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Biomedical subjects

R J Higgins

Publications and source records attributed to R J Higgins.

At least 109 records · Page 6Linked to original sources
PubMed1983

Glial proteins in canine distemper virus-induced demyelination. A sequential immunocytochemical study.

A temporal series of demyelinating lesions in experimental canine distemper virus (CDV) infection was examined with immunohistological techniques demonstrating myelin basic protein (MBP), myelin-associated glycoprotein (MAG), and glial fibrillary acidic protein (GFAP) on serial sections. The earliest lesions were characterized by decreased MBP and MAG and increased GFAP. During the further progression of the disease, MBP and MAG losses continued to match each other. There was no indication of MAG loss preceding the disappearance of MBP. In the more advanced lesions there was a marked decrease of GFAP positive cells. Since these findings differed considerably from similar immunohistochemical studies in progressive multifocal leukoencephalopathy (PML) where demyelination results from oligodendroglial infection, it was concluded that the oligodendroglial cell body is not the primary target of CDV. The marked astroglial changes were also considered to contribute to demyelination in CDV infection but the mechanism by which this happens remains unknown.

Animals↗
PubMed1983

Spontaneous lower motor neuron disease with neurofibrillary accumulation in young pigs.

A spontaneous neurologic disease occurred in six 5 weeks old Yorkshire pigs of both sexes from four litters sired by one boar. Clinically, the disease was characterized initially by bilateral posterior ataxia and weakness which rapidly progressed to tetraplegia by 10 weeks of age. By light microscopy, there was bilateral neuronal chromatolysis, degeneration and loss restricted to motor nuclei in the ventral horns of the spinal cord, in the medulla oblongata and midbrain. In addition to diffuse Wallerian-type degeneration in the spinal cord white matter and ventral peripheral nerve roots, there was prominent neurogenic atrophy of skeletal muscle. Ultrastructurally, the perikaryon and processes of affected neurons contained massive accumulations of single 10 nm diameter neurofilaments. Copper concentrations of both the commercially prepared ration and the livers were within normal limits.

Animals↗
PubMed1982

Experimental canine distemper encephalomyelitis in neonatal gnotobiotic dogs. A sequential ultrastructural study.

The ultrastructural morphogenesis of neuronal degeneration and necrosis and patterns of associated myelin and axonal degeneration were studied in gnotobiotic dogs neonatally infected with neurovirulent R252 strain of canine distemper virus (CDV-R252). Distemper virus-infected neurons underwent a distinct sequence of ultrastructural changes culminating in direct viral-induced necrosis beginning after 21 days post inoculation (DPI). Viral-induced neuronal cytolysis occurs apparently independently of anti-viral immune mechanisms of immunologic destruction. Viral nucleocapsid aggregates in postsynaptic axosomatic and axodendritic complexes and in structurally intact axons provided morphologic evidence for viral-induced functional modulation of synaptic transmission and possible trans-synaptic interneuronal viral spread. There were secondary degenerative axonal and myelin changes, particularly in heavily myelinated tracts. There was no evidence of primary demyelination. Active phagocytosis of degenerating axons and myelin debris in foci of virus-associated necrosis was apparently restricted to CDV-containing macrophages. Demonstration of a productive CDV infection of choroid plexus epithelium 10 DPI and thereafter was identified as an intracranial source of free infectious virus.

Animals↗
PubMed1982

Canine lymphocyte cultures in vitro: evaluation of peripheral blood lymphocyte response to mitogens.

Lymphocytes from dog peripheral blood have been stimulated in vitro with 3 different mitogens (Con A, PHA and PWM). Culture medium was RPMI 1640 enriched with either autologous plasma, fetal calf serum of a newly described defined serum substitute. In such cultures the number of surviving and activated cells was measured by cytofluorometry and the proliferation was assessed by thymidine incorporation. In unstimulated cultures, up to 70% of all cells had disappeared (died) during the first 42 hours of incubation, whereas the number of viable cells was reduced to 50-60% in mitogen stimulated cultures. Of the surviving lymphocytes, between 25-40% of the cells appeared to have an elevated RNA-content (activated or G1 cells). By comparison between thymidine incorporation and number of mitogen induced G1 cells, a very high correlation was found (r=0.92). However, the Slope of the regression line was much lower than expected. The low thymidine incorporation per activated cell was primarily related to the high cell death and a resulting dilution of tritiated thymidine. Indeed, preliminary results suggested that the same thymidine incorporation per G1b cells could be obtained if peripheral blood lymphocytes were washed immediately before pulsing as could be obtained with lymph node cells without washing.

Animals↗
PubMed1982

Immunoperoxidase labeling of canine distemper virus replication cycle in Vero cells.

An indirect immunocytochemical labeling technique, using horseradish peroxidase-conjugated antibody was used to detect the intracellular and surface membrane localization of canine distemper virus (R252-CDV) antigens during productive virus replication in infected Vero cells. Specific labeling of intracellular viral antigens was restricted to rough nucleocapsid aggregates. Surface membrane labeling correlated directly with the appearances both of virus-specific membrane spikes and buds and of mature virions. Syncytial cell formation was associated with labeled cytoplasmic nucleocapsid, but there was no evidence of productive CDV formation on surface membranes. The immunoperoxidase technique provided precise ultrastructural antigenic localization with concomitant preservation of excellent ultrastructural detail within single virus-infected cells during CDV replication cycle in vitro.

Animals↗
PubMed1981

Dysmyelination in Chow Chow dogs: further studies in older dogs.

The ultrastructure of myelin deficiency in Chow Chow dogs was studied in the spinal cord of a 15-month-old and a 3-year-old animal. It was found that myelination progresses with age in these dogs but is still deficient at the age of 3 years. The findings included axons with thin or uncompacted myelin sheaths, separated from each other by massive astrocytosis, and bizarre myelin formations. Normal numbers of morphologically normal oligodendrocytes were present in the myelin-deficient areas. The disease in these Chow Chow dogs consists of a strongly retarded myelination which is possibly due to a dysfunction or delay in glial maturation.

Animals↗
PubMed1981

Canine distemper virus-associated cardiac necrosis in the dog.

An age-related canine distemper virus-associated cardiomyopathy characterized by multifocal myocardial degeneration necrosis and mineralization with minimal inflammatory cell response was found in gnotobiotic Beagle pups. Of the 30 dogs infected experimentally at 5 to 7 days of age with virulent R252 strain of canine distemper virus, 11 had gross or microscopic cardiac involvement as early as 16 days post-infection. The 25 dogs similarly infected at 10 to 21 days of age, the uninfected age-matched controls, and pups infected at 5 to 7 days of age with avirulent R252 canine distemper virus had no cardiac lesions. Although the lesions are attributed to a direct viral effect, they occur against a background of other canine distemper virus-related changes including immunosuppression, anemia and encephalomyelitis. All these factors may have a modifying role in the development of this age dependent susceptibility to virus-associated myocardial necrosis.

Animals↗
PubMed1981

Lesions of the enamel organ of developing dog teeth following experimental inoculation of gnotobiotic puppies with canine distemper virus.

Ten 7-day-old gnotobiotic Beagle puppies were inoculated intraperitoneally with virulent canine distemper virus (R252-CDV). The dogs were killed and perfused with paraformaldehyde/glutaraldehyde from eight to 36 days after inoculation. The developing teeth of the mandibles were examined by light microscopy, and the teeth from three dogs were examined by electron microscopy. Necrosis of individual cells in the stratum intermedium of the developing tooth was the first change, detectable at day 9 post-inoculation. At day 16 post-inoculation, there was disorganization of the ameloblasts. In the stratum intermedium, multinucleate giant cells and large eosinophilic cytoplasmic viral inclusions were prominent. Ultrastructurally, these inclusions consisted of clusters of tubular aggregates typical of canine distemper virus nucleocapsids. At 28 to 36 days post-inoculation, the changes were seen in the reduced enamel epithelium. Multinucleate cells were seen, but no inclusions. Some necrotic cells were seen. In these teeth, ameloblastic cells of the root were morphologically normal. Our results suggest that distemper virus affects developing teeth by direct infection of the enamel organ.

Animals↗
PubMed1980

Mastitis and abortion in dairy cattle associated with Leptospira of the serotype hardjo.

Following a sudden drop in milk yield in a large dairy herd, leptospiral mastitis due to serotype hardjo was diagnosed serologically and by isolation of the organism from the milk and urine of affected cows. Two milkers subsequently became ill and developed titres to the Hebdomadis serogroup. During the same period the neighbouring herd experienced poor milking performance and a series of abortions and serological evidence suggested recent hardjo infection. The common source of infection appeared to be infected down calving heifers.

Abortion, Veterinary↗
PubMed1980

Plasmalogenase and phospholipase A1, A2, and L1 activities in white matter in canine distemper virus-associated demyelinating encephalomyelitis.

Three weeks after inoculation of 24-day-old gnotobiotic dogs with Snyder-Hill canine distemper virus, white matter samples were taken from the primary predilection sites for canine distemper virus-associated demyelination. The plasmalogenase activity in extracts was nearly 6-fold greater than control values for a dog with extensive demyelination and was not detectable in tissue from a dog with non-demyelinating lesions. Acid and neutral phospholipases A1 and A2 were assayed in homogenates and extracts with phosphatidyl ethanolamine substrates. Phospholipase A2 activities at both pH 4.3 and pH 6.8 were less in the dog with severe demyelinating lesions than in dogs with less severe lesions. Phospholipase A1 activities were generally similar for all four dogs. The marked elevation of plasmalogenase activity in demyelinating tissue may be associated with a release from the plasmalogens of arachidonic acid which is converted to oxygenated metabolites that may then be responsible for the inflammation. Phospholipases acting on phosphatidyl ethanolamine do not seem to be involved in the pathogenesis of demyelination associated with canine distemper virus.

Animals↗