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Biomedical subjects

J Anson

Publications and source records attributed to J Anson.

At least 37 records · Page 2Linked to original sources

A study of the possible mechanisms underlying the convulsant actions of a linear expanded xanthine.

The actions of a mixture of the 4- and 9-chloro derivatives of the linear expanded xanthine 5,7-diethyl-2-chloroimidazo[4,5-g]quinazoline-6,8 (5H,7H)-dione (chloro-DCQD) on the isolated olfactory cortex slice of the rat have been investigated. Chloro-DCQD evoked a slowly-developing depolarization which intensified over a drug application period of at least 4 min. A pharmacological investigation of the response showed that it was not mediated by blockade of potassium channels or activation of voltage-gated sodium channels, by a stimulant action at receptors to gamma-aminobutyric acid (GABA), excitatory amino acids or acetylcholine, or by antagonism of adenosine receptors. Chloro-DCQD (2.5 mM) potentiated responses evoked by N-methyl-D-aspartate (NMDA), L-aspartate and L-glutamate, probably by overcoming the magnesium ion block of the ion channel of the NMDA receptor complex. Chloro-DCQD (2.5 or 5 mM) also increased pyramidal cell excitability and abolished GABA-mediated postsynaptic inhibition but did not affect the excitability of, or neurotransmitter release from, the terminals of the lateral olfactory tract. Chloro-DCQD competitively antagonized the inhibitory actions of adenosine on the olfactory cortex. These effects are consistent with the reported convulsant actions of chloro-DCQD.

Animals↗

Intrasellar balloon inflation for treatment of symptomatic empty sella syndrome.

Intrasellar extradural placement of a detachable vascular balloon via a transsphenoidal approach was performed successfully in a patient with primary empty sella syndrome, relieving headache and visual field defect. This technique offers an alternative approach to other methods of treating symptomatic empty sella syndrome that require packing of the sella with fat, muscle, cartilage, or bone.

Adult↗

Aneurysmal bone cyst of the thoracic spine: treatment by excision and segmental stabilization with Luque rods.

Preoperative radiological evaluation with magnetic resonance imaging and computed tomography was valuable in planning the surgical management of a destructive lesion of the posterior elements of the thoracic spine that was causing spinal cord compression in an 18-year-old woman. Preoperative recognition of bilateral involvement of the pedicles in addition to the laminae and spinous process led to use of prophylactic segmental stabilization of the spine with Luque rods after successful excision of an aneurysmal bone cyst. This case provides an example of the usefulness of computed tomographic scanning and magnetic resonance imaging in assessing the distribution and location of vertebral tumor and its potential effect on spinal stability. The efficacy of combining radical excision with stabilization for treatment of aneurysmal bone cysts of the spine is emphasized.

Adolescent↗

The parameters of death: a consideration of the quantity of information in a life table using a polynomial representation of the survivorship curve.

How much unique information is contained in any life table? The logarithmic survivorship (lx) columns of 360 empirical life tables were fitted by a weighted fifth degree polynomial, and it is shown that six parameters are adequate to reproduce these curves almost flawlessly. However, these parameters are highly intercorrelated, so that a two-dimensional representation would be adequate to express the similarities and differences among life tables. It is thus concluded that a life table contains but two unique pieces of information, these being the level of mortality in the population which it represents, and the relative shape of the underlying mortality curve.

Actuarial Analysis↗

Mortality and living conditions: relative mortality levels and their relation to the physical quality of life in urban populations.

The general inverse association between mortality and the availability of material resources has been well established in large populations. Using data for Israeli urban locations, we show that indirectly standardized mortality ratios (SMR) are well able to capture this relationship in small populations for which reliable age specific mortality data are not available; and that they are inversely related to the standard of living, as measured by a variety of census based indicators. It is thus suggested that SMRs offer a ready indicator of living standards in populations for which more specific indicators may not be readily accessible.

Female↗

Women's health and labour force status: an enquiry using a multi-point measure of labour force participation.

Previous research indicates that working women are healthier than housewives, that the unemployed are less healthy than those currently employed, and that transitions into and out of paid work may be particularly associated with poor health. Women respondents in the 1979 U.S. National Health Interview Survey were divided into five categories: the long term employee, the newly employed, the unemployed, the recently non-employed and the housewife. The categories were compared on six measures of self-reported health and illness behaviour, controlling for age, SES, marital status, and age of youngest child. As expected the long term employees were the healthiest, followed by the recently employed; the unemployed and the housewives were not distinguishable in terms of their health; and the recently non-employed were the least healthy. This pattern was found for both the total sample, and for the sub sample of married mothers. The dynamic relationship between employment status and health, is discussed.

Adolescent↗

Possible presynaptic actions of 2-amino-4-phosphonobutyrate in rat olfactory cortex.

1 The effect of 2-amino-4-phosphonobutyrate (APB) on facilitation at the lateral olfactory tract (LOT)-superficial pyramidal cell synapse of the olfactory cortex has been studied by recording the relative changes in amplitude of the N-waves evoked on stimulation of the LOT by pairs of stimuli. 2 Although APB (0.01 to 5 mM) reduced the amplitude of the conditioning response there was an overall increase in facilitation over conditioning intervals of up to 1700 ms which was concentration-dependent and inversely related to the concentration of extracellular calcium (1.25 to 5 mM). 3 The L-(+)-isomer of APB was more potent than the D-(-)-form in increasing synaptic facilitation. 4 The potassium channel blockers 4-aminopyridine (0.25 mM), 3,4-diaminopyridine (0.1 mM), tetraethylammonium (10 mM) and catechol (1 mM) all reduced facilitation but failed to antagonize the increase in facilitation produced by APB (1 mM). In contrast, all 4 drugs antagonized APB-induced reductions in the amplitude of the conditioning response. 5 APB (1 mM) significantly reduced the K+-evoked release of endogenous aspartate and glutamate but not of gamma-aminobutyric acid from slices of olfactory cortex. 6 It is suggested that APB reduces the amplitude of the conditioning response and increases synaptic facilitation by reducing transmitter release from the LOT terminals. The mechanism is unlikely to involve activation of terminal potassium currents.

Amino Acids↗

Excitatory and inhibitory effects of dopamine on synaptic transmission in the rat olfactory cortex slice.

A study has been undertaken of the effects of dopamine on excitatory transmission at the lateral olfactory tract (LOT)-superficial pyramidal cell synapse of the rat olfactory cortex slice by measuring the effects of bath-applied dopamine on the amplitudes and latencies of the surface field potentials evoked on submaximal LOT stimulation in a total of 32 preparations. In 7 (22%) slices, dopamine had no detectable effects on transmission. In the remaining preparations, dopamine (1-250 microM) depressed transmission in a concentration-dependent manner. This action was unaffected by nadolol (10 microM), phentolamine (10 microM) and picrotoxin (25 microM) but was antagonized by chlorpromazine (10 microM) and trifluoperazine (0.2 and 0.5 microM) and mimicked by bromocriptine (0.01-5 microM) and apomorphine (0.25-25 microM). Investigation of the effects of dopamine on stimulus input-evoked potential output relationships indicated that the inhibitory effect of dopamine on transmission was mediated by a reduction in pyramidal cell excitability. In 6 slices (24% of those sensitive to dopamine) low dopamine concentrations (0.1-1 microM) facilitated transmission at the LOT-superficial pyramidal cell synapse. This excitatory effect was antagonized by nadolol and phentolamine (10 microM) and also by 100 microM 2-amino-5-phosphonovalerate (an antagonist of excitatory amino acid receptors of the N-methyl-D-aspartate type) but was unaffected by chlorpromazine (10 microM) and trifluoperazine (0.2 and 0.5 microM). By a comparison with the effects of noradrenaline on transmission, it is concluded that the excitatory effects of dopamine are mediated either indirectly by the release of noradrenaline or by a direct interaction of dopamine with adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Adenosine A1 receptors mediate the inhibitory effects of exogenous adenosine in the rat olfactory cortex slice.

A study has been undertaken to identify the category of receptors mediating the inhibitory effects of adenosine on evoked activity in slices of olfactory cortex in the rat. The approach has been to measure the relative potencies of adenosine and a range of structural analogues [2-chloroadenosine, 2' deoxyadenosine, cyclohexyladenosine, (-)-5'N-ethyl-carboxamide adenosine and N6(L-2-phenylisopropyl)adenosine] required to: inhibit excitatory transmission at the lateral olfactory tract-pyramidal cell synapse; inhibit the specific binding of [3H]cyclohexyladenosine to membrane preparations and evoke formation of cyclic AMP. In contrast to the relative concentrations of the analogues necessary to increase levels of cyclic AMP, those required to inhibit synaptic transmission were characteristic of a selectivity for adenosine A1 receptors. The presence of adenosine A1 receptors has been demonstrated directly by characterizing the binding of [3H]cyclohexyladenosine to membranes prepared from slices of olfactory cortex. It is concluded that inhibition of transmission at the lateral olfactory tract-pyramical cell synapse by adenosine is mediated by receptors of the A1 category.

Adenosine↗

An unlikely role for cyclic AMP in the mediation of the excitatory and inhibitory effects of noradrenaline on transmission in the olfactory cortex.

Simultaneous measurements have been made of the actions of noradrenaline and other agonists, alone and in the presence of appropriate antagonists, on synaptic transmission and cyclic AMP levels in the rat olfactory cortex. The possible role of cyclic AMP as an obligatory mediator of the excitatory and inhibitory actions of noradrenaline is discussed.

Animals↗

Excitatory and inhibitory effects of noradrenaline on synaptic transmission in the rat olfactory cortex slice.

An investigation has been made of the effects of noradrenaline on excitatory transmission at the lateral olfactory tract (LOT)-superficial pyramidal cell synapse of the rat olfactory cortex slice by measuring the effects of bath-applied noradrenaline on the amplitudes and latencies of the field potentials evoked on LOT stimulation. Low concentrations of noradrenaline (0.1-5 microM) facilitate transmission whereas higher doses (20-250 microM) depress transmission. Both these effects were completely blocked by non-selective alpha- and beta-adrenoceptor antagonists, by 2-amino-5-phosphonovaleric acid (an antagonist of excitatory amino acid receptors of the N-methyl-D-aspartate type) and by the methylxanthine theophylline. The depressant effects of noradrenaline were mimicked by bath application of GABA or adenosine and specifically antagonized by bicuculline and picrotoxin. In parallel experiments, noradrenaline (100 microM) significantly increased the potassium-evoked release of endogenous aspartate, glutamate and GABA, proposed transmitters of the olfactory cortex, although the effect on GABA release was specifically antagonized by 2-amino-5-phosphonovaleric acid. Noradrenaline (100 microM) also significantly increased the potassium-evoked release of D-[3H]aspartate, an effect antagonized by a number of alpha- and beta-adrenoceptor antagonists. It is concluded that at low concentrations, noradrenaline facilitates transmission at the LOT-superficial pyramidal cell synapse by increasing excitatory amino acid neurotransmitter release. This effect is mediated by both alpha- and beta-adrenoceptors although the primary site of release is unknown. At higher concentrations of noradrenaline, the increased levels of excitatory transmitters release sufficient endogenous GABA (and possibly adenosine) to cause an overall depression of transmission. These conclusions are supported by the results of a series of experiments in which the effects of noradrenaline on stimulus input-evoked field potential output relationships were assessed. It is not possible to exclude additional direct effects of noradrenaline on membrane excitability.

Adenosine↗

The effect of isoproterenol and hydroxyurea on the presence of ubiquitin and protein A24 in the rat salivary gland.

The in vivo administration of hydroxyurea for 12 h counteracts DNA synthesis and cell cycling stimulated by 72 h of isoproterenol treatment in rat salivary gland, as determined by fluorescence-activated flow cytometry. Hydroxyurea has little effect on [3H]leucine incorporation (protein synthesis) of the nuclear proteins soluble in 0.35 M NaCl, when examined by polyacrylamide gel chromatography and autoradiography from electrostatically sorted nuclei of (G0 + G1) and (G2 + M) phases of the in vivo cell cycle. Differential incorporation of [3H]leucine into nuclear proteins was observed during various phases of the cell cycle. Proteins 'X' and 'Z', observed in stained gel chromatographs of the 0.35 M NaCl-soluble nuclear proteins, were identified by biochemical analyses as ubiquitin and protein A24, respectively. Ubiquitin appeared transiently while A24 increased in gel chromatograms concomitant with progressive quiescence of the salivary gland induced by hydroxyurea.

Amino Acids↗

Baclofen: effects on evoked field potentials and amino acid neurotransmitter release in the rat olfactory cortex slice.

A study has been made of the in vitro effects of (+/-)- and (-)-baclofen on the evoked field potentials and release of endogenous amino acid neurotransmitter candidates (aspartate, glutamate, GABA and possibly taurine) which accompany electrical stimulation of the excitatory input to the olfactory cortex slice, the lateral olfactory tract. Baclofen appears to reduce the excitatory input to the GABA-utilizing inhibitory interneurones; this action was manifest as a drug-induced abolition of the field potential known as the P-wave (IC50 for (-)-baclofen, 1.7 +/- 0.4 microM) together with a simultaneous reduction in the synaptically evoked release of aspartase and glutamate from the cut surface of slices. Both these actions of baclofen exhibited concentration dependence and stereospecificity and were not antagonized by picrotoxin (25 microM) thereby suggesting that they are directly related. The consequence of this action of baclofen was the abolition of GABA-mediated presynaptic and postsynaptic inhibition together with their respective field potential correlates, the late N- and I-waves. (+/-)-Baclofen (5 and 25 microM) also inhibited the potassium-evoked release of aspartate and glutamate from small cubes of tissue but, except at a high concentration (1 mM), had no effect on GABA release. Baclofen (up to 1 mM) did not affect transmission either at the lateral olfactory tract-superficial pyramidal cell synapse, a site where aspartate is the likely neurotransmitter, or at the superficial pyramidal cell collateral-deep pyramidal cell excitatory synapse. It is proposed that: (i) the actions of baclofen on the olfactory cortex are the result of inhibition of aspartate and glutamate release, probably from deep pyramidal cell collaterals; and (ii) not all neurones utilizing excitatory amino acids as their neurotransmitters are subject to the inhibitory action of baclofen.

Animals↗

The modulating effect of isoproterenol on DNA replication and protein synthesis. Synthesis patterns of the HMG proteins from electrostatically sorted salivary gland nuclei during the in vivo cell cycle.

Within 96 h after initial isoproterenol administration, DNA replication and cell cycling were activated, as reflected in the bimodal distribution of nuclear fluorescence determined by flow-microfluorometric techniques. A group of proteins, the cetyltrimethylammonium bromide extractable nuclear proteins (CTAB-proteins), isolated form electrostatically sorted nuclei of rat salivary glands, was shown by staining and autoradiography after two-dimensional electrophoresis to undergo differential synthesis during various phases of the in vivo cell cycle after isoproterenol administration. Stained chromatographs revealed quantitative differences in protein synthesis. Gel autoradiography was a more sensitive technique than staining for detecting nuclear protein synthesis during cell cycling. As observed in the autoradiographs of the CTAB-proteins, isoproterenol initiated two distinct periods of protein synthesis in the salivary gland cell cycle: one during the 2C population G0/G1), and one during the 4C population (G2/M). Protein synthesis after isoproterenol administration was much more dramatic in the 2C (isoproterenol) population, where five new spots were seen. There was less radioactive incorporation in the 4C (isoproterenol) population. Two spots 'a' and 'b' that demonstrate differential protein synthesis in stained gel chromatographs and gel autoradiographs were shown to have electrophoretic mobilities, molecular weights and amino acid compositions highly similar to those of HMG1 and HMG2, respectively. A positive correlation could also be drawn between quantitative levels of 'a' and 'b' and their levels of incorporation during cellular activity with HMG (high mobility group) proteins. For example protein 'b' (HMG2) was consistently more abundant in proliferating cell populations than in the quiescent ones. Autoradiographic patterns of the CTAB-proteins indicated that proteins 'a' and 'b' were synthesized during the G0/G1 phase of the cell cycle, as were the majority of CTAB-proteins.

Amino Acids↗

Patterns of endogenous amino acid release from slices of rat and guinea-pig olfactory cortex.

A study has been made of the effects of depolarizing stimuli on the release of endogenous amino acid neurotransmitter candidates (aspartate, glutamate, GABA and taurine) from in vitro preparations of rat and guinea pig olfactory cortex. Exposure of small cubes of olfactory cortex tissue from either species to potassium chloride (50 mM) was accompanied by a calcium-dependent release of aspartate, glutamate and GABA. A similar release pattern was evoked by protoveratrine A (100 muM) although the release was largely calcium-independent. Neither agent led to increased release of taurine. Electrical stimulation of the excitatory input (lateral olfactory tract) of freshly prepared, synaptically intact olfactory cortex slices of both species induced significant release of aspartate and GABA from the uncut pial surface and of aspartate, GABA and glutamate from the cut surface. Evoked taurine release occurred from both surfaces of rat olfactory cortex slices but no release was detected from guinea pig olfactory cortex slices. These patterns of release were unaffected by changes in stimulus frequency and were mimicked by protoveratrine A (100 muM) applied to one or other surface. Preincubation of slices from rats for 2 led to loss of tissue amino acids and to changes in their release patterns; the presence of glutamine (5 mM) during preincubation prevented the loss of amino acids but did not alter their pattern of release. Because of the close similarities between both the electrophysiological properties and the patterns of amino acid release it is concluded that there is probably an identity of amino acid neurotransmitters (aspartate, glutamate and GABA) in rat and guinea pig olfactory cortex. The role of taurine in the rat olfactory cortex is unknown but would seem unlikely to be that of a neurotransmitter. The results are discussed: (i) in terms of the cellular origins of the released amino acids; and (ii) wit respect to apparent experimental discrepancies which have appeared in the literature.

Amino Acids↗

Characterisation of the adrenoceptor mediating changes in cyclic adenosine 3'-5' monophosphate in chick cerebral hemispheres.

Noradrenaline, adrenaline, isoprenaline and salbutamol induced marked accumulations of cyclic AMP in incubated slices of chick cerebral hemispheres. Isoprenaline was both more potent and more powerful than adrenaline or noradrenaline and the increase in cyclic AMP elicited by the catecholamines was powerfully antagonized by the beta-adrenoceptor antagonist propranolol but not by the alphapadrenoceptor blocker phentolamine. The order of potency of the catecholamines isoprenaline greater than adrenaline greater than noradrenaline and the ability of the non-catechol salbutamol to stimulate cyclic AMP accumulation in chick cerebral slices suggests that the beta-adrenoceptro may resemble that found in the lung (beta2) rather than that in the heart (beta1). Propranolol proved to be a very potent antagonist of the cyclic AMP response induced by isoprenaline in vivo. Beta-adrenoceptor blockade was still evident 12 hrs after a single injection of the durg although only negligible amounts of 3H-propranolol could be detected in cerebral tissue after 2 hrs.

Albuterol↗