Biomedical subjects

M Hay

Publications and source records attributed to M Hay.

At least 55 records · Page 3Linked to original sources

PubMed1994

Calcium-activated potassium channels in rat visceral sensory afferents.

The purpose of the present study was to describe, at the single-channel level, the activity of a calcium-sensitive potassium channel in rat visceral-sensory neurons which has been suggested to be involved in sensory neuron excitability. Single-channel recordings in the inside-out configuration identified a 220 pS conductance calcium-activated potassium channel (KCa). From a -20 mV holding potential, increasing [Ca2+]i from 0.01 microM to 1.0 microM increased the open probability of this channel 92% (from 0.12 to 0.23). However, from a +20 mV holding potential, increasing [Ca2+]i from 0.01 to 1.0 microM increased the open probability by 326% (from 0.15 to 0.64). In addition, this large conductance KCa channel was blocked by TEA (1.0 microM) and charybdotoxin (40 microM) when applied to the external surface. These results are the first to characterize a large conductance KCa channel in the sensory afferent neurons of the rat nodose ganglia and should further expand the understanding of the ionic currents involved in the regulation of sensory afferent neuronal activity.

Animals↗

PubMed1994

An intermediate conductance calcium-activated potassium channel in rat visceral sensory afferent neurons.

Whole-cell and single channel recordings were used to characterize an intermediate conductance calcium-activated potassium (KCa) channel in sensory neurons of the nodose ganglion. From a -80 mV holding potential, the total outward current in these neurons was increased when extracellular calcium was raised from 0.02 to 5 mM. This calcium-evoked outward current was not blocked by either charybdotoxin (50 nM) or apamine (40 nM). In the inside-out patch configuration, the current-voltage relationship for this channel was linear between -60 and +60 mV in symmetrical 145 mM potassium aspartate (KAsp) and possessed a conductance of approximately 60 picosiemens (pS). Increasing [Ca2+]i from 0.01 microM to 1.0 microM markedly increased the cumulative open probability of this channel and the effect of increasing [Ca2+]i on these channels was not voltage dependent. In the outside-out patch configuration, neither tetraethylammonioum (TEA), (1 mM), apamine (40 nM) or charybdotoxin (ChTx) (50 nM) had any effect on the activity of this channel. These results provide new evidence for the existence of pharmacologically distinct intermediate conductance KCa channel in sensory afferent neurons.

Animals↗

PubMed1994

Molecular maturation of cell adhesion systems during mouse early development.

During cleavage, the mouse embryo expresses a variety of cell adhesion systems on its cell surfaces. We have reviewed biogenetic and assembly criteria for the formation of the uvomorulin/catenin, tight junction and desmosome adhesion systems as the trophectoderm differentiates. Each system reveals different mechanisms regulating molecular maturation. Adhesion processes contribute to the generation of distinct tissues in the blastocyst by modifying the expression pattern of blastomeres entering the non-epithelial inner cell mass lineage. Cell adhesion also influences the spatial organisation, but rarely the timing of expression, of proteins involved in trophectoderm differentiation.

Animals↗

PubMed1994

The effects of exercise on the oral consumption of morphine and methadone in rats.

Endogenous opioid peptides have been hypothesised to play a regulatory role in exogenous opiate agonist dependence. It was hypothesised that exercised rats would demonstrate increased beta-endorphin (beta EP) levels and decreased exogenous opiate intake. After providing morphine or methadone as their sole liquid, drug preference levels were determined by amounts of exogenous opiate consumed when rats were offered a choice between drugged and nondrugged solutions. Treatment animals were exercised in a treadmill and were found to consume significantly less exogenous opiate than control animals. Plasma, pituitary, and whole brain beta EP levels were nonsignificantly higher in exercised animals. Differences were observed in the drug ingestion patterns of morphine- and methadone-exposed rats.

Administration, Oral↗

PubMed1994

A- and C-type rat nodose sensory neurons: model interpretations of dynamic discharge characteristics.

1. Neurons of the nodose ganglia provide the sole connection between many types of visceral sensory inputs and the central nervous system. Electrophysiological studies of isolated nodose neurons provide a practical means of measuring individual cell membrane currents and assessing their putative contributions to the overall response properties of the neuron and its terminations. Here, we present a comprehensive mathematical model of an isolated nodose sensory neuron that is based upon numerical fits to quantitative voltage- and current-clamp data recorded in our laboratory. Model development was accomplished using an iterative process of electrophysiological recordings, nonlinear parameter estimation, and computer simulation. This work is part of an integrative effort aimed at identifying and characterizing the fundamental ionic mechanisms participating in the afferent neuronal limb of the baroreceptor reflex. 2. The neuronal model consists of two parts: a Hodgkin-Huxley-type membrane model coupled to a lumped fluid compartment model that describes Ca2+ ion concentration dynamics within the intracellular and external perineuronal media. Calcium buffering via a calmodulin-type buffer is provided within the intracellular compartment. 3. The complete model accurately reproduces whole-cell voltage-clamp recordings of the major ion channel currents observed in enzymatically dispersed nodose sensory neurons. Specifically, two Na+ currents exhibiting fast (INaf) and slow tetrodotoxin (TTX)-insensitive (INas) kinetics; low- and high-threshold Ca2+ currents exhibiting transient (ICa,t) and long-lasting (ICa,n) dynamics, respectively; and outward K+ currents consisting of a delayed-rectifier current (IK), a transient outward current (I(t)) and a Ca(2+)-activated K+ current (IK,Ca). 4. Whole-cell current-clamp recordings of somatic action-potential dynamics were performed on enzymatically dispersed nodose neurons using the perforated patch-clamp technique. Stimulus protocols consisted of both short (< or = 2.0 ms) and long (> or = 200 ms) duration current pulses over a wide range of membrane holding potentials. These studies clearly revealed two populations of nodose neurons, often termed A- and C-type cells, which exhibit markedly different action-potential signatures and stimulus response properties. 5. Using a single set of equations, the model accurately reproduces the electrical behavior of both A- and C-type nodose neurons in response to a wide variety of stimulus conditions and membrane holding potentials. The structure of the model, as well as the majority of its parameters are the same for both A- and C-type implementations.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1994

Glutamate metabotropic receptor inhibition of voltage-gated calcium currents in visceral sensory neurons.

1. Metabotropic glutamate receptors (mGluRs) have been suggested to modulate neurotransmission of glutamatergic pathways via autoreceptive action. Visceral sensory afferents and baroreceptor afferents in particular are thought to utilize L-glutamate (L-glu) as a primary neurotransmitter. The purpose of this study was to investigate whether visceral sensory afferents possess a mGluR and determine the effect of mGluR activation on voltage-gated calcium currents in these neurons. 2. Activation of mGluRs by the selective agonist trans-(+/-)-1-amino-1,3-cyclopentanedicarboxylic acid (t-ACPD) reversibly suppressed the voltage-gated calcium currents in visceral sensory afferents of the nodose ganglion. Concentrations of t-ACPD ranging from 50 to 1,000 microM consistently decreased the evoked calcium current with a maximum suppression of the peak current of 25-30%. This response was repeatable and reversible within a given cell. 3. Metabotropic GluR activation selectively decreased the high-threshold calcium current evoked from step potentials greater than -30 mV and had no effect on the low-threshold calcium current. The inhibitory effects of t-ACPD on the high-threshold channel was partially blocked by omega-conotoxin (omega-CTx-GVIA) suggesting that at least part of the effects of mGluR inhibition of the voltage-gated calcium current is because of a modulation of the omega-CTx-GVIA sensitive high-threshold current. 4. Finally, the inhibitory effects of quisqualate (quis) on the high-threshold calcium current were blocked by pretreatment of the neurons with pertussis toxin (PTX). These results suggest that visceral sensory afferents do possess a PTX-sensitive mGluR and activation of this receptor results in the inhibition of a omega-CTx-GVIA sensitive high-threshold calcium channel.

Afferent Pathways↗

PubMed1993

Increases in cytosolic Ca2+ in rat area postrema/mNTS neurons produced by angiotensin II and arginine-vasopressin.

It is well established that neurons in the dorsal medulla, including the area postrema and the medial nucleus tractus solitarius (mNTS), are involved in the central actions of circulating peptides such as angiotensin II (ANG II) and arginine vasopressin (AVP). This report describes a preparation that permits the identification and maintenance of area postrema/mNTS neurons in culture in which the cellular and potentially subcellular responses to neurotransmitters and neuropeptides on area postrema/mNTS cells can be investigated. Following 15-21 days in culture, the effects of ANG II and AVP on changes in intracellular Ca2+ concentration ([Ca2+]i) were examined. Both ANG II and AVP resulted in a rapid and transient increase in [Ca2+]i reaching maximum in 15 s and returning towards baseline values within 180 s. The ANG II-mediated increase in [Ca2+]i was almost completely abolished by the selective angiotensin AT1 receptor subtype antagonist, losartan (DuP 753). These results suggest that ANG II and AVP modulate area postrema/mNTS neuronal activity by increasing intracellular Ca2+.

Angiotensin II↗

PubMed1993

Involvement of the area postrema in the regulation of sympathetic outflow to the cardiovascular system.

The circumventricular organs of the brain have been implicated in the central regulation of the cardiovascular system. The area postrema, which is the only circumventricular organ in the hindbrain, has received less attention than the others, but recent studies suggest that it may play an important role in the regulation of the cardiovascular system. Studies in rats and rabbits indicate that angiotensin II (Ang II)-dependent hypertension is abolished by lesioning of the area postrema. Additional studies indicate that the hypertension associated with Ang II involves a resetting of the arterial baroreflex to a higher pressure. This upward resetting requires an interaction of neurons in the area postrema with barosensitive neurons terminating in the medial nucleus tractus solitarius (mNTS). Another peptide, arginine vasopressin (AVP), has been shown to enhance the sympathoinhibitory influence of the arterial baroreflex via an action at the area postrema. Studies in rabbits suggest that the sympathoinhibitory response is due to resetting of the baroreflex to a lower pressure. Electrophysiological studies, using an in vitro brain slice preparation, have shown that activation of area postrema neurons projecting to the mNTS alters the responsiveness of mNTS neurons to afferent inputs. It is postulated that alpha-adrenergic mechanisms are involved in these interactions.

Animals↗

PubMed1993

Characteristics and zona binding ability of FRESH and cooled domestic cat epididymal spermatozoa.

Maintenance of genetic diversity within endangered species is important for ensuring healthy populations. Because unexpected deaths can occur, it would be advantageous to salvage gametes to effect posthumous participation in species reproduction. Using the domestic cat as a model for nondomestic felids, this investigation was undertaken to determine epididymal sperm cell characteristics, capacitation timing and the effects of storage temperature on fertilizing ability. In Study 1, the timing of capacitation was evaluated by examining zona attachment of spermatozoa to in vitro matured oocytes at 30-min intervals for 5 h. In Study 2, the ability of freshly collected (FRESH) and overnight cooled (COOL) epididymal spermatozoa to undergo capacitation and nuclear decondensation was evaluated using the zona attachment and zona-free hamster ova penetration assays. From Study 1, mean characteristics (n=29) for epididymal sperm cell motility and progressive status were 51.9% and 3.1+/-0.1, respectively, with a concentration of 80.3 x 10(6) spermatozoa/ml and 51% morphologically normal cells. Zona attachment (n >/= 25 ova/time interval) by sperm cells occurred at each time interval, but both the mean number of attached sperm cells/zona and the percentage of zonae with attached spermatozoa reached maximum values at 240 min (12.0+/-2.1 and 89.7%, respectively; P<0.05). In Study 2, overnight cooling did not affect progressive status of motility (3.3+/-0.1) or the percentage of morphologically normal spermatozoa (53.2+/-4.4) compared with that of FRESH (2.9+/-0.1, 50.7+/-3.2%) samples; however, motility was 14% lower (P<0.05) in the COOL vs FRESH group. Hamster ova penetration and the mean number of sperm cells attached/zona were greater in the COOL (28%, 18.6+/-5.7) than in the FRESH (5%, 7.4+/-2.0) group (P<0.05). However, it is speculated that the increased sperm-zonae interaction may have been the result of acrosomal damage. Nevertheless, these data demonstrate that domestic cat epididymal sperm cells have the ability to capacitate and undergo the first stages of fertilization.

Journal Article↗

PubMed1993

Combined Essex-Lopresti and radial shaft fractures: case report.

We present the case of a patient with multiple trauma, including a radial shaft fracture, a distal radioulnar joint dislocation, and a fracture-dislocation of the radial head. The combined open reduction of the radial shaft and head and the closed reduction of the distal radioulnar joint allowed early range of motion exercises and return to a functional level.

Adult↗

PubMed1993

Association of silicosis, lung dysfunction, and emphysema in gold miners.

BACKGROUND: In an earlier study of gold miners men with silicosis were found to have abnormal lung function, including airflow obstruction and reduced diffusing capacity. In a follow up study a sample of these men was examined by computed tomography to determine whether emphysema accounted for these abnormalities, which are associated with silicosis in this working population. METHODS: A sample of 70 men from a cohort of older gold miners with and without silicosis who had worked underground for a mean period of 29 years was examined by computed tomography to determine whether each man had emphysema. In addition, each man had lung function tests and routine chest radiography (125 kV). RESULTS: A total of 48 men had emphysema on examination by computed tomography. On the basis of the results in a chest radiograph 55 of the men had silicosis. Emphysema was related to silicosis, being present in five of the 15 men without silicosis and in 43 of the 55 with silicosis. Diffuse emphysema was apparent in two men without silicosis (14%) and in 25 men with silicosis (45%). The proportion of men with diffuse emphysema increased from 14% in those with International Labour Organisation category 0 nodule profusion to 46% in those with category 1, 48% in those with category 2, and 67% in those with category 3. Emphysema was also related to smoking: eight of the 18 who had never smoked and 40 of the 52 smokers had emphysema. All of those who had never smoked and had emphysema had silicosis with category 2/2 or greater nodule profusion. Lung function tests showed changes associated with silicosis that could be explained by the associated emphysema. CONCLUSIONS: In this population emphysema occurred in association with silicosis and accounted for the abnormalities in lung function associated with silicosis.

Gold↗

PubMed1993

Acute resetting of the carotid sinus baroreflex by aortic depressor nerve stimulation.

The effect of prolonged aortic depressor nerve (ADN) stimulation on carotid sinus baroreflex regulation of arterial pressure (AP) and renal sympathetic nerve activity (RSNA) was examined in anesthetized rabbits. Ramp increases in carotid sinus pressure (CSP) were repeated before and after 5 min of bilateral ADN stimulation. One minute after ADN stimulation the curve relating AP to CSP had shifted up and to the right, characterized by significant increases (P < 0.05) in the maximum (91 +/- 2 to 101 +/- 3 mmHg; mean +/- SE), midpoint (118 +/- 7 to 125 +/- 8 mmHg CSP), and minimum (45 +/- 3 to 53 +/- 4 mmHg) of the AP reflex curve. There was a parallel shift downward of the curve relating RSNA to CSP, characterized by significant decreases in the maximum [100 +/- 0 to 66 +/- 8% of maximum control RSNA value (%max)], the range (90 +/- 2 to 59 +/- 8%max), and the gain (-1.0 +/- 0.2 to -0.5 +/- 0.1%max/mmHg) of the RSNA reflex curve. Values returned to control within 10 min of cessation of ADN stimulation. These results suggest that central neurons processing baroreflex information from one set of mechanoreceptors can be reset by convergent signals arising from another baroreceptor site.

Animals↗

PubMed1993

Localisation of tight junction protein cingulin is temporally and spatially regulated during early mouse development.

The molecular maturation of the tight junction in the mouse early embryo has been investigated by monitoring the distribution of cingulin, a 140 x 10(3) M(r) peripheral (cytoplasmic) membrane constituent of the junction, at different stages of development and in different experimental situations. Although tight junction formation does not begin until compaction at the 8-cell stage, cingulin is detectable in oocytes and all stages of cleavage, a factor consistent with our biochemical analysis of cingulin expression (Javed et al., 1992, Development 117, 1145-1151). Using synchronised egg and embryo stages and isolated cell clusters, we have identified three sites where cingulin is localised, the cytocortex, punctate cytoplasmic foci and tight junctions themselves. Cytocortical cingulin is present at the cumulus-oocyte contact site (both cell types), in unfertilised and fertilised eggs and in cleavage stages up to 16-cell morulae, particularly at microvillous domains on the embryo outer surface (eg. apical poles at compaction). Embryo manipulation experiments indicate that cortical cingulin is labile and dependent upon cell interactions and therefore is not merely an inheritance from the egg. Cingulin cytoplasmic foci are evident only in outer cells (prospective trophectoderm) from the 32-cell stage, just prior to cavitation, and decline from approx. 8 hours after cavitation has initiated. The appearance of these foci is insensitive to cycloheximide treatment and they colocalise with apically derived endocytic vesicles visualised by FITC-dextran, indicating that the foci represent the degradation of cytocortical cingulin by endocytic turnover. Cingulin is detectable at the tight junction site between blastomeres usually from the 16-cell stage, although earlier assembly occurs in a minority (up to 20%) of specimens. Cingulin assembly at the tight junction is sensitive to cycloheximide and is identifiable approx. 10 hours after cell adhesion is initiated and ZO-1 protein assembles. Collectively, our results indicate that (i) cingulin from nonjunctional sites does not contribute to tight junction assembly and (ii) the molecular maturation of the junction appears to occur progressively over at least two cell cycles.

Animals↗

PubMed1993

Tight junction protein cingulin is expressed by maternal and embryonic genomes during early mouse development.

The expression of the tight junction peripheral membrane protein, cingulin (140 x 10(3) M(r), was investigated in mouse eggs and staged preimplantation embryos by immunoblotting and immunoprecipitation. Polyclonal antibody to chicken brush cingulin detected a single 140 x 10(3) M(r) protein in immunoblots of unfertilised eggs and all preimplantation stages. Relative protein levels were high in eggs and early cleavage stages, declined during later cleavage and increased again in expanding blastocysts. Quantitative immunoprecipitation of metabolically labelled eggs and staged embryos also revealed a biphasic pattern for cingulin synthesis with relative net levels being high in unfertilised eggs, minimal during early cleavage, rising 2.3-fold specifically at the onset of compaction (8-cell stage, when tight junction formation begins), and increasing further at a linear rate during morula and blastocyst stages. Cingulin synthesis in eggs is not influenced by fertilisation (or aging, if unfertilised), but this level declines sharply after first cleavage. These results indicate that cingulin is expressed by both maternal and embryonic genomes. The turnover of maternal cingulin (unfertilised eggs) and embryonic cingulin at a stage before tight junction formation begins (4-cell stage) is higher (t1/2 approximately 4 hours) than cingulin synthesised after tight junction formation (blastocysts; t1/2 approximately 10 hours). This increase in cingulin stability is reversed in the absence of extracellular calcium. Cingulin synthesis is also tissue-specific in blastocysts, being up-regulated in trophectoderm and down-regulated in the inner cell mass. Taken together, the results suggest that (i) cingulin may have a role during oogenesis and (ii) cell-cell contact patterns regulate cingulin biosynthesis during early morphogenesis, contributing to lineage-specific epithelial maturation.

Animals↗

PubMed1993

Biogenesis of structural intercellular junctions during cleavage in the mouse embryo.

The preimplantation embryo differentiates the trophectoderm epithelium which, from the 32-cell stage, generates the blastocoel of the blastocyst and, after implantation, gives rise to most extraembryonic lineages of the conceptus. Trophectoderm differentiation begins at compaction (8-cell stage) when cell-cell adhesion, mediated by uvomorulin, and epithelial cell polarisation first occur. Here, we review our work on the biogenesis of tight junctions and desmosomes during epithelial differentiation. Tight junction construction begins at compaction and appears to be a gradual process, both at morphological and molecular levels. This maturation pattern may be due in part to sequential expression of tight junction constituents from the embryonic genome. Tight junction formation is dependent upon uvomorulin adhesion but can be inhibited by different means without apparently disturbing cell adhesion or polarisation. Cell interactions appear to regulate tight junction tissue specificity, in part by controlling the level of synthesis of constituents. Desmosome formation begins at the 32-cell stage, particularly as the embryo initiates blastocoel accumulation, and, in contrast with tight junction formation, does not appear to be a gradual process. Thus, nascent desmosomes appear mature in terms of their molecular composition. Desmosomal proteins are synthesised well in advance of desmosome formation but the synthesis of the principal glycoprotein components begins at the blastocyst stage and may regulate the timing of junction assembly. Implications of these differing patterns of biogenesis for the embryo are discussed.

Animals↗

PubMed1993

Open half-pin insertion for distal radial fractures.

Twenty-two patients with unstable distal radial fractures were treated with external fixation using the open technique for half-pin insertion. Of the final study group of 19 patients, 7 (37%) demonstrated early pin-tract drainage, which resolved within 2 weeks after insertion. No pin loosening, pin change, pin breakage, infection, dorsal sensory nerve entrapment or irritation, tendon injury, or additional radial fracture occurred. Wrist range of motion in flexion/extension was 51/47 degrees, and the grip strength ratio (injured versus non-injured side) was approximately 61% on follow-up (average, 8 months). The open technique has proved efficacious in reducing complications associated with external fixation.

Adult↗

PubMed1992

Seizures and neurocysticercosis in black men.

Men from a working population of black gold-miners were studied prospectively during an 8-month period to determine the incidence and aetiology of seizures in this population. Computed tomography (CT) of the brain was the primary investigation. From the total population of 97,000, 175 men with seizure disorders were admitted to the study and of these 165 underwent brain CT. In addition 138 subjects, who had brain CT for reasons other than seizures during the study period, served as controls. Sixty-three patients (38%) and 20 controls (14%) (P less than 0.0005) were considered to have definite or possible neurocysticercosis (NCC). Focal cerebral atrophy was the next most common abnormality and was found in 38 patients (23%) and 4 controls (3%) (P less than 0.0005). Otherwise unsuspected diagnoses, including tuberculoma, cerebral contusion and subdural haematoma, were made on CT in 10 cases. In 43% of patients with definite NCC, there was CT evidence of active disease and these subjects might be suitable candidates for treatment with antiparasitic chemotherapy. The high frequency of NCC in both the seizure patients and the control group indicates a need for more active public health measures. CT of the brain was extremely useful in determining seizure aetiology in this population.

Brain Diseases↗

PubMed1992

Comparison of cefotaxime with ceftriaxone given intramuscularly 12-hourly for community-acquired pneumonia.

Cefotaxime 1 g intramuscularly (i.m.) 12-hourly was compared with ceftriaxone 1 g i.m. 12-hourly in adult patients requiring hospitalization with uncomplicated community-acquired pneumonia. Fifty-two patients were enrolled and two were subsequently withdrawn, leaving 50 patients who completed the study; 23 received cefotaxime and 27 received ceftriaxone. Clinical cure was achieved in 49 of the 50 patients (98%). One treatment failure occurred in a patient who received ceftriaxone. The only significant pathogen isolated from the pretreatment sputum cultures was Streptococcus pneumoniae (50%). All isolates were sensitive to both drugs. Cefotaxime 1 g i.m. 12-hourly was as effective as ceftriaxone in the treatment of patients with uncomplicated community-acquired pneumonia requiring hospital admission.

Adult↗