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Biomedical subjects

J Chalmers

Publications and source records attributed to J Chalmers.

At least 19 recordsLinked to original sources
PubMed1992

Sympathetic preganglionic neurons projecting to the adrenal medulla and aorticorenal ganglion in the rabbit.

The distribution of sympathetic preganglionic neurons (SPN) projecting to the adrenal medulla and the aorticorenal ganglion in the rabbit was studied using a dual retrograde transport technique. The B subunit of cholera toxin (CTB) was injected into the left adrenal medulla and wheatgerm agglutinin-apo-horseradish peroxidase-7 nm gold (WGA-apo-HRP-gold) was injected into the left aorticorenal ganglion. Retrogradely transported CTB was detected by immunohistochemistry, while gold particles were detected by silver intensification. SPN projecting to the adrenal medulla were observed in segments T2-L2 of the spinal cord in 5 rabbits, with the majority of cells within segments T6-T11 (79%). SPN projecting to the aorticorenal ganglion were seen in segments T2-L1 of the spinal cord in 5 rabbits, with the greatest number of the cells within T6-T11 (81%). Only a small number of doubly labelled cells (1%) were found in two rabbits. The results suggest that despite their similar segmental distribution SPN projecting to the adrenal medulla or the aorticorenal ganglion belong to separate populations and few, if any, individual SPN have axonal projections to both locations.

Adrenal Medulla↗
PubMed1992

Substance P immunoreactive boutons form synapses with feline sympathetic preganglionic neurons.

In this study, the relationship between substance P-immunoreactive boutons and antidromically activated sympathetic preganglionic neurons was examined by light and electron microscopy. Sympathetic preganglionic neurons in the T2-T4 spinal segments of the cat were identified by intracellular recording and antidromic activation from the corresponding white ramus. Neurons were filled with lucifer yellow and then stained to reveal, simultaneously, substance P and lucifer yellow immunoreactivity. All of the neurons examined with the light microscope (n = 13) received appositions from substance P-immunoreactive boutons. Appositions were found on all parts of the neuron, including the somata, dendrites, and axon initial segment. In most cases (11/13) few close appositions were seen; however, two neurons received large numbers of appositions from substance P-immunoreactive boutons. On one neuron, 16 substance P-immunoreactive varicosities that were identified as being closely apposed at the light microscope level were serially sectioned and examined with the electron microscope. Of these 16 varicosities, eight either directly contacted the neuron or formed morphologically identifiable synapses. The remaining eight varicosities were separated from the neuron by thin glial processes. Two other sympathetic preganglionic neurons that were examined ultrastructurally also received substance P-immunoreactive synapses and close contacts. These findings suggest that substance P-containing nerve fibres could affect all sympathetic preganglionic neurons but are likely to be important in regulating the activity of only a small proportion of these neurons.

Animals↗
PubMed1992

Sympathetic preganglionic neurons in rabbit spinal cord that project to the stellate or the superior cervical ganglion.

The segmental distribution of sympathetic preganglionic neurons in the rabbit spinal cord that project to the stellate or the superior cervical ganglion was determined using retrograde tracing with cholera toxin B subunit from the stellate ganglion and wheat germ agglutinin-apo-horseradish peroxidase-gold from the superior cervical ganglion. Sympathetic preganglionic neurons that projected to the stellate ganglion were located in spinal segments T1 to T10. Sympathetic preganglionic neurons projecting to the superior cervical ganglion were found in segments T1 to T8. Both types of neuron had somata that were elongated in the rostrocaudal direction, and dendrites that were mainly confined to the intermediolateral cell column. Almost 95% of the neurons supplying the superior cervical ganglion had axons that passed through the stellate ganglion.

Animals↗
PubMed1992

The metabolism of aminoacetone to methylglyoxal by semicarbazide-sensitive amine oxidase in human umbilical artery.

The aliphatic amine aminoacetone has been described previously as a product of mitochondrial metabolism of threonine and glycine. Here, aminoacetone is shown to be deaminated to methylglyoxal by supernatants obtained by low speed centrifugation (600 g/10 min) of human umbilical artery homogenates, and also by membrane fractions isolated by high speed centrifugation (105,000 g/60 min) of these supernatants. Metabolism of 100 microM aminoacetone was completely inhibited by 1 mM propargylamine and MDL 72145, drugs which are capable of inhibiting the membrane-bound semicarbazide-sensitive amine oxidase (SSAO) activity found in vascular smooth muscle cells, whereas 1 mM pargyline and deprenyl which are inhibitors of monoamine oxidase, were without inhibitory effect. Estimated kinetic constants (at pH 7.8) for aminoacetone metabolism were Km = 92 microM; Vmax = 270 nmol/hr/mg protein. In addition, aminoacetone was a competitive inhibitor (Ki = 83 microM and 128 microM in low speed supernatants and high speed membrane fractions, respectively) of [14C]benzylamine metabolism by SSAO in this tissue. Aminoacetone would appear to be an endogenously occurring amine with a Km for metabolism by SSAO far lower than other aliphatic and aromatic biogenic amines examined previously as potential physiological substrates for the human vascular enzyme and possible implications of this are discussed.

Acetone↗
PubMed1992

Interactions of endogenous opioid and excitatory amino acid inputs to the caudal ventrolateral medulla of the rat.

This study investigated the cardiovascular consequences of interactions between endogenous opioid and excitatory amino acid inputs to the caudal ventrolateral medulla of the anaesthetised rat. Drugs were injected bilaterally into the functionally identified depressor region of the caudal ventrolateral medulla. The opioid antagonist, naloxone (2.5-8.0 nmol/side) elicited a dose-dependent decrease in blood pressure and a bradycardia. The NMDA-receptor antagonist, 2-amino, 5-phosphonovaleric acid (2-APV; 1.25-500 pmol/side), dose-dependently increased blood pressure but had little effect on heart rate. After the maximum dose of naloxone, the pressor response to both 1.25 and 25 pmol/side of 2-APV was attenuated by 89 and 66%, respectively. By contrast, the pressor response, elicited by injection of the GABA agonist, muscimol (1 pmol/side), was not affected. After 2-APV (500 pmol/side), the depressor response to 2.5 nmol/side of naloxone was enhanced by 84%, although this effect was lost when a larger dose of naloxone (5 nmol/side) was used. 2-Amino,5-phosphonovaleric acid also potentiated the depressor response to a submaximal dose of the GABA antagonist, bicuculline (2 pmol/side). The results suggest firstly that, in the caudal ventrolateral medulla, excitatory amino acid inputs are functionally less important when tonic opioid effects are blocked. This interaction appears to be pharmacologically specific. Secondly, tonic inhibitory inputs, whether due to opioids or to GABA, are functionally more effective after excitatory amino acid inputs are antagonized.

2-Amino-5-phosphonovalerate↗
PubMed1992

Haemodynamic and neurohumoral response in heart failure produced by rapid ventricular pacing.

OBJECTIVE: The aim was to determine the exact sequence of hormone changes during the progression of fluid retention in a canine model of "congestive cardiac failure" induced by rapid right ventricular pacing, and during recovery when pacing is stopped. METHODS: Rapid ventricular pacing at a rate of 250 pulses.min-1 was used in six mongrel dogs with implanted right ventricular pacemakers. Right heart haemodynamics were measured by means of Swan Ganz catheterisation, allowing flow measurement by thermodilution and pressure measurement by external manometry. Plasma renin activity, arginine vasopressin, and atrial natriuretic factor were assayed on venous blood samples by radioimmunoassay. Noradrenaline was assayed by high pressure liquid chromatography. RESULTS: The onset of rapid pacing was accompanied by a fall in cardiac output and a rise in pulmonary arterial, pulmonary capillary wedge, and right atrial pressures. Noradrenaline and atrial natriuretic factor rose. Plasma renin activity showed an initial fall followed by a rise, and arginine vasopressin was unchanged in the first 8 h. When rapid pacing was continued for a further 35 d, clinical signs of fluid retention appeared by day 28, by which time cardiac output had fallen, and central pressures risen further. Atrial natriuretic factor peaked at around 14 d whereas plasma renin activity, arginine vasopressin, and noradrenaline tended to reach a plateau at about d 20 and then to show further increases as clinical signs of fluid retention appeared; this was most marked with plasma renin activity. Cessation of pacing at d 35 caused a rapid reversal (increase) of cardiac output but a more gradual reversal (decrease) of right heart pressures over 5 d; only wedge pressure returned to base line. Arginine vasopressin and plasma renin activity fell rapidly to around 40% of the final pacing levels and reached basal values after 8 h and 48 h respectively. Noradrenaline fell after 8 h and reached basal levels in 5 d. Atrial natriuretic factor fell quickly by 60% after 8 h but remained above basal levels for 5 d. At the end of pacing, body weight fell rapidly in conjunction with a large diuresis. CONCLUSIONS: These findings are compatible with a major role of one or more of renin, vasopressin, and noradrenaline in the pathophysiology of the fluid retention of heart failure; the manifestations are not counteracted by the rise in atrial natriuretic factor.

Animals↗
PubMed1992

Ventral medulla stimulation increases blood pressure and spinal cord amino acid release.

Microdialysis in combination with HPLC and fluorescence detection was used to measure the release of endogenous amino acids from the region of the intermediolateral cell column of rat thoracic spinal cord in response to electrical stimulation of the rostral ventrolateral medulla (RVLM). Stimulation of the RVLM led to a marked rise in blood pressure (74 +/- 6 mm Hg) accompanied by an immediate increase in the release of glutamate (80%) and aspartate (50%). Small increases in the release of glycine and taurine were found, but there were no changes in alanine and serine release. These results suggest that the RVLM pressor pathway to the thoracic spinal cord may use, at least in part, excitatory amino acids as neurotransmitters, supporting previous pharmacological and neuroanatomical investigations of this bulbospinal pathway.

Alanine↗
PubMed1992

Kainic acid injection in NTS evokes hypertension and c-fos expression in spinal cord.

Kainic acid injected into rat nucleus tractus solitarius (NTS) caused a slowly developing hypertension, with a 2-fold increase in Fos-immunoreactive (Fos-IR) nuclei in the area of the presympathetic bulbospinal neurons in the rostral ventrolateral medulla (RVLM) and a widespread activation of sympathetic preganglionic neurons (SPN) in the spinal cord, particularly in the mid to lower thoracic cord. The highest segmental concentration of Fos-IR SPN was in T8, with Fos-IR nuclei increased 12-fold compared with the vehicle injected group. More than 60% of retrogradely labelled sympathoadrenal neurons in T8 were Fos-IR after kainic acid injection, consistent with the 60-fold increases in plasma adrenaline levels observed in these rats.

Animals↗
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↗