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Biomedical subjects

J A Kiernan

Publications and source records attributed to J A Kiernan.

At least 19 recordsLinked to original sources
PubMed1992

Primary lateral sclerosis. Clinical features, neuropathology and diagnostic criteria.

Eight patients with a homogeneous syndrome of progressive symmetric spinobulbar spasticity were studied. Clinical features were limited to those associated with dysfunction of the descending motor tracts and included spastic quadriparesis, pseudobulbar affect, spastic dysarthria, hyper-reflexia and bilateral Babinski signs. Lower motor neuron findings were absent and higher cognitive function preserved. Median age of onset was 50.5 yrs and median disease duration was 19 yrs. Neuropathologic features (including morphometric analysis) in the single autopsied case confirmed the selective involvement of the motor cortex. There was complete absence of Betz cells from layer 5 of the precentral cortex and the remaining pyramidal cells were significantly smaller than those seen in normal controls. Magnetic resonance imaging (MRI) revealed atrophy of the precentral gyrus and positron emission tomography (PET) scans showed diminished glucose [18F]fluorodeoxyglucose uptake in the pericentral cortex. Magnetic motor cortex stimulation revealed markedly prolonged central motor conduction times. The literature is reviewed and diagnostic criteria for primary lateral sclerosis based on clinical, laboratory and imaging features are proposed.

Aged↗
PubMed1991

Changes in sizes of cortical and lower motor neurons in amyotrophic lateral sclerosis.

It has been suggested that the degeneration of lower motor neurons in amyotrophic lateral sclerosis (ALS) is a transneuronal event, secondary to the loss of corticospinal and corticobulbar neurons. In an attempt to test this hypothesis, the cross-sectional areas of pyramidal cells in layer 5 of the foot and tongue areas of the precentral gyri were measured in 12 cases of the classical sporadic form of ALS, and in 10 control subjects. The areas of motor neurons in the hypoglossal nuclei and in the ventral horns of segment L4 of the spinal cord were also measured. The number of neurons per 20 microns section of ventral horn or hypoglossal nucleus provided a more reliable index of severity of lower motor neuron loss at the time of death than did a semiquantitative score derived from clinical observations. Cortical neurons and lower motor neurons were significantly smaller in the cases of ALS than in the controls. In the cortex this change included, but was not confined to, the largest neurons. These observations indicate that shrinkage precedes neuronal death. There was no correlation, positive or negative, between the numbers of surviving lower motor neurons and the mean sizes of pyramidal cells in layer 5 of the corresponding areas of the precentral gyri. The absence of such a correlation indicates that functionally related cortical and lower motor neurons probably degenerate independently, and not from a transsynaptic effect. Neuronal shrinkage has been observed in other diseases in which interconnected systems of neurons degenerate. The possible association of shrinkage with cytoskeletal degradation is discussed.

Adult↗
PubMed1991

Relationship between myeloperoxidase activity and the ontogenic response of rat gastric mucosa to ethanol.

We have examined the gastric luminal content of Na+, K+, and protein and mucosal levels of myeloperoxidase in rats between the ages of 10 and 60 days in response to luminal instillation of ethanol (20 and 50% w/v). In control animals the appearances of ions and protein and myeloperoxidase activities were low and similar in all age groups. Luminal content of cations and protein increased in response to both 20 and 50% ethanol and were greater in animals older than 20 days when compared with younger rats. However, ethanol treatment resulted in a significant degree of mucosal cellular disruption and erosions in both young and mature rats. Myeloperoxidase activities in response to ethanol were not greater than control until animals were older than 20 days. Treatment of rats aged 10-60 days with intraperitoneal glycogen (1%) resulted in peritoneal granulocyte infiltration. The concentration of peritoneal cells increased as animals aged. With the exception of day 15, the myeloperoxidase content of the peritoneal leukocytes did not vary significantly at other ages examined. These data suggest that (1) mucosal efflux of Na+, K+, and protein in response to luminal ethanol increase as rats age from 10 to 60 days; (2) the ontogenic development of ethanol-induced cation and protein appearance parallel the increase in myeloperoxidase activity in the gastric mucosa; and (3) the increase in mucosal myeloperoxidase activity in response to ethanol likely reflects increased granulocyte infiltration as rats age.

Age Factors↗
PubMed1990

A circulating exogenous protein can enter enteric nervous tissue in the rat.

Previous studies of the permeation of circulating protein tracers yielded conflicting results in the enteric nervous system. We show that within 5 min of intravenous injection, horseradish peroxidase (HRP) enters all the extracellular spaces of the ganglia and connecting strands of the submucous and myenteric plexuses of the rat's small intestine, including the clefts between neuroglial cells and neurons. The tracer is still there after 10 min, but is nearly all gone 30 min after injection. Enteric neurons, like others with somata in peripheral ganglia, are therefore probably accessible to plasma proteins and to substances with smaller molecules that are protein-bound when circulating in the blood.

Animals↗
PubMed1990

Resistance of myenteric neurons in the rat's colon to depletion by 1,8-dihydroxyanthraquinone.

Earlier reports have suggested that anthraquinone purgatives in excessive amounts cause degeneration of neurons in the enteric nervous system. Danthron (1,8-dihydroxyanthraquinone) was administered to rats in their drinking water for four months. The effects of the drug on the total number of neurons and on the immunoreactivity of eight putative neurotransmitters in the myenteric plexus of the colon have been assessed. No differences were found between the treated animals and their controls, indicating that the drug does not kill myenteric neurons. These results agree with recent observations on the effects of senna in rats and mice, and do not support earlier claims that myenteric neurons are killed by anthraquinone purgatives.

Animals↗
PubMed1990

Degranulation of mast cells in the trachea and bronchi of the rat following stimulation of the vagus nerve.

In the trachea and bronchi of the atropinized rat, the proportion of degranulating mast cells (defined as having one or more granules outside the body of the cell in a 10-microns thick section) was increased from 35-40% to 48-55% following electrical stimulation of one or both vagus nerves for 3 min. The increase occurred bilaterally, though it was greater on the stimulated side. The degranulation of mast cells was prevented by transection of the nerve rostral to the nodose ganglion 8-10 days before stimulation. Pre-treatment of rats with capsaicin also prevented the degranulation of mast cells that otherwise would have followed stimulation of the vagus nerve. These observations indicate that tracheo-bronchial mast cells discharge their granules in response to the activity of capsaicin-sensitive axons of neurons whose cell bodies are rostral to the nodose ganglion. These are probably substance P-containing polymodal nociceptive neurons of the jugular ganglion. If similar neurons exist in man, axon reflexes in their intrabronchial branches would be expected to stimulate the release of mast cell-derived agents that cause bronchoconstriction in asthma.

Animals↗
PubMed1990

An immunohistochemical study of the myenteric plexus of the colon in the rat and mouse.

Immunohistochemical methods were used to determine the localisation of immunoreactivities to a variety of antigens involved in neurotransmission in the myenteric plexus of the colon in the rat and mouse. The findings in the two species were closely similar. Five neuronal types have been identified. (i) The axons of extrinsic noradrenergic sympathetic neurons, immunoreactive for tyrosine hydroxylase, supply the ganglia and the circular muscle. (ii) Bombesin immunoreactive intrinsic neurons with unbeaded axons are largely confined to the ganglia and tracts of the plexus. These neurons probably contain gastrin-releasing peptide, which is the mammalian analogue of bombesin. (iii) Somatostatin immunoreactive intrinsic neurons have long, beaded axons within the myenteric plexus and also outside the plexus, between the longitudinal and circular muscle layers. (iv) Intrinsic neurons containing opioid peptides (beta-endorphin, met-enkephalin, leu-enkephalin), have beaded axons that cannot be traced for long distances. They contact all the cell bodies in the ganglia and extend also into the interganglionic tracts and the smooth muscle. (v) Substance P immunoreactive somata and axons are present throughout the myenteric plexus and provide dense innervation to the smooth muscle. Extrinsic substance P immunoreactive sensory axons are probably also present.

Animals↗
PubMed1989

Sennosides do not kill myenteric neurons in the colon of the rat or mouse.

Effects of senna on the myenteric plexus of the colon were investigated in view of earlier reports that this anthraquinone cathartic depletes the plexus of its intrinsic neurons. Rats and mice were given purgative doses of sennosides in their drinking water for 4 and 5 months, respectively. Body growth was reduced, and the weight of the colon with its contents was increased relative to the weight of the whole body in the treated animals. The latter change was attributed to depressed propulsive motility of the large intestine. Total numbers of myenteric neurons were determined from whole-mount preparations stained with Cuprolinic Blue-magnesium chloride, which selectively coloured the neuronal somata. The number of neurons in the rat's colon was unaffected by treatment with senna, but the colons of the treated mice contained significantly more neurons than those of their controls. Staining with antisera to 10 putative neurotransmitters or their associated enzymes revealed immunoreactive somata and axons in the myenteric plexus. Treatment with senna was not associated with absence of neuronal somata or fibres stainable with any of the antisera in either species. Thus, there was no evidence of toxic destruction of any identifiable population of neurons that might have been too small to affect the total counts. We conclude that senna does not kill myenteric neurons in the colon of the rat or mouse.

Administration, Oral↗
PubMed1989

The effect of sialoadenectomy on gastric mucosal integrity in the rat: roles of epidermal growth factor and prostaglandin E2.

Removal of the salivary glands (SALX) in rats has been shown to increase the susceptibility of gastric mucosa to ulcerogens. In the present study, we have investigated the role of specific salivary glands in this response. In addition, we have examined whether a functional link exists between the salivary glands, epidermal growth factor (EGF), and prostaglandin E2 (PGE2) by determining whether SALX decreases the responsiveness of the mucosa to the protective actions of either of both of these agents. Removal of the parotid salivary glands did not significantly increase ulceration in response to intragastric administration of 100% w/v ethanol. Animals were examined 60 min after ethanol administration. Removal of the submandibular-sublingual gland complexes was associated with a significant increase in the area of mucosal damage and a decrease in gastric pit depth in ethanol-treated animals when compared with sham-operated control rats. Furthermore, in both SALX and control animals, exogenous PGE2 and EGF resulted in a dose-dependent reduction in both groups of animals, although the protective effects of PGE2 and EGF were attenuated in SALX rats. PGE2 and EGF administered in combination resulted in the same degree of protection in both SALX and control rats. Sialoadenectomy resulted in a reduction in mucosal PGE2 synthesis. EGF administration did not consistently increase mucosal PGE2 synthesis. Conversely, sialoadenectomy did not reduce mucosal levels of EGF nor did exogenous PGE2 consistently increase salivary or mucosal content of EGF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Intestinal anastomosis in the rat facilitated by a rapidly digested internal splint and indigestible but absorbable sutures.

A stenosis is produced when a rat's transected small intestine is repaired with a conventional inverting line of silk or catgut sutures. In the new technique, the cut surfaces are apposed over a splint made of dry macaroni of suitable diameter, and then joined end-to-end with polyglactin stitches. The internal splint is quickly softened and digested. The suture material is absorbed without concomitant inflammation, and does not interfere with the cutting of sections for histology. Examination revealed, in every case, a fully patent anastomosis with alignment of the layers of the intestinal wall. This is preferable to an inverting anastomosis for investigations of intestinal wound healing and for physiological studies of the propagation of movements along the gut.

Absorption↗
PubMed1988

Binding and biological actions of prostaglandin E2 and I2 in cells isolated from rabbit gastric mucosa.

1. We have investigated the binding of the tritiated forms of prostaglandin E2 (PGE2) and a stable analogue of prostacyclin (Iloprost) to isolated cells of rabbit oxyntic mucosa. 2. The highest degree of specific [3H]PGE2 binding occurred in a cellular fraction enriched in parietal cells. [3H]Iloprost binding occurred predominantly in cells identified as mucous cells. 3. PGE2 binding to the parietal cell fraction was associated with its ability to inhibit histamine-stimulated aminopyrine accumulation by these cells. Iloprost binding did not correlate with a biological action on the parietal cells. 4. PGE2 and Iloprost reduced Trypan Blue staining in cells exposed to 10% (w/v) ethanol. Iloprost (10(-8) to 10(-6) M) reduced Trypan Blue staining in cells identified as mucous and parietal cells. PGE2 (10(-8) M) significantly reduced Trypan Blue staining in parietal cell-enriched fractions. 5. Cyclic AMP stimulation in response to either prostanoid occurred most potently on non-parietal cell fractions. However PGE2 or Iloprost binding affinities did not correlate with cyclic AMP formation. 6. These data provide evidence for true PGE2 receptors on oxyntic mucosal cells. The receptors appear to mediate inhibition of acid secretion. Iloprost binds to sites which might mediate cellular protection.

Aminopyrine↗
PubMed1987

Specific, selective, and complete staining of neurons of the myenteric plexus, using cuprolinic blue.

Wholemounts consisting of both muscular layers of the rat's intestine have been stained with Cuprolinic blue and magnesium chloride. The procedure, which is specific for RNA, gives selective coloration of the somata of the neurons of the myenteric plexus. The neuronal nucleoli and Nissl substance are the only blue structures in such preparations. For descriptive and quantitative work, Cuprolinic blue is more selective than other cationic dyes, and it colors more neurons than can be shown by staining for mitochondrial NADH diaphorase. The absence of background color enables neurons to be identified more confidently and counted more quickly than is possible with other techniques, in which nuclei or mitochondria in smooth muscle and neuroglial cells are also stained. Numbers of myenteric neurons determined using the new method are higher than those obtained by other means.

Animals↗
PubMed1986

Reinnervation of skeletal muscle in the tongue by preganglionic parasympathetic vagal neurons.

Reinnervation of the skeletal muscle in the tongue following vago-hypoglossal anastomosis was studied by means of retrograde labelling with horseradish peroxidase and anterograde labelling with the autoradiographic tracing method combined with acetylcholinesterase staining for motor endplates. The proximal stump of the transected vagus nerve was anastomosed to the distal stump of the transected hypoglossal nerve in the neck, or in the thorax below the emergence of the recurrent laryngeal fibres. After 2-3 months, reinnervation of the tongue by vagal fibres was studied. Control cases in which the hypoglossal nerve was transected, but anastomosis was not performed, revealed that innervation of the lingual muscle is derived entirely from the hypoglossal nerves. Following unilateral vago-hypoglossal anastomosis a reduced number of fine nerve fibres terminated in relation to the acetylcholinesterase-stained endplates on the side of the anastomosis. At no time were fibres on either side observed to form sprouts which crossed the midline. Horseradish peroxidase (HRP) was injected into the tongue to determine the origin of the fibres that reinnervated the lingual muscle following anastomosis. On the side of the anastomosis, HRP-labelled neurons were present within the dorsal motor nucleus of the vagus and were absent from the hypoglossal nucleus. When the anastomosis was performed in the neck, neurons within the nucleus ambiguous were also labelled with HRP, but this was not observed following anastomosis in the thorax below the recurrent laryngeal nerve. When tritiated amino acids were injected into the dorsal motor nucleus of the vagus, the motor endplates on the anastomosed side of the tongue were labelled autoradiographically. This labelling could not be abolished by transecting both hypoglossal nerves, confirming that the labelling was due to reinnervation by vagal fibres. It is concluded that anastomosis of the proximal end of the transected vagus nerve to the distal end of the transected hypoglossal nerve is followed by regeneration of the vagal fibres which cross the anastomosis and reinnervate the denervated motor endplates in the tongue. The cell bodies of origin are located within the dorsal motor nucleus of the vagus and are preganglionic parasympathetic neurons.

Anastomosis, Surgical↗
PubMed1985

The action of chromium(III) in fixation of animal tissues.

Chromic salts have been studied as fixatives of mammalian tissues for light microscopy, and the binding of the metal has been examined histochemically. Tissues bind chromium(III) from aqueous solutions less acid than pH 2.5; the metal attaches mainly to collagen and basement membranes. Solutions containing chromium(III) as the only active ingredient cannot be used as fixatives because they destroy cytoplasm and cause great structural distortion. When mixed with other fixative agents, however, chromic salts can bring about considerable improvement in structural preservation. In aqueous mixtures more acid than pH 2, and in aqueous-methanolic solutions in the pH range 4.0-5.3, a chromic salt provides only a nonspecific osmotic effect: little or no metal is bound to the tissue, and an aluminium or a sodium salt can be effectively substituted. In less acid (pH 2.3-3.2) aqueous mixtures, the beneficial action of chromium(III) cannot be imitated by aluminium or sodium ions. Chromium(III) forms coordinate bonds that cross-link ionized carboxyl groups of macromolecules. The reaction occurs so slowly that such cross-links can internally strengthen a tissue only after the structure has been stabilized by rapidly acting fixative agents. Thus, a valuable future use of chromic salts may be in a post-fixation treatment to protect specimens against the adverse effects of embedding in paraffin wax. Chromium(III) might also be useful for enhancing the opacity of collagen fibrils in electron microscopy.

Aluminum↗
PubMed1985

Partial purification from mammalian peripheral nerve of a trophic factor that ameliorates atrophy of denervated muscle.

Atrophy in a denervated muscle results from the disuse caused by paralysis of the muscle, and from the loss of special nerve-derived trophic substances. Crude preparations of protein from rat or sheep sciatic nerves have been shown to prevent the nondisuse atrophy of the rat's extensor digitorum longus muscle when injected into the denervated muscle daily for 1 week. Aqueous extracts of sheep sciatic nerves were fractionated by gel-liquid chromatography. After each step of purification, the trophic activities of the various fractions were assayed in the rat. Cross-sectional areas of type IIB muscle fibers in the denervated extensor digitorum longus were measured to determine which injected fraction contained the active principle. Affinity chromatography on concanavalin A-agarose revealed that the trophic substance was a glycoprotein. Further fractionation by gel filtration indicated that the active substance had a molecular weight in the range of 90,000 to 130,000. Ion-exchange chromatography on DEAE-cellulose yielded an active fraction containing substances with isoelectric points between 7.0 and 7.2, determined by polyacrylamide gel isoelectric focusing. This active fraction was resolved into 15 bands on sodium dodecyl sulfate-gel electrophoresis. Two bands had apparent molecular weights of 91,300 and 127,400. The active factor was shown thus to be a glycoprotein, molecular weight approximately 100,000, isoelectric point approximately 7.0. It may be one of two protein bands that are similar to it in molecular weight.

Animals↗
PubMed1985

Axonal and vascular changes following injury to the rat's optic nerve.

The optic nerve of the rat has been examined by light and electron microscopy, and also for vascular permeability to fluorescently labelled albumin, 2 days to 34 weeks after crushing in the orbit. The operation was usually followed by loss of 20-70% of the retinal ganglion cells. Axons could be followed from the retina into the optic nerve at all postoperative times, but they always ended anterior to the lesion. Evidence of feeble regenerative growth of optic axons was seen in the first few postoperative weeks: bifurcating fibres and fibres that turned back towards the eye were present within the optic nerve anterior to the lesion. At the site of crushing, the optic nerve eventually became a thin cord of astroglia, surrounded and partly infiltrated by collagenous connective tissue. Long argyrophilic fibres were conspicuous in the intracranial part of the crushed optic nerve from the seventh to the fourteenth postoperative week. These were shown by electron microscopy to be degenerating myelinated axons that had not been phagocytosed. It was conceivable that axons from the contralateral retina could have sprouted at the chiasma and grown into the degenerated optic nerve. This possibility was excluded by tracing anterograde axonal transport of horseradish peroxidase injected into the contralateral eye. Intravenously injected fluorescent protein entered the connective tissue of the orbit and the connective tissue trabeculae of the optic nerve, but it did not permeate into the central nervous tissue except at the lamina cribrosa, where the optic axons pierce the sclera. Permeability at this site was the same on the operated and unoperated sides. Abnormal permeability of the vasculature was seen at the site of crushing the optic nerve. Fluorescence there was strongest in the first two postoperative weeks and was not seen after the third week. A much less conspicuous defect of barrier function occurred in the intracranial portion of the crushed optic nerve, from the seventh to the fourteenth postoperative week. The responses of the optic nerve of the rat to axotomy contrast markedly with those of the goldfish, in which the blood vessels become permeable to protein throughout the optic pathway and the axons regenerate successfully. Various attempts were made to increase or prolong the opening of the blood-optic nerve barrier in the rat, in the hope of enhancing axonal regeneration, but these endeavours were all unsuccessful.

Animals↗
PubMed1984

Effect of nerve extract on number of acetylcholine receptors in denervated muscles of rats.

We have shown elsewhere that injection of an extract of peripheral nerves reduces the atrophy of denervated muscle fibers in vivo. Denervated muscle fibers exhibit supersensitivity to acetylcholine owing to the production of extrajunctional acetylcholine receptors. We sought to determine whether or not injection of nerve extract can influence the numbers of acetylcholine receptors in normal, immobilized, or denervated extensor digitorum longus muscles of rats. The receptors were assayed by measuring the binding of 125I-alpha-bungarotoxin. Normally innervated muscles injected with nerve extract exhibited slightly increased binding of the toxin, but this was due to the injections per se. Immobilization caused a small, transient increase in binding of alpha-bungarotoxin, whereas denervated muscles bound considerably more toxin than innervated controls. The nerve extract did not reduce or prevent the increase in acetylcholine receptors caused by denervation but instead caused an even greater increase. We concluded that the neurotrophic factor extracted from peripheral nerve that is responsible for the maintenance of the sizes of the fibers probably does not down-regulate extrajunctional acetylcholine receptors. The limitation of acetylcholine receptors to the end-plate regions is probably effected by a different mechanism which has yet to be elucidated.

Acetylcholine↗