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Biomedical subjects

I Marshall

Publications and source records attributed to I Marshall.

At least 19 recordsLinked to original sources
PubMed1992

Nitric oxide synthesis inhibitors attenuate calcitonin gene-related peptide endothelium-dependent vasorelaxation in rat aorta.

The effect of inhibitors of nitric oxide synthesis were examined on the endothelium-dependent relaxation induced by acetylcholine and human alpha-calcitonin gene-related peptide (CGRP) on rat isolated aortic rings preconstricted with noradrenaline. The endothelium-dependent vasorelaxation induced by acetylcholine and CGRP was inhibited by NG-monomethyl-L-arginine (L-NMMA) and NG-nitro-L-arginine (L-NOARG) in a concentration-related fashion. The inhibition of endothelium-dependent relaxation by L-NMMA and L-NOARG was partially reversed by L-arginine but not by D-arginine for both acetylcholine and CGRP. The data presented suggests that CGRP, like acetylcholine; relaxes the rat aorta via the release of nitric oxide.

Acetylcholine↗
PubMed1992

Eye-tracking dysfunction in the affective psychoses and schizophrenia.

Smooth pursuit eye movements to a sinusoidally moving target were recorded using the electro-oculogram in 49 subjects with bipolar disorder, 19 with major depressive disorder and 61 with definite schizophrenia, and compared with 145 normal controls. The signals were analysed in the frequency domain to yield a signal to noise ratio that is known to relate to accuracy of smooth pursuit. Smooth pursuit was found to be significantly poorer in schizophrenics than in bipolars, major depressed or controls. Eye-tracking performance was independent of the effects of neuroleptics, tricyclic antidepressants or lithium, and was not altered by the severity of depression in the affective psychoses. There was a small, but significant worsening of smooth pursuit with age in controls and schizophrenics, but this did not account for the group differences. The results support the view that among the major psychoses eye-tracking dysfunction is specific to schizophrenia.

Adolescent↗
PubMed1992

Novel signal transduction pathway mediating endothelium-dependent beta-adrenoceptor vasorelaxation in rat thoracic aorta.

1. Isoprenaline (3 x 10(-8)-10(-5) M), salbutamol (3 x 10(-7)-10(-4) M) and forskolin (3 x 10(-9)-3 x 10(-7) M) relaxed rat isolated thoracic aortic rings contracted with noradrenaline (10(-7) M). Removal of the endothelium from the aortic rings abolished the effect of acetylcholine (10(-6) M) and completely prevented the vascular relaxation induced by isoprenaline, salbutamol or forskolin. 2. The isoprenaline concentration-relaxation curve was shifted in parallel to the right about 10 fold by propranolol (3 x 10(-7) M) with no change in the maximum response, showing that the relaxation was mediated by a beta-adrenoceptor. 3. The inhibitor of nitric oxide synthesis, NG-nitro-L-arginine (L-NOARG; 10(-5) M), shifted the isoprenaline relaxation curve to the right and reduced the maximum response. 4. Isoprenaline (10(-6) M) relaxed noradrenaline-induced tone by approximately 95% and at the same time increased levels of adenosine 3':5'-cyclic monophosphate (cyclic AMP) 4 fold and guanosine 3':5'-cyclic monophosphate (cyclic GMP) 12 fold in the aortic rings. Sodium nitroprusside (3 x 10(-8) M) relaxed noradrenaline-evoked tone by 82% without changing levels of cyclic AMP but raised cyclic GMP 19 fold. 5. Forskolin (10(-7) M) relaxed noradrenaline-induced tone by approximately 41% and, like isoprenaline, increased levels of cyclic AMP (2.5 fold) and cyclic GMP (12 fold) in the aortic rings. 6. Removal of the endothelium abolished the relaxant effects of isoprenaline (10(-6) M) and also the associated accumulation of cyclic AMP and cyclic GMP.7. L-NOARG (10- M) inhibited the relaxant responses and accumulation of cyclic GMP induced by isoprenaline (10-6 M) and forskolin (10- M) without affecting the associated cyclic AMP accumulation.8. It is concluded that, in the rat aorta, isoprenaline acts through a P-adrenoceptor on the endothelium to raise cyclic AMP and that this may, directly or indirectly, release nitric oxide to evoke vascular relaxation via the increase in cyclic GMP. The importance of this novel transduction pathway for cardiovascular regulation remains to be determined.

Albuterol↗
PubMed1992

Human alpha-calcitonin gene-related peptide stimulates adenylate cyclase and guanylate cyclase and relaxes rat thoracic aorta by releasing nitric oxide.

1. The signal transduction pathway for vasorelaxation induced by human alpha-calcitonin gene-related peptide (human alpha-CGRP) was studied in rat thoracic aortic rings preconstricted with noradrenaline (10(-7) M). 2. Vasorelaxation by human alpha-CGRP was inhibited by haemoglobin (10(-6) M) and methylene blue (10(-5) M) but was unaffected by ibuprofen (10(-5) M). 3. Acetylcholine caused a 16 fold increase in levels of guanosine 3':5'-cyclic monophosphate (cyclic GMP) with levels of adenosine 3':5'-cyclic monophosphate (cyclic AMP) being unaltered. Human alpha-CGRP caused a 12 fold increase in levels of cyclic GMP but, in contrast to acetylcholine, evoked a 2.5 fold rise in levels of cyclic AMP. The rises in cyclic nucleotides evoked by human alpha-CGRP and acetylcholine were dependent on the presence of an intact endothelium. 4. NG-nitro-L-arginine (L-NOARG: 10(-5) M), which inhibits nitric oxide synthetase, inhibited the relaxant response to human alpha-CGRP and cyclic GMP accumulation without affecting the cyclic AMP accumulation. 5. The data presented in this paper suggests that human alpha-CGRP relaxes the rat thoracic aorta by releasing nitric oxide and stimulating guanylate cyclase. The stimulation of adenylate cyclase by human alpha-CGRP probably precedes the activation of nitric oxide synthase but could be unrelated to the relaxant response.

Acetylcholine↗
PubMed1991

Acoustic reflectometry for airway measurement. Principles, limitations and previous work.

Acoustic pulse reflectometry is a relatively recent technique which allows the non-invasive measurement of human airways. The technique consists of guiding an acoustic impulse through the subject's mouth and into the airway. Suitable analysis of the resulting reflection (the 'echo') allows a reconstruction of the area-distance function. The non-invasive nature of the technique offers significant advantages over the established methods of x-ray cephalometry and CT scanning, and makes it very attractive for the investigation of ENT problems and sleep apnoea, and in the anaesthetic management of patients. This paper describes the theory and limitations of acoustic reflectometry, discusses previous work, and suggests some modifications: it is currently being implemented clinically.

Acoustics↗
PubMed1991

Stasis oedema in the elderly: are diuretics necessary?

Diuretic therapy was discontinued in 15 elderly patients. None of these patients had evidence of uncontrolled cardiac failure or hypertension, and they all had received diuretics long-term. Two patients required resumption of diuretics due to the development of cardiac failure or severe leg oedema. In the remaining 13 patients, mean leg volume increased by 8.2%. Discontinuation of diuretic therapy in elderly patients is associated with a small but significant worsening of lower limb oedema.

Aged↗
PubMed1989

Comparison of potassium hydroxide digestion and a modified Kato technique for the semi-quantitative estimation of Schistosoma mansoni eggs in faeces.

A simple method for the semi-quantitative estimation of eggs of Schistosoma mansoni in stools, based on digestion of faeces in 4% potassium hydroxide (KOH), is described. The relative performance of KOH digestion and a modified Kato method showed that the former was more sensitive and that the KOH/Kato ratio for the geometric mean number of eggs per gram, in stools positive by both methods, was 3.51.

Feces↗
PubMed1988

Central cardiovascular effects of calcitonin gene-related peptide: interaction with noradrenaline in the nucleus tractus solitarius of rats.

The haemodynamic responses to microinjections of rat or human calcitonin gene-related peptide (CGRP) into the nucleus tractus solitarius (NTS) of rats were studied. 40 fmol rCGRP did not significantly modify cardiovascular parameters, but 0.2 pmol decreased blood pressure and heart rate (HR), whereas 2 pmol produced a pressor response with no effect on HR. hCGRP elicited a transient fall in blood pressure when administered at the highest dose (2 pmol), but had no effects when given at 0.2 pmol. A possible functional relationship with catecholamines was also investigated. The hypotensive response to 20 nmol noradrenaline (NA) was significantly modified by simultaneous administration of a low dose (40 fmol, ineffective alone) of rCGRP. When rCGRP (40 fmol) was coinjected simultaneously with an ineffective dose (10 pmol) of NA, a hypotensive response was observed. Our results provide evidence that rCGRP may play a role in the control of cardiovascular homeostasis in the NTS, and suggest a functional interaction between this peptide and NA.

Animals↗
PubMed1988

Human alpha-calcitonin gene-related peptide (CGRP) is a potent vasodilator in human mesenteric vasculature.

1. The effect of human alpha-calcitonin gene-related peptide (CGRP) and sodium nitroprusside have been measured on human isolated mesenteric vasculature and on rings of human superior mesenteric artery and saphenous vein. 2. When noradrenaline (10(-5) M) was used as the vasoconstrictor in preparations perfused with Krebs solution at constant flow, human alpha-CGRP was 10 times more potent than sodium nitroprusside in evoking dose-dependent falls in perfusion pressure. 3. Human alpha-CGRP and sodium nitroprusside were about equipotent at relaxing rings of superior mesenteric artery contracted by noradrenaline (10(-6) M). When the tone of saphenous vein rings was raised by noradrenaline (10(-6) M), human alpha-CGRP did not relax the vascular smooth muscle. 4. The results show that human alpha-CGRP is a potent vasodilator in human arterial preparations and may act preferentially on arterioles rather than large arteries.

Aged↗
PubMed1987

A microvolt calibrator.

A simple, versatile calibrator for use with electrophysiological instrumentation is described. A novel feature of the device is the simulation of patient electrode resistances.

Calibration↗
PubMed1986

Cardiovascular effects of human and rat CGRP compared in the rat and other species.

In the anaesthetised rat, human and rat CGRP (calcitonin gene-related peptide) which differ by 4 out of 37 amino acids, when given intravenously, lowered blood pressure and increased heart rate. The effects of human CGRP were unaltered by either propranolol or by mepyramine plus cimetidine. In the rat isolated perfused heart the peptides decreased coronary perfusion pressure and evoked a tachycardia. The latter effect was not seen in the rabbit isolated heart, although human CGRP increased coronary flow. The two peptides were equipotent at increasing the rate and force of contraction in the rat isolated right atrium, effects unaltered by propranolol. In the guinea-pig isolated atrium, rat CGRP was 10 times as potent as a chronotropic agent than as an inotrope, unlike human CGRP which was equipotent. In conclusion, human and rat CGRP probably acted directly on the cardiovascular system to produce their qualitatively similar effects.

Animals↗
PubMed1986

Human and rat alpha-CGRP but not calcitonin cause mesenteric vasodilatation in rats.

A single gene encodes both calcitonin and the calcitonin gene-related peptide (CGRP). Human and rat alpha-CGRP were compared with sodium nitroprusside in the rat and rabbit isolated mesenteric vascular preparation perfused at constant flow. In the presence of the vasoconstrictor noradrenaline (10(-5) M), rat alpha-CGRP was about 10 times as potent as either human alpha-CGRP or sodium nitroprusside as a vasodilator in the rat mesenteric vasculature. In the rabbit mesenteric vasculature the order of potency was rat alpha-CGRP greater than human alpha-CGRP greater than sodium nitroprusside. Human and salmon calcitonin showed no vasodilator activity at doses 100 times greater than human alpha-CGRP. These results show that human and rat alpha-CGRP are potent vasodilators in the mesenteric vasculature, an effect not mimicked by the alternative gene product, the plasma calcium lowering hormone calcitonin.

Animals↗
PubMed1986

Postjunctional inhibition of contractor responses in the mouse vas deferens by rat and human calcitonin gene-related peptides (CGRP).

The effects of rat and human alpha-calcitonin gene-related peptide (CGRP) were compared in the mouse and rabbit isolated vas deferens preparation contracted by either field stimulation or acetylcholine. The peptides were about equipotent at inhibiting twitch responses of the mouse vas deferens to field stimulation at 0.2 Hz (IC50 12 +/- 4 nM and 15 +/- 3 nM, rat and human alpha-CGRP respectively). Rat alpha-CGRP was less potent at inhibiting responses to 10 Hz than to either 0.2 Hz or 1.0 Hz stimulation. The potency of rat alpha-CGRP at 1.0 Hz was unaltered by halving the calcium concentration of the Krebs solution. The inhibitory effect of human alpha-CGRP was not antagonized by either propranolol (300 nM) or idazoxan (300 nM), although in the same tissues these latter two drugs reduced responses to isoprenaline and clonidine respectively. Rat alpha-CGRP (100 nM) and human alpha-CGRP (1.0 microM) did not alter the uptake of [3H]-noradrenaline (30 nM) into mice isolated vasa deferentia. Rat alpha-CGRP (3-100 nM) did not alter the fractional release per pulse (1.0 Hz, 100 pulses) of tritium from vasa preloaded with [3H]-noradrenaline, although at the same time the peptide inhibited responses of the smooth muscle to field stimulation. Rat and human alpha-CGRP were equipotent at inhibiting contractions of the mouse vas deferens evoked by acetylcholine although the peptides were less potent than against twitch responses. In the rabbit vas deferens neither rat nor human alpha-CGRP (3 nM-1 microM) inhibited either twitch responses or acetylcholine contractions. 7 These results suggest that rat and human alpha-CGRP inhibit contractor responses of the mouse vas deferens not by interference with adrenergic mechanisms, but through postjunctional (possibly CGRP) receptors. A similar mechanism may underlie effects ofCGRP in other tissues. The rabbit vas deferens appears to lack the CGRP 'receptors'.

Acetylcholine↗
PubMed1986

Expression and function of the human calcitonin/alpha-CGRP gene in health and disease.

Studies on the structure and expression of the rat and human calcitonin gene provide a remarkable example by which a combination of molecular, immunocytochemical and pharmacological techniques have led to the identification of a novel gene product, the calcitonin gene-related peptide, a peptide of unexpected tissue distribution and biological activity. Future studies at the molecular level will provide insight into post-transcriptional mechanisms by which a single gene can give rise to discrete mRNAs in a tissue-specific manner. The isolation and characterization of the CGRP receptor, and hence the site(s) and mechanism(s) of action of the CGRP family within the vasculature, will also add significantly to our understanding of molecular mechanisms involved in the modulation of cardiovascular function in man. Furthermore, the role and mechanism of action of the CGRP peptide family in the central and peripheral nervous systems remains to be elucidated. It is also apparent that measurement of circulating plasma levels of CGRP may be of diagnostic and prognostic value, providing information concerning the onset and progression of lung and thyroid carcinoma. Our analysis of the structure and expression of the calcitonin/alpha-CGRP gene also demonstrates, for the first time, the molecular basis of large calcitonin secretion by lung carcinoma cells. Whether the expression of this gene in lung carcinoma cell-lines can truly be described as 'ectopic' is however questionable, in the light of recent immunocytochemical evidence which demonstrates that the lung is a major source of CGRP producing cells in the rat (see Springall et al., 1984).

Amino Acid Sequence↗