Biomedical subjects

K M Charlton

Publications and source records attributed to K M Charlton.

15 recordsLinked to original sources

PubMed1992

The distribution of Challenge virus standard rabies virus versus skunk street rabies virus in the brains of experimentally infected rabid skunks.

The proposal that the bizarre behavioral changes which occur during rabies infection are due to selective infection of limbic system neurons was further studied in skunks (a species important in naturally occurring disease). A detailed immunohistochemical study of brains of skunks experimentally infected with either Challenge virus standard (CVS) or street rabies virus revealed only trace amounts of viral antigen in many limbic system neurons and marked differences in viral distribution between street and CVS virus. These data were collected during early stage rabies when behavioral changes occur. Areas which contained heavy accumulations of street rabies virus but low amounts of CVS rabies virus were the neuronal perikarya and processes of the dorsal motor nucleus of the vagus, midbrain raphe, hypoglossal and red nuclei. In contrast, large accumulations of CVS virus were found in the Purkinje cells of the cerebellum, the habenular nuclei and in pyramidal cells throughout the cerebral cortex, while corresponding areas in all street virus-infected skunks contained minimal antigen. These findings were very consistent for animals of the same experimental group and between skunks inoculated both intramuscularly and intranasally with skunk street virus. Skunks inoculated intramuscularly with CVS rabies virus failed to develop rabies. Since, in this model, street virus infection generally produces furious rabies and CVS infection results in dumb rabies, we speculate that the behavioral changes which occur in these two different clinical syndromes are due to the heavy and specific accumulation of virus in different regions of the CNS. These results show that regions other than those of the limbic system may also be involved in the pathogenesis of behavior changes in rabid animals.

Animals↗

PubMed1992

Oral rabies vaccination of skunks and foxes with a recombinant human adenovirus vaccine.

A new recombinant rabies vaccine (human adenovirus 5 containing the rabies glycoprotein gene) was given to striped skunks (Mephitis mephitis) and red foxes (Vulpes vulpes). Groups of skunks received the vaccine in baits, by direct instillation into the mouth, or intramuscularly. Foxes were given vaccine by direct instillation into the oral cavity (DIOC). Selected groups of vaccinated skunks and foxes were challenged with street rabies virus. There were high rates of seroconversion (generally with high antibody titers) in both foxes and skunks, with survival of all challenged vaccinated animals (all challenge controls developed rabies). In skunks, vaccine given DIOC was effective over a broad range of doses (10(8.7), 10(7.6) and 10(6.4) median tissue culture infective doses). There was no evidence of pathogenic effects. The results indicate that this adenovirus recombinant has considerable potential as a wildlife oral rabies vaccine.

Adenoviruses, Human↗

PubMed1992

Consideration of inactivated rabies vaccines as oral immunogens of wild carnivores.

An experimental beta-propiolactone (BPL)-inactivated rabies virus vaccine was evaluated for the oral immunization of captive raccoons (Procyon lotor) and red foxes (Vulpes vulpes). None of 10 red foxes administered a single 1.0 ml dose of BPL-inactivated rabies virus vaccine (PM strain; 100 or 500 micrograms protein) per os developed detectable anti-rabies virus-neutralizing antibodies (VNA) at any time over 8 wk of observation. Foxes were excluded from further study. In two different groups of five to six raccoons, each administered a single 1.0 ml dose of BPL-inactivated rabies virus vaccine (ERA strain) per os, at concentrations of 100 or 400 micrograms protein, only a single animal in each group demonstrated evidence of seroconversion within 4 wk. In contrast, instillation of a single dose (500 micrograms protein) of BPL-inactivated rabies virus vaccine (ERA strain), directly into the small intestine via fiberoptic endoscope, or ERA vaccine (800 micrograms protein) instillation to the buccal cavity by needle-less syringe, resulted in the production of rabies-specific VNA and protection against lethal rabies infection in three of six, and in four of six raccoons, respectively; all seven control raccoons succumbed to street virus challenge. These preliminary challenge studies, while somewhat encouraging, demonstrate that considerable quantities of purified viral antigen are required for even minimal oral efficacy against lethal rabies infection. At the present time, therefore, potent, self-replicating, attenuated, or recombinant viruses offer the most versatile, economic, efficacious, and safe solutions to terrestrial rabies control of free-ranging carnivores.

Administration, Oral↗

PubMed1979

Niemann-Pick disease in a poodle dog.

A 5-month-old minature Poodle dog had widespread cytoplasmic vacuolation of neurons in the central nervous system and foamy macrophages in the lung, spleen, renal lymph node, liver, adrenal gland and intestine. Concentric membranous cytoplasmic inclusions were seen in the neurons of the central nervous system by electron microscopy. There was no sphingomyelinase in the brain tissue. Sphingomyelin and cholesterol were increased in brain, kidney and liver. A diagnosis of Niemann-Pick Disease was based on absence of sphingomyelinase activity, as well as on histologic, histochemical and chemical findings.

Animals↗

PubMed1979

Experimental rabies in skunks: immunofluorescence light and electron microscopic studies.

Striped skunks (Mephitis mephitis) were inoculated into the abductor digiti quinti muscle with street rabies virus isolated from salivary glands of rabid skunks. Using the immunofluorescence technique, antigen was detected in muscle cells at the inoculation site before it was detected in the central nervous system. Neurons and their processes in nearly all regions of the brain, spinal cord, cerebrospinal ganglia, and peripheral nerves contained antigen in terminal stages of the disease. Electron microscopically, matrix (viral nucleocapsid), virions, and anomalous viral products were mainly in neuronal perikarya and dendrites, and less often in myelinated axons. Matrices, virions, and crystalloid structures were in muscle fibers at the inoculation site. Viral budding occurred on endoplasmic reticulum, neurotubules, and neuronal plasma membrane. In the brain and dorsal horn of the spinal cord, virus budded from the postsynaptic and adjacent dendritic or perikaryal plasma membrane. There was simultaneous esotropic uptake of these particles by adjacent axon terminals. The results strongly suggest that direct transneuronal transfer of virus from perikarya and dendrites to adjacent axon terminals is a mechanism in dissemination of rabies in the central nervous system of striped skunks. Variation in the length of the incubation period may be due partly to replication or virus in myocytes at the inoculation site and subsequent transfer to peripheral nerves.

Animals↗

PubMed1979

Experimental oral and nasal transmission of rabies virus in mice.

Weanling female white Swiss mice were exposed to challenge virus standard rabies virus and street virus isolates from various domestic and wild animals. Virus was given free choice as suspension or as infected mouse brain by stomach tube, by single injection of suspension into the oral cavity of unanesthetized mice, by repeated injection into the oral cavity of anesthetized mice and by single application to the external nares of anesthetized mice. Challenge virus standard virus in mouse brain suspension and a suspension of skunk salivary glands infected with street virus (titers greater than or equal to 10(6)MICLD50/0.03 ml) consistently produced high rates of infection in mice exposed intranasally, low to high rates of infection in mice exposed by forced feeding and other artificial methods of oral exposure and very low rates of infection when given free choice. Street virus isolates passaged intracerebrally in mice had titers less than or equal to 10(4.5) MICLD50/0.03 ml and rarely caused rabies in mice exposed orally or nasally by any method. The results indicate that with the isolates used, virus of high titer (greater than or equal to 10(6)MICLD50/0.03 ml) is required to consistently produce infection in mice by the nasal route and that the mucosa of the nasal cavity probably is the chief route of infection even after oral administration.

Animals↗

PubMed1979

Experimental rabies in skunks: oral, nasal, tracheal and intestinal exposure.

Striped skunks (Mephitis mephitis) were exposed to challenge virus standard rabies virus by feeding infected mouse brain in suspension or as intact brain free choice, by forced feeding of suspension, and by intranasal, intratracheal and intraintestinal instillation of suspension. All of five skunks exposed intranasally, two of five exposed intratracheally and two of ten exposed by forced feeding developed rabies. None of the skunks exposed to challenge virus standard virus, by other methods, became rabid. Most of the survivors, when challenged intramuscularly with street rabies virus at six months, developed rabies. The results indicate that the skunk is much more susceptible to challenge virus standard rabies virus given intranasally than by the other methods used. When disease occurs following oral administration, infection may be associated with prolonged contact with buccal mucosa or accidental contact with nasal mucosa. Survivors had little or no protection when challenged intramuscularly with street rabies virus.

Animals↗

PubMed1977

Hepatic lesions and bacterial changes in mice during infection of Fusobacterium necrophorum.

Liver abscesses were induced in male albino mice within 1 week after intraperitoneal inoculation of viable Fusobacterium necrophorum LA19 culture. Fusobacteremia was transitory and reached a peak 2 h after inoculation then sharply declined until its disappearance 24 h post inoculation. By contrast, the number of fusobacteria in the liver increased rapidly during the first 4 h post inoculation and continued to do so less rapidly until the last sampling time (48 h post inoculation). There were small or large areas of necrosis, usually surrounded by inflammatory cells, small focal accumulations of lymphocytes, plasma cells, and macrophages in areas of parenchyma with no degenerations, generalized proliferation of Kupffer cells, and a few accumulations of fibrin and leukocytes on the surface. Ultrathin sections of infected liver tissues reveled both intact and partially degraded F. necrophorum cells enclosed in phagocytic and digestive vacuoles of mononuclear cells, The results indicate that macrophages play a key role in the pathogenesis of liver abscesses.

Animals↗

PubMed1977

Spontaneous listeric encephalitis and neuritis in sheep. Light microscopic studies.

Sixteen of 17 sheep with spontaneous listeric encephalitis had neuritis characterized by diffuse and focal intrafascicular and perineural accumulations of lymphocytes, plasma cells, macrophages and neutrophils in one or more cranial nerves. Nine sheep had extensive trigeminal neuritis which was usually unilateral. Brain lesions were mainly in the stem and were foci of macrophages or neutrophils or both, malacia, neutrophilic neuronophagia, vascular cuffing, and meningitis. Lesions in the brain and trigeminal ganglia were most severe on the same side as the affected trigeminal nerve. Gram-positive bacilli were in proximal parts of cranial nerves in foci of inflammatory cells and occasionally in morphologically intact nerve fibers. Organisms in the brain were in phagocytes in areas of inflammation and in scattered neurons and axons. The results were consistent with centripetal migration of the infectious agent along one or more branches of the trigeminal nerve to the brain and dissemination in the brain stem occurring, at least partly, along fiber tracts. Intraaxonal movement of bacteria probably is a mechanism involved in the pathogenesis of this disease.

Animals↗

PubMed1977

Spontaneous listeric encephalitis in sheep. Electron microscopic studies.

The brainstems of four sheep with spontaneous listeric encephalitis had scattered small foci of inflammatory cells (neutrophils or macrophages, or both) with scattered fragments of degenerating nerve fibers and glial cells. In extensive areas of malacia in the pons and medulla oblongata, there was loss of parenchyma with massive accumulation of macrophages, a few neutrophils, lymphocytes and plasma cells. In both types of lesions, phagocytes contained debris of myelin and axons, lipid vacuoles and occasionally bacteria. Neutrophils contained bacteria in phagocytic and digestive vacuoles. No bacteria were detected in macrophages but were detected in neurons and in one axon in tissue previously used for paraffin sections.

Animals↗

PubMed1977

Necrotizing encephalitis in skunks caused by Herpes simplex virus.

Herpes simplex virus was isolated from the brain of a wild skunk (Mephitis mephitis) which had clinical neurological disease. In the brain of this skunk and in brain of skunks inoculated intracerebrally, there were areas of necrosis in the grey matter of the cerebral cortex and to a lesser extent in the brain stem. Intranuclear inclusions occurred in neurons and glial cells with vascular cuffing by mononuclear cells and a few neutrophils. Skunks inoculated intravenously had extensive focal necrosis in the liver and adrenal glands.

Adrenal Glands↗

PubMed1976

Meningoencephalomyelitis in horses associated with equine herpesvirus 1 infection.

During an outbreak of abortion caused by equine herpesvirus 1, a neurologic disease characterized clinically by dullness and ataxia occurred in several mares. Equine herpesvirus 1 was isolated from brain and lung of two severely affected mares. Histologically, both mares had disseminated meningoencephalomyelitis characterized by necrotizing arteritis, focal malacia in grey and white matter of brain and spinal cord, and accumulation of lymphocytes and neutrophils in paravertebral ganglia. Eosinophilic intranuclear inclusion bodies occurred in foci of necrosis in thyroid adenomas of both mares.

Abortion, Veterinary↗

PubMed1976

The mouse inoculation test in rabies diagnosis: early diagnosis in mice during the incubation period.

Brain tissue from 64 rabies suspect specimens were inoculated intracerebrally into twenty 9-12 gm adult Swiss white mice. Two mice from each specimen were killed on specific days postinoculation and examined for the presence of rabies virus by the fluorescent antibody staining technique. In this way a positive diagnosis was made in the majority of cases between postinoculation days 4 and 12 when the incubation period of these same specimens ranged between eight and 20 days.

Animals↗

PubMed1975

Characterization of endotoxin from Fusobacterium necrophorun.

Endotoxic lipopolysachharide (LPS) was obtained from phenol-water extraction of cell walls prepared from mass-cultivated Fusobacterium necrophorum. The LPS was relatively free of nucleic acids and low in protein, and constituted about 4% of the cell walls. Upon acid hydrolysis, some of the components detected were hexosamines (7.0%), neutral and reducing sugars (50.5%), heptose (6.4%), 2-keto-3-deoxyoctonate (0.8%), lipid A (21.0%), and phosphorus (1.7%). Under electron microscopy the LPS appeared mainly as ribbon-like trilaminar structures, and upon chemical treatment it displayed a behavior resembling that reported in certain enterobacterial LPS. The LPS was lethal to mice, 11-day-old chicken embryos, and rabbits. Endotoxicity in mice was enhanced at least 1,380-fold by the addition of 12.5 mug of actinomycin D. Induced tolerance to lethal effect of the endotoxin and rapidly acquired resistance to infection by F. necrophrum viable cells were also demonstrated in mice. The endotoxin produced both localized and generalized Shwartzman reactions as well as biphasic pyrogenic responses in rabbits. These results firmly establish the presence of a classical endotoxin in F. necrophorum, thus providing strong support to our recent suggestion that cell wall-associated components may contribute significantly to the pathogenicity of F. necrophorum.

Animals↗

PubMed1975

Cardiac lesions in rats fed rapeseed oils.

Fully refined rapeseed oils containing different amounts of erucic acid (1.6%, 4.3% and 22.3%) were fed, at 20% by weight of diet, to weanling male and female Sprague-Dawley rats for periods up to 112 days. Transient myocardial lipidosis characterized by accumulation of fat droplets in myocardial fibers was marked in male and female rats fed oxidized and unoxidized rapeseed oil containing 22.3% erucic acid, moderate with rapeseed oil containing 4.3% erucic acid and very slight in rats fed rapeseed oil containing 1.6% erucic acid. Peak intensity of myocardial lipidosis occurred at three to seven days and regressed thereafter. Focal myocardial necrosis and fibrosis occurred in male rats fed rapeseed oils containing different levels of erucic acid for 112 days. The incidence of myocardial necrosis and fibrosis was markedly lower in female rats, and the incidence of these lesions in either sex was not affected by the state of oxidation of these oils. In a second experiment, male rats were fed diets containing crude, partially refined or fully refined rapeseed oils. There was no correlation between the number of foci of myocardial necrosis and fibrosis and the state of refinement of the oils, but there were generally fewer lesions in rats fed those oils having the lowest levels of erucic acid.

Animals↗