Search PubMed⌕ Search

Biomedical subjects

M J Cullen

Publications and source records attributed to M J Cullen.

At least 91 records · Page 5Linked to original sources

Regeneration of mammalian skeletal muscle following the injection of the snake-venom toxin, taipoxin.

Taipoxin, a toxin isolated from the venom of the snake Oxyuranus scutellatus was injected subcutaneously into the anterolateral aspect of one hind limb of the rat. The toxin caused a necrotising myopathy in the underlying muscle. The ultrastructural characteristics of the regeneration that followed the administration of the myotoxin were studied. Regeneration occurred within the surviving basal lamina tubes from a population of spared satellite cells. Myotubes were formed by 3 days and small immature muscle fibres by 5 days. The regenerative response was total and very rapid. Highly activated satellite cells were found in apparently undamaged fibres in the toxin-damaged muscles. Many of these cells appeared to be motile, having cytoplasmic processes which seemed to be passing through the basal lamina of the parent muscle fibres.

Animals↗

An investigation of the optimum culture conditions for a differentiated culture of sheep thyroid cells.

Primary cultures of differentiated sheep thyroid were investigated to assess the effect of varying the media, sera, hormones and the initial cell number plated on the culture life span. Iodide uptake and follicular morphology were used as indices of differentiation. It was found that the effect of variations in the type of medium and the concentration and type of serum used was very small. The addition of all the hormones used - insulin, hydrocortisone and thyrotrophic hormone - had a synergistic effect on the iodide trapping ability of the culture system. A cell number of approximately 1 x 10(6) cells per 25 cm2 flask was found to be optimum for the development of differentiation in the cultures.

Animals↗

Phagocytosis of the A band following Z line, and I band loss. Its significance in skeletal muscle breakdown.

A band phagocytosis, following Z line and I band loss, is described in polymyositis, in epsilon amino caproic acid induced myopathy and in an experimental myositis of guinea pigs. It is far less prominent in Duchenne muscular dystrophy. This form of necrosis is always associated with lesions in the plasma membrane. It is argued that the ensuing ionic equilibration with the extracellular fluid allows activation of a calcium activated proteinase (CAP) which digests the Z line. Breakdown of the myofibrils into individual A bands promotes rapid phagocytosis of the myofibre contents and facilitates regeneration of the muscle.

Aminocaproic Acid↗

Low-dose radioisotope scanning and quantitative analysis in the diagnosis of congenital hypothyroidism.

Quantitative thyroid scanning using low doses of 99mTc sodium pertechnetate (1.85-3.7 MBq) was performed in 38 cases of congenital hypothyroidism. Of these 38 cases, 29 were scanned at 14 +/- 6 days old, and 9 at 1 year old. The scans show the full range of gland anatomy from athyreotic to normal. All morphologically normal scans had grossly increased uptakes of 99mTc. The incidence of the various thyroid anatomies was different in each age group. The average radiation dose to the thyroid was 2.29 mGy, with at least 70% of patients receiving a dose of 3.0 mGy or less. Such low doses of 99mTc should allow further scanning in later life. Neonatal thyroid scanning reveals the aetiology of congenital hypothyroidism and enables the clinician to assess the short- and long-term needs of the child.

Congenital Hypothyroidism↗

Freeze-fracture characterization of isolated myelin and axolemma membrane fractions.

The macromolecular organization of membranes isolated from the rabbit optic nerve and tract was analyzed using the freeze-fracture technique. A myelin fraction and two axolemma-enriched fractions were prepared from a preparation of myelinated axons isolated by flotation in a buffered salt-sucrose medium. In the myelinated axon preparation, axolemma and myelin membranes were easily identified. Larger areas of the axon membrane and myelin membrane totally lacked intramembranous particles. The particles remaining on the myelin membrane formed patches of evenly distributed elongated and globular particles. In contrast, the particles remaining on the axolemma were globular in shape and tightly clustered. Particle clustering and particle-free areas were not characteristic of either the axolemma or myelin membrane of whole nerves fixed in situ and processed for freeze-fracture. The isolated myelin membrane fraction contained a large number of vesicles completely lacking intramembranous particles. Of the remaining membrane vesicles, profiles with dispersed elongated and globular particles predominated. A small percentage of vesicles displayed intramembranous particles of the same size, shape and clustering pattern as that seen on the axolemma of the myelinated axon preparation. The two axolemma fractions were enriched in membrane containing tightly clustered globular particles. Particle-free vesicles as well as some myelin membrane vesicles were also seen in the axolemma fractions.

Animals↗

An unusual organelle in a case of Duchenne muscular dystrophy.

A new organelle found in a case of Duchenne muscular dystrophy is described. It was located at the periphery of a regenerated myofibre close to a satellite cell. It was roughly spherical in shape and 0.30-0.35 micrometers in diameter. Its internal structure was examined in serial and tilted sections, and consisted of parallel arrays of laminae or, possibly, filaments. The nature of the organelle is briefly discussed.

Child↗

Screening for congenital hypothyroidism in the Republic of Ireland.

A national pilot study for detecting congenital hypothyroidism by radioimmunoassay of thyroid-stimulating hormone concentrations in dried blood was incorporated into the newborn screening programme in Ireland on 1 August 1979. The programme has been monitored by a steering committee and follows the guidelines set by the European Society of Paediatric Endocrinologists. During the first 12 months 76 224 infants were screened and 19 cases confirmed, giving an incidence of 1:4012. Fifty infants (0.07%) were recalled for a serum sample, though most of the recalls (31; 0.04%) occurred during the first three months, before the methodology had become established. No case was detected clinically. At recall only three of the 19 affected infants had obvious features, and nine inconspicuous features. Organisation was directed at early diagnosis and treatment, the mean age at beginning treatment being 15 days. These results confirm the efficacy of screening for congenital hypothyroidism and suggest that capital and running costs will be offset by savings in maintenance treatment of untreated patients. Screening does not, however, remove the need for continued vigilance, and clinicians should request thyroid-function tests in any suspected case.

Age Factors↗

The radiobiological response of the thyroid. Part I: Sheep thyroid cells in culture as a radiobiological model.

A system for culturing sheep thyroid cells in vitro is described. The properties of the cultures may be manipulated so that they preserve in vitro the follicular architecture typical of the thyroid, or so that they undertake cellular proliferation. The cultured cells also undertake iodide metabolism. These growth and differentiation characteristics can be preserved for at least three weeks, which is sufficient time for assay of many radiobiological end-points.

Animals↗

The radiobiological response of the thyroid. Part II: Response of sheep thyroid cell in vitro to single doses of X rays.

The response of sheep thyroid cells in culture to single doses of X or gamma rays is described. In the absence of cellular proliferation the cells are unusually radioresistant, showing little sign of interphase death at doses up to 9 krad. The follicular morphology characteristic of thyroid cells in vivo is also very radioresistant. Iodide trapping is reduced to 50% of the control value by doses of the order of 2 krad. When proliferation is induced the cells may be assayed for postirradiation survival using a clonogenic endpoint. The survival curves are sigmoid with a Do of 410 rad and a very low extrapolation number.

Animals↗

Longterm cultures of sheep thyroid cells.

A thyroid tissue culture system has been established in which follicular morphology can be preserved for at least 30 days. The system is highly dependent on whether or not the medium supporting the cells is changed during the culture period. The high levels of TSH (40 mU/ml) normally used in thyroid culture systems enhance follicular morphology but are not a prerequisite for differentiation. In the absence of medium changes follicular morphology improves for up to 20 days after initiation of the culture. Thereafter, the cells die unless the medium is changed. If differentiation is to be preserved after 20 days the medium into which the cells are transferred must be "conditioned" by preincubation with thryoid cultures. Regular medium changes into fresh medium causes the cultures to lose their differentiated characteristics and revert to a conventional monolayer. The capacity of these cultures to trap iodide has been quantified using a new method. The method is based on comparison of the 125I--iodide retained by thyroid cells with that retained in a undifferentiated established cell line (CHO--K1). The results demonstrated that trapping can be preserved for at least 20 days in cells cultured in the presence of TSH, provided the medium is not changed; and that under appropriate conditions the cells can trap iodide even in the absence of TSH stimulation. The extent to which the above cultures proliferate is also investigated. At the relatively high innoculation of cells used in primary cultures little proliferation takes place even when the cells are stimulated by TSH. However, regular medium changed induce some growth. In the absence of medium changes the cells die after 15-20 days. Those grown in the presence of TSH live slightly longer than those grown in its absence. Subculturing thyroid cells and innoculating them at low densities in Petri dishes leads to substantial cell proliferation whether or not TSH is present. The doubling time of cells in these cultures is the order of 1 to 2 days. The population resulting from this growth exhibit both epithelial and fibroblast like morphology although the former predominates. When cells from primary thryoid cultures are reseeded at very low concentrations (approximately 10(3) cells/Petri dish) about 3-10 per cent of the population give rise to viable macroscopic clones.

Animals↗