Search PubMed⌕ Search

Biomedical subjects

D N Landon

Publications and source records attributed to D N Landon.

At least 37 records · Page 2Linked to original sources
PubMed1988

The characterization of experimental gliosis by quantitative nuclear magnetic resonance imaging.

Quantitative nuclear magnetic resonance imaging techniques were used to study the development of astrocytic gliosis following a cortical freezing injury in 4 cats, and the findings compared with the histological and ultrastructural appearances of the affected white matter. In the first week after lesioning, the acutely oedematous white matter was apparent as a region of signal abnormality with very prolonged T1' and T2' relaxation times. Following resolution of this oedema, the images remained normal for a period of approximately three months. After this latent period they became abnormal once again, and the abnormal signal was most evident in images emphasizing differences between tissues in T1' and proton density, but not T2'. The light and electron microscopic appearances of the corresponding tissue were of astrocytic gliosis in each animal. Measurement of the relaxation times, T1' and T2', of the abnormal regions revealed an increase in T1' without a corresponding change in T2'. The T2' magnetization decay characteristics were consistently monoexponential, in contrast to the clearly biexponential T2 decay which has previously been demonstrated in the presence of acute vasogenic oedema. These findings suggest that the pattern of change of the relaxation times and T2 magnetization decay might provide a means of distinguishing between lesions in multiple sclerosis which are predominantly gliotic, and those containing significant amounts of oedema.

Animals↗
PubMed1987

Quantitative nuclear magnetic resonance imaging: characterisation of experimental cerebral oedema.

Magnetic resonance imaging (MRI) has been used quantitatively to define the characteristics of two different models of experimental cerebral oedema in cats: vasogenic oedema produced by cortical freezing and cytotoxic oedema induced by triethyl tin. The MRI results have been correlated with the ultrastructural changes. The images accurately delineated the anatomical extent of the oedema in the two lesions, but did not otherwise discriminate between them. The patterns of measured increase in T1' and T2' were, however, characteristic for each type of oedema, and reflected the protein content. The magnetisation decay characteristics of both normal and oedematous white matter were monoexponential for T1 but biexponential for T2 decay. The relative sizes of the two component exponentials of the latter corresponded with the physical sizes of the major tissue water compartments. Quantitative MRI data can provide reliable information about the physico-chemical environment of tissue water in normal and oedematous cerebral tissue, and are useful for distinguishing between acute and chronic lesions in multiple sclerosis.

Animals↗
PubMed1986

Emery-Dreifuss syndrome.

A young adult male is described with muscular dystrophy of probable X-linked recessive inheritance. An onset of muscle weakness in late adolescence was preceded by contractures of the neck and elbows dating back to childhood. The distribution of muscle weakness was proximal in the upper limbs and both proximal and distal in the lower. The mixed pattern of muscle involvement in the legs favours the view that cases of Emery-Dreifuss muscular dystrophy with proximal weakness in both the upper and lower limbs and X-linked scapuloperoneal muscular dystrophy represent the same disorder. A muscle biopsy in the present case showed unique appearances.

Adult↗
PubMed1986

Magnetic resonance imaging of experimental cerebral oedema.

Triethyl tin(TET)-induced cerebral oedema has been studied in cats by magnetic resonance imaging (MRI), and the findings correlated with the histology and fine structure of the cerebrum following perfusion-fixation. MRI is a sensitive technique for detecting cerebral oedema, and the distribution and severity of the changes correlate closely with the morphological abnormalities. The relaxation times, T1 and T2 increase progressively as the oedema develops, and the proportional increase in T2 is approximately twice that in T1. Analysis of the magnetisation decay curves reveals slowly-relaxing and rapidly-relaxing components which probably correspond to oedema fluid and intracellular water respectively. The image appearances taken in conjunction with relaxation data provide a basis for determining the nature of the oedema in vivo.

Animals↗
PubMed1985

Chronic optic nerve compression. An experimental study.

Chronic progressive compression of the optic nerve in the cat was produced by an inflatable silicon rubber balloon implanted in the orbit. Within the first week the predominant pathological change was demyelination. Both partially and completely demyelinated fibres were seen at all stages of the experiments but by the fifth week some axons had been remyelinated by oligodendrocytes despite the continued presence of the balloon. The myelin sheaths of the new internodes were abnormally thin and short, and many showed an atypical paranodal organization. There was evidence of breakdown of some of the new internodes. The pathophysiology of optic nerve compression in man is reviewed.

Animals↗
PubMed1985

Pattern and extent of demyelination in the optic nerves of mice infected with Semliki Forest virus and the possibility of axonal sprouting.

The optic nerves of all mice infected with Semliki Forest virus (SFV) showed patchy demyelination, although the extent of demyelination varied between animals. There was a significant increase in small diameter unmyelinated fibres in the optic nerves of SFV infected mice, paralleled by a loss of small myelinated fibres, suggesting that the smaller myelinated fibres may be more susceptible to virus-induced demyelination. The small unmyelinated fibres were more numerous in the peripheral region of the optic nerve trunk, where blood vessels are found in greater numbers. In addition, a particularly large increase in the proportion of unmyelinated fibres which had diameters of less than 0.2 microns suggested the possibility of axonal sprouting.

Animals↗
PubMed1984

Synthesis of leukotriene B4, and prostanoids by human alveolar macrophages: analysis by gas chromatography/mass spectrometry.

Human alveolar macrophages, obtained during diagnostic bronchoscopy, were maintained in monolayer culture. Challenge of these cells (greater than 95% purity) with 1.2 mg/ml zymosan A particles (opsonized with human serum) was followed by a rapid release of leukotriene B4 into the medium, 7.28 +/- 5.99 ng/mg cell protein at 2 h (mean +/- S.D.4, n = 4). Leukotriene B4 was identified and measured by a novel technique employing capillary column gas chromatography coupled to negative ion chemical ionization mass spectrometry. The release of thromboxane B2, prostaglandins D2, E2, F2 alpha and the lysosomal enzyme N-acetyl-beta-D-glucosaminidase was also measured. Thromboxane B2 was the most abundant metabolite of arachidonic acid released into the culture medium (65.2 +/- 14.8 ng/mg cell protein 2 h after the addition of zymosan A, n = 4), and the synthesis of thromboxane B2 was inhibited by greater than 90% in 1 microM Na flurbiprofen. Inhibition of cyclooxygenase activity was accompanied by a 2-fold increase in leukotriene B4 synthesis.

Gas Chromatography-Mass Spectrometry↗
PubMed1984

A new mitochondrial myopathy. Biochemical studies revealing a deficiency in the cytochrome b-c1 complex (complex III) of the respiratory chain.

A 20-year-old Chilean girl presented with lifelong ptosis and fatiguable weakness which was initially thought to be due to a congenital myasthenic syndrome. Studies of an intercostal muscle biopsy showed normal endplate morphology, abundant acetylcholinesterase activity and a normal number of junctional acetylcholine receptors as determined by radiochemical assay, but a high proportion of the muscle fibres contained large peripheral aggregations of abnormal mitochondria. Biochemical investigation of mitochondria isolated from the vastus lateralis muscle demonstrated a hitherto unreported respiratory chain deficiency localized to complex III.

Adult↗
PubMed1983

New approaches to the study of human dystrophic muscle cells in culture.

Tissue culture provides a system for studying the growth and differentiation of muscle cells in a controlled environment. Several studies have been carried out on diseased muscle cells in culture in attempts to elucidate the aetiology of Duchenne muscular dystrophy (DMD) but the results were equivocal. Work in our laboratory in recent years has yielded an improved method for preparing primary muscle cell cultures from dissociated biopsies which permits the morphological and biochemical evaluation of these cultures at all stages of growth and development. Our results have shown abnormalities in cell behaviour, ultrastructure and creatine kinase synthesis. The background to these studies is reviewed. Recently we have developed a cell cloning procedure that allows the accumulation of a large number of cells from a single selected cell. We can with this technique monitor quantitative and qualitative cellular and cytochemical differences between individual cell types without the ambiguities inherent in the use of mixed cell populations. The results obtained with 4 different clonal preparations derived from dystrophic muscle have shown that a number of specific features were expressed by each of the 4 clones with respect to their growth pattern, ultrastructure, synthesis of muscle specific protein and cell surface antigen. These findings clearly illustrate the potential of these cloning procedures for studying the genetic expression of homogeneous cell populations derived from normal adult human muscle and patients with X-linked muscle disease.

Cells, Cultured↗
PubMed1982

Mitochondrial encephalomyopathies: biochemical studies in two cases revealing defects in the respiratory chain.

We describe two patients with mitochondrial myopathies who presented with complex multisystem diseases predominantly affecting the central nervous system. In both cases the disease ran a fluctuating clinical course, eventually leading to profound impairment of intellectual function. In Case 1 dementia was associated with optic atrophy, absent pupillary responses, impaired eye movements and generalized dystonic rigidity without evidence of weakness or loss of muscle bulk. In Case 2 myoclonus preceded the onset of ataxia, generalized weakness and mental confusion by several years. Biochemical studies on isolated muscle mitochondria revealed defects in the mitochondrial respiratory chain which were located at NADH-CoQ reductase in Case 1, and at cytochrome b in Case 2. This study illustrates the potential value of muscle biopsy in the diagnosis of unusual and otherwise unexplained cerebral syndromes in man, even in the absence of muscle weakness.

Biopsy↗
PubMed1981

Alterations in the number and affinity of junctional acetylcholine receptors in a myopathy with tubular aggregates. A newly recognized receptor defect.

This paper reports the findings in a 32-year-old man who presented in adult life with a myasthenic syndrome characterized by dysphagia, dysphonia, fluctuating ptosis, episodic diplopia and a variable weakness of the limbs and trunk. Electromyography showed a small decremental response, increased neuromuscular jitter and blocking of some components. Histochemical and electron microscopic studies revealed changes in end-plate morphology and prominent tubular aggregations within the muscle fibres. Radiochemical investigations using di-iodinated 125I-alpha-bungarotoxin demonstrated a reduction in the number of AChR and alterations in receptor affinity which suggested an abnormality of the AChR macromolecule.

Adult↗
PubMed1980

The morphology of rat soleus neuromuscular junctions treated in vitro with purified beta-bungarotoxin.

Pairs of isolated rat soleus nerve-muscle preparations were maintained in vitro in oxygenated Ringer solution containing 3 microgram/ml beta-bungarotoxin prepared by the method of MacDermot et al. End-plate potentials and twitch tensions generated in response to continuous stimulation via the nerve at 0.5 Hz were recorded from one muscle, while miniature end-plate potential amplitude and frequencies were monitored in the corresponding unstimulated member of the pair. The results obtained were compared with the fine structure of end-plates from identical preparations sampled after varying periods of intoxication, and from unpoisoned muscles maintained for comparable times in vitro. The electron micrographs obtained were analyzed quantitatively using simple stereological techniques. Our results show that: (1) nerve terminal synaptic vesicle content declines for the first hour of intoxication but returns to near normal levels following conduction block; (2) there is a rapid increase in the 'coated' vesicle population of the nerve terminals, both attached to the plasmalemma and within the terminal cytoplasm, which persists to the end of the experiment; and that (3) there is no significant increase in the incidence of damaged mitochondria within the poisoned nerve terminals. These findings are discussed in relation to previous observations and the putative mechanisms of action of beta-bungarotoxin.

Animals↗
PubMed1980

Remyelination during optic nerve compression.

The structural changes produced in cat optic nerve by incremental chronic compression have been investigated by light and electron microscopy. Within the first week extensive demyelination occurred; some fibres underwent Wallerian degeneration and there was marked proliferation of astrocytic processes. After 5 weeks of compression remyelinated fibres were seen and occurred in all longer-term animals despite the maintenance of compression, but some partially and completely demyelinated fibres persisted. Myelin thickness had not returned to normal in the remyelinated fibres after 19 weeks and was often strikingly variable. The significance of these observations is discussed in the light of the recent demonstration of the restoration of central conduction by remyelination.

Animals↗
PubMed1980

Remyelination during optic nerve compression.

An inflatable silicone rubber balloon implanted in the orbit has been used to simulate an expanding orbital tumour. The changes produced in the compressed cat optic nerve have been investigated by light and electron microscopy. Within the first week extensive demyelination occurred; some fibres degenerated completely and there was marked proliferation of astrocytic processes. Some partially and completely demyelinated axons were seen throughout the period studied but after 5 weeks many axons had become remyelinated. Remyelinated fibres were seen in all longer-term animals despite the continued presence of the orbital mass. The significance of these observations is discussed in the light of the physiology of conduction in demyelinated and remyelinated central axons.

Animals↗
PubMed1979

A mitochondrial myopathy with a deficiency of respiratory chain NADH-CoQ reductase activity.

This paper presents data on two sisters with a mitochondrial myopathy characterised by weakness, marked exercise intolerance and a fluctuating lactic acidaemia. Both patients also experienced episodes of increased weakness which could be brought on by unaccustomed activity, going without food or by taking small quantities of alcohol. Metabolic studies during exercise showed a marked and sudden rise in blood lactate and pyruvate levels. Biochemical studies in one case showed that mitochondrial respiratory rates were markedly decreased with all NAD-linked substrates tested but were normal with succinate and with TMPD + ascorbate. The mitochondrial cytochrome components were normal as determined by low temperature spectroscopy and the addition of uncoupler did not enhance state 3 respiratory rates utilising NAD-linked substrates. It was concluded, therefore, that the mitochondrial lesion was located at the level of the NADH-CoQ reductase complex.

Adult↗