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Biomedical subjects

J Chalmers

Publications and source records attributed to J Chalmers.

At least 127 records · Page 7Linked to original sources
PubMed1992

Axonal projections from respiratory centres towards the rostral ventrolateral medulla in the rat.

1. Efferent pathways from brainstem respiratory centres towards bulbospinal tyrosine hydroxylase immunoreactive neurons were identified in the rat using a combination of electrophysiology, retrograde and anterograde tract-tracing, and immunohistochemistry. 2. Varicose axons originating from respiratory centres were found in close apposition to bulbospinal tyrosine hydroxylase immunoreactive neurons in the ventrolateral medulla. 3. These findings support the idea that respiratory rhythms in sympathetic nerves may be due to a synaptic connection between brainstem respiratory neurons and bulbospinal tyrosine hydroxylase immunoreactive neurons of the C1 cell group.

Animals↗
PubMed1992

Amino acid neurotransmitters in hypertension.

There is compelling evidence for the participation of excitatory and inhibitory amino acids in the neural regulation of blood pressure in the normotensive rat. This is most clearly evident in the neural pathways which form the baroreceptor reflex arc. Excitatory amino acids are contained in baroreceptor afferents, neurons in the nucleus tractus solitarius (NTS) and neurons in the rostral ventrolateral medulla (RVLM). Inhibitory neurons in the caudal ventrolateral medulla (CVLM) contain gamma-aminobutyric acid. Electrophysiological and pharmacological evidence indicates that amino acid neurotransmitters are critically important to the normal function of these integrative sites in the baroreceptor reflex. Spontaneously hypertensive rats (SHR) differ from Wistar Kyoto (WKY) controls in their responses to stimulation, inhibition or lesions of neurons in the baroreceptor arc. One week after baroreceptor denervation, blood pressure is elevated in WKY but not in SHR. Stimulation of the CVLM results in a greater fall in pressure in SHR than WKY, whereas injection of tetrodotoxin into the CVLM results in a smaller increase in pressure in SHR. Blockade of glutamate receptors in the spinal cord attenuates the response to stimulation of the RVLM in both SHR and WKY, but reduces resting blood pressure in SHR only. These experiments suggest that altered activity in amino acid pathways contributes to the pathogenesis of hypertension in SHR.

Amino Acids↗
PubMed1992

An audit of non-insulin-dependent diabetics attending a district general hospital diabetic clinic: implications for shared care between hospital and general practice.

An audit of all 466 non-insulin-dependent diabetic patients first diagnosed between 1979 and 1981 at a district general hospital in Fife was carried out. This involved the retrospective examination of their medical records and follow up of the patients to 1989 with particular reference to mortality and the development of complications. Throughout the study period the hospital, which has a total catchment population of about 160,000, operated a policy of encouraging all newly diagnosed diabetics to be referred to hospital for assessment and management. One hundred and eighty-nine diabetics (41%) died during the follow-up period. In both sexes they had an excess mortality, compared with the Scottish population of the same sex and age in 1981, of approximately 20% at 40 years of age. This increased to double or above between the ages of 60 and 70. The principal underlying cause of death was attributed to macrovascular disease, including 70 (37%) certified as ischaemic heart disease, 33 (17%) as cerebrovascular disease and 10 (5%) as other diseases of circulation. Thirty-five (8%) diabetics developed macrovascular and 23 (5%) microvascular complications during follow-up. We conclude that non-insulin-dependent diabetics have a high mortality, principally from macrovascular causes. A simple audit of mortality is suitable for measuring their care. General practitioner diabetic mini-clinics for the follow-up of non-insulin-dependent diabetic patients will have smaller numbers of patients to review compared with the traditional follow-up clinics seen in most district general hospitals. These may allow earlier detection and treatment of hypertension and dyslipidaemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Different populations of parvalbumin- and calbindin-D28k-immunoreactive neurons contain GABA and accumulate 3H-D-aspartate in the dorsal horn of the rat spinal cord.

The colocalization of parvalbumin (PV), calbindin-D28k (CaBP), GABA immunoreactivities, and the ability to accumulate 3H-D-aspartate selectively were investigated in neurons of laminae I-IV of the dorsal horn of the rat spinal cord. Following injection of 3H-D-aspartate into the basal dorsal horn (laminae IV-VI), perikarya selectively accumulating 3H-D-aspartate were detected in araldite embedded semithin sections by autoradiography, and consecutive semithin sections were treated to reveal PV, CaBP and GABA by postembedding immunocytochemistry. Perikarya accumulating 3H-D-aspartate were found exclusively in laminae I-III, and no labelled somata were found in deeper layers or in the intermediolateral column although the labelled amino acid clearly spread to these regions. More than half of the labelled cells were localized in lamina II. In this layer, 16.4% of 3H-D-aspartate-labelled perikarya were also stained for CaBP. In contrast to CaBP, PV or GABA was never detected in neurons accumulating 3H-D-aspartate. A high proportion of PV-immunoreactive perikarya were also stained for GABA in laminae II and III (70.0% and 61.2% respectively). However, the majority of CaBP-immunoreactive perikarya were GABA-negative. GABA-immunoreactivity was found in less than 2% of the total population of cells stained for CaBP in laminae I-IV. A significant proportion of the GABA-negative but PV-immunoreactive neurons also showed CaBP-immunoreactivity in laminae II and IV. These results show that out of the two calcium-binding proteins, CaBP is a characteristic protein of a small subpopulation of neurons using excitatory amino acids and PV is a characteristic protein of a subpopulation of neurons utilizing GABA as a transmitter. However, both proteins are present in additional subgroups of neurons, and neuronal populations using inhibitory or excitatory amino acid transmitters are heterogeneous with regard to their content of calcium-binding proteins in the dorsal horn of the rat spinal cord.

Animals↗
PubMed1991

An X-linked zinc finger gene mapping to Xq21.1-q21.3 closely related to ZFX and ZFY: possible origins from a common ancestral gene.

We describe a new zinc finger gene sequence (CMPX1 or HGM symbol ZNF6; isolated by cross-hybridization of ZFY to clones in a testis cDNA library) which possesses a zinc finger domain closely related to the transcriptional activator gene ZFX. The putative acidic activation domain is only 11.5% homologous with ZFX, whereas the putative DNA binding domain shares 75% homology and shows the same organisation composed of a basic two fingered repeat unit. ZNF6 has an unusually large 5' untranslated region (UTR) of 1.2 Kb which contains 26 potential ATG initiation codons, only one of which is associated with a long open reading frame. Southern and Northern blot analysis has shown that this 5' UTR is shared with many other sequences in the genome and transcribed associated with a large range of mRNA species. In situ hybridisation, analysis of somatic cell hybrids and male individuals carrying deleted X chromosomes have mapped the gene to Xq21.1-q21.3. The gene is highly conserved amongst the primates, in the mouse and can be detected weakly in the genome of a metatherian mammal (possum). Dosage in male and female mice indicates that it is also X-linked in this species. Possible origins of ZFX, ZFY and CMPX1 from a common ancestral gene are discussed.

Amino Acid Sequence↗
PubMed1991

Glutamate in spinally projecting neurons of the rostral ventral medulla.

Phosphate activated glutaminase (PAG), an enzyme of glutamate synthesis, was localized by immunohistochemistry in all PNMT-immunoreactive and all serotonin-immunoreactive neurons in the rostral ventral medulla of the rat. Between 71 and 83% of bulbospinal neurons localised in the rostral ventral medulla projecting to the intermediolateral cell column in the upper thoracic spinal cord contained PAG immunoreactivity. Of these bulbospinal PAG-immunoreactive neurons 17-27% contained PNMT immunoreactivity and 9-16% contained serotonin immunoreactivity. Other bulbospinal PAG-immunoreactive neurons (60-70%) contained neither PNMT- nor serotonin immunoreactivity. The results provide anatomical evidence suggestive of a glutamatergic input to the sympathetic preganglionic neurons of the spinal cord arising from different populations of neurons located in the rostral ventral medulla.

Animals↗
PubMed1991

Endogenous opioids tonically inhibit the depressor neurones in the caudal ventrolateral medulla of rabbits: mediation through delta- and kappa-receptors.

In the present studies, an attempt was made to elucidate the role of endogenous opioid inputs to the depressor region of the caudal ventrolateral medulla in the tonic regulation of arterial pressure and to examine the subtype(s) of receptor underlying any observed effects by use of receptor-specific antagonists. The depressor region of the caudal ventrolateral medulla in chloralose-anesthetized, artificially ventilated rabbits was functionally identified by injection of l-glutamate (5 nmol). Bilateral injection of the non-selective opioid antagonist naloxone (0.3, 5 and 20 nmol) into the caudal ventrolateral medulla produced a dose-dependent depressor response, accompanied by a bradycardia, suggesting a tonically active inhibitory opioid input to this region. Bilateral injection of the selective delta-receptor antagonist ICI 174,864 (0.3 nmol) or of the kappa-receptor antagonist nor-binaltorphimine (1 nmol), also markedly reduced both arterial pressure and heart rate. In contrast, injection of the mu-selective antagonist beta-funaltrexamine (0.3-0.6 nmol) produced no effect on arterial pressure or heart rate. These data support the hypothesis that tonically active endogenous opioid inputs, possibly enkephalinergic and/or dynorphinergic, inhibit the depressor neurones of the caudal ventrolateral medulla in the rabbit through activation of delta- and kappa-receptors. Surprisingly, injection of the opioid agonists leu-enkephalin (1 nmol) or dynorphin 1-13 (0.1 nmol), but not the selective mu-receptor agonist DAGO (1 nmol), in the depressor area of the caudal ventrolateral medulla also induced naloxone-sensitive (5 mg/kg, i.v.) decreases in both arterial pressure and heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1991

Opioid innervation of the caudal ventrolateral medulla is not critical for the expression of the aortic depressor nerve response in the rabbit.

We investigated the influence of endogenous opioids in the caudal ventrolateral medulla (CVLM) on the expression of the baroreflex response induced by the electrical stimulation (50 Hz, 0.2 ms, 11 V, 10 s) of the aortic depressor nerve. We used microinjection of selective opioid antagonists into the functionally identified depressor area of the CVLM in chloralose-anesthetized rabbits. Injection of vehicles or the mu-antagonist beta-funaltrexamine (0.3 nmol) into the CVLM had no effects, while naloxone (20 nmol), ICI 174,864 (delta-antagonist, 0.3 nmol) or nor-binaltorphimine (kappa-antagonist, 1 nmol) abolished the depressor response, but themselves all elicited a tonic depressor effect as well. In contrast, intravenous naloxone (5 mg/kg) induced a small but significant increase in arterial pressure and did not alter the depressor response. Hypotensive hemorrhage induced a decrease in arterial pressure similar to that seen with local injection of naloxone into the CVLM, but did not change the reflex, suggesting that the reflex abolition was not due to the decrease in basal arterial pressure per se. CVLM injection of glutamate (10 nmol) or the GABA-antagonist bicuculline (0.1 nmol), non-opioid agents which activate CVLM and induce a tonic depressor effect, also abolished the depressor response suggesting that the reflex abolition was secondary to general activation or disinhibition of the CVLM. Thus, although the CVLM is tonically inhibited by endogenous opioid inputs acting via delta- and kappa-receptors, our data provide no evidence that opioid neurons which provide input to this region constitute a specific and integral component in mediating the aortic depressor response. However, the more general role that opioids play in tonically influencing the resting level of activity in the CVLM, is nevertheless very important in enabling the normal expression of this baroreflex.

Animals↗
PubMed1991

Perceived risk, stigma, and potential economic impacts of a high-level nuclear waste repository in Nevada.

This study investigates the potential impacts of the proposed nuclear waste repository at Yucca Mountain, Nevada, upon tourism, retirement and job-related migration, and business development in Las Vegas and the state. Adverse impacts may be expected to result from perceptions of risk, stigmatization, and socially amplified reactions to "unfortunate events" associated with the repository (major and minor accidents, discoveries of radiation releases, evidence of mismanagement, attempts to sabotage or disrupt the facility, etc.). The conceptual underpinnings of risk perception, stigmatization, and social amplification are discussed and empirical data are presented to demonstrate how nuclear images associated with Las Vegas and the State of Nevada might trigger adverse economic effects. The possibility that intense negative imagery associated with the repository may cause significant harm to Nevada's economy can no longer be ignored by serious attempts to assess the risks and impacts of this unique facility. The behavioral processes described here appear relevant as well to the social impact assessment of any proposed facility that produces, uses, transports, or disposes of hazardous materials.

Humans↗
PubMed1991

Severe amnesia after hypoglycemia. Clinical, psychometric, and magnetic resonance imaging correlations.

OBJECTIVE: To determine the correlation between clinical, psychometric, and magnetic resonance imaging (MRI) findings after an episode of hypoglycemic coma resulting in amnesia. RESEARCH DESIGN AND METHODS: Detailed psychometric assessment, especially memory testing, performed with MRI in a man with severe amnesia after hypoglycemic coma. RESULTS: Psychometric testing confirmed impaired immediate recall. MRI findings were consistent with a lesion in the left temporal lobe. CONCLUSIONS: This is the first description of MRI in determining the neurological damage in hypoglycemic coma.

Adult↗
PubMed1991

Recurrent common peroneal palsy in association with the Ehlers-Danlos syndrome. A case report.

We report a patient with type III Ehlers-Danlos syndrome, presenting with recurrent footdrop, who had electrophysiologic evidence of a conduction block of the common peroneal nerve followed by complete resolution. We feel that this case supports the possible link between Ehlers-Danlos syndrome and multiple pressure sensitive neuropathy (tomaculous neuropathy), alluded to by Schady and Ochoa (1984).

Adult↗
PubMed1990

Central serotonergic mechanisms in cardiovascular regulation.

This paper reviews the role of central serotonin-containing neurons in the control of blood pressure. Central serotonin nerves have their cell bodies in the brainstem in a number of discrete collections, from where they ascend to ramify throughout the brain, descend to terminate in the spinal cord, or send shorter projections terminating in medulla, pons, and midbrain. Activation of one important ascending serotonin pathway innervating the preoptic region of the hypothalamus causes an increase in blood pressure. Activation of a bulbospinal serotonin projection descending from the ventrolateral medulla (the B3 cell group) to terminate in the intermediolateral cell column (IML) also evokes a pressor response. This pressor response is independent of that elicited by stimulation of the ventrolateral medulla in the adjacent but separate area containing the C1 adrenaline cell group. The pressor action appears to depend on increased release of serotonin, as detected by microdialysis in the area of the IML, and to be mediated by serotonin receptors of the 5HT1 subclass, probably located on sympathetic preganglionic neurons. It is possible that neuroactive excitatory amino acids, such as glutamate or aspartate, and neuropeptides such as substance P, also play a part in the pressor response evoked by stimulation of the ventrolateral medulla in the area of the lateral B3 serotonin cells. This descending serotonin pathway also appears important in mediating the hypotensive action of the antihypertensive drugs methyldopa and clonidine.

Animals↗
PubMed1990

Quantitative analysis of spinally projecting adrenaline-synthesising neurons of C1, C2 and C3 groups in rat medulla oblongata.

Spinal projections of the phenylethanolamine N-methyltransferase (PNMT) immunoreactive neurons of the medulla were investigated using a combination of immunohistochemistry and retrograde transport of colloidal gold particles conjugated to cholera toxin B subunit (CTB-gold). The PNMT-containing adrenergic neurons were localised in three groups, the C1 group in the rostral ventrolateral medulla, the C2 group in the nucleus tractus solitarius/dorsal vagal motor complex in the dorsal medulla and the C3 group in the mediodorsal medulla. The C1 group contained 72% of the medullary PNMT-IR neurons, while C2 comprised 13% and C3 15% of the medullary PNMT-IR neuron population. CTB-gold was injected in the area of the intermediolateral cell column in either upper (T2-T4) or lower (T8-T9) thoracic spinal cord and retrogradely labelled cells were found in the areas of the C1, C2 and C3 groups and in other regions of the medulla which did not contain PNMT-IR neurons. After tracer injections bilaterally at levels T2-T4, retrograde labelling suggested that at least 21% of all medullary PNMT-IR neurons projected to these levels. As a proportion of each group, 26% of C1, 9% of C2 and 33% of C3 neurons projected spinally to T2-T4. After tracer injections bilaterally at levels T8-T9, retrograde labelling suggested that at least 17% of all medullary PNMT-IR neurons projected to these levels. As a proportion of each group, 16% of C1, 9% of C2 and 30% of C3 neurons projected spinally to T8-T9. These figures represent minimum numbers since it is impossible to ensure that every neuron has equal access to the tracer. The results demonstrate that contrary to previous belief, the PNMT-IR innervation of the spinal cord derives from PNMT-IR neurons in the dorsal medulla, as well as from the rostral ventrolateral medulla. Indeed 24% of the PNMT-IR neurons terminating at spinal cord levels T2-T4, and 35% of those terminating at levels T8-T9, derive from the dorsal (C2 and C3) medullary cell groups. Since the PNMT-IR projections are directed towards the intermediolateral cell column, it seems likely that all three groups of medullary adrenaline-containing neurons contribute to the regulation of sympathetic outflow.

Animals↗