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J Fraher

Publications and source records attributed to J Fraher.

10 recordsLinked to original sources
PubMed2001

Early development of rat ventral root transitional zone: an immunohistochemical and morphometric study.

Bundles of ventral motoneuron axons cross the white matter of the spinal cord, emerge through the cord surface at the CNS-PNS transitional zone (TZ) and continue in the PNS as ventral rootlets. This study identifies immunohistochemical and morphometric changes which characterise the key events in early TZ formation in the rat. E18 is a landmark stage, since it is then that the major events of TZ differentiation are initiated. In the glial processes associated with the TZ, vimentin expression decreases, while that of GFAP increases. In the proximal rootlets the transient expression of CNS markers such as GFAP and of neural adhesion molecules such as HNK-1/N-CAM begin to decrease. Their resulting differential expression clearly defines the CNS-PNS interface. These changes coincide with the arrival of glial nuclei at the TZ. Cell clusters which appear on proximal ventral rootlet surfaces shortly after their emergence from the cord, have by E18 formed an extensive matrix of processes which segregates the axon bundle. This comprises the earliest of two well-defined barriers across the axon bundle. An important function may be to prevent Schwann cell invasion of the cord. Cluster cells display some immunohistochemical features in common with Schwann cells. The second barrier becomes fully established only at P2 and forms the definitive CNS-PNS interface. It consists of processes arising from astrocytes surrounding the TZ. Changes in the nuclear density of the cell types correspond closely to their segregating activity. The immunohistochemical and ultrastructural changes complement one another to deepen and enhance understanding of TZ development.

Animals↗
PubMed1998

A strong myelin thickness-axon size correlation emerges in developing nerves despite independent growth of both parameters.

The axon determines whether or not it is myelinated by the Schwann cell. At maturity there is a positive correlation between sheath thickness and axon calibre. This correlation is initially very low or absent, but gradually strengthens during development. This increase could come about because the axon continuously controls Schwann cell myelinating activity, so that a given axon calibre is associated with a particular myelin sheath thickness, an interaction which would entail the Schwann cell continuously monitoring and responding to axon size. This seems unnecessarily complex. This theoretical study shows that the strong correlation between the 2 parameters within a given myelinated fibre population may come about in a much simpler way than outlined above. This is demonstrated by modelling the growth and myelination of a hypothetical population, utilising data from earlier studies on cervical ventral motoneuron axon development. The hypothesis tested shows that the only instructive interactions by the axon on the Schwann cell necessary for the strong correlation between the 2 parameters to emerge are for the initiation of myelination, its continuation and its termination. These could result from a single stimulus being switched on, persisting for a time and being switched off. Under this influence, the Schwann cell is assumed to proceed to form the myelin sheath at a constant rate which it itself inherently determines, in the absence of any quantitative influence exerted by the axon. This continues until the stimulus for myelination ceases to emanate from the axon. The validity of the hypothesis is demonstrated, because the resulting myelin-axon relationships correspond closely to those observed during development.

Animals↗
PubMed1997

Symposium on glial interfaces in the nervous system: development and repair.

This Anatomical Society symposium, held at University College, Cork in September 1995 was the first of its kind. The objective was to stimulate and facilitate constructive interaction between experts on topics relating to the various types of glial barrier which form partitions within the nervous system. Some of these barriers are transient and are found only during development, for example, those which define the limits of developing nuclei or fibre bundles. Others are permanent, such as those at the transitional zones which separate the CNS and PNS milieux at nerve root attachments to the neuraxis. Still others, such as glial scars, are seen only following injury when they tend to inhibit neurite regeneration. In experimental circumstances, for example following irradiation or chemical damage, glial barriers may be broken down and even relocated. This may be associated with Schwann cell invasion of the CNS and, experimentally, with Schwann cell and glial cell transplantation into demyelinated areas. Such transplantation studies are in turn related to remyelination and CNS axon regeneration and the factors which facilitate these. Twelve review lectures were given on these topics. Five articles based on these communications are reproduced here. The underlying theme was the relationship between advances in the understanding of fundamental nervous tissue biology, especially as related to glial cells, and potential developments aimed at treating CNS demyelinating diseases and achieving CNS regeneration.

Journal Article↗
PubMed1996

Node distribution and packing density in the rat CNS-PNS transitional zone.

The density of nodes of Ranvier was examined at CNS, PNS, and transitional zone (TZ) levels of rat lumbar ventral motoneurone fibres. It was found to be significantly greater in the TZ than at the other levels: The difference was sevenfold for the ventral root and at least fourfold for central fibre levels. Node distribution and spacing was examined within the two main types of TZ found in rat ventral rootlets: the first, in which the TZ is short and is approximately on a level with the surface of the cord; and the second, in which it is much longer and extends into the proximal part of the rootlet. Node spacing was estimated as nearest neighbour distance, the true distance between adjacent node centres. This is a better estimate of node spacing than simple density since it measures the actual linear distance between nodes over which any interaction between them would be likely to take place. Despite marked differences in the dimensions of the two types of TZ, nearest neighbour distance distribution was very similar in each, suggesting that similar mechanisms may influence their spacing during development. The TZ contains especially large amounts of interstitial tissue, mainly composed of astrocyte processes, separating the fibres traversing it. The proportion of the TZ composed of interstitium was over three times that in the ventral root and nearly twice that at the CNS level studied. The large amounts of astrocytic tissue in the TZ may be related to the high packing density of nodes. It may function to regulate extracellular ionic concentrations in the TZ and to maintain a stable ionic environment for the transitional nodes.

Animals↗
PubMed1995

Glial-Schwann cell specialisations at the central-peripheral nervous system transition of a cyclostome: an ultrastructural study.

This study describes for the first time the central (CNS)-peripheral (PNS) nervous system transitional zone (TZ) of a member of the vertebrate class Agnatha, namely, the sea lamprey. It is concerned in particular with the glial tissue contribution to the TZ and the Schwann cell-CNS interface. Plastic-embedded specimens of spinal cord and nerve roots were examined using light and electron microscopy. At the TZ of each root a glial barrier, continuous with and similar in form to the surrounding glia limitans, stretches across the nerve bundle. In possessing such a barrier the lamprey TZ follows the general vertebrate pattern and differs from the Cephalochordata and invertebrates where a corresponding barrier is absent. The glial barrier is of similar thickness to the glia limitans generally, unlike in the mammal where it is thicker at the TZ than elsewhere. All lamprey axons are unmyelinated peripherally and most of them traverse the glial TZ barrier singly in individual tunnels. In this they resemble mammalian axons of similar calibre (which are, however, myelinated), but differ from unmyelinated mammalian axons, which generally traverse it in bundles. The lamprey TZ has specialisations not found in mammals. These include prominent, multiple interconnected strata of microfilament bundles which are continuous deeply with glial filament bundles and which lie under the surface plasmalemma of the glia limitans, to which they are connected by hemidesmosomes. Features of the mature lamprey TZ resemble those of developing mammalian TZs. For example, slender Schwann cell processes extend below the cord surface and become closely apposed to glial processes. In addition, together with the axon, the TZ glial processes and the basal lamina, they bound an extensive periaxonal network of spaces at the TZ, into which fine Schwann cell processes project. Accordingly, the networks could represent a primitive form of node gap.

Animals↗
PubMed1994

Differential pharmacology of cloned human and mouse B2 bradykinin receptors.

The pharmacology of cloned B2 bradykinin receptors heterologously expressed in cell lines lacking any endogenous bradykinin receptors was analyzed. The possibility of B2 bradykinin receptor heterogeneity had been proposed on the basis of numerous studies in various tissue preparations. The results reported here permit a direct evaluation of some of these hypotheses by examining the pharmacological properties of cloned bradykinin receptors. A cloned human B2 bradykinin receptor was stably transfected into Chinese hamster ovary cells. The data suggest that in response to bradykinin (BK), the cloned receptor activates both phosphatidylinositol hydrolysis and arachidonic acid release by independent pathways. Thus, the activation of these two second messenger pathways does not require the existence of two B2 bradykinin receptor subtypes. A mouse gene encoding the B2 bradykinin receptor was isolated, and the coding region was expressed in COS-7 cells. This murine receptor exhibited the pharmacological properties of a "classical" B2 bradykinin receptor. A comparison of the pharmacological profiles of cloned human and murine homologs of the B2 bradykinin receptor indicates that both receptors bind agonists with similar properties. However, the two receptors differ dramatically in their affinity for some peptide antagonists. The mouse receptor has a 60- to 80-fold higher affinity for [D-Arg0Hyp3, Thi5,8,D-Phe7]BK and [D-Arg0,Hyp3,D-Phe7]BK than its human homolog. Thus, the species of a bradykinin receptor can have a significant effect on its pharmacology. The cloning, expression, and pharmacological comparison of human and mouse B2 bradykinin receptor genes indicate that some of the previous reports of B2 receptor subtypes can be explained by species differences in a single B2 bradykinin receptor gene.

Amino Acid Sequence↗
PubMed1978

The learning of radiological anatomy by medical students.

Teaching radiographic anatomy to pre-clinical medical students is important as it relates anatomical studies to clinical medicine and the same time prepares them for the radiology they will encounter in their clinical years. A programme is described in which radiographic anatomy is comprehensively covered without proving too great a commitment to clinical radiologists. The programmes consist of exhibits of X-rays in the dissecting room, slide-lecture demonstrations and a permanent museum of radiological anatomy. This programme has worked well and there has been a very favourable student response.

Anatomy↗