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Biomedical subjects

J M Allen

Publications and source records attributed to J M Allen.

At least 217 records · Page 12Linked to original sources

The inhibitory effect of aspirin on lymphatic contractility.

Spontaneous contractions and those elicited by two different methods of electrical stimulation were studied in isolated segments of bovine mesenteric lymphatic vessels. The effect of aspirin (a cyclo-oxygenase inhibitor) on spontaneous and evoked contractions of isolated lymphatic vessels was investigated. Aspirin at doses of 10(-6) M or greater depressed both spontaneous and action potential-dependent evoked contractions, but failed to inhibit contractions evoked by high current field stimulation. These latter contractions were rapidly depressed by the application of D600. When aspirin was applied for five minute periods, inhibition never occurred within the period of drug administration but was delayed, with maximum inhibition occurring approximately 10 min after washout of the drug. It is concluded that the inhibitory action of aspirin is unlikely to be a non-specific depression of the contractile mechanism, but rather a reduction in excitability probably as a result of cyclo-oxygenase inhibition.

Action Potentials↗

Release of neuropeptide Y in response to splanchnic nerve stimulation in the conscious calf.

Plasma concentrations of neuropeptide Y were determined by means of a specific radioimmunoassay in the conscious calf. Significantly higher concentrations were found in the adrenal venous effluent (102 +/- 34 pmol/l) compared to systemic arterial plasma (11 +/- 7 pmol/l). Stimulation of the splanchnic nerves at 40 Hz in bursts for 1 s at 10 s intervals resulted in a slow sustained rise in plasma neuropeptide Y in both adrenal (peak 1124 +/- 217 pmol/l and peripheral (peak 771 +/- 182 pmol/l) samples. Experiments performed in adrenalectomized calves produced a closely similar release of neuropeptide Y when the nerves were stimulated intermittently in the same pattern and under the same conditions. Stimulation of the splanchnic nerves at 4 Hz continuously resulted in a smaller response. Pre-treatment with hexamethonium completely abolished the rise in plasma neuropeptide Y concentrations.

Adrenal Glands↗

Neuropeptide tyrosine (NPY): a newly discovered peptide is present in the mammalian respiratory tract.

Neuropeptide tyrosine (NPY), a newly discovered peptide known to modulate blood vessel diameter and smooth muscle tone, has been found in many mammalian organs. Its distribution is similar to that of sympathetic nerve fibres and NPY immunoreactivity has been found in noradrenergic ganglion cells. In a study of the respiratory tract of four mammalian species--man, cat, guinea pig, and rat--NPY immunoreactivity has been localised to nerve fibres. NPY immunoreactive nerve fibres were found in the adventitia of blood vessels and in the airway smooth muscle. Its distribution was strikingly similar to that of sympathetic nerve fibres as demonstrated by dopamine-beta-hydroxylase antibodies. The mean (SD) concentrations of NPY in the guinea pig respiratory tract, as determined by radioimmunoassay of tissue extracts, were: upper trachea 3.3 (0.7), lower trachea 2.0 (0.5), and major bronchus 3.5 (1.1) pmol/g. During developmental studies in man NPY immunoreactive nerve fibres were first observed at 20 weeks' gestation in the trachea, and fibres gradually extended down into the intrapulmonary airways after birth. NPY immunoreactive nerve fibres have a distribution and developmental pattern similar to that of sympathetic nerve fibres in the respiratory tract. The finding of NPY immunoreactivity in nerve fibres in the mammalian respiratory tract adds to the growing number of peptides having potent biological actions found in this organ, and shows that the lung possesses a rich peptidergic system, which may influence pulmonary function.

Adolescent↗

Effects of peptide YY and neuropeptide Y on gastric emptying in man.

Neuropeptide Y (NPY) and peptide YY (PYY) are two structurally related peptides. PYY has been identified within endocrine cells and NPY within nerves of the gastrointestinal tract. Infusion of PYY at a low dose at a nominal rate of 2 pmol/kg/min resulted in an increment of 59.2 +/- 7.1 pmol/1 in plasma concentration and a significant delay in gastric emptying of glucose. Infusion of NPY at the same rate produced similar plasma concentrations (52.5 +/- 1.1 pmol/1) and had no significant effect on the rate of gastric emptying.

Adolescent↗

High concentrations of a novel peptide, neuropeptide Y, in the innervation of mouse and rat heart.

A newly discovered bioactive peptide, neuropeptide Y (NPY), has been found in the innervation of the mouse and rat heart by immunocytochemistry, NPY-immuno-reactive nerves were very dense around the nodal tissues. They also surrounded the coronary arteries and arterioles and were found in close association with the cardiac muscle. The distribution of NPY-containing nerves paralleled that of noradrenergic fibers, demonstrated by the use of antibodies to the catecholamine-converting enzymes tyrosine hydroxylase and dopamine beta-hydroxylase. Furthermore, NPY was seen to be present in a proportion of intrinsic neurons mostly found in the atria and in close proximity to the nodal tissue. The concentrations of extractable NPY-immunoreactive material (about 150 pmol/g in whole mouse heart) by far surpasses those of the other peptides so far reported in the cardiac tissue. High performance liquid chromatography demonstrated the NPY immunoreactivity to elute in a single sharp peak, in an identical position to brain NPY.

Animals↗

Neuropeptide tyrosine (NPY) immunoreactivity in norepinephrine-containing cells and nerves of the mammalian adrenal gland.

The application of immunocytochemistry at both light and electron microscopic levels has revealed neuropeptide tyrosine (NPY)-immunoreactive material to be localized to norepinephrine-containing endocrine cells in the adrenal medulla and also to varicose nerve fibers penetrating the adrenal cortex of several mammalian species, including horse, cat, rat, guinea pig and mouse. Correlative electron microscopic immunostaining has revealed that enkephalin and NPY immunoreactivities are co-localized to the same norepinephrine-containing secretory granules. High concentrations of NPY have been extracted from the mouse adrenal gland (1243.7 +/- 122.8 pmol NPY/g wet tissue; mean +/- SE). Chromatographic analysis has shown the extracted material to correspond with pure natural NPY.

Adrenal Medulla↗

The metabolism of intravenously infused neurotensin in man and its chromatographic characterization in human plasma.

The metabolism of iv infused neurotensin (NT) was studied and its disappearance half-time compared with that of infused N-terminal octapeptide of NT 1-8 in six normal subjects by RIA with antisera directed against the C- and N-terminal regions of the NT molecule. The disappearance half-time of NT in circulating plasma was 1.4 min measured with the C-terminal antibody and 6.0 min measured with the N-terminal antibody. The disappearance half-time of NT 1-8 was 30 min measured with the N-terminal antibody. Gel filtration and high pressure liquid chromatographic analysis indicated that a substantial amount of immunoreactive NT in the plasma of subjects infused with synthetic NT was eluted at the NT 1-8 position and a lesser amount of plasma NT-like immunoreactivity was eluted with synthetic NT. These findings suggest that NT is readily metabolized in the circulation to NT 1-8. A significant rise in the mean plasma concentration of pancreatic polypeptide was produced by NT, but not by NT 1-8, infused at 2.4 pmol kg-1 min-1. No changes in the mean plasma concentrations of insulin, glucose, or cholesterol were demonstrated during either infusion. The present study suggests that the rapid degradation of NT in man to its N-terminal metabolite may be one of the mechanisms for its bioinactivation in plasma.

Adult↗

Effect of single dose of omeprazole on the gastrointestinal peptide response to food.

The gastrointestinal peptide response to food was assessed in 6 healthy subjects following oral administration of 40 mg omeprazole. There was a small but statistically significant increase in basal plasma gastrin six hours after the dose of omeprazole, but the post-prandial plasma gastrin was not significantly increased. There was no significant effect on basal or post-prandial levels of somatostatin, insulin, pancreatic glucagon, enteroglucagon, gastric inhibitory polypeptide, pancreatic polypeptide, motilin, neurotensin, cholecystokinin, secretin, vasoactive intestinal peptide and gastrin-releasing peptide or blood glucose concentration.

Adult↗

Neuropeptide Y-immunoreactive nerves in the uvea of guinea pig and rat.

Neuropeptide Y (NPY)-immunoreactivity has been localized to a rich network of fibres in the uvea of guinea pig and rat. In the iris, NPY-immunoreactive nerves were present in iridial smooth muscle and around blood vessels; similarly throughout the choroid a dense network of NPY-immunoreactive fibres was found surrounding the choroidal vascularization. Following sympathectomy a marked decrease of NPY-immunoreactivity, in particular in the iris and less marked in the choroid, was noted, indicating that these fibres may originate at least in part from neuronal cell bodies in the superior cervical ganglion. The close relationship of the NPY-immunoreactive fibres to blood vessels in both anterior and posterior uvea is consistent with the established vasoconstrictor action of this peptide.

Animals↗

Neuropeptide Y in neuroblastoma X glioma hybrid cells. Response to dexamethasone and nerve growth factor.

High concentrations of a newly-identified biologically potent peptide, neuropeptide Y, have been demonstrated in 3 related mouse neuroblastoma-derived clonal cell lines, N18TG2 0.35 pmol/mg protein, NG108-15 0.44 pmol/mg protein and NCB-20 0.39 pmol/mg protein. The NG108-15 cell line was chosen for further evaluation. Dexamethasone (10 microM) and nerve growth factor (10 ng/ml) resulted in a 2-fold increase in cellular neuropeptide Y concentrations. The response to dexamethasone was demonstrated to be dose-dependent. Exposure to both agents in combination resulted in a more than additive effect, indicating synergism.

Animals↗

Infusion of a novel peptide, PHI, in man. Pharmacokinetics and effect on gastric secretion.

PHI, infused in man, achieved plateau plasma levels of 297 pmoles/1. The plasma half life was 3.1 min, metabolic clearance rate was 16.4 ml/kg/min and estimated volume of distribution was 73.2 ml/kg. No subjective side effects were noted during the infusion and there was no significant alteration in submaximal pentagastrin stimulated gastric acid or pepsin secretion.

Adult↗

Neuropeptide Y in phaeochromocytomas and ganglioneuroblastomas.

Tumour tissue from nineteen patients with phaeochromocytomas and nine with ganglioneuroblastomas contained large numbers of neuropeptide Y (NPY) producing cells and extracts of these tumours had very high concentrations of immunoreactive NPY. Plasma NPY concentrations were also raised, averaging 460 pmol/l in patients with tumours of the sympathetic chain and 55 pmol/l in healthy controls. Since plasma NPY is straightforward to measure and relatively stable, its estimation may prove helpful as a screening tests for phaeochromocytoma.

Adrenal Gland Neoplasms↗

Neuropeptide Y distribution in the rat brain.

A massive neuronal system was detected by immunocytochemistry and radioimmunoassay with antibodies to neuropeptide Y, the recently isolated peptide of the pancreatic polypeptide family. Immunoreactive cell bodies and fibers were most prevalent in cortical, limbic, and hypothalamic regions. Neuropeptide Y was extracted in concentrations higher than those of any other peptide hitherto discovered in the mammalian brain. Column chromatography of brain extracts and double immunostaining experiments indicate that neuropeptide Y is the endogenous brain peptide responsible for immunostaining of pancreatic polypeptide-like immunoreactivity in the mammalian brain.

Animals↗

Advanced carcinoma of the prostate: treatment with a gonadotrophin releasing hormone agonist.

Ten patients with advanced progressive adenocarcinoma of the prostate were treated with a long acting analogue of gonadotrophin releasing hormone. Eight of these patients responded to treatment in terms of pain relief and clinical regression of tumour. Serum gonadotrophin and testosterone concentrations were significantly suppressed by the end of the second week of treatment, testosterone concentrations being comparable with those achieved by castration. The two patients who failed to respond had both relapsed previously when receiving conventional treatment, and neither showed any endocrine response to the analogue. Superagonists of gonadotrophin releasing hormone may be the treatment of choice in adenocarcinoma of the prostate, but further trials are required to establish long term safety and efficacy.

Acid Phosphatase↗

Neuropeptide tyrosine (NPY)--a major cardiac neuropeptide.

A newly discovered bioactive peptide, neuropeptide tyrosine (NPY), has been found in the human cardiac nervous system. Dense concentrations of NPY-immunoreactive nerve fibres were found in association with nodal tissue (atrioventricular node 22.1 +/- 3.7 pmol/g). NPY nerve fibres were seen in close contact with cardiac muscle fibres and were also found around the coronary vessels (19.6 +/- 6.2 pmol/g). Analysis of the peptide by high-performance liquid chromatography demonstrated that it was present in a single molecular form, closely similar or identical to that of the isolated bioactive peptide. Cardiac function in man has long been known to be influenced by cholinergic and adrenergic nerves. There now appears to be a further component of the nervous system in the human heart, involving peptidergic nerves containing NPY.

Basal Ganglia↗