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M J Cullen

Publications and source records attributed to M J Cullen.

126 records · Page 7Linked to original sources
PubMed1976

Cytological organization of the dorsal lateral geniculate nuclei in mutant anophthalmic and postnatally enucleated mice.

The dorsal lateral geniculate nuclei (dLGN) of anophthalmic and early postnatally enucleated mice were studied to determine the role retinal fibres play in the differentiation of postsynaptic target structures. Cell counts indicate that retinal fibres are necessary for the development and maintenance of the normal number of dLGN neurons and glia. This retinal fibre dependence is greater for animals enucleated on postnatal day 3 than for animals with a congenital absence of optic axons. Golgi analysis reveals, however, that the lack of retinal fibres does not preclude the development of the thalamo-cortical and intrinsic types of dLGN neuron. Ultrastructural analysis reveals that in anophthalmic and early postnatally enucleated mice, dLGN synaptic sites normally occupied by optic axon terminals become innervated by large terminals containing round synaptic vesicles and mitochondria with an electron dense matrix. Significantly, the formation of these replacement terminals does not seem to depend upon either the previous existence of retinal fibres or the postnatal stage at which retinal fibres are removed. The possibility that some of these large replacement terminals originate from cortical or recurrent collateral axons is considered.

Animals↗
PubMed1975

The jumping mechanism of Xenopsylla cheopis. II. The fine structure of the jumping muscle.

The ultrastructure of the trochanteral depressor muscle of the oriental rat flea is described. It is shown to be similar to that of the tubular leg muscles of other insects except in the volume and arrangement of the sarcoplasmic reticulum. The sarcoplasmic reticulum occupies approximately 18% of the volume of the muscle fibres. It is in three configurations:a regular array of parallel tubules opposite the A-band, a collar of sacculi involved in the formation of the dyads at the edge of the A-band and a loosely woven arrangement of tubules around the I-band. This tripartite arrangement of the sarcoplasmic reticulum and its large surface area is discussed in relation to the action of the muscle as the main propulsive muscle in the jump of the flea.

Animals↗
PubMed1975

The ultrastruct of normal human muscle in relation to fibre type.

A quantitative analysis using a stereological point-counting method was made of the volume fractions of the components of healthy human muscle in an attempt to distinguish between Type I and Type II fibres ultrastructurally. The Z-line widths of each fibre were also measured using the 38.5 nm axial periodicity in the I-band as a reference measurement. There was a wide range of values for the parameters measured. The volume of mitochondria was 5.14 plus or minus 1.85% (mean plus or minus standard deviation, n=24 fibres), the volume of the membrane systems was 1.59 plus or minus 0.31%, the volume of the sarcoplasm was 9.37 plus or minus 2.50% and the volume of lipid was 0.63 plus or minus 0.43%. The width of the Z-lines was 89.0 plus or minus 18.65 nm. The results show that no single feature can be used to distinguish fibre types reliably. If 2 factors are measured and certain assumptions are made, it is possible to classify about 50% of the fibres examined. These conclusions are discussed in relation to other workers' findings on the effects of age, sex and athleticism on the ultrastructure of muscle.

Adult↗
PubMed1975

Stages in fibre breakdown in Duchenne muscular dystrophy. An electron-microscopic study.

A scheme is presented which divides the process of fibre breakdown in Duchenne muscular dystrophy into 5 sequential stages. In Stage 1 the fibre appears superficially normal although there are subtle changes in the relative volumes of the fibre components. In Stage 2 localised overcontraction of the myofibrils results in excessive stretching of the sarcomeres in other regions of the fibre. This continuing process results in the formation of contraction clumps in which the contractile filaments form an increasingly homogeneous mass. By the final stage the normal structural features of the fibre have completely disappeared and it is invaded by macrophages. It is suggested that the central process of myofibril clumping results from a localised inability of the sarcomeres to relax which implies a defect in the mitochondria, Z-line or sarcoplasmic reticulum. This is discussed in relation to other workers' findings of a decrease in the calcium-accumulating capacity of the sarcoplasmic reticulum in Duchenne muscular dystrophy.

Basement Membrane↗
PubMed1975

An electrophysiological and morphological study of normal and denervated chicken latissimus dorsi muscles.

1. Some electrophysiological and morphological properties of 'fast' (singly innervated) and 'slow' (multiply innervated) muscle fibres were studied in normal and denervated posterior and anterior latissimus dorsi muscles of the young chickens. 2. Normal singly and multiply innervated muscle fibres are capable of generating action potentials which in all qualitative respects are similar. 3. The action potentials of multiply innervated muscle fibres are of lower amplitude and slower maximum rate of rise than action potentials in singly innervated muscle fibres. 4. Denervation causes the resting membrane potential and the maximum rate of rise of the action potential to fall. The changes are greater in singly innervated than in multiply innervated fibres, but in neither case are as great as in mammalian skeletal muscle fibres after surgical denervation. 5. In neither singly nor multiply innervated muscle fibres do the action potentials generate any 'resistance' to tetrodotoxin as a result of denervation. 6. The diameter of multiply innervated fibres is increased after denervation, but it is reduced in singly innervated fibres. The number of myofilaments increases in multiply innervated fibres, but decreases in single innervated fibres. In both types of muscle fibre the volume fraction of myofibrils is decreased. 7. In the singly innervated muscle fibres there is an increase in the volume fraction of mitochondria. 8. In the singly innervated muscle fibres, there is some rearrangement of the membrane systems in that some of the transversely orientated triads are replaced by longitudinally orientated dyads.

Action Potentials↗
PubMed1971

Effects of norethandrolone on the transport and peripheral metabolism of thyroxine in patients lacking thyroxine-binding globulin. Observations on the physiological role of thyroxine-binding prealbumin.

Studies of the effect of norethandrolone on the transport and peripheral metabolism of thyroxine were carried out in four patients lacking thyroxine-binding globulin. Before norethandrolone administration, values for serum protein-bound iodine (PBI) were decreased (1.8 +/-0.5 mug/100 ml) and the proportion of free thyroxine increased (0.036 +/-0.008%). As a result, values for the absolute concentration of free thyroxine iodine were at the lower end of the normal range (0.63 +/-0.12 mmug/100 ml). During the control thyroxine-turnover study, the thyroxine distribution space was strikingly increased (18.2 +/-7.9 liters) and the fractional rate of thyroxine turnover moderately increased (17.1 +/-11.3%/day), as compared to the expected mean values for normal subjects. Therefore, calculated values for the daily rate of thyroxine clearance were increased even more, ranging between 255 and 500% of normal values. However, owing to the low PBI in these patients, the daily disposal of thyroxine iodine was similar to that expected in normals on the basis of age and weight. During the administration of norethandrolone, the thyroxine-binding capacity of the thyroxine-binding prealbumin increased strikingly in all patients, values averaging 162% of those found during the control period. This increase was associated with a highly significant increase in PBI (133% of control values) and a small but significant decrease in the proportion of free thyroxine, resulting in no significant change in the absolute concentration of free thyroxine iodine. In all four patients, administration of norethandrolone was associated with a pronounced decrease in the thyroxine distribution space to values which averaged 69% of those found during the control period. Values for the fractional rate of thyroxine turnover increased slightly. As a result, thyroxine-clearance rate decreased in all patients. Owing to the reciprocal changes in clearance rate and PBI, no significant change in total daily thyroxine disposal was observed. The present studies reveal that when the thyroxine-binding prealbumin is increased in patients lacking thyroxine-binding globulin, several indices of peripheral thyroxine transport and metabolism are altered. However, these changes were small, even in the absence of thyroxine-binding globulin. It is suggested, therefore, that the effect of changes in thyroxine-binding prealbumin would be even smaller in individuals in whom thyroxine-binding globulin is present.

Adult↗
PubMedDate not supplied

Plasma membrane cytoskeleton of muscle: a fine structural analysis.

The discovery of dystrophin and its definition as the causative molecule in Duchenne Muscular Dystrophy has led to a renewed interest in the molecular structure of the muscle fiber plasma membrane and its association with the extracellular basal lamina. The original identification of dystrophin gave credence to the possibility that the plasma membrane of the muscle fiber may be highly organized and involved in maintaining appropriate homeostasis in this actively contracting cellular system. In this review, we examine the currently known members of the muscle fiber plasma membrane cytoskeleton and the interactions that occur between the different members of this complex using histological, electron microscopic, and confocal methods. From our studies and others cited in this review, it is clear that the dystrophin cytoskeletal complex is not completely understood and component molecules continue to be discovered. Perhaps equally importantly, currently defined molecules (such as alpha-actinin or neuronal nitric oxide synthase) are being recognized as being specifically associated with the complex. What is striking from all of the studies, to date, is that while we are able to identify members of the dystrophin cytoskeletal complex and while we are able to associate mutations of individual molecules with disease(s), we are still unable to truly define the roles of each of the molecules in maintaining the normal physiology of the muscle fiber.

Actinin↗
PubMedDate not supplied

The effects of intrahippocampal BDNF and NGF on spatial learning in aged Long Evans rats.

Spatial learning rate was compared in cognitively impaired aged rats infused with either brain-derived neurotrophic factor (BDNF) or nerve growth factor (NGF). BDNF or NGF was infused into the dorsal hippocampus/third ventricle while animals were being trained on the Morris water maze. Training continued until all rats met a spatial learning criterion. Seven weeks later, they were tested for retention of the task, and sacrificed for assessment of hippocampal high-affinity choline uptake (HACU) or hypothalamic biogenic amine levels. NGF, but not BDNF, improved spatial learning rate in aged rats and increased hippocampal choline uptake weeks after withdrawal of NGF. Although BDNF did not improve spatial learning, it did induce a partial, long-term normalization of the elevated hypothalamic 5-HT levels observed in our aged rats. These data suggest that (1) intrahippocampal/intraventricular infusion of NGF can improve the learning rate of aged, spatial learning-impaired rats, and that this improvement in acquisition could be associated with increased hippocampal cholinergic activity, and (2) that the BDNF-induced normalization of hypothalamic 5-HT levels in aged rats was not sufficient to improve learning rate in aged, spatial learning-impaired rats.

Aging↗
PubMedDate not supplied

The cost of managing diabetic foot ulceration in an Irish hospital.

BACKGROUND: Little is known about the economic impact of diabetic foot ulceration in the Irish healthcare setting. AIM: Audit of diabetic foot ulcer admissions in St James's Hospital between April 2001 and March 2002. METHODS: Hospital charts were reviewed and costs were calculated on the length of patients' hospital stay and the cost of individual investigations performed. RESULTS: Thirty patients were admitted with diabetic foot ulceration as the primary complaint. Amputation was performed in eight patients, two patients with a non-healing ulcer died. The average duration of each hospital admission was 20.3+/-30.7 days. Net in-hospital expenditure was 704,689, an average of 23,489.63 per hospital admission. CONCLUSIONS: The management of diabetic foot ulceration has a significant economic impact on the Irish healthcare budget. Treatment should therefore be focused on primary prevention through specialised foot clinics and a multidisciplinary team approach to reduce this economic burden.

Aged↗
PubMedDate not supplied

Muscle fibre size and shape in Duchenne muscular dystrophy.

A method for measuring fibre area and shape which obviates variabilities inherent in diameter measuring techniques was applied to dystrophic and normal human muscle. It was seen that the mean fibre area in patients with Duchenne muscular dystrophy (DMD) increases with age at a greater rate than that of the controls until approximately 5 years-of-age, when it decreases rapidly. This is due to an increasing population of small regenerating, regenerated or split fibres. The shape of fibres was expressed as a form factor and it was seen that the fibres measured from DMD biopsies were less regular in shape than the controls due to constraints placed on the normal growth of regenerating fibres by the proliferation of connective tissue.

Age Factors↗
PubMedDate not supplied

Histochemical fibre typing and ultrastructure of the small fibres in Duchenne muscular dystrophy.

Fibre type differentiation was carried out on 20 biopsies from Duchenne Muscular Dystrophy (DMD) sufferers using the acid-preincubated reaction for myofibrillar ATPase. Fibres, classified as either type 1, type 2 or 2C, were counted and their minimum diameters (least fibre axis) measured. Particular attention was paid to the population of small fibres that becomes increasingly prominent with the increasing age of the patient. Type 1 fibres were always predominant in the fibre population as a whole. The numbers of type 2 fibres declined with the increasing age of the patients while the numbers of 2C fibres increased. All fibre types were represented in the population of small fibres and the ratio of the numbers of types 1:2:2C fibres was approximately 1:1:3. Ultrastructural examination of the small fibres showed them to be at varying stages of regeneration and differentiation. The continuous presence of regenerating fibres in DMD while the muscles are wasting implies that while regeneration can be initiated it becomes increasingly constrained or restricted as the disease progresses. The cause of this restriction and whether it is related to the basic genetic lesion is unknown. It is suggested that the accumulation of fibrous connective tissue interferes with growth, either directly, in the formation of pseudomyotendinous junctions, or indirectly, by reducing nutrient exchange with the vascular system.

Adenosine Triphosphatases↗
PubMedDate not supplied

Spatial relationship of the C-terminal domains of dystrophin and beta-dystroglycan in cardiac muscle support a direct molecular interaction at the plasma membrane interface.

Dystrophin and beta-dystroglycan are components of a complex of at least nine proteins (the dystrophin-glycoprotein complex) that physically link the membrane cytoskeleton in skeletal and cardiac muscle, through the plasma membrane, to the extracellular matrix. Mutations in the dystrophin gene, which result in an absence or a quantitative or qualitative alteration of dystrophin, cause a subset of familial dilated cardiomyopathies as well as Duchenne and Becker muscular dystrophy. Biochemical studies on isolated skeletal muscle molecules indicate that dystrophin is bound to the glycoprotein complex via beta-dystroglycan, with the C-terminus of beta-dystroglycan binding to the cysteine-rich domain and first half of the C-terminal domain of dystrophin. Ultrastructural labeling has demonstrated a close spatial relationship between dystrophin and beta-dystroglycan in intact skeletal muscle, but no previous ultrastructural labeling studies have examined the dystrophin/beta-dystroglycan interaction in cardiac muscle. In the present study, we have applied complementary immunoconfocal microscopy and double immunogold fracture-label, a freeze-fracture cytochemical technique that allows high-resolution visualization of labeled membrane components in thin section and in platinum-carbon replicas, to investigate the spatial relationship between dystrophin and beta-dystroglycan in rat cardiac muscle. When immunogold probes of two different sizes for the two proteins were used, "doublets" representing side-by-side antibody labeling were demonstrated in en face views at the level of the plasma membrane. The results support the conclusions that dystrophin and beta-dystroglycan directly interact at the cytoplasmic face of the rat cardiac muscle plasma membrane.

Animals↗