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Biomedical subjects

J S Kelly

Publications and source records attributed to J S Kelly.

At least 73 records · Page 4Linked to original sources
PubMed1989

Electrophysiology of adult rat facial motoneurones: the effects of serotonin (5-HT) in a novel in vitro brainstem slice.

Studies of adult rat motoneurones using in vitro slice preparations are rare. We here describe a novel brainstem slice of the adult rat containing the facial motor nucleus (FMN). Data obtained for facial motoneurones (FM) by intracellular recording indicate that they display several passive and active properties seen in other rat cranial and spinal motoneurones. Bath application of serotonin (5-HT) evokes a reversible depolarization of FMs which is associated with an increase in input resistance due to a reduction in potassium permeability. This effect is unaffected by tetrodotoxin indicating a postsynaptic site of action.

Action Potentials↗
PubMed1989

3H-imipramine binding to freshly prepared platelet membranes in depression.

3H-Imipramine binding was measured in freshly prepared platelet membranes from 47 drug-free major depressives and 46 healthy controls. Where possible, platelet binding in depressed subjects was repeated following treatment. A significant negative correlation was found between Bmax and assay protein concentration and Bmax values were corrected for this effect. Adjusted Bmax was significantly lower (by 14%) in female depressed patients than in female control subjects, and the difference was of similar magnitude premenopausally and postmenopausally. No such difference was found in males. Kd did not differ significantly between depressed and control subjects. Multiple regression analysis confirmed significant effects on Bmax of presence of depressive illness, age (positive correlation), and season (higher in summer). Within the depressed sample, Bmax was significantly lower in those subjects with obsessional features. Endogenicity (Research Diagnostic Criteria or Newcastle), dexamethasone suppression test result, drug-free interval, family history of depression, depressive psychosis, suicidal ideation, and past history of suicide attempts were not significantly related to Bmax. Paired comparisons revealed no significant effect on Bmax of 6 weeks' treatment with imipramine, maprotiline, or BRL 14342 or of a course of electroconvulsive therapy.

Adult↗
PubMed1989

Efficacy of noninvasive transcutaneous cardiac pacing patients undergoing cardiac surgery.

Noninvasive transcutaneous cardiac pacing (NTP) is a rapid, safe, and easily utilized form of emergency cardiac pacing, with hemodynamics similar to right ventricular endocardial pacing. Although the technique has proven effective for hemodynamically significant bradycardias and early use during cardiopulmonary resuscitation, NTP under anesthetic conditions has been poorly characterized. In particular, it is unknown to what degree the multiple physiologic perturbations of cardiac surgery and cardiopulmonary bypass (CPB) affect myocardial thresholds and the efficacy of the unit itself. Patients undergoing procedures utilizing CPB (n = 23) were studied in an effort to address these issues. All patients were able to be paced at all points throughout the 24-h study interval, although four patients developed hemodynamic instability during this period causing their exclusion from additional investigation. Only one patient requested discontinuation from the study due to discomfort. A statistically significant increase in mean current requirements for capture was demonstrated over time (P less than 0.0001), with baseline thresholds being significantly less than other study points (P less than or equal to 0.05). Thresholds following chest wall closure were significantly greater than all other study points (P less than or equal to 0.05), possibly due to accumulation of pericardial and mediastinal air. Multiple measured variables changed significantly during the study, but only increases in cardiac output and core temperature were related to statistically significant increases in current thresholds (P less than or equal to 0.05). Increasing age and pump time were of borderline importance. NTP represents an effective pacing alternative in cardiac surgical patients.

Adult↗
PubMed1988

Amphetamine-induced dopamine release in the rat striatum: an in vivo microdialysis study.

The effects of a number of biochemical and pharmacological manipulations on amphetamine (AMPH)-induced alterations in dopamine (DA) release and metabolism were examined in the rat striatum using the in vivo brain microdialysis method. Basal striatal dialysate concentrations were: DA, 7 nM; dihydroxyphenylacetic acid (DOPAC), 850 nM; homovanillic acid (HVA), 500 nM; 5-hydroxyindoleacetic acid (5-HIAA), 300 nM; and 3-methoxytyramine (3-MT), 3 nM. Intraperitoneal injection of AMPH (4 mg/kg) induced a substantial increase in DA efflux, which attained its maximum response 20-40 min after drug injection. On the other hand, DOPAC and HVA efflux declined following AMPH. The DA response, but not those of DOPAC and HVA, was dose dependent within the range of AMPH tested (2-16 mg/kg). High doses of AMPH (greater than 8 mg/kg) also decreased 5-HIAA and increased 3-MT efflux. Depletion of vesicular stores of DA using reserpine did not affect significantly AMPH-induced dopamine efflux. In contrast, prior inhibition of catecholamine synthesis, using alpha-methyl-p-tyrosine, proved to be an effective inhibitor of AMPH-evoked DA release (less than 35% of control). Moreover, the DA releasing action of AMPH was facilitated in pargyline-pretreated animals (220% of control). These data suggest that AMPH releases preferentially a newly synthesised pool of DA. Nomifensine, a DA uptake inhibitor, was an effective inhibitor of AMPH-induced DA efflux (18% of control). On the other hand, this action of AMPH was facilitated by veratrine and ouabain (200-210% of control). These results suggest that the membrane DA carrier may be involved in the actions of AMPH on DA efflux.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

Pathogenesis of post-herpetic neuralgia.

A model of post-herpetic neuralgia is put forward based on the physiological effects of herpes simplex type-1 virus infection of rat dorsal root ganglion neurons in tissue culture. This virus causes these normally electrically silent neurons to produce spontaneous action potentials. Furthermore, pairs of neurons tend to have synchronised discharges. This coupling is not synaptically mediated, but due to presumed electrical junctions. It is proposed that post-herpetic neuralgia is caused by abnormal impulses arising in dorsal root ganglion neurons as a direct result of viral infection.

Action Potentials↗
PubMed1987

Direct excitatory effects of neuropeptide Y (NPY) on rat hippocampal neurones in vitro.

Intracellular recordings from granule cells of the rat dentate gyrus show neuropeptide Y (NPY) applied by pressure ejection from pipettes containing 1.2-12 microM by pressures of less than 200 kPa for 1-5 s in duration to consistently evoke membrane depolarisations accompanied by a reduction in membrane resistance. The depolarisations were accompanied by an increase in excitability. Since the depolarisations evoked by NPY were not attenuated by either tetrodotoxin or kynurenic acid a direct excitatory action of NPY is postulated.

Action Potentials↗
PubMed1987

Neuroleptics decrease calcium-activated potassium conductance in hippocampal pyramidal cells.

Intracellular recordings were made from pyramidal CA1-neurones of the hippocampal slice preparation. Bath application of a wide variety of neuroleptics was found to depress the slow afterhyperpolarization, which is mediated in these neurons by a calcium-dependent potassium conductance occurring following a burst of spikes. The depression of this conductance took place in the presence of calcium spikes of normal amplitude and duration, and except in the case of trifluoperazine, without alteration in resting membrane potential or input resistance.

Animals↗
PubMed1987

The location of GABAB receptor binding sites in mammalian spinal cord.

GABAB binding sites in rat spinal cord have been detected by receptor autoradiography using 3H-GABA in the presence of isoguvacine. The sites could be demonstrated throughout the spinal cord grey matter. The maximum concentration of GABAB sites occurred in lamina II with substantial amounts in other laminae of the dorsal horn. Much lower levels were detected in the ventral horn. Unilateral rhizotomy reduced the number of GABAB sites in the dorsal horn without affecting levels in the ventral horn. The greatest reduction occurred in lamina II with 18% loss 2 days after surgery, 23% after 4 days, 25% after 6 days, and 48% after 15 days. The change after 15 days was comparable to that produced 4 months after neonatal capsaicin administration (50 mg/kg). The only apparent difference between rhizotomy and capsaicin treatment occurred in lamina IV, where rhizotomy produced a greater reduction than capsaicin. 3H-Neurotensin binding in sections from the same animals was unaltered after rhizotomy, indicating a lack of change in the populations of neurons containing neurotensin-binding sites. This would support the view that up to 50% of GABAB binding sites are located on nerve terminals. The greater reduction in lamina IV after rhizotomy would suggest that GABAB sites may be present on large-diameter afferent fibres that terminate in this region as well as on smaller-diameter C and A delta fibres.

Animals↗
PubMed1987

The ventral and dorsal lateral geniculate nucleus of the rat: intracellular recordings in vitro.

1. The membrane properties and the electrotonic structure of neurones in the ventral and dorsal lateral geniculate nucleus (l.g.n.) of the rat were studied using an in vitro slice preparation. 2. Following electrophysiological characterization, horseradish peroxidase (HRP) was injected intrasomatically and the morphological features of impaled cells were characteristic of principal neurones of the rat ventral and dorsal l.g.n. 3. Neurones in the ventral l.g.n. had a higher input resistance but similar membrane time constants (tau o) and resting potentials than cells in the dorsal l.g.n. 4. Using a simple neuronal model, the electrotonic length (L) and the dendritic to somatic conductance ratio (rho) were calculated and found to be similar for cells in both divisions of the l.g.n. The mean value of L (0.7) and rho (1.5) suggest that both groups of neurones are electrotonically compact. 5. The width and after-hyperpolarization of directly evoked action potentials, but not their threshold or their amplitude, were different between cells of the ventral and dorsal l.g.n. 6. At potentials more negative than -55 mV, a slow rising and falling potential could be evoked in each neurone (n = 310) of the dorsal l.g.n. but only in three cells of the ventral l.g.n. (n = 94). The electrophysiological and pharmacological properties of this potential were identical with those of the low-threshold Ca2+-dependent potential observed in other thalamic nuclei. 7. These results indicate that some of the passive and active membrane properties of ventral and dorsal l.g.n. neurones are different. The implications of these findings for the control of the integrative capability and the response of l.g.n. neurones to visual stimulation are discussed.

Action Potentials↗
PubMed1987

On the excitatory post-synaptic potential evoked by stimulation of the optic tract in the rat lateral geniculate nucleus.

1. The electrophysiological and pharmacological properties of the excitatory post-synaptic potentials (e.p.s.p.) evoked by electrical stimulation of the optic tract were studied in projection neurones of the ventral and dorsal lateral geniculate nucleus (l.g.n.) of the rat in vitro. 2. No difference was found in the rise time of e.p.s.p.s. recorded in the dorsal and ventral l.g.n. and in their threshold for action potentials. At membrane potentials more negative than -60 mV, e.p.s.p.s. in the dorsal l.g.n. were always followed by a Ca2+-dependent potential. Its amplitude could easily reach threshold for generating an action potential and thus evoke firing from an e.p.s.p. that was subthreshold at resting potential. No Ca2+ potential was observed to follow e.p.s.p.s. recorded in the ventral l.g.n. 3. At resting potential the excitability of dorsal and ventral cells was unaffected following an initial shock to the optic tract. However, in dorsal neurones, at potentials more negative than -60 mV, the presence of Ca2+ potentials evoked by the e.p.s.p.s. resulted in a period of decreased excitability. 4. Using intrasomatic injection of Cs+ the reversal potential (E) of the e.p.s.p. and of the depolarization produced by glutamate could be measured in the same l.g.n. neurone. They were: Eepsp, -0.9 mV; and Eglut, -3.9 mV. 5. gamma-D-glutamylglycine (DGG), an excitatory amino acid antagonist, reversibly inhibited the e.p.s.p. and depolarization produced by quisqualate and glutamate by a competitive action. The concentration of DGG that produced 50% inhibition (IC50) was 2.7 mM. 6. D-2-amino-5-phosphonovalerate (APV), the potent and selective N-methyl-D-aspartate (NMDA) antagonist, had no effect on the e.p.s.p. both in the presence and absence of Mg2+. The isomers of 2-amino-4-phosphonobutyrate (APB) were inactive or had a non-specific action on the e.p.s.p. 7. No difference could be detected in either the reversal potential or the action of the antagonists between neurones of the dorsal and the ventral l.g.n. 8. These results suggest that Ca2+-dependent potentials play an important role in modulating synaptic efficacy in principal neurones of the dorsal l.g.n. The quisqualate/kainate nature of the optic nerve receptors and the similarity of Eepsp and Eglut constitute strong support in favour of a glutamate-like substance as the transmitter of the optic nerve.

2-Amino-5-phosphonovalerate↗
PubMed1986

Platelet high affinity adrenoceptor binding sites labelled with the agonist [3H]UK-14,304, in depressed patients and matched controls.

Increased numbers of platelet high affinity alpha 2-adrenoceptors binding sites have been reported in depressed patients using the agonist radioligand [3H]clonidine, whereas no differences from controls have been found using antagonist radioligands. We have measured platelet high affinity alpha 2-adrenoceptors in 13 depressed patients and 14 well-matched controls using a new selective agonist radioligand, [3H]UK-14,304. Unlike previous studies using [3H]clonidine, we find no differences in Bmax or KD of the high affinity alpha 2-adrenoceptor binding sites between the 2 groups.

Adult↗
PubMed1986

Postsynaptic action of kynurenic acid in the rat dentate gyrus.

Quantal analysis was performed on excitatory postsynaptic potentials (EPSP) recorded with intracellular electrodes from granule cells of the rat dentate gyrus, before, during and after the iontophoretic application of kynurenic acid. In this way a reduction in the EPSP caused by kynurenic acid was shown to be accompanied by an appropriate reduction in quantal size whilst the average number of quanta released per impulse was unchanged. The reduction in quantal size parallelled the reduction in the amplitude of the EPSP and is thus consistent with an action of kynurenic acid at a postsynaptic site. In addition, on a number of cells kynurenic acid reduced the depolarization evoked by L-glutamate by an equivalent amount and it is thus proposed that the synaptic transmitter is glutamate-like.

Animals↗
PubMed1986

Platelet radioligand binding and neuroendocrine challenge tests in depression.

The purpose of this work was to examine the number and function of alpha 2-adrenoceptors and the number of serotonin uptake sites in depressed patients and controls. Platelet alpha 2-adrenoceptors and platelet serotonin uptake sites were labelled with [3H]yohimbine and [3H]imipramine respectively. Central alpha 2-adrenoceptor function was assessed by growth hormone and other responses to challenge with the alpha 2-agonist clonidine. No overall difference in the binding parameters was observed between the control and depressed groups, but the results highlight the importance of drug-free interval, menopausal status and membrane protein concentration within the binding assays in the interpretation of such studies. The growth hormone response to clonidine tended to be blunted in depressed females and was significantly blunted in the subgroup of depressives who failed to suppress plasma cortisol concentrations in response to dexamethasone. Depressed subjects also showed a smaller decrease in diastolic blood pressure and a smaller increase in sedation than control subjects.

Adult↗
PubMed1986

Immunocytochemical and biochemical studies with the monoclonal antibody 69A1: similarities of the antigen with cell adhesion molecules L1, NILE and Ng-CAM.

We have previously raised a monoclonal antibody (69A1) which recognises a cell-surface antigen expressed on rat cerebellar neurons both in culture and in tissue sections of the developing cerebellum prior to postnatal day 17. In our current study we have undertaken a detailed analysis of the loss of labelling from the molecular layer of the cerebellum and show that this parallels the gradient of fibre maturation in this zone. This loss of labelling occurred in paraformaldehyde-fixed tissues but not in unfixed or acetone-fixed sections, suggesting it is the result of antigen modification rather than antigen loss. In cultures of dorsal root ganglia antibody 69A1 labelled neurones and some Schwann cells. Antigen 69A1 was immunoprecipitated from lysates of cultured cerebellar cells and appeared as two bands when separated by SDS-PAGE with apparent molecular weights of ca. 210 and 150 kDa. The antigen is distinct from N-CAM but shows similarities with the L1, nerve growth factor-inducible large external glycoprotein (NILE) and Ng-CAM group of cell adhesion molecules.

Age Factors↗
PubMed1986

The effect of 6-hydroxydopamine, reserpine and cold stress on the neuropeptide Y content of the rat central nervous system.

Neuropeptide Y has previously been detected in neurons throughout the rat brain and spinal cord. On histochemical grounds, the neuropeptide Y-containing cell bodies have been subdivided into two groups: those in the brain stem in which colocalization with noradrenaline and adrenaline has been demonstrated and those in other brain regions where no catecholamine coexistence is found. In this paper the regional distribution of neuropeptide Y has been investigated in the rat brain by a specific neuropeptide Y radioimmunoassay, before and after the destruction of catecholaminergic nerve terminals by the administration of intraventricular 6-hydroxydopamine. Despite massive reductions in brain catecholamines, the neuropeptide Y level was unchanged in the cerebral cortex, striatum, spinal cord and hippocampus. A minor reduction in neuropeptide Y was found in the hypothalamus. Reserpine treatment, which is known to deplete brain nerve terminal stores of catecholamines, likewise did not result in any loss of neuropeptide Y. Cold stress which increases noradrenergic turnover in the rat brain stem had no effect on neuropeptide Y levels. These results suggest that the bulk of neuropeptide Y in the rat brain and spinal cord may not be stored in catecholaminergic nerve terminals.

Animals↗
PubMed1986

Effect of reserpine, phenoxybenzamine and cold stress on the neuropeptide Y content of the rat peripheral nervous system.

The effect of reserpine treatment on the neuropeptide Y content of the rat adrenal gland, heart, kidney and vasculature was studied using a specific radioimmunoassay. One hour after reserpine administration (5 mg/kg) the neuropeptide Y concentration in the adrenal gland was significantly reduced and after 4 h a similar reduction was seen in the heart and kidney. After 48 h, neuropeptide Y concentrations were reduced in all tissues. The greatest reduction occurred in the cardiac septum (77%) and the least in the inferior vena cava (25%). Phenoxybenzamine (2 mg/kg) also caused a reduction in neuropeptide Y concentrations which was less marked than after reserpine, except in the adrenal gland where it was similar. Cold stress caused no change in neuropeptide Y concentrations. The neuropeptide Y depletion induced by reserpine was compared to that following 6-hydroxydopamine. In the heart and pial arteries both drugs caused a similar neuropeptide Y depletion whilst in the pineal gland and renal artery 6-hydroxydopamine had more effect than reserpine. The implications of these results on NPY storage sites are discussed.

Animals↗
PubMed1986

Changes in excitability induced by herpes simplex viruses in rat dorsal root ganglion neurons.

The physiological properties of rat sensory neurons infected with herpes simplex type 1 viruses and maintained in cell culture were studied using intracellular recording techniques. Two syncytial (cell fusing) and two nonsyncytial strains of virus were examined; individual strains of virus had different effects on neuronal excitability. The nonsyncytial viruses caused a loss of tetrodotoxin-sensitive low-threshold action potentials and blocked hyperpolarization-activated inward rectification, but did not alter the resting membrane potential, depolarization-activated outward rectification, or render the cells leaky. These effects develop progressively over the period 5-15 hr postinfection. One syncytial strain of virus induced spontaneous electrical activity that appeared to be the result of discrete electrical coupling between sensory neuron processes; as a result, action potential discharge is synchronized in coupled neurons. A second syncytial strain of virus rendered neurons inexcitable; however, in these experiments the input resistance fell to low values, possibly as a result of extensive coupling between sensory neurons. Viral replication in sensory neurons was demonstrable with indirect immunofluorescence using an antibody to herpes simplex viruses and correlated with the onset of virally induced changes in excitability. Virally triggered changes in excitability were blocked by the specific herpes virus antimetabolite acyclovir, suggesting that viral adsorption and penetration are by themselves insufficient to evoke changes in excitability. These results suggest that herpes viruses have selective effects on the excitable mechanisms in sensory neurons that are not simply the result of a general loss of membrane conductances or the disruption of transmembrane ion gradients.

Action Potentials↗