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Biomedical subjects

R J Higgins

Publications and source records attributed to R J Higgins.

At least 73 records · Page 4Linked to original sources
PubMed1989

Chronic relapsing demyelinating encephalomyelitis associated with persistent spontaneous canine distemper virus infection.

This is the first report of spontaneous canine distemper virus (CDV) infection in a dog associated with chronic progressive multiphasic neurological disease. Initial neurological deficits in the pelvic limbs progressed rapidly to paraplegia with almost complete remission after 9 weeks. Then another acute episode occurred with severe thoracic limb deficits and cerebellar dysfunction and progressive neurological deterioration over 3 months with rising serum neutralizing (SN) anti-CDV titers in the serum and cerebrospinal fluid (CSF). Three neuropathologically distinct lesions of spinal cystic necrosis, chronic demyelinating foci in the cerebellum and acute demyelinating encephalitis in the pons were identified. Persistent CDV antigen was demonstrated immunocytochemically only in acute lesions and atypically restricted to neurons. However, the immunological mechanism associated with the distinct remissions and exacerbations and CDV antigen clearance from chronic demyelinating lesions but persistence in acute lesions, despite a vigorous anti-CDV serologic response, was not defined.

Animals↗
PubMed1989

Atypical rotavirus and villous epithelial cell syncytia in piglets.

Histopathological examination of small and large intestine from piglets with enteritis has shown the presence of epithelial multinucleate syncytia. Syncytia were associated with a specific type of atypical rotavirus infection, determined by electron microscopy and polyacrylamide gel electrophoresis analysis of viral RNA. The observations are consistent with similar previously described natural or experimental infections in other animals.

Animals↗
PubMed1989

A sheep model for MPTP induced Parkinson-like symptoms.

Administration of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) causes behaviors reminiscent of idiopathic Parkinson's disease in man and other primates, but development of such symptomology has not been reported to date in other species. We now report a sheep model which responds to administration of low levels of the compound with well defined, apparently permanent symptomology very similar to that seen in primates. Histological examination indicates drug dependent destruction of the substantia nigra which, in sheep, lacks the high levels of neuromelanin present in primates. Following infusion of either MPTP or MPP+, only the metabolite MPP+ was detected in serum with this metabolite demonstrating a very long half life. The rapid disappearance of MPTP suggests that its potency will be directly related to a function of body size and inversely related to heart rate.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1989

Polyneuropathy in feline Niemann-Pick disease.

Two related cats, aged 5 months and 7 months, and 1 unrelated cat, aged 4 months, presented with signs of a progressive neuromuscular disease. Detailed electrophysiological studies suggested a primary demyelinating polyneuropathy, which was confirmed by muscle and nerve biopsies and on necropsy examination. Light and electron microscopic findings indicated a lysosomal storage disease, which was diagnosed as sphingomyelinase deficiency (Niemann-Pick disease) by enzyme analysis and lipid fractionation, although significant biochemical differences existed between the 2 related cats and the third cat. Several lines of evidence suggest that these 2 related cats were affected with a variant of type A Niemann-Pick disease, whereas cat 3 represented classic Niemann-Pick disease type A.

Animals↗
PubMed1989

MPTP-induced Parkinson-like disease in sheep: clinical and pathologic findings.

Eight ewes, divided into two groups based on age, with group 1 7-8 and group 2 1-3 years old, respectively, were administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intravenously (IV) at cumulative doses of 2.0 to 34.6 mg/kg body weight. Two group 1 sheep, given cumulative doses of 2 and 8.5 mg/kg, developed persistent severe neurologic signs of body stiffness and rigidity, paucity of movement, intention body tremors, and abnormal body posture and stance similar to those signs in MPTP-induced disease in people and primates. After their acute onset, these persistent signs were nonprogressive up to the observation period of 32 days post infusion. None of the younger ewes had persistent neurologic symptoms at equivalent cumulative doses (9.0 mg/kg). The only pathologic changes were microscopic lesions in the central nervous system, consisting of bilaterally symmetrical neuronal chromatolysis and necrosis limited to the substantia nigra and locus ceruleus. These lesions were found in two persistently affected and two younger sheep, suggesting age-based differences in dose response and the threshold of clinical expression of disease. Serum MPTP half-life was 11 days. Thus sheep exposed to MPTP could be an alternative model to the primate for the comparative study of clinical, pathologic, and biochemical mechanisms in MPTP neurotoxicity and Parkinson's disease in people.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1988

Intraspinal epidermoid cyst in a dog.

A 2-year-old female Rottweiler was examined because of progressive gait deficits consistent with transverse myelopathy between the T2 and L3 spinal cord segments. Myelography confirmed an intramedullary spinal cord lesion between T13 and L1, so the dog was euthanatized. At necropsy, an intramedullary epidermoid cyst was confirmed in the T13 and L1 spinal cord segments. The epidermoid cyst probably resulted from a congenital cause.

Animals↗
PubMed1988

31P NMR spectroscopy of the in vivo metabolism of an intracerebral glioma in the rat.

The in vivo high-energy phosphorus metabolic profile and pH of an experimental intracerebral C6 glioma in rats was examined using surface coil 31P NMR spectroscopy. Initially, phosphorus-containing metabolites of the glioma were characterized by in vivo 31P surface coil spectroscopy of subcutaneously implanted tumors and by high-resolution NMR studies of perchloric acid (PCA) extracts of both freeze-clamped subcutaneous tumor tissue and cultured cells. These studies demonstrated that the C6 glioma has reduced levels of phosphocreatine (PCr) compared to the levels found in normal rat brain. Thus, reduced spectral PCr levels were useful as a metabolic indicator for monitoring the spatial selectivity of tumor metabolism distinct from that of adjacent normal brain tissue. To maximize 31P NMR signals from intracerebral tumors, tumor cells were stereotaxically placed superficially in the brain. Proton magnetic resonance imaging (1H MRI) was used to determine the size and location of the resultant brain tumors in order to preselect rats with large superficial tumors for spectroscopic study. 31P NMR spectra of the glioma tumors revealed a consistent reduction in the PCr/ATP ratio, an increase in the Pi/ATP ratio, and a slightly increased tissue pH. No correlation was found between levels of Pi/ATP and tumor pH in subcutaneous or intracerebral gliomas and the amount of necrosis as determined histologically. This study demonstrates that phosphorus metabolites of an experimental brain tumor in the rat can be monitored in vivo with minimal contributions from adjacent normal brain tissue metabolites using surface coil 31P NMR spectroscopy.

Adenosine Triphosphate↗
PubMed1988

Carbohydrate metabolism of the rat C6 glioma. An in vivo 13C and in vitro 1H magnetic resonance spectroscopy study.

Surface coil 13C nuclear magnetic resonance (NMR) spectroscopy was used to investigate the in vivo carbohydrate metabolism of rat C6 gliomas during and after infusion with [1-13C] glucose. In vivo 1H-decoupled 13C NMR spectra of the glioma following infusion with [1-13C]glucose revealed the direct production of [3-13C]lactic acid, [1-13C]glycogen, and [4-13C], [3-13C], and [2-13C]glutamate/glutamine. Lactate levels of in vivo gliomas increased and reached steady state levels during [1-13C]glucose infusion, and decreased following termination of infusion. Complementary in vitro studies using supernatant media collected from C6 glioma cells incubated with media containing [1-13C] or [6-13C]glucose and glutamine were examined by 1H NMR spectroscopy. The [3-(13C/12C)]lactate ratios obtained from 1H spectra of supernatant media containing [1-13C]glucose revealed the percentage of glucose metabolized through the hexose monophosphate shunt to be 10.01 +/- 0.85% (n = 3), while similar measurements of media containing [6-13C]glucose and glutamine showed that glutaminolysis contributed 9.0 +/- 1.0% of total lactate production under these conditions. Enzymatic analysis of media determined lactate production to be 139 +/- 9 nmol per 10(6) cells per h (n = 4). These measurements demonstrate the ability of NMR to monitor brain tumor carbohydrate metabolism both in vitro and in vivo.

Animals↗
PubMed1988

Radiation dose response of normal brain.

Dose response relationships were determined after hemibrain x-irradiation of normal beagle dogs. Radiation doses of 11.5, 13.5, 14.3, and 17 Gy were delivered in a single dose and results were compared to previous studies using doses of 15 and 30 Gy. Brain injury was quantified using computed tomography (CT), with serial studies obtained monthly up to 1 year following irradiation. Quantitative endpoints included low density volume and contrast enhancement. Doses above 14.3 Gy resulted in high lethality 5-8 months following irradiation, and an LD50 of 14.9 Gy was calculated. At these lethal doses, low density volume representing edema, demyelination, and necrosis had a similar response with an ED50 of 14.6 Gy. Radiation-induced decreases in white matter density appeared 5-6 months after sublethal doses (less than or equal to 14.3 Gy) and the volume of tissue characterized by this low density increased with time and dose. This sublethal low density change had an ED50 of 12.8 Gy, and may reflect a loss or generalized atrophy of glial cells and/or myelin. These results show that: (a) the dose response curves obtained after hemibrain x-irradiation are extremely steep; and (b) at least two processes may be involved in the development of late radiation damage, one that is rapid upon onset (a "delayed acute" reaction) and the other which is a slower and more degenerative process.

Animals↗
PubMed1988

Toxicity of repeated doses of organophosphorus esters in the chicken.

Hens were repeatedly exposed to paraoxon (PO, phosphonothioic acid, diethyl paranitrophenyl ester), the chemical warfare agent VX/phosphorofluoridic acid, methyl-S-(2-[bis(1-methylethyl)amino/ethyl)O-ethyl ester], or the neuropathic DFP [phosphorofluoridic acid, bis(1-methylethyl)ester] as evidence was sought for nerve or other tissue damage following long-term treatments at high dose levels. Thirty-day and 90-d trials were performed in which each bird was injected 3 or 5 times per week with atropine as protection, weighed, their eggs collected, and their blood enzymes (cholinesterases creatine kinase, and lactic dehydrogenase) and locomotion periodically examined. Muscle and brain enzymes were assayed at the end of the experiments. Doses of PO and VX were at or above LD50 levels. DFP doses were lowered with each run to estimate a no-observable-effect level for organophosphate-induced delayed-neuropathy (OPIDN). No abnormalities attributable to repeated exposures to either PO or VX were found, even though acute, short-term symptoms of toxicity appeared after each injection. No evidence for OPIDN was obtained with repeated exposures to PO and VX under conditions where OPIDN was caused by DFP. Histological signs of OPIDN appeared in the spinal cord without gross symptoms of ataxia following repeated treatments of 25 mg/kg of DFP. The results of one experiment suggested that exposure to protective injections of atropine delays the appearance of the locomotor symptoms of the DFP-induced neuropathy.

Animals↗
PubMed1988

Atropine and DFP-induced delayed neurotoxicity.

Atropine is often given as an antidote for acute cholinergic effects in studies of a delayed neuropathy (OPIDN) caused by some organophosphorus esters. These experiments examined if atropine would also affect the onset and/or severity of signs of OPIDN. Chickens were given one to six 200 micrograms/kg doses of diisopropyl phosphorofluoridate (DFP) with or without 20 mg/kg atropine (IM). Locomotion, brain neurotoxic esterase (NTE) activity, and histology of the nervous system were examined. The results demonstrated that atropine treatments delayed onset of the signs of OPIDN and may have slightly increased brain NTE activity in vivo. Relatively high levels (Ki: approximately 3.0 mM) of atropine inhibited NTE activity in vitro.

Animals↗
PubMed1987

31P NMR spectroscopy of an experimentally induced intracerebral tumor in mice.

31P surface coil NMR spectroscopy was used to evaluate in vivo high-energy phosphorus metabolism in the brains of mice with experimentally induced primary intracranial and subcutaneous KHT sarcomas. 31P spectra of subcutaneous KHT tumors revealed a lack of detectable phosphocreatine (PCr) levels in the tumor as compared to the relatively high endogenous levels of PCr in normal mouse brain. As the intracerebral tumor size increased, there was a reduction in spectral PCr levels over a 23-day postinoculation period in situ in the brain. No histologic or spectroscopic evidence of tumor-associated necrosis or hypoxia was found. This study demonstrates that surface coil 31P NMR spectroscopy can be used to monitor changes in high-energy phosphate metabolism associated with progressive growth of an experimentally induced mouse brain tumor in situ.

Animals↗
PubMed1987

Equine protozoal myeloencephalitis.

Equine protozoal myeloencephalitis (EPM) is a disease that produces neurologic signs of brain or spinal cord dysfunction. The causative organism is believed to be a Sarcocystis species of protozoa. A definitive diagnosis can only be made on histopathology of affected spinal cord or brain. No preventive measures or documented treatment is available at this time for suspected cases of EPM.

Animals↗
PubMed1987

Neurovirulence of the UC-2 and UC-8 strains of bluetongue virus serotype 11 in newborn mice.

In vivo and in vitro experiments were done to investigate whether the difference in neurovirulence between the two strains of bluetongue virus 11, UC-2 and UC-8, is based on a different capability to gain access to the brain from the subcutaneous inoculation site or on a different tropism for neural cells. In newborn Balb/c mice subcutaneous inoculation of UC-8 at doses between 10(-0.2) plaque forming units (PFU) and 10(4.8) PFU caused a severe necrotizing encephalitis whereas UC-2 at doses of up to 10(4.4) PFU did not affect newborn Balb/c mice. However, intracranial inoculation of 10(2.4) PFU of either virus strain produced severe necrotizing encephalitis. In vitro both virus strains infected dissociated brain cell cultures similarly. Double labelling immunofluorescent staining with markers specific for neural cells did not reveal differences in the target cells for the two viruses. The difference in neurovirulence between UC-2 and UC-8, therefore, appears to be determined by the ability of UC-8 to infect the brain from a subcutaneous inoculation site.

Animals↗
PubMed1987

Border disease. Virus-induced decrease in thyroid hormone levels with associated hypomyelination.

Border disease (BD) was induced in lambs by inoculation of their dams at 50 days gestation with Border disease virus (BDV) isolate #31. At birth, the clinically affected lambs had diffuse spinal cord hypomyelination, confirmed by immunocytochemical staining for myelin-associated glycoprotein and myelin basic protein. In the BD lambs, large numbers of thyroid follicular epithelial cells and scattered pituitary cells contained BDV antigen by immunofluorescence staining. Double labeling techniques demonstrated the BDV-infected pituitary cells to contain growth hormone, adrenocorticotrophic hormone, prolactin, or luteinizing hormone. Cells containing thyroid stimulating hormone were rare and were not positive for BDV antigen. Infection of the pituitaries and thyroid glands caused no detectable morphologic changes as compared to controls. The BD lambs had statistically significantly (p less than 0.05) lower mean serum concentrations of thyroxine and L-3,3',5-triiodothyronine as compared to age-matched uninfected controls. Similar significant differences in the mean plasma levels of growth hormone and thyroid stimulating hormone were not found. In addition, the BD lambs had a statistically significant (p less than 0.05) lower mean activity of the myelin-associated, thyroid hormone dependent enzyme, 2',3'-cyclic nucleotide-3'-phosphodiesterase in spinal cord tissue. Although not conclusive, these results indicate that the hypomyelination in BD may be due to depressed levels of circulating thyroid gland hormones secondary to a noninflammatory and noncytolytic infection of the thyroid gland by BDV. This is one of the first reports indicating that a virus-induced hormonal alteration may cause a congenital lesion in animals.

Animals↗
PubMed1987

Experimentally induced ovine border disease: extensive hypomyelination with minimal viral antigen in neonatal spinal cord.

Border disease (BD) was experimentally induced in 9 lambs by inoculation of their dams with the BD-31 strain of border disease virus (BDV) at 50 days of gestation. These ewes developed serum-neutralizing antibody titers to BDV. The diagnosis of BD in their lambs was confirmed by hairy birthcoats, intrauterine growth retardation, tremors, and hypomyelination. Three clinically healthy age-matched control lambs, whose dams had been given an inoculum containing only BDV-free cell culture supernatant, were studied in parallel. There were significant differences in birth weights and in the lengths of the right tibiae and radii between the affected and the control lambs. There was a gradient in severity of clinical neurologic signs among the affected lambs, which directly correlated with the severity of hypomyelination in their spinal cords. However, the difference in severity of the neurologic deficits did not correlate with differences either in the precolostral serum-neutralizing antibody titers to BDV in these lambs or in the number of BDV antigen-containing cells in their spinal cords. Only approximately 0.01% to 0.3% of spinal cord cells, both in gray matter and white matter, were BDV antigen positive in the affected lambs. These results indicate that extensive infection of CNS cells with their subsequent destruction or functional alteration may not be a critical part of the pathogenesis of the hypomyelination in BD.

Animals↗