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Biomedical subjects

A C Palmer

Publications and source records attributed to A C Palmer.

At least 19 recordsLinked to original sources
PubMed2007

Pontine infarction in a dog with unilateral involvement of the trigeminal motor nucleus and pyramidal tract.

An unusual case of unilateral trigeminal neuronopathy in a dog is reported, in which the motor nucleus of the trigeminal nerve and the ipsilateral corticospinal tract were destroyed, apparently by a cerebrovascular accident (stroke). Hemiplegia did not occur. Neuropathological changes are described, including remyelination by Schwann cells in the central nervous system. The case illustrates the importance of central nervous system post-mortem examination when establishing causes of cranial nerve paralysis.

Animals↗
PubMed2001

Multimerization of monocyte chemoattractant protein-1 is not required for glycosaminoglycan-dependent transendothelial chemotaxis.

Chemokines interact with specific G-protein-coupled cell-surface receptors and with glycosaminoglycans (GAGs), such as heparan sulphate. Although chemokines often form multimers in solution, this process may be enhanced following interaction with GAGs on the cell surface, or within the extracellular matrix. However, the significance of multimerization for chemokine function remains controversial. In the present study, a fusion protein was prepared between the prototypical human CC chemokine, monocyte chemoattractant protein-1 (MCP-1; also known as CCL-2) and a large secreted placental alkaline phosphatase (SEAP) moiety. This fusion protein (MCP-1-SEAP) remained monomeric under conditions that promote oligomerization of the native chemokine. Radioligand binding showed that both native MCP-1 and MCP-1-SEAP competed for the same site on the surface of HEK-293 cells expressing the CCR2b chemokine receptor. The interaction between either chemokine species and endothelial cell surface GAGs was antagonized by the addition of the heparan sulphate-like molecule, heparin. Both MCP-1 and MCP-1-SEAP induced a Ca(2+)-flux in the THP-1 monocytic cell line, and were equally effective at promoting transendothelial chemotaxis of mononuclear immune cells, with maximal migration being produced by treatment with 12 nM of either species. In each case this chemotactic response was almost completely antagonized by the addition of heparin. The importance of interaction between either native MCP-1 or MCP-1-SEAP and cell-surface GAGs for transcellular migration was demonstrated by the almost complete absence of leucocyte chemotaxis across monolayers of GAG-deficient mutant cells. In summary, this study shows that multimerization is neither necessary for, nor potentiates, the biological activity of MCP-1. However, the results do clearly demonstrate the importance of the interaction between MCP-1 and cell-surface heparan sulphate for transmonolayer leucocyte chemotaxis.

3T3 Cells↗
PubMed2001

Progressive encephalomyelopathy and cerebellar degeneration in 10 captive-bred cheetahs.

Progressive ataxia, with head tremor, developed in 10 captive-born cheetah cubs under six months of age. The condition was usually preceded by coryza and an ocular discharge. Initially the ataxia and weakness affected the hindquarters, then the forelegs, and head tremor developed later. Significant pathological changes were confined to the central nervous system. There was widespread Wallerian degeneration in the funiculi of the spinal cord (except those in the dorsal columns), in the medulla and in the cerebellum. In the cerebellum there was degeneration of Purkinje cells and of the molecular and granular cell layers. There was chromatolysis in the Purkinje cells, the ventral horn cells of the spinal cord and in the neurons of the lateral vestibular nucleus. The olivary nucleus was necrotic. There were foci of inflammatory cells in the molecular layer of the cerebellum and in the medulla. The cause of the disease remains unknown.

Acinonyx↗
PubMed2001

Histological diagnosis of mucopolysaccharidosis IIIA in a wire-haired dachshund.

A four-year-old wire-haired dachshund developed progressive neurological signs of ataxia, intention tremor and finally dysuria. Two years later, histopathology showed that neurons throughout the brain and spinal cord were distended with lipopigment which was also present in macrophages. Ultrastructurally, the pigment in the neurons occurred predominantly as electron-dense membranous whorls and stacks. There were a few vacuolated macrophages in the meninges. Hepatocytes were highly vacuolated and electron microscopy suggested that they were empty membrane-bound vesicles. The disease was diagnosed as mucopolysaccharidosis IIIA because of its similarity to other biochemically confirmed cases in the same breed and in a New Zealand huntaway dog. Additional lesions included calcium oxalate uroliths, severe secondary calcification of tissues including the brain and storage deposits in some neurons, and lesions which may have been associated with high levels of the substrate, heparan sulphate.

Animals↗
PubMed2000

Examination of the function of RANTES, MIP-1alpha, and MIP-1beta following interaction with heparin-like glycosaminoglycans.

Chemokines are a group of small proteins that have a variety of functions, including the activation and recruitment of immune cells during episodes of inflammation. In common with many cytokines, it has been observed that chemokines have the potential to bind heparin-like glycosaminoglycan molecules, which are normally expressed on proteoglycan components of the cell surface and extracellular matrix. The significance of this interaction for chemokine activity remains a subject of debate. In this study, Chinese hamster ovary cells were transfected separately with the human chemokine receptors CCR1 and CCR5, and these receptors were shown to induce an intracytoplasmic Ca(2+) flux and cellular chemotaxis following stimulation with the natural CC chemokine ligands (MIP-1alpha, RANTES (regulated on activation normal T cell expressed), and MIP-1beta). In further experiments, mutant CHO cells, with a defect in normal glycosaminoglycan (GAG) expression, were also transfected with, and shown to express similar levels of, CCR1 and CCR5. Although these receptors were functional, it was found that the mutant cells required exposure to higher concentrations of ligands than the wild-type cells in order to produce the same intracytoplasmic Ca(2+) flux. Radioligand binding experiments demonstrated that specific chemokine receptors expressed by wild-type cells had a significantly greater affinity for MIP-1alpha than similar receptors expressed by GAG-deficient mutants. However, there was no significant difference between these cells in their affinity for RANTES or MIP-1beta. In conclusion, it has been demonstrated clearly that GAG expression is not necessary for the biological activity of the chemokines MIP-1alpha, RANTES, or MIP-1beta. However, the presence of cell surface GAGs does enhance the activity of low concentrations of these chemokines by a mechanism that appears to involve sequestration onto the cell surface.

Animals↗
PubMed2000

Triage of patients for a rapid (5-minute) electrocardiogram: A rule based on presenting chief complaints.

STUDY OBJECTIVE: A rule based on presenting chief complaints can identify patients for a rapid (5-minute) ECG and decrease delays in treatment of patients with acute myocardial infarction (MI). METHODS: The presenting chief complaint was electronically collected on all patients treated in a community teaching hospital emergency department. A rule for ordering ECG on patient presentation to the ED was developed from a model set of patients presenting from July through December 1994 (22,717 patients) and then tested on a validation set of patients from January through May 1995 (18,759 patients). Outcome measures (delay in performance of ECG and delay in administration of thrombolytic agents) were prospectively collected on written data sheets before (April 1993-May 1995, n=67) and after (June 1995-March 1997, n=128) implementation of the rule at the study hospital. RESULTS: On the model set, 193 patients had the final diagnosis of MI, with 5 chief complaints having the best performance in identifying patients with acute MI and comprising the rapid ECG rule: older than 30 years with chest pain (130 [67.4%] patients); older than 50 years with syncope (5 [1%] patients); weakness (12 [6.2%] patients); rapid heart beat (2 [1%] patients); and difficulty breathing or shortness of breath (20 [10.4%] patients). On the validation set, 142 patients had the final diagnosis of MI, with the rule performing better than chest pain in identifying patients for a "stat" ECG (sensitivity 93.7% versus 67. 4% [95% confidence interval (CI) of the difference, 15.6% to 33.8%]), although a larger percentage of ED patients would receive a stat ECG (7.3% versus 6.3% [95% CI of the difference, 0.7% to 1.7%]). During the model and validation period, 44 (13.1%) of 335 patients with MI received thrombolytic agents. The rule had higher sensitivity on patients with MI treated with thrombolytic agents compared with patients with MI not treated with thrombolytic agents (sensitivity 100% versus 86.4% [95% CI of the difference, 1.7% to 20. 3%] and specificity of 90.4% versus 93.8% [95% CI of the difference, 3.0% to 3.8%]). For the 4-year study period, outcome improved after the implementation of the rule: mean delay in performing ECGs in patients with MI who were administered thrombolytic agents decreased from 10.0 to 6.3 minutes (95% CI of the difference, 1.1 to 6.4), and mean delay in administering thrombolytic agents decreased from 36.9 to 26.1 minutes (95% CI of the difference, 3.5 to 17.7). CONCLUSION: Use of a rule based on chief complaints can identify patients with MI for immediate ECG and decrease delays in performing ECGs and administration of thrombolytic agents.

Adult↗
PubMed1999

Modulation of recombinant human cardiac L-type Ca2+ channel alpha1C subunits by redox agents and hypoxia.

1. Whole-cell patch clamp recordings were used to investigate the modulation by reducing and oxidizing agents of recombinant human cardiac L-type Ca2+ channel alpha1C subunits stably expressed in human embryonic kidney (HEK 293) cells. 2. The oxidizing agents thimerosal (10 microM) and p-chloromercuribenzene sulphonic acid (PCMBS; 2 microM to 2 mM) caused irreversible inhibition of Ca2+ channel currents. The reducing agent 1,4-dithiothreitol (DTT; 2 mM) was without effect on Ca2+ channel currents, but reversed the inhibitory actions of thimerosal and PCMBS. 3. Ca2+ channel currents were also inhibited by pretreatment with the methanethiosulphonate compound (2-aminoethyl)methanethiosulphonate (MTSEA, 2.5 mM), but were unaffected by identical pretreatment with (2-sulphonatoethyl)methanethiosulphonate (MTSES, 10 mM). The effects of MTSEA could be fully reversed by DTT (2 mM). The degree of current inhibition caused by 200 microM PCMBS was not significantly affected by pretreatment with MTSEA, and following PCMBS treatment, MTSEA caused a similar degree of inhibition to that observed in cells that were not previously treated with PCMBS. These findings suggested that distinct thiol groups were modulated by these two agents. 4. Hypoxic inhibition of Ca2+ channel currents was unaffected by pretreatment of cells with MTSEA but was fully prevented by treatment with PCMBS. Our results indicate that distinct cysteine residues on the alpha1C subunit can undergo redox modulation and in so doing alter channel function. Some, but not all, of these residues appear to be associated with the mechanism underlying inhibition of this channel by hypoxia.

Calcium Channel Blockers↗
PubMed1998

Paralysis in hedgehogs (Erinaceus europaeus) associated with demyelination.

Paraplegia affected 14 hedgehogs (Erinaceus europaeus) in a wildlife rescue hospital over a period of six months. Postmortem examination revealed demyelination in the brain and spinal cord and an inflammatory response in the meninges, choroid plexus and CNS. The peripheral nervous system was not affected. In the spleen, lungs and liver there was an accumulation of megakaryocytes and other evidence of extramedullary haemopoiesis, but there was no haematological evidence of anaemia. The pattern of disease incidence and the nature of the changes in the CNS suggest they were of viral origin, but no causal agent was isolated and the possibility of a neurotoxin cause cannot be ruled out.

Animals↗
PubMed1998

Inhibition of recombinant human cardiac L-type Ca2+ channel alpha1C subunits by 3-isobutyl-1-methylxanthine.

Inhibition of ion channels by the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) and related compounds has been demonstrated in various cell types, including the neuromuscular junction, GH3 cells and vascular smooth muscle cells. These effects may be unrelated to the actions of these compounds on cellular metabolism, intracellular Ca2+ stores and phosphodiesterase inhibition. In this study, the inhibition of recombinant human cardiac L-type Ca2+ channel alpha1C subunits by IBMX was examined using the whole-cell configuration of the patch clamp technique. Inhibition was repeatable, voltage-independent and associated with increased apparent channel inactivation. The actions of IBMX were unaffected in the presence of inhibitors of protein kinases A and G. The non-xanthine phosphodiesterase inhibitor rolipram had a small inhibitory effect on currents, but this was also unaffected by a protein kinase A inhibitor. These effects of IBMX could not be attributed to release of Ca2+ from intracellular stores. Our findings indicate that methylxanthines can inhibit the cardiac L-type Ca2+ channel alpha1C subunit in the absence of auxiliary subunits by an undetermined, possibly direct mechanism.

1-Methyl-3-isobutylxanthine↗
PubMed1997

Hypoxia inhibits the recombinant alpha 1C subunit of the human cardiac L-type Ca2+ channel.

1. Whole-cell patch clamp recordings were used to investigate the effects of hypoxia on recombinant human L-type Ca2+ channel alpha 1C subunits stably expressed in human embryonic kidney (HEK 293) cells. 2. Ca2+ channel currents were reversibly inhibited by hypoxia (PO2 < 90 mmHg). The degree of inhibition depended on the charge carrier used, Ca2+ currents being more O2 sensitive than Ba2+ currents. 3. Hypoxic inhibition of Ca2+ channel currents was more pronounced at lower activating membrane potentials (< or = +30 mV), and was associated with a slowing of activation kinetics. Current inactivation and deactivation were unaffected by hypoxia. 4. Since hypoxia similarly regulates native L-type Ca2+ channels in vascular smooth muscle cells, our results suggest that hypoxic regulation of L-type Ca2+ channels arises from modification of structural features of the alpha 1 subunit common to cardiac and smooth muscle L-type channels.

Animals↗
PubMed1997

Regulation of [Ca++]i in human neuroblastoma (SH-SY5Y) cells expressing recombinant rat angiotensin1A receptors by angiotensin II and carbachol.

The ability of angiotensin II (AII) to regulate [Ca++]i in human neuroblastoma (SH-SY5Y) cells stably expressing recombinant rat AT1A receptors was investigated using microfluorimetric methods, and compared to responses obtained by stimulation of native muscarinic receptors. Applications of AII or carbachol produced biphasic rises of [Ca++]i, but in Ca++-free solutions (containing 1 mM ethylene glycol-bis (beta-aminoethyl ether)N,N,N,'N'-tetraacetic acid), both agonists produced only transient monophasic rises of [Ca++]i, and second applications were without effect. Application of Ca++(o) (2.5 mM) to cells after exposure to either agonist produced a Ni2+-sensitive rise of [Ca++]i in the absence of agonist ("capacitative Ca++ influx"). After removal of Ca++(o), both AII and carbachol elicited a second rise of [Ca++]i. Thapsigargin (1 microM) prevented these second rises of [Ca++]i. During capacitative Ca++ influx, application of AII failed to produce a further rise of [Ca++]i. In contrast, carbachol produced a further rise of [Ca++]i, attributable to activation of both nicotinic and muscarinic receptors, because it was reduced (but not abolished) by mecamylamine (1 microM) and was observed when muscarine was used as the agonist. Thus, activation of recombinant AT1A and muscarinic receptors in SH-SY5Y cells leads to mobilization of Ca++ from a common intracellular pool, and stimulates capacitative Ca++ influx. Muscarinic (but not AII) receptor occupancy is capable of stimulating an additional Ca++ influx pathway.

Angiotensin II↗
PubMed1997

Nature and incidence of bubbles in the spinal cord of decompressed goats.

The nature of so-called autochthonous bubbles was investigated. Their presence in compressed/decompressed goats was compared with that in animals killed before decompression and in controls. Ten goats (group 1) were subjected to compression/decompression in air. Clinical signs of spinal decompression sickness usually occurred. Within 35 min of surfacing, the animals were given a lethal dose of thiopentone sodium, i.v.. Spinal cords were fixed by immersion in 10% formol saline. Histologically autochthonous bubbles appeared to arise from rupture of over-distended blood vessels. The incidence of grossly dilated empty vessels (GDEV) was recorded. Seven goats (group 2) were similarly compressed but killed before decompression. In five animals of group 1 there was a greater number of GDEV than in controls (group 3, seven animals) but in the other five animals the incidence was similar to the controls. The incidence of GDEV in group 2 was greater than in the controls (P < 0.05). The percentage of sections of spinal cord in which the meninges also contained GDEV was assessed. In all except two animals in group 1, the percentage was higher than in the controls, whereas in group 2 the percentage was higher than in the controls. The experiments show that autochthonous bubbles arise as an artifact and that intravascular bubbles arise in situ.

Animals↗
PubMed1995

The effect of the angiotensin II (AT1A) receptor stably transfected into human neuroblastoma SH-SY5Y cells on noradrenaline release and changes in intracellular calcium.

A stable cell line expressing the angiotensin II (AII) receptor has been obtained by transfecting the human neuroblastoma SH-SY5Y with the plasmid pCEP4 containing the entire coding region of the rat angiotensin AII receptor AT1A. Angiotensin II (AII; 1-100 nM) evokes the release of [3H]noradrenaline ([3H]NA) in this cell line. Pretreatment with 100 nM 12-O-tetradecanoylphorbol-13-acetate (TPA) enhances the AII-evoked release of [3H]NA approximately two-fold. Removal of extracellular Ca2+ ([Ca2+]o) decreases 100 nM AII-evoked release of [3H]NA by over 50% both in the presence and absence of TPA. AII increases intracellular Ca2+ ([Ca2+]i) in this cell line which is consistent with the AT1A receptor being coupled to phospholipase C. Pretreatment with 100 nM TPA for 8 min attenuated the effect of AII on [Ca2+]i. The effects of AT1A receptor stimulation are therefore regulated differently in this cell line by activation of protein kinase C (PKC). Thus a useful cell line has been obtained from the human neuroblastoma SH-SY5Y in which to study at the molecular level the mechanism(s) by which AII regulates NA release.

Angiotensin II↗
PubMed1995

Encephalomyelopathy in young cats.

Nineteen cats, aged three to 16 months, developed neurological signs including hindleg paralysis, head shaking, nystagmus, defective vision and reduced proprioception. Most of the animals were in cat colonies in research centres and were derived from specific pathogen-free stock. One was referred from veterinary practice. Over 40 per cent of litters could be affected constituting a serious commercial loss. Wallerian degeneration affected long tracts in the spinal cord and variously in the brain stem and cerebral white matter. In seven animals there was loss of Purkinje cells in the cerebellum and in eight there was neuronal loss in the spinal cord. Gliosis accompanied all changes. Although no viral agent was isolated the clinical pattern of the disease and evidence from other cases reported in the literature suggest an infectious cause.

Animals↗
PubMed1994

Generalised ceroid-lipofuscinosis and brown bowel syndrome in Cocker spaniel dogs.

The ceroid-lipofuscinoses comprise a group of inherited storage diseases of human beings and animals that are characterised by progressive neurodegenerative disease and the accumulation within cells of a fluorescent lipopigment. A distinct syndrome occurs in Cocker spaniel dogs in which there is a generalised accumulation of a lipofuscin-like pigment, with such a heavy accumulation in smooth muscle that the intestine and other organs have a brown discolouration. Such discolouration is not observed in other forms of ceroid-lipofuscinosis. Dogs are clinically affected in adulthood and show progressive hind limb paresis, incoordination, and deficient postural reactions and proprioception. Spinal reflexes may be exaggerated. Behavioural or temperament changes, seizures or blindness may occur.

Journal Article↗
PubMed1992

Cerebral vasculopathy in divers.

Brains from 12 amateur and 13 professional divers, all but one of whom died accidentally, were examined neuropathologically. Grossly distended, empty vessels (presumably caused by gas bubbles) were found in the brains of 15 out of 22 divers who died from diving accidents. Perivascular lacuna formation was found in cerebral and/or cerebellar white matter in three amateurs and in five professionals. In addition to lacuna formation, hyalinization of vessel walls was present in the brains of three amateurs and five professionals. Necrotic foci in grey matter occurred in seven cases and perivascular vacuolation of white matter occurred in seven cases. The vascular changes probably arose from intravascular gas bubble formation. In one professional diver, there was also unilateral necrosis of the head of the caudate nucleus.

Adult↗