Search PubMed⌕ Search

Biomedical subjects

R J Higgins

Publications and source records attributed to R J Higgins.

At least 37 records · Page 2Linked to original sources
PubMed1998

Determination of the frequency and distribution of vascular and parenchymal amyloid with polyclonal and N-terminal-specific PrP antibodies in scrapie-affected sheep and mice.

Brains from 17 histopathologically confirmed cases of scrapie, five of which had congophilic vascular amyloid, were stained immunohistochemically for prion protein (PrP) using a polyclonal antibody. Two clinically suspect but pathologically unconfirmed cases of natural sheep scrapie and the brains of four mice infected with the 111A murine scrapie strain were also examined. Selected sections containing amyloid were stained with each of two peptide antibodies which recognise the N-terminal amino acid residues which are lost following protease digestion of the disease-specific isoform of PrP. The mice infected with the 111A murine scrapie strain had large numbers of hypermature plaques. All the amyloid plaques from both natural sheep scrapie brains and experimental murine brains were heavily immunostained by the polyclonal and both peptide antibodies. In addition, disease-specific accumulations of PrP were detected in endothelial cells or in the intima of blood vessels of the cerebral cortex of sheep scrapie brains. The affected blood vessels were located in areas which otherwise lacked typical scrapie pathology. Vascular accumulations of PrP were also found in leptomeningeal and choroid plexus blood vessels. Vascular amyloid was found mainly in the neocortex. Vascular amyloid and disease-specific parenchymal accumulations of PrP were found in two sheep which showed clinical signs of scrapie but lacked its typical vacuolar pathology. These results show that the mature amyloid of scrapie is composed of, or contains a substantial proportion of, whole length PrP protein. Thus truncation of PrP is not essential for the aggregation of PrP into amyloid. The vascular amyloid of natural sheep scrapie originates from the accumulation and release of PrP from endothelial cells presumably following systemic scrapie infection. The topography of vascular amyloid distribution in Great Britain differs from that reported in the Netherlands. As amyloid deposition in mice is largely controlled by the strain of the infecting agent it is possible that the strain of the agent may influence vascular amyloid deposition.

Amyloid↗
PubMed1998

Late-onset progressive spinocerebellar degeneration in Brittany Spaniel dogs.

Eight Brittany Spaniel dogs, seven females and one male, between 7 and 14 years old presented with clinical neurological signs of spinocerebellar disease of about 6 months to 4 years duration. Clinically the dogs had a dramatic forward "saluting" movement of the thoracic limbs, hypermetria of the pelvic limbs, cerebellar ataxia and intention tremors. Terminally, dogs crawled in a crouched thoracic posture with neck extension. Lesions were confined to cerebellum, medulla oblongata and spinal cord. The most severe lesion was diffuse Purkinje cell loss with massive neurofilament accumulation in degenerating cells. There was some bilateral neuronal degeneration in the dorsal horns of the spinal cord and in the gracilis and cuneate nuclei. There was bilateral sporadic axonal degeneration in the dorsal columns and lateral and ventromedial areas of the spinal cord. The etiology of this syndrome was not determined.

Animals↗
PubMed1997

Cytokeratin-filament expression in epithelial and non-epithelial tissues of the common carp (Cyprinus carpio).

Cytokeratin expression in mammals is generally restricted to epithelial cells and has been utilized to differentiate epithelial from nonepithelial tissues in these species. Since cytokeratins have been shown to be highly conserved during vertebrate evolution, the objective of the present study has been to ascertain the expression pattern of cytokeratins in tissues of the common carp (Cyprinus carpio). A panel of 10 anti-human cytokeratin antibodies was evaluated using a streptavidin-biotin-peroxidase complex detection system. Tissues were fixed in 10% neutral-buffered formalin, 100% ethanol or methacarn. Only formalin-fixed tissues were pre-digested with trypsin prior to immunostaining. Formalin-fixed tissues generally resulted in a less intense, more diffuse staining pattern with considerable background compared with ethanol and methacarn and was therefore the least desirable fixative. The diverse staining pattern observed with the various antibodies used in this study was consistent with previous findings in other teleosts. The results confirm that cytokeratin expression in teleosts is fundamentally different from that in mammals and therefore should be used as a method to differentiate epithelial cell types in these species only with discretion.

Journal Article↗
PubMed1997

Intravascular malignant T-cell lymphoma (malignant angioendotheliomatosis) in a cat.

A 7-year-old spayed female Siamese cat was presented with a 7-day history of ataxia, circling to the right, and involuntary micturition and defecation. Cerebrospinal fluid analysis showed increased protein content and relative eosinophilia. At necropsy, there was flattening of the cerebral cortical gyri of the right frontal and parietal lobes, and both kidneys had multiple wedge-shaped cortical indentations. Histologically, the cerebral cortex contained several extensive malacic foci, and the kidneys had multifocal parenchymal degeneration and atrophy. There was multifocal partial to complete thrombosis of renal interlobar arteries and of the right middle cerebral artery and meningeal branches; these thrombi contained large anaplastic round cells, which often invaded the arterial wall. Many smaller vessels within the kidneys and brain were occluded with clusters of similar cells, without thrombosis or vascular wall invasion. The neoplastic round cells had immunohistochemical staining properties of T lymphocytes.

Animals↗
PubMed1997

Neuronal vacuolation and spinocerebellar degeneration in young Rottweiler dogs.

With the recent epizootic of bovine spongiform encephalopathy in Europe, the differential diagnosis of neuronal vacuolation and spongiform change in other species has become critically important. Four Rottweiler puppies of both sexes, presented at 3-8 months of age, had clinical signs of generalized weakness and ataxia that started at 6 weeks of age. In all pups, neurologic examination detected an ataxia and tetraparesis, most severe in the pelvic limbs, and slowed proprioceptive placing reactions. Subsequently, there was rapid progressive neurologic deterioration, with severe placing deficits, knuckling, severe ataxia, and quadraparesis by 8 months of age. At necropsy, no gross lesions were observed. Microscopic lesions were restricted to the nervous system. The major lesion in all dogs was an intracytoplasmic neuronal vacuolation that was most prominent in the cerebellar roof nuclei and in nuclei of the extrapyramidal system. Similar vacuolation was found in neurons in both dorsal nerve root ganglia, myenteric plexus, and other ganglia of the autonomic nervous system. The single or multiple empty vacuoles were between 1 and 45 microm in diameter. A mild spongiform change was seen in the adjacent neuropil. Purkinje cell vacuolation and degeneration with segmental cell loss was seen in the oldest dog. In ventromedial and dorsolateral areas of the spinal cord white matter, there was mild bilaterally symmetrical axonal degeneration. Immunoblotting and immunocytochemical staining of the brain for protease-resistant scrapie prion protein was negative. All forms of vacuoles were negative for immunohistochemical staining with a variety of lectins. Ultrastructurally, the vacuoles were bound by a single membrane and contained granular material and sometimes membranous profiles. There was mild distension of the cytocavitary network but no unequivocal connection with the vacuoles was found. Axosomatic and axodendritic synapses in affected neurons were intact both ultrastructurally and with synaptophysin immunostaining. The clinicopathologic findings were different from those seen in the other neurologic diseases of Rottweilers. The age of the dogs, distribution and type of the lesions, ultrastructural findings, and negative immunoblotting most likely rule out the possibility of a scrapie agent-associated spongiform encephalopathy. However, the etiology of this new disease was not determined.

Animals↗
PubMed1997

Attaching and effacing E. coli. Microscopic and ultrastructural observation of intestinal infections in pigs.

Pigs aged from neonate to 8 weeks with naturally occurring diarrhoea were submitted to a Veterinary Investigation Centre for routine diagnosis. They were retrospectively found to be infected with "attaching and effacing" E. coli (AEEC) on histological and ultrastructural examination of the intestinal tract. Subcultures of E. coli isolated from some of the affected pigs were tested against standard anti-sera and probed for the presence of verotoxin (VT) and "cae" genes. One strain of E. coli was positive for the VT gene and three VT-negative strains possessed the "cae" gene. This preliminary report suggests that in naturally occurring diarrhoea of suckling and weaned pigs, AEEC infection can be identified by histological examination of the intestinal mucosa and confirmed by electron microscopy, in the abscence of infection by recognised enteric pathogens on microbiological examination.

Adhesins, Bacterial↗
PubMed1996

Equine papillary ependymoma.

A 17-year-old Arabian gelding with progressive neurologic signs had a velvety, reddish brain tumor protruding from the ventral midline caudal to the optic chiasma. Histologically, the tumor had a papillary formation with a single layer of elongate cells radially oriented around a central fibrovascular core. Intracytoplasmic globular inclusions were positive for glial fibrillary acidic protein and weakly positive for vimentin. Ultrastructurally, these inclusions were comprised of whorling intermediate filaments. Neoplastic cells also had cytoplasmic interdigitations and numerous zona adherens and often rested on a basal lamina. The tumor was diagnosed as a papillary ependymoma.

Animals↗
PubMed1995

Regiospecific intestinal absorption of the HIV protease inhibitor L-735,524 in beagle dogs.

PURPOSE: To evaluate regional intestinal absorption and the feasibility of sustained release dosage form development for an HIV protease inhibitor, L-735,524, METHODS: L-735,524 free base or sulfate salt was administered orally as suspension, solution or in solid dosage forms to fasted or fed Beagle dogs. Delayed-release dosage forms with "slow" or "fast" in vitro dissolution rates were evaluated in vivo to assess plasma concentration profiles. In addition, drug was administered directly into the jejunum or colon of animals, and drug concentrations determined in portal circulation to characterize absorption from these sites. RESULTS: L-735,524 sulfate was well absorbed orally form a solution or capsule formulation if fasted animals' stomachs were preacidified with citric acid solution. A free base suspension, delivered in divided doses to fed animals, was also well absorbed. Prototype extended release dosage forms of L-735,524 produced a reduction in peak plasma levels but failed to prolong absorption and extend plasma concentrations compared to an immediate release capsule. Administration of L-735,524 sulfate solution (pH < 3) as bolus solution or by infusion into the jejunum resulted in rapid but incomplete absorption compared to oral gavage. The free base suspension (pH 6.5) delivered into jejunal or colonic regions did not produce measurable systemic plasma concentrations. CONCLUSIONS: Extended release formulations did not prolong absorption of L-735,524 in dogs. Optimal L-735,524 absorption was dependent on solubility in an acidic environment in the duodenum.

Administration, Oral↗
PubMed1994

Polioencephalomalacia associated with the ingestion of ammonium sulphate by sheep and cattle.

In the latter part of 1991 an unusual neurological disease was recognised on several farms in England. This report describes the case histories and clinical, biochemical and pathological findings in six calves and two lambs aged from two to 44 weeks obtained from five of these farms. Laminar cerebrocortical necrosis and severe bilateral necrosis of the thalamus and/or striatum progressing to cavitation were recognised in their brains. These changes are similar to those of experimental sulphate toxicity. Morbidity rates of 16 to 48 per cent and mortality rates of 0 to 8 per cent were recorded. The affected animals did not respond to vitamin B1 treatment; the erythrocyte transketolase levels of in-contact cattle and of one untreated affected calf and one untreated lamb were within the normal range. All five farms had recently introduced a proprietary concentrate ration containing ammonium bicarbonate. After this ration was withdrawn no new cases of nervous clinical disease were observed. It is suggested that, in at least some cases, the morphology and topography of lesions may distinguish sulphate induced polioencephalomalacia from that of sporadic thiamine-dependent cerebrocortical necrosis.

Ammonium Sulfate↗
PubMed1994

Avian embryonic brain reaggregate culture system. I. Characterization for organophosphorus compound toxicity studies.

An avian reaggregate culture system was characterized biochemically and morphologically for use in acute and chronic organophosphorus compound (OP) toxicity studies. Ten-day-old chick embryo brains were dissociated, reaggregated, and maintained in a chemically defined, serum- and antibiotic-free media. Acetylcholinesterase (ACHE), neuropathy target esterase (NTE), and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) were examined due to inhibition of these enzymes as a result of acute OP toxicity (ACHE) or delayed toxicity (NTE, CNP). The selected enzymes also indicate reaggregate neuronal (ACHE, possibly NTE), oligodendroglial (CNP), and astrocytic (glutamine synthetase (GS)) activities. Enzyme activities were compared to those in age-matched chick embryo and hatched chick brains. Reaggregate ACHE specific activity was similar to or higher than that of chick embryo or hatched chick. Reaggregate NTE specific activity was initially similar to that of 10-day-old chick embryo, and then increased but subsequently averaged 7.8 nmol/min/mg protein. In chick brain, NTE peaked at hatching and averaged 28 nmol/min/mg protein thereafter. Reaggregate CNP specific activity ranged from 103 to 426 nmol/min/mg protein, whereas activity gradually increased in chick embryo brain to an average of 140 nmol/min/mg protein posthatching. The mean GS activity ranged from 0.15 (Culture Day 4) to 1.09 nmol/min/mg protein (Culture Day 62). Mean protein values per flask ranged from 2.47 to 7.58 mg. Ultrastructurally, myelination was detected at Culture Day 7 and synapses at Day 6. The biochemical and ultrastructural features demonstrate that this reaggregate culture is a practical and sensitive in vitro system for studying both the acute and the long-term neurotoxicological effects of organophosphorus compounds.

Acetylcholinesterase↗
PubMed1994

Avian embryonic brain reaggregate culture system. II. NTE activity discriminates between effects of a single neuropathic or nonneuropathic organophosphorus compound exposure.

Biochemical responses after a single exposure to either a neuropathic or a nonneuropathic organophosphorus compound (OP) were compared using chick embryonic brain cell reaggregates. Ten-day-old chick embryo brains were dissociated and then reaggregated and maintained in a chemically defined, serum-free medium without antibiotics. Seven days later, these cultures were treated for 20 min with either neuropathic diisopropyl phosphorofluoridate (DFP, 10(-4) M) or nonneuropathic paraoxon (10(-6) M). Reaggregates were assayed for acetylcholinesterase (ACHE), neuropathy target esterase (NTE), and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) activities for up to 32 days after exposure. These enzymes were examined due to inhibition of activity as a result of acute OP toxicity (ACHE) or delayed toxicity (NTE, CNP). DFP inhibited > 95% of NTE activity immediately after exposure. By Postexposure Day 2, NTE specific activity was 22% of untreated activity but was similar to the untreated group levels by Postexposure Day 7. Paraoxon exposure did not affect NTE activity. Both paraoxon and DFP inhibited > 99% of ACHE activity immediately after exposure. By Postexposure Day 2, ACHE specific activity in paraoxon-exposed cultures had recovered while ACHE remained 56% inhibited in DFP-exposed cultures. Both paraoxon- and DFP-exposed cultures recovered ACHE activity immediately following OP exposure if treated postexposure with an oxime reactivator, 2-pralidoxime. CNP specific activity was not affected by either paraoxon or DFP. These results demonstrated distinct differences in reaggregate NTE and ACHE activities after single exposure to neuropathic DFP and nonneuropathic paraoxon similar to those in avian in vivo assays.

Acetylcholinesterase↗
PubMed1994

Neuropathology of organophosphate-induced delayed neuropathy (OPIDN) in young chicks.

To examine the phenomenon of apparent age resistance of young chicks to organophosphate-induced delayed neuropathy (OPIDN), groups of either 2- or 10-week-old chicks were exposed subcutaneously daily for 4 days to the neuropathic organophosphate (OP), di-isopropylfluorophosphate (DFP, 1 mg/kg), the non-neuropathic OP, paraoxon (PO, 0.25 mg/kg) or atropine (20 mg/kg). Subsequently, all birds were examined at post-exposure intervals (calculated from the last day of exposure) for up to 56 days for neurological deficits and morphological lesions in the central and peripheral nervous systems (CNS, PNS). Clinically, none of the birds in the 2-week-old groups, or in the 10-week-old PO or atropine exposed groups had neurological deficits. However, all birds in the 10-week-old DFP exposed group developed ataxia by 7 days post-exposure (DPE) and then progressive paralysis. Therefore, all birds in the 10-week-old groups were killed at 14 DPE. Pathologically, the 2-week-old DFP exposed chicks had increasingly severe lesions of Wallerian-like degeneration predominantly in the spinal cord from 7 DPE and subsequently. In the 10-week-old DFP exposed chicks, the degenerative lesions of OPIDN were first detected in the CNS at 3 DPE and then with equally increasing severity in the CNS and PNS up to 14 DPE. A higher incidence of neuronal necrosis and chromatolysis in ventral motor horn neurons of spinal cord grey matter and in dorsal root ganglia occurred in both the DFP exposed age groups compared with those lesions in other groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1993

Deficit of inhibitory glycine receptors in spinal cord from Peruvian Pasos: evidence for an equine form of inherited myoclonus.

Inherited myoclonus in Poll Hereford calves and spasticity in the spastic mouse (spa/spa) are characterized by myoclonic jerks of the skeletal musculature which occur spontaneously and in response to sensory stimuli, symptoms resembling those in subconvulsive strychnine poisoning. The primary, biochemical defect in these myoclonic animals is a deficit of inhibitory glycine receptors in the central nervous system. We now report the occurrence of similar stimulus-induced myoclonus in individual, pure-bred Peruvian Paso horses and an associated, specific deficiency in the density of [3H]strychnine binding to inhibitory glycine receptors sites in spinal cord of these animals. Specificity of the deficit was confirmed by a demonstrated lack of change in the density of several other receptor types in affected spinal cord, including muscarinic receptors and GABAA/benzodiazepine receptors. In light of the existence of genetically-inherited myoclonus in other species, these results suggest the occurrence of an equine form of the disorder.

Animals↗
PubMed1993

Photodynamic therapy for nasal and aural squamous cell carcinoma in cats.

Eighteen random-bred cats with a total of 19 nasal or aural squamous cell carcinomas were treated with photodynamic therapy, using aluminum phthalocyanine tetrasulfonate as the photosensitizer. Cats were irradiated at power densities of 100 mW/cm2 and energy densities of 100 J/cm2. Successful outcome was obtained in 10 tumors after 1 treatment, and 2 more tumors had complete responses after 1 or 2 additional treatments. Treatments were more effective in tumors of stage T2 or earlier. Five tumors had partial responses, and the response of 2 tumors could not be evaluated. The treatment was safe and well tolerated by most cats, although we found that cats should be kept out of sunlight for 2 weeks after treatment.

Animals↗