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Biomedical subjects

W F Blakemore

Publications and source records attributed to W F Blakemore.

At least 109 records · Page 6Linked to original sources
PubMed1989

Primary hyperoxaluria (L-glyceric aciduria) in the cat: a newly recognised inherited disease.

The clinical features of a newly recognised inherited disease, primary hyperoxaluria in the cat, are reported. Affected cats developed acute renal failure between five and nine months old owing to the deposition of oxalate crystals in the tubules of the kidney. In addition to the signs attributable to kidney failure the affected animals became profoundly weak; there was evidence of denervation atrophy in skeletal muscle, and accumulations of neurofilaments were found in the proximal axons of the ventral horn cells and dorsal root ganglion cells of the spinal cord. Examination of urine from affected cats revealed L-glyceric aciduria and intermittent hyperoxaluria suggesting that the disease is a feline analogue of the human disorder, primary hyperoxaluria type 2. This supposition was confirmed by liver enzyme studies.

Acute Kidney Injury↗
PubMed1989

Evidence of oligodendrocyte infection and degeneration in canine distemper encephalomyelitis.

Canine distemper encephalomyelitis is an important neurological disease of the dog and is also of comparative medical interest. With some viral strains, demyelinating encephalomyelitis is seen; whether or not oligodendrocyte infection occurs has remained controversial. By examining very early white matter lesions unequivocal oligodendrocyte infection has been identified. Accordingly the direct effect of virus on oligodendrocyte viability must be weighed in considering the pathogenesis of this canine CNS infection.

Animals↗
PubMed1989

The relationship between type-1 astrocytes, Schwann cells and oligodendrocytes following transplantation of glial cell cultures into demyelinating lesions in the adult rat spinal cord.

Remyelination of ethidium bromide induced areas of demyelination in the adult rat spinal cord is normally carried out by Schwann cells. When CNS cultures containing large numbers of oligodendrocytes, oligodendrocyte precursors and type-1 astrocytes were injected into such lesions 3 days after the injection of ethidium bromide, remyelination was carried out by oligodendrocytes. When cultures deficient in type-1 astrocytes, prepared by shaking off and subculturing top-dwelling cells, were used there was only a modest increase in the extent of oligodendrocyte remyelination over that seen in uninjected lesions; the majority of axons being remyelinated by Schwann cells. To prove that these Schwann cells were mainly locally derived, shaken cultures were injected into lesions prepared in areas of the spinal cord locally X-irradiated with 40 Grays to inhibit host repair. In these animals the extent of oligodendrocyte remyelination achieved was similar to that seen when unshaken cultures (rich in type-1 astrocytes) were injected into lesions made in non-irradiated tissue. These results indicate that type-1 astrocytes control Schwann cell remyelination of CNS axons.

Animals↗
PubMed1989

Enzymological characterization of a feline analogue of primary hyperoxaluria type 2: a model for the human disease.

This paper concerns an enzymological investigation into a putative feline analogue of the human autosomal recessive disease primary hyperoxaluria type 2. The hepatic activities of D-glycerate dehydrogenase, using both D-glycerate and hydroxypyruvate as substrates, and glyoxylate reductase, which are the deficient enzyme activities in human primary hyperoxaluria type 2, were markedly depleted in four affected cats (0-6% of controls). The activities of a number of other enzymes, lactate dehydrogenase, glutamate dehydrogenase, D-amino acid oxidase, aspartate:2-oxoglutarate amino-transferase, glutamate:glyoxylate aminotransferase and alanine:glyoxylate aminotransferase (the deficient enzyme in primary hyperoxaluria type 1) were unaltered. The intracellular distribution of D-glycerate dehydrogenase and glyoxylate reductase in cat liver was shown to be cytosolic, as they are in human liver. The activities of D-glycerate dehydrogenase and glyoxylate reductase were determined in unaffected related cats and putative heterozygotes were identified. The correlation between D-glycerate dehydrogenase and glyoxylate reductase activities in the related cats and their combined deficiency in the affected cats confirmed previous suggestions that they are identical gene products.

Alcohol Oxidoreductases↗
PubMed1989

Lymphocyte-myelin sheath interactions in acute experimental allergic encephalomyelitis.

Using a passively transferred acute model of experimental allergic encephalomyelitis (EAE) in the rat, inflammatory central nervous system (CNS) lesions were shown to develop rapidly, peak and then resolve. An unusual feature of the lesions in the CNS was the presence of pyknotic cells within myelin sheaths. A sequence of observations indicated that such cells were lymphocytes which had insinuated themselves into the myelin sheath by passage along the interperiod line. The presence of lymphocytes within myelin sheaths, a process which did not lead to demyelination, was considered to represent a change which reflects the specificity of the immune response in this disease. The detection of this change in other CNS autoimmune diseases, notably those associated with virus infections, may be important as an indicator of pathogenetically relevant lymphocyte-myelin interactions.

Acute Disease↗
PubMed1989

Observation on the presence of Listeria monocytogenes in axons.

The brains from 16 sheep diagnosed as listerial encephalitis on the basis of clinical signs and histopathology were examined to determine the types of inflammatory cells present and for bacteria. Listeria monocytogenes were detected by immunocytochemistry in the brains of the 16 sheep and were also demonstrated in the trigeminal ganglion from the same side as the most severely affected side of the medulla. Bacteria were observed within myelinated axons in white matter tracts of the brain and in peripheral nerve axons of the trigeminal nerve. Their location in axoplasm was confirmed by electron microscopy. In order to investigate whether axonal presence can be equated with axonal transport, a model of infection has been established in mice in which bacteria are injected into the sciatic nerve. Paralysis of the injected leg occurs 7-12 days later and examination of the spinal cord reveals lesions very similar to those found in the brains of affected sheep.

Animals↗
PubMed1988

Observations on demyelinating lesions induced by Theiler's virus in CBA mice.

We examined demyelinating lesions in the spinal cord of CBA mice infected with the BeAn strain of Theiler's virus to see if it was possible to document the sequence of changes which result in demyelination. It was found that the lesions which develop in the late stages of the disease were progressive. Therefore, by examining the different zones of a single lesion, it was possible to follow a sequence of changes which lead to demyelination. There was a clear progression from normal myelin, to vacuolated myelin, to myelin phagocytosis, to demyelinated axons, to remyelinated axons. Virus was detected in degenerating oligodendrocytes in the area showing myelin vacuolation by both electron microscopy and immunocytochemistry, a finding which indicated that virus infection precedes demyelination. The area of normal myelin which surrounded the zone of vacuolated myelin was infiltrated by lymphocytes, indicating that lymphocytic infiltration preceded viral replication and oligodendrocyte degeneration. Our observations indicate that cells of the immune system may play a role in the initiation of virus replication which appears to be a prerequisite for demyelination.

Animals↗
PubMed1988

Extensive oligodendrocyte remyelination following injection of cultured central nervous system cells into demyelinating lesions in adult central nervous system.

Following the injection of central nervous system (CNS) cell cultures, prepared from 1-day-old rats and maintained in vitro for 7 days, into irradiated, demyelinating lesions in the spinal cord of adult isologous animals, extensive remyelination of axons by oligodendrocytes was observed. In addition, astrocytes, within the transplanted cell suspension, established normal relationships with oligodendrocytes, axons and other tissue elements, which led to the establishment of large CNS territories throughout the lesions. Outside these CNS domains, Schwann cells, which are present in the transplanted cell suspension, myelinated groups of axons. These observations indicate that the irradiated, ethidium bromide lesion provides an in vivo environment, devoid of the influences of host glia, in which to examine the interactions of transplanted glial cells with demyelinating axons.

Animals↗
PubMed1988

A murine model of Streptococcus suis type 2 meningitis in the pig.

When young or adult mice were infected experimentally with isolates of Streptococcus suis type 2 of known pathogenicity for pigs, the organisms produced disease, young mice being more susceptible than adults. An isolate of S suis type 2 less pathogenic for pigs also appeared less pathogenic in mice. The organism could be reisolated from infected mice for up to 42 days. Inoculum size was one factor influencing the likelihood of an individual mouse developing meningitis following intravenous inoculation. Transmission of the organism from inoculated to in-contact mice occurred in young mice after intravenous or oral administration. These studies indicate that the behaviour of S suis type 2 in mice resembles its behaviour in pigs.

Animals↗
PubMed1987

Recognition of 'trembler', a hypomyelinating condition in the Bernese mountain dog.

An account is given of a hypomyelinating condition, 'trembler', in the Bernese mountain dog. The condition is manifested clinically as a tremor of the limbs and head which becomes more intense with excitement or stress and which disappears with sleep. The tremor, which is first noticeable between two and eight weeks old, may persist throughout life but decline with age. Examination of plastic embedded tissue obtained post mortem from two, nine-week-old animals showed hypomyelination of the spinal cord. Preliminary examination of breeding data suggests that the condition may be inherited as an autosomal recessive.

Animals↗
PubMed1987

Rat Schwann cell remyelination of demyelinated cat CNS axons: evidence that injection of cell suspensions of CNS tissue results in Schwann cell remyelination.

Injection of a suspension of embryonic rat central nervous system (CNS) cells into an area of persistent demyelination, produced in the cat spinal cord by injecting ethidium bromide into an area previously exposed to 40 Grays of x-irradiation, results, initially, in Schwann cell remyelination of the demyelinated axons. However, the Schwann cells are subsequently rejected; a response which confirms that the remyelinating cells are of rat origin.

Animals↗
PubMed1987

Schwann cell remyelination of CNS axons following injection of cultures of CNS cells into areas of persistent demyelination.

The injection of suspensions of central nervous system (CNS) cells, prepared by standard methods from 4-day-old rat brain and maintained in vitro for 10 days, into areas of persistent demyelination in rat spinal cord resulted in extensive remyelination of axons by Schwann cells. As control lesions injected with medium showed no remyelination, the most likely explanation of this finding is that 'CNS cultures' contain a small population of Schwann cells which are stimulated to proliferate by the demyelinated axons.

Animals↗
PubMed1987

Node-like axonal undercoating in the optic nerve of heterozygous myelin-deficient rats.

Focal regions of node-like axonal undercoating occur occasionally in the myelin-deficient rat spinal cord. In the optic nerve of heterozygous myelin-deficient rats, areas of amyelination are present, within which many axons show regions of node-like undercoating. These structures were most easily seen when fixation resulted in round axonal profiles. In one-year-old rats, these structures were common. The ubiquitous association of patches of axonal undercoating with regions of chronic amyelination and demyelination indicates that chronically demyelinated axons differ structurally from recently demyelinated axons. It is possible that such axons may have lost their ability to recruit myelin-forming cells.

Age Factors↗
PubMed1987

Observations on the migratory behaviour of Schwann cells from adult peripheral nerve explant cultures.

The migration of Schwann cells from adult sciatic nerve explant cultures has been examined by time-lapse photomicrography. Analysis of Schwann cell migratory behaviour indicates that the initial outwandering by individual Schwann cells was random. Although chance cell-cell contacts resulted in temporary immobilization of pairs of cells, stable multicellular structures did not form during this initial phase. As local cell densities increased, Schwann cells assembled networks within which Schwann cell movement continued to be observed. A second form of Schwann cell outgrowth was observed from degenerating fibres in which arrays of highly oriented Schwann cells migrated away from their basal lamina tubes onto the culture dish. These observations of Schwann cell random migration, network self-assembly and coordinated extratubal migration are considered to highlight aspects of Schwann cell behaviour, independent of axonal influences, which may have relevance to their role in peripheral nerve repair following nerve section.

Animals↗
PubMed1987

The effect of L3T4 T cell depletion on the pathogenesis of Theiler's murine encephalomyelitis virus infection in CBA mice.

Theiler's murine encephalomyelitis virus (TMEV) gives rise to a biphasic disease of the central nervous system (CNS) following intracranial inoculation of susceptible strains of mice. The early phase, during the first month, resembles poliomyelitis and in the late phase the mice suffer from inflammatory demyelination reminiscent of multiple sclerosis. In order to investigate the role of helper T cells in the acute and chronic phases of the disease we depleted mice of their L3T4 T cells in vivo with rat monoclonal antibodies, prior to infection and prior to the onset of clinical signs of demyelination. Mice depleted of their helper cells failed to produce antibodies to TMEV and consequently were unable to clear virus from the CNS and died within the first month of infection. Depletion of T cells before the demyelinating phase of the disease resulted in a marked decrease in the incidence of disease from 77% of the immunocompetent animals with clinical signs of paralysis to 36%. Immunocompetent TMEV-infected mice also developed antibodies against myelin suggesting that autoimmune mechanisms may play a role in TMEV-induced demyelination.

Animals↗
PubMed1986

GM1 gangliosidosis (type 1) in a cat.

A kitten with clinical and morphological symptoms of a neurovisceral lysosomal-storage disease has been shown to have a marked deficiency of acidic beta-D-galactosidase in the brain, kidney and spleen. Chromatography on concanavalin A-Sepharose and inhibition studies with 2,5-dihydroxymethyl-3,4-dihydroxypyrrolidine, a selective inhibitor of the neutral broad-specificity beta-D-galactosidase, have shown that the residual beta-D-galactosidase at pH 4.0 in the tissues of the affected cat is due to the neutral beta-D-galactosidase and that there is a complete deficiency of the acidic (lysosomal) beta-D-galactosidase. There is marked accumulation in all tissues and excretion in the urine of neutral oligosaccharides. Analysis of these oligosaccharides by fast-atom-bombardment mass spectrometry and g.l.c. suggests that they arise from the incomplete catabolism of N-glycans of glycoproteins. The ganglioside content of all the tissues is elevated, and it has been shown by t.l.c. that the concentration of a ganglioside fraction with a mobility similar to that of GM1 ganglioside is particularly increased. There is also some evidence of accumulation of glycosaminoglycans in the brain. The clinical symptoms, the complete deficiency of acidic beta-D-galactosidase and the storage products in visceral organs all suggest that this is a case of feline GM1-type gangliosidosis comparable with the severe infantile (Type 1) form of the disease in humans.

Alkaloids↗