, preliminary pedigree analysis suggests that the gene for canine C3 deficiency is apparently not closely linked to the major histocompatibility complex of the dog. Thus, it appears that C3 deficiency in Brittany spaniel dogs not only shares biochemical and clinical features with C3 deficiency in humans, but also shares some genetic characteristics with the human disorder.

Alleles↗
PubMed1986

Injury of nigral neurons exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: a tyrosine hydroxylase immunocytochemical study in monkey.

Six monkeys treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine developed a Parkinsonian syndrome (rigidity, akinesia, flexed posture and tremor). In both high and low dose groups, neurons in the substantia nigra were selectively damaged. At high dose levels, nigral neurons were severely damaged, but because the monkeys died, the evolution of the pathology could not be studied. At low dose levels, some nigral neurons survived, and a significant number of these nerve cells showed reductions in the immunoreactivity of tyrosine hydroxylase. Axonal pathology was conspicuous in the nigrostriatal pathway. Loss of the immunoreactivity of tyrosine hydroxylase in perikarya may represent a retrograde axonal reaction, a potentially reversible response. The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model should prove useful for investigating abnormalities occurring as a consequence of dysfunction of the nigrostriatal system, for examining processes associated with repair of damaged neuronal systems, and for developing and testing therapeutic approaches designed to prevent or ameliorate the Parkinsonian syndrome.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

Phosphorylated neurofilament antigens in neurofibrillary tangles in Alzheimer's disease.

Neurofibrillary tangles (NFT) are a hallmark of Alzheimer's disease (AD), and their presence correlates with the presence of dementia. A major constituent of NFT is the insoluble paired helical filament which shares some antigenic relationships with normal cytoskeletal elements, particularly neurofilaments. If neurofilament proteins (200, 145-160, and 68 kilodaltons [kd]) participate in the formation of NFT, the distribution of these constituents might be expected to be abnormal. To examine this issue, we used immunocytochemical methods to localize phosphorylated and nonphosphorylated epitopes of neurofilament proteins in hippocampal neurons of controls and patients with AD. Normally, the 200-kd neurofilament protein is not phosphorylated in the perikarya of neurons. However, in AD, many pyramidal neurons contained immunoreactive phosphorylated neurofilaments. Patterns of immunoreactivity (linear, flame-shaped, or skein-like within perikarya) greatly resembled the appearance of silver-stained NFT. This pattern of immunoreactivity was not present in hippocampal pyramidal neurons in controls, except in one aged patient in whom adjacent silver-stained sections revealed a few NFT. Patterns of immunoreactivity with antibodies for nonphosphorylated neurofilament proteins were similar in control and AD neurons. Our results indicate that some NFT are associated with abnormal distributions of high molecular weight phosphorylated neurofilament proteins. One domain of the 200-kd protein is believed to be a component of the side arms which link neurofilaments and interact with microtubules. Abnormal interactions of perikaryal neurofilaments could play a role in the genesis of NFT, and this abnormality of the cytoskeleton could contribute to the dysfunction of neurons at risk in AD.

Aged↗
PubMed1985

Senile plaques in cortex of aged normal monkeys.

The density, type, and distributions of cortical senile plaques were determined in 6 aged rhesus monkeys. Plaque densities were highest in prefrontal and temporal cortices and lowest in occipital cortex. Neurite plaques contained many argentophilic neurites and little amyloid, mixed plaques had both neurites and amyloid, and amyloid plaques showed significant amounts of amyloid and fewer numbers of neurites. As total plaque density increased, there was a linear increase in the density of amyloid plaques, suggesting that plaques evolve from neurite, to mixed, to amyloid types.

Aging↗
PubMed1985

Glutamic acid decarboxylase-like immunoreactive neurites in senile plaques.

In the neocortex of an aged (26-year-old) rhesus monkey, a small percentage of abnormal neurites within some senile plaques (defined by the presence of amyloid) were immunoreactive for glutamic acid decarboxylase. This suggests that gamma-aminobutyric acid-synthesizing neurons may contribute to plaque formation in the aged brain.

Aging↗
PubMed1985

The clinical manifestations of a genetically determined deficiency of the third component of complement in the dog.

The clinical manifestations of a genetically determined deficiency of C3 were examined in a closed colony of dogs. One hundred and twelve dogs, including twenty C3-deficient dogs, were studied over a period of 6 years. Five of the C3-deficient dogs developed significant bacterial infections, such as pneumonia, sepsis, and pyometra, which were caused by Clostridium spp., Escherichia coli, and Klebsiella spp. Two of the C3-deficient dogs who had had significant infections also subsequently developed renal disease. Secondary amyloidosis was the predominant renal lesion in one dog. The predominant renal lesion in the second dog was membranoproliferative glomerulonephritis, although some amyloid was also present. The two dogs with renal disease also had positive rheumatoid factors. No other clinical or serological evidence of autoimmune disease or immune complex disease has been found. None of the dogs heterozygous for C3 deficiency, and none of the homozygous normal dogs in the colony has developed significant bacterial infections or renal disease. Thus, dogs deficient in C3, like C3-deficient humans, demonstrate both an increased susceptibility to infection and renal disease.

Animals↗
PubMed1985

Catecholaminergic neurites in senile plaques in prefrontal cortex of aged nonhuman primates.

Immunocytochemical studies, using a polyclonal antibody directed against tyrosine hydroxylase, identified catecholaminergic axons in prefrontal cortex of young and aged nonhuman primates. Aged monkeys, who showed cortical senile plaques in silver stains, had swollen tyrosine hydroxylase-immunoreactive axons in neocortex. Some of these abnormal processes were associated with deposits of amyloid (visualized by thioflavin-T fluorescence) and were similar in appearance to neurites demonstrated by silver impregnation methods. This study provides evidence for structural abnormalities in catecholaminergic axons/nerve terminals in the neocortices of aged primates.

Adrenergic Fibers↗
PubMed1985

Canine inherited ataxia: ultrastructural observations.

Canine Inherited Ataxia is inherited as an autosomal recessive trait in Gordon Setters. This animal model shares features with certain human cerebellar degenerations and offers the opportunity to examine brain tissue at various stages during the evolution of disease. The present investigation focuses on the morphometric and ultrastructural changes of cerebellar neurons. Purkinje and granule cells are the principal intrinsic neurons at risk. The size of Purkinje cells decreases, axonal degeneration is an important feature of the pathology, and synaptic abnormalities occur in the cerebellar glomeruli and deep nuclei of the cerebellum. The sequence and nature of synaptic changes in the molecular layer suggest that the degenerative process begins in Purkinje cells and that granule cells may be secondarily affected.

Afferent Pathways↗
PubMed1985

Neurobiological studies of transmitter systems in aging and in Alzheimer-type dementia.

Dysfunction and death of specific neuronal systems are important processes occurring in aging and in Alzheimer's and in Parkinson's disease. The neuropathology and neurochemistry of some of the neuronal systems at risk in these settings are subjects of active research; the nature and consequences of these cellular pathologies have begun to be clarified. The availability of animal models (including aged monkeys, macaques with cholinergic deficiencies, and monkeys with MPTP-induced nigrostriatal pathology, all of which recapitulate certain features of human aging or disease) allow the opportunity to assess the efficacies of new pharmacotherapies, neural grafts, and trophic factors. These approaches can be monitored by behavioral testing and, in some instances, by in vivo imaging methods, which can in turn be correlated with morphologic and chemical analyses of brain. Demonstration of the efficacy of these procedures in nonhuman primates would have profound implications on the development of new therapies designed to alleviate the effects of aging and disease on the human brain.

Acetylcholinesterase↗
PubMed1984

Somatostatinergic neurites in senile plaques of aged non-human primates.

Using a polyclonal antibody directed against somatostatin, normal somatostatin-positive neurons and fibers were seen in the amygdala and periamygdaloid cortex of both young and aged macaques. In addition, immunoreactive structures, identical in appearance to neurites demonstrated by silver impregnation methods, were seen in the amygdala of one aged monkey that exhibited numerous senile plaques. Some of these immunoreactive neurites were associated with deposits of amyloid, as seen with thioflavin-T stains, suggesting that these were neurites of senile plaques. This study provides direct evidence for abnormalities in peptidergic neurons in brains of aged non-human primates.

Aging↗
PubMed1984

Evidence for cholinergic neurites in senile plaques.

In the neocortices and amygdalae of young and aged macaques, cholinergic axons were identified by means of a monoclonal antibody to bovine choline acetyltransferase. Many fine, linear, immunoreactive profiles were seen in these animals. In the older animals, some cholinergic axons showed multifocal enlargements along their course. In some instances, neurites with choline acetyltransferase immunoreactivity were associated with deposits of amyloid (visualized with thioflavin T fluorescence). The appearance of these amyloid-associated abnormal cholinergic processes was similar to that of neurites in senile plaques, as shown by conventional silver impregnation techniques. Cholinergic systems thus give rise to some of the neurites within senile plaques.

Aging↗
PubMed1984

Neuroaxonal dystrophy of Rottweiler dogs.

Five Rottweiler dogs were examined because of progressive ataxia of thoracic and pelvic limbs of several months' to 4 years' duration. Hypermetria, especially of the thoracic limbs, and head incoordination and tremors were obvious features in the 3 older dogs. None of the dogs had evidence of weakness or loss of conscious proprioception. An electroencephalogram in 1 severely affected dog was normal. Electromyograms in 2 severely affected dogs were normal except for some positive sharp waves and fibrillation potentials in the interosseus muscles of all 4 feet. Cerebrospinal fluid evaluations of 2 severely affected dogs were normal. A reduced number of sensory nerve endings, compared with age-matched controls, was seen on histologic examination of a conjunctival biopsy specimen in 1 severely affected dog. An antemortem diagnosis of neuroaxonal dystrophy was suspected from the signalment, history, and neurologic examination findings. The diagnosis was confirmed on the basis of microscopic findings in 3 dogs necropsied.

Animals↗
PubMed1984

Autosomal dominant inheritance of hereditary canine spinal muscular atrophy.

Hereditary canine spinal muscular atrophy ( HCSMA ) is a motor neuron disease in Brittany spaniels. Three phenotypes are recognized (accelerated, intermediate, and chronic) and are distinguished on the basis of rate of progression and age at onset. Breeding studies within a kindred of more than 125 dogs (Brittany spaniel and beagle-Brittany outcrosses ) have established an autosomal dominant inheritance for HCSMA . Pups homozygous for the trait have accelerated disease whereas heterozygous dogs have intermediate or chronic disease. The reason for the two phenotypes in heterozygotes is under study. HCSMA provides a unique opportunity to study the genetic and pathophysiological mechanisms of a motor neuron disease, and findings may have broad relevance to investigations of autosomal dominant degenerative disorders of the central nervous system.

Animals↗
PubMed1984

Acetylcholinesterase activity in senile plaques of aged macaques.

A modified acetylcholinesterase (AChE)-histochemical technique, which demonstrates axonal morphology to a high degree, was used to examine the neocortices of aged monkeys. This approach disclosed slender linear axonal profiles in young animals. In older monkeys, there was a variety of abnormalities of AChE-containing fibers, including multifocal distensions of individual fibers and aggregations of neurite-sized, AChE-rich swellings. Combined with thioflavin-T staining to visualize amyloid, this histochemical technique showed that some of these AChE-containing fibers were present in proximity to deposits of amyloid. This association suggests that abnormal AChE-rich axons participate in the formation of some senile plaques in the neocortices of aged nonhuman primates. While it is probable that many of these AChE-rich fibers are axons of cholinergic neurons residing in the basal forebrain, it is also likely that some of these fibers are derived from noncholinergic neuronal populations known to synthesize AChE. Immunocytochemical strategies can be used to assess the involvement of other systems, including cholinergic, noradrenergic, dopaminergic, somatostatinergic, and serotonergic neurons in the formation of senile plaques in the brains of aged nonhuman primates.

Acetylcholinesterase↗