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M J Cullen

Publications and source records attributed to M J Cullen.

At least 73 records · Page 4Linked to original sources
PubMed1988

A quantitative study of myonuclear and satellite cell nuclear size in Duchenne's muscular dystrophy, polymyositis and normal human skeletal muscle.

The dimensions of myonuclei and satellite cell nuclei in Duchenne's muscular dystrophy (DMD), polymyositis, and normal controls were compared in order to determine whether differences in satellite cell populations (previously reported by these and other authors) could be attributable to changes in the relative dimensions, thereby biasing the counts. The nuclei were measured directly from semithin resin sections using computerized measuring techniques, thereby avoiding errors due to photographic enlargement. In both the control and polymyositic groups, the satellite cell nuclei (8.30 microns and 8.81 microns respectively) were significantly shorter than the myonuclei (11.75 microns and 13.00 micron). Dystrophic myonuclei (10.98 microns) were significantly shorter than polymyositic myonuclei, but dystrophic satellite cell nuclei (11.62 microns) were significantly longer than both polymyositic and normal control satellite cell nuclei. The mean nuclear area in transverse sections was significantly greater in both myopathies than in the control material for both myonuclei and satellite cell nuclei. Myonuclei were significantly larger than satellite cell nuclei in all groups. When the values for the lengths of the nuclei were used to adjust previous estimates of satellite cell populations, it was found that earlier conclusions were still valid, i.e., that there is a significant increase in the number of satellite cells in the dystrophic muscle fibre population.

Adolescent↗
PubMed1988

Ultrastructure of the skeletal muscle in the X chromosome-linked dystrophic (mdx) mouse. Comparison with Duchenne muscular dystrophy.

Ultrastructurally there are some clear differences in the pathology of muscle in X chromosome-linked muscular dystrophy of the mouse (mdx) and Duchenne muscular dystrophy (DMD). In particular the mouse muscle does not become infiltrated by large aggregations of connective tissue. It has been proposed that the differences are due to secondary biochemical changes consequent on the absence of dystrophin in both conditions. If this is the case, attention should be directed to the earliest ultrastructural changes held in common by both disorders. The most conspicuous of these, preceding myofibril breakdown, is dilation of the sarcoplasmic reticulum. Any physiological link between this and the absence of dystrophin remains to be determined. We suggest that in the mdx mouse, the widespread myofibre necrosis occurring at 3-4 weeks is triggered by increased mechanical demands causing the lack of dystrophin to become critical at this time. Subsequent regeneration of the myofibres appears to be almost completely successful. The ultimate failure of regeneration in DMD, in contrast, may be due to an additional factors acting in DMD exacerbating the lack of dystrophin. This additional factor may be associated with the plasma membrane lesions (not seen in mdx). Alternatively there may be factors present in the mouse that compensate for the lack of dystrophin. It is pointed out that to understand better the different processes occurring in mdx and DMD we need to learn more about the factors which control the balance between the growth of muscle and the growth of connective tissue in both normal and pathological human and mouse muscle.

Animals↗
PubMed1988

Freeze-fracture analysis of myelin membrane changes in Wallerian degeneration.

Transection of mouse sciatic nerves produced microscopic changes in the myelin sheaths distal to the transection. Studied with freeze-fracture, these microscopic changes were correlated with alterations in the macromolecular organization of nerve membranes. In control mice, sciatic nerve myelin contained randomly distributed intramembranous particles. In the early stages of myelin breakdown the lamellae split and large areas of myelin membrane lacked intramembranous particles. The remaining particles clustered with a greater than normal density. Degenerating myelin was found within Schwann cells which still had an outer mesaxon and a normal distribution of intramembranous particles on the cell outer membrane. As the degeneration proceeded, myelin ovoids formed which completely lacked intramembranous particles. The findings suggest that during Wallerian degeneration there is a progression of myelin changes leading to the eventual loss of myelin intramembranous particles. These observations are morphological evidence that Schwann cells remove components from selective portions of their membrane during Wallerian degeneration.

Animals↗
PubMed1988

Atypical persisting fibres in explants of human muscle cocultured with embryonic nerve cells.

When samples of human muscle are cocultured with embryonic mouse spinal cord, the muscle fibres usually regenerate to form a bundle of new myotubes which become innervated and develop cross-striations and contractions. However, we have noticed that in some cultures of 6 biopsies of human muscle, there were fibres which "persisted" in the cultures for long periods of time without being replaced by regenerated myotubes. At both the light and electron microscopic levels, they appeared to be mature muscle with well-organized myofibrils, intact plasma membranes and closely-apposed basal laminae. At least some of the fibres contained adult myosin heavy chains. They were only found in freshly-cultured samples, and appeared to be associated with younger patients, but were not associated with any particular muscle condition. The nature of these persisting fibres is discussed, and we emphasize the need for sequential observation of cultures to ensure that fibres which have regenerated in culture are distinguished from those which have persisted from the original biopsy.

Adolescent↗
PubMed1988

Lipid storage myopathy associated with low acyl-CoA dehydrogenase activities.

A man with a painful proximal myopathy had excess lipid deposition in skeletal muscle, excretion of dicarboxylic acids in urine and low acyl-CoA dehydrogenase activities in skeletal muscle mitochondria. In addition he had little immunoreactive short-chain and medium-chain acyl-CoA dehydrogenase enzyme protein compared with normal controls. Following treatment with riboflavin there was considerable improvement in his clinical condition which was confirmed by further biochemical and morphological investigations.

Acyl-CoA Dehydrogenases↗
PubMed1987

A qualitative and quantitative study of the ultrastructure of regenerating muscle fibres in Duchenne muscular dystrophy and polymyositis.

Quantitative and qualitative ultrastructural analyses were made of selected small muscle fibres from muscle biopsies from 23 patients with Duchenne muscular dystrophy (DMD) and 10 with polymyositis. It is argued that the fibres selected were regenerating. The myofibrillar content of the fibres was similar in both samples. In both there was considerable misalignment of the myofibrils but their orientation tended to improve as the content increased. The mitochondrial content was similar in the two samples but there were more ultrastructural abnormalities in the DMD population. The concentration of glycogen was elevated and the sarcoplasmic reticulum (SR) was much more commonly dilated in the DMD patients. Dilated SR is the prenecrotic change seen most frequently in mature muscle fibres in DMD and seems to be the first ultrastructural manifestation of the disease process. Its occurrence in the regenerating fibres suggest that the primary genetic lesion is being recapitulated in successive generations of fibres.

Biopsy↗
PubMed1987

Calcium channel blocker drugs and diabetic control.

Calcium channel blockers are now widely used and there have been case reports of hyperglycemia with nifedipine. In a double-blind, randomized, crossover study of the effects of 4 weeks of therapy, each with two dihydropyridine calcium channel blocker drugs, nifedipine and nicardipine, glucose tolerance, plasma insulin levels, and hemoglobin A1 were assessed in 20 patients with non-insulin-dependent diabetes (mean age 59 years). There was no significant difference in glucose tolerance on active therapy (AUC: control, 548.3 +/- 24.8; nifedipine, 559.3 +/- 41.0; and nicardipine, 589.3 +/- 40.3). Similarly, despite producing significant hemodynamic effects, these drugs produced no significant effect on plasma insulin and hemoglobin A1 levels. Calcium channel blocker drugs may be useful alternatives to thiazide diuretics and beta-blockers in the treatment of ischemic heart disease and hypertension, especially in patients with diabetes.

Adult↗
PubMed1986

A morphological/biochemical study on the actions of corticosteroids on rat skeletal muscle.

Four corticosteroid hormones were administered (5 mg/kg/day) to rats over 6 to 10 days. Both biochemical and microscopic techniques were employed to determine the influence of these corticosteroids on the fine structure and growth of five striated muscles. Throughout, dexamethasone and triamcinalone were more potent than prednisone or cortisone in influencing muscle growth. The corticosteroids' action on the heart was anabolic, increasing its RNA and protein content. In contrast, the same corticosteroids were catabolic against fast-twitch muscles (e.g., extensor digitorum longus), inducing appreciable atrophy. However, slow-twitch muscles (e.g., soleus) were more resistant to these hormones, exhibiting an intermediate response between that of the heart and fast-twitch muscles. Only minor morphological changes were found in both fast and slow muscles 10 days after the corticosteroid treatments. The hormones' atrophic effects on skeletal muscle primarily arose from the corticosteroid's ability to inhibit protein synthesis, via decreases in the muscles' ribosomal capacities. Whole-body protein synthesis was also suppressed by these corticosteroids, but to a lesser extent than in the whole skeletal musculature.

Adrenal Cortex Hormones↗
PubMed1986

A quantitative comparison of satellite cell ultrastructure in Duchenne muscular dystrophy, polymyositis, and normal controls.

Failure of the muscle to regenerate successfully is an important feature of the pathology of Duchenne muscular dystrophy (DMD). It is known that this is not due to a numerical reduction in the population of satellite cells. We have therefore examined the ultrastructural composition of the satellite cells in 25 DMD cases and compared them with satellite cells from normal subjects and from polymyositis patients to try to identify morphological features that might be associated with an impaired developmental competence. Profiles of randomly and serially sectioned satellite cells were analyzed stereologically to obtain nuclear and cytoplasmic areas. Within the cytoplasm, the areas occupied by mitochondria, rough endoplasmic reticulum (RER), and Golgi apparatus were measured. Micropinocytotic vesicles (MPVs) at the periphery of the cells were counted. The nucleus to cytoplasm ratios and mitochondrial, RER, and Golgi volume fractions were not significantly different in the three satellite cell samples. The cells in the DMD sample contained more MPVs than those in the normal subjects. This is attributed to a generalized cell response to a physiologically altered environment in the diseased muscle.

Adolescent↗
PubMed1986

Neurosecretion of arginine vasopressin by an olfactory neuroblastoma causing reversible syndrome of antidiuresis.

A 26-year-old woman with the syndrome of inappropriate antidiuresis demonstrated complete recovery following the resection of an olfactory neuroblastoma. Tissue arginine vasopressin levels by radioimmunoassay, immunohistochemical staining of the tissue arginine vasopressin, postoperative normalization of plasma arginine vasopressin levels, and the clinical resolution are evidence in support of a neurally derived tumor being the direct source of neurosecretion of arginine vasopressin rather than neurohypophyseal secretion or secretion from non-neural tissues, as reported to date in the etiology of the syndrome of inappropriate antidiuresis.

Adult↗
PubMed1986

Cerebellar structure and function in the murine mutant "jolting".

The morphology of the cerebellar cortex of the murine mutant "jolting" and its phenotypically normal littermate was studied. The general organisation of the cerebellum of normal mice was similar in all respects to that described for other vertebrate species. In "jolting" mice aged 4 months or more there was a marked loss of Purkinje cells and spheroids were present on Purkinje cell axons. An ultrastructural examination showed that the spheroids contained randomly orientated neurofilaments, degenerating mitochondria and autophagic vacuoles. The abnormalities in the cerebellum appeared confined to the Purkinje cells. Extracellular recordings were made of the electrical activity of the cerebellar cortex of anaesthetised mice. In the cerebellar cortex of "jolting" animals, Purkinje cells generated little spontaneous activity, but complex discharges resulting from climbing fibre inputs were indistinguishable from normal. The abnormal electrical activity of Purkinje cells in "jolting" mice could be seen in animals as young as 3 weeks. It was concluded that the "jolting" mouse suffers from a cerebellar ataxia.

Action Potentials↗
PubMed1986

Isolation of ducts from the pancreas of copper-deficient rats.

A technique is described, involving tissue dissociation and micro-dissection, for the isolation of interlobular ducts from the pancreas of copper-deficient rats. The average length and outside diameter of the isolated ducts were 589.0 +/- 18.6 and 78.1 +/- 1.6 micron (mean +/- S.E.M., n = 425) respectively. Between twenty and fifty ducts could be obtained from each pancreas. Frequently, the smaller intralobular ducts, which had outside diameters of between 15 and 25 micron, were observed as branches of the interlobular ducts. Light and electron microscopy showed that the isolated ducts were structurally intact, and that the epithelial cells possessed all the typical ultrastructural features of duct cells within the gland of copper-replete rats. The isolated ducts consumed oxygen at a rate of 2.27 +/- 0.55 ml O2/min X 100 g wet weight duct epithelium (n = 6). The concentrations of ATP, ADP and AMP in the ducts were 3.78 +/- 0.81, 0.68 +/- 0.19 and 0.41 +/- 0.13 mmol/l duct epithelium (n = 8) respectively. These data give values for ATP:ADP and ATP:AMP ratios of 5.6:1 and 9.2:1 respectively, and an energy charge of 0.85 +/- 0.01 (n = 8) suggesting that the epithelial cells are healthy and in a stable metabolic state. In the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (0.67 mM), the basal concentration of cyclic AMP in the isolated ducts was 17.4 +/- 0.7 mumol/l duct epithelium (n = 3). Secretin (0.1 nM-1 microM) caused a dose-related increase in cyclic AMP content up to a maximum of 376.0 +/- 85.3 mumol/l duct epithelium (n = 4). This indicates that the epithelial cells possess secretin receptors, and that these receptors can be functionally linked to adenylate cyclase.

Adenine Nucleotides↗
PubMed1986

Morphological, biochemical and secretory studies on rat pancreatic ducts maintained in tissue culture.

Interlobular ducts were isolated from the pancrease of copper-deficient rats and maintained in culture on polycarbonate filter rafts. Within 8 h the ends of the ducts had sealed. This was followed by a marked dilatation of the lumen, a flattening of the epithelium against the surrounding connective tissue layer and an over-all swelling of the duct. Apart from a reduction in their height, a fall in the number of intracellular fat droplets and a widening of intercellular spaces, epithelial cells within the cultured ducts retained all the ultrastructural characteristics of those in freshly isolated preparations. The basal concentration of adenosine 3',5'-phosphate (cyclic AMP) in the cultured ducts was 43.3 +/- 6.8 mumol.1-1 duct epithelium (n = 5) and was increased to 188.9 +/- 55.2 mumol.l-1 duct epithelium (n = 5) in the presence of 10(-8) M secretin. The basal rate of fluid secretion, measured using micropuncture techniques, was 0.16 +/- 0.03 nl.h-1.nl-1 duct epithelium (n = 12). This was increased 14-fold by 10(-8) M secretin while the dose of the hormone required for half-maximal secretion was about 2 X 10(-11) mol.l-1. The concentration of chloride ions in secreted fluid and perifusion buffer were similar. Variation in culture time up to 52 h had no effect on fluid secretion, and the response to secretin was dependent on the presence of bicarbonate ions in the perifusion fluid. N6,O2-dibutyryl adenosine 3',5'-phosphate (dibutyryl cyclic AMP) also increased fluid secretion but caerulein had no effect. We suggest that isolated ducts secrete fluid at comparable rates to ducts in situ within the pancrease of copper-replete rats.

Animals↗
PubMed1985

Long-term culture of differentiated human thyroid tissue.

Human thyroid cells obtained during surgery have been maintained in monolayer culture for at least 2 months and without loss of morphological or functional differentiation. Samples as small as 0.5 g could be cultured but best results were obtained with samples of 5-10 g. The technique used was developed in this laboratory for sheep tissue and was applicable without significant modification to human tissue. It depends on the complete absence of media changes at any time during the culture period. Energy substrates are replenished by the addition of concentrated glucose solutions to the existing media at carefully monitored intervals. Differences in both morphology and function could be observed between cultures derived from patients with different diseases, suggesting that the technique could have predictive value.

Animals↗
PubMed1984

A comparative study of the transverse tubular system of the rat extensor digitorum longus and soleus muscles.

An ultrastructural comparison was made between the transverse tubular systems of the extensor digitorum longus (fast twitch) and the soleus (slow twitch) muscles in the rat. Quantitative measurements were made of the volume fraction, surface to volume ratio, surface density and foot density of the T system membrane. The values for the volume fraction and surface density were approximately 50% higher in the fast twitch (extensor digitorum longus) than the slow twitch (soleus) muscle. The dimensions of the tubules and hence the surface to volume ratio was the same in the two muscles. There was no difference in the spacing of the feet, so the reported three to fivefold difference in charge movement cannot be associated with a difference in foot density. Material lying within the lumen of the T tubules was observed in the majority of tubule profiles. This material, not hitherto described, was particulate or, more commonly, laminar in form.

Animals↗
PubMed1983

Electron microscopic study of intramembranous changes in protein-extracted peripheral nervous system myelin.

Sciatic nerves from young mice were incubated for 2-8 hours in 0.5% Triton X-100 in 0.5 M ammonium acetate, a solution which solubilizes the large and small basic proteins of the myelin sheath. As previously noted (Peterson and Gruener, 1978), myelin sheaths from treated nerves extensively split and unravelled along major dense lines. Small focal areas of compact myelin remained. In freeze-fracture replicas, areas of myelin with lamellar splitting contained few intramembranous particles, while membrane areas with greater than normal densities of particles were associated with the patches of compact myelin membrane. Fixation for as short a time as 15 minutes stabilized the myelin membrane enough to prevent the Triton X-100 effects, even when incubations were extended to 20 hours. Controls, both untreated and 0.5 M ammonium acetate-treated nerves, had predominantly compact myelin sheaths; their leaflets were covered with numerous intramembranous particles. The data suggest that Triton X-100 alters the compact structure of peripheral nervous system myelin. In areas where lamellae are split and separated, there is a loss of intramembranous particles. It appears that the loss of intramembranous particles is related to the removal of the basic proteins which are located in major dense line regions of compact myelin sheaths.

Animals↗