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Biomedical subjects

J M Allen

Publications and source records attributed to J M Allen.

At least 199 records · Page 11Linked to original sources
PubMed1985

Localisation of neuropeptide Y in nerves of the rat cardiovascular system and the effect of 6-hydroxydopamine.

The distribution of neuropeptide Y (NPY) in the rat cardiovascular system has been examined by radioimmunoassay, chromatographic analysis of tissue extracts, and immunocytochemistry. High concentrations of NPY were identified throughout the heart and within the major blood vessels of the rat in particular in the renal and superior mesenteric arteries. NPY-immunoreactivity was localised to dense plexuses of nerves in the adventitia of the arteries. Treatment of rats with 6-hydroxydopamine resulted in a significant reduction of NPY concentrations in the major vessels. A depletion of extractable NPY was also seen in the heart of the treated animals. Only few degenerated NPY-containing nerve fibres (swollen and fragmented) were observed in the heart and in the adventitia of the blood vessels. It is concluded that NPY containing nerves of the heart and blood vessels are sensitive to treatment with 6-hydroxydopamine. The pharmacological properties of this peptide suggest that these NPY-containing nerve fibres may act as efferent vasoconstrictor nerves to the blood vessels.

Adrenergic Fibers↗
PubMed1985

Increased content of neuropeptide Y in human pheochromocytoma cell cultures.

Cells from three human pheochromocytomas grown in monolayer culture for 21 days contained markedly greater amounts of neuropeptide Y (NPY) than freshly dissociated cells from the same tumors. The content of NPY did not consistently correlate with the extent of neurite outgrowth in the cultures and was not further increased in the presence of nerve growth factor. The content of NPY was decreased in the presence of 10(-5) M dexamethasone in two cultures. The findings suggest that human pheochromocytoma cultures may be useful in studies of cellular and molecular mechanisms regulating NPY production, and that these mechanisms may differ somewhat from those regulating production of other regulatory peptides in cultures of the same tumors.

Adrenal Gland Neoplasms↗
PubMed1985

Incorporation of radiolabelled amino acids into the sulphur-containing metabolites of paracetamol by the hamster.

Various radiolabelled forms of the amino acids cysteine, methionine and serine were co-administered with paracetamol to the hamster to investigate the biosynthesis of the thiomethyl metabolites of paracetamol. T.l.c. and h.p.l.c. were used to determine the presence of sulphur-containing metabolites in the urine. Paracetamol sulphate and the 3-cysteine, mercapturate and thiomethyl derivatives were all detected in urine, along with the 3-methylsulphoxide after hydrolysis. No paracetamol-3-methylsulphone was detected. Both cysteine and methionine acted as sulphur donors via glutathione. The methyl group of the thiomethyl derivatives originated from methionine in a reaction system believed to involve cysteine conjugate-beta-lyase and the thiomethyl shunt.

Acetaminophen↗
PubMed1985

Spontaneous proliferative lesions of the adrenal medulla in aging Long-Evans rats. Comparison to PC12 cells, small granule-containing cells, and human adrenal medullary hyperplasia.

Aging rats of the Long-Evans strain spontaneously develop diffuse and nodular hyperplasia of the adrenal medulla in association with other abnormalities commonly encountered in human multiple endocrine neoplasia syndromes. The cells which comprise the adrenal nodules resemble those in the parent tumor of the rat PC12 pheochromocytoma cell line in that they show varying degrees of spontaneous or nerve growth factor-induced neurite outgrowth in culture and they contain little or no epinephrine. In addition, cells from at least some of the nodules contain immunoreactive neurotensin and neuropeptide-Y, which are also found in PC12 cells. There are a number of striking resemblances between the cells in adrenal nodules and the small granule-containing cells in the normal rodent adrenal. The findings suggest that spontaneous rat adrenal medullary nodules and PC12 cells might be derived from small granule-containing cells, or that cells within the nodules might regain properties of immature chromaffin cells and acquire characteristics of small granule-containing cells and of PC12 cells in the course of neoplastic progression. They further suggest a possible relationship between proliferative capacity and neurotransmitter phenotype in the adult rat adrenal medulla. By virtue of their sparse epinephrine content and their small granules, the cells in adrenal medullary nodules of Long-Evans rats differ from those in adrenal medullary nodules of humans with multiple endocrine neoplasia syndromes.

Acetylcholinesterase↗
PubMed1984

Neuropeptide Y in the human male genital tract.

Neuropeptide Y (NPY) was found in high concentrations in the male genital tract. NPY levels were highest in the seminal vesicles, prostate, corpus cavernosum and vas deferens, where large numbers of immunoreactive nerve fibres were detected. Considerable quantities were also found in the epididymis and spongiosum. Lower concentrations were found in the glans penis, testis and foreskin. The presence of a large number of nerves containing NPY suggest that this active neuropeptide may play a role in control of genital function.

Adult↗
PubMed1984

Presence of neuropeptide Y in human circle of Willis and its possible role in cerebral vasospasm.

Neuropeptide Y (NPY) has been demonstrated in the human circle of Willis by specific radioimmunoassay. Concentrations were similar in cadaver and peroperative specimens. NPY concentrations were highest around the basilar bifurcation (2.9 +/- 1.0 pmol/g), anterior cerebral artery (2.7 +/- 0.5 pmol/g), and carotid trifurcation (2.4 +/- 0.6 pmol/g). Concentrations were lowest in the basilar artery (1.0 +/- 0.4 pmol/g). Intracarotid administration of NPY (50 pmol to 2 nmol) to rats reduced mean cerebral cortical blood flow by 40-98%. This vasoconstriction lasted for at least 2 h. These findings suggest that NPY may be involved in the cerebral vasospasm which follows subarachnoid haemorrhage and in the maintenance of normal vascular tone.

Animals↗
PubMed1984

Neuropeptide Y in human spinal cord.

The distribution of a newly described peptide, neuropeptide Y (NPY) within the human spinal cord has been determined using radioimmunoassay and immunocytochemistry. Higher concentrations were found in the lumbar (49.9 +/- 6.8 pmol/g) and sacral (47.0 +/- 10.6 pmol/g) regions than in the cervical (27.6 +/- 2.7 pmol/g) and thoracic spinal cord (33.8 +/- 5.3 pmol/g). Immunocytochemistry revealed numerous nerve fibers containing NPY in the spinal cord; these were particularly concentrated in the substantia gelatinosa of the dorsal horn. In the ventral spinal cord NPY-containing nerves were sparse becoming more abundant in lumbosacral segments.

Adult↗
PubMed1984

The distribution and origin of a novel brain peptide, neuropeptide Y, in the spinal cord of several mammals.

The distribution of neuropeptide Y [NPY]-immunoreactive material was examined in the spinal cord and dorsal root ganglia of rat, guinea-pig, cat, marmoset, and horse. Considerable concentrations of NPY and similar distribution patterns of immunoreactive nerve fibres were found in the spinal cord of all species investigated. The dorsal root ganglia of the cat and the horse contained numerous immunoreactive nerve fibres, but in these species, as in the other three studied [rat, guinea-pig, marmoset], no positively stained cell bodies were found. Neuropeptide Y-immunoreactive nerves were observed at all levels of the spinal cord, being most concentrated in the dorsal horn. In the rat, guinea-pig, and marmoset, there was a marked increase of NPY-immunoreactive fibres in the lumbosacral regions of the spinal cord, and this was reflected by a considerable increase of extractable NPY. Estimations of NPY-immunoreactive material in the various regions of the rat spinal cord were as follows: cervical, 13.8 +/- 1.0; thoracic, 21.1 +/- 2.5; lumbar, 16.3 +/- 2.9; sacral, 92.4 +/- 8.5 pmol/gm wet weight of tissue +/- SEM. In the ventral portion of the guinea-pig spinal cord they were as follows: cervical, 7.1 +/- 1.2; thoracic, 8.2 +/- 3.6; lumbar, 22.6 +/- 7.0; sacral, 36.7 +/- 9.5 pmol/gm wet weight of tissue +/- SEM. Analysis of spinal cord extracts by reverse phase high performance liquid chromatography [HPLC] demonstrated that NPY-immunoreactive material elutes in the position of pure NPY standard. No changes in the concentration and distribution of the NPY-like material in the rat spinal cord were observed following a variety of surgical and pharmacological manipulations, including cervical rhizotomy, sciatic nerve section and ligation, and local application of capsaicin [50 mM] to one sciatic nerve. It is therefore suggested that most of the NPY-immunoreactive material in the spinal cord is derived either from intrinsic nerve cell bodies or from supraspinal tracts.

Animals↗
PubMed1984

Neuropeptide Y in the guinea-pig biliary tract.

High concentrations of neuropeptide Y (NPY) have been demonstrated in the gall bladder (16.7 +/- 5.4 pmol/g), cystic duct (25.4 +/- 9.2 pmol/g) and common bile duct (54.7 +/- 11.5 pmol/g) of the guinea-pig using a recently developed radioimmunoassay. Immunoreactive NPY containing nerves were demonstrated in all layers of the biliary tree using immunocytochemistry, being particularly dense in the myenteric and mucosal plexuses.

Animals↗
PubMed1984

Ontogeny of a novel peptide, neuropeptide Y (NPY) in rat brain.

Changes in the concentration of a newly discovered peptide, neuropeptide Y (NPY) have been determined in the developing rat brain using a recently developed radioimmunoassay and chromatographic analysis. NPY was present in the brain stem (14.8 +/- 5.6 pmol/g) and diencephalon (12.1 +/- 12.1 pmol/g) in the earliest embryos studied (14 days postconception), but appeared only on the 19th day postconception in the cerebral cortex. The concentrations of NPY showed a rapid postnatal rise in all regions examined. The finding of NPY early in the development of the embryonic rat brain and particularly in caudal regions has some similarities to the pattern of development of the catecholaminergic system.

Age Factors↗
PubMed1984

Neuropeptide Y (NPY) in PC12 phaeochromocytoma cultures: responses to dexamethasone and nerve growth factor.

High concentrations of a novel regulatory peptide, neuropeptide Y, have been identified within the PC12 rat phaeochromocytoma cell line by radioimmunoassay and chromatographic analysis. The cellular concentration of this peptide has been demonstrated to be predominantly influenced by the presence of nerve growth factor. After 14 days in culture in the presence of dexamethasone, NPY concentrations were 0.19 +/- 0.03 pmol/mg protein, whereas following similar exposure to nerve growth factor, concentrations were 3.44 +/- 0.19 pmol/mg protein. Addition of nerve growth factor to the dexamethasone-treated cells resulted in a rise in NPY concentration to 0.90 +/- 0.08 pmol/mg over 7 days, whereas addition of dexamethasone to the cells treated with nerve growth factor resulted in no further rise in NPY concentration. The concentrations of NPY far exceed those previously reported for neurotensin in PC12 cells, under the same culture conditions. These two peptides appear also to be regulated by different mechanisms.

Adrenal Gland Neoplasms↗
PubMed1984

The effect of previous endocrine therapy on responses to a single dose of an LHRH analogue.

Serum concentrations of gonadotropins, testosterone and dehydrotestosterone were determined in patients receiving conventional endocrine therapy for advanced metastatic adenocarcinoma of prostate. The effect over 4 h of a single dose of a long acting analogue of LHRH was determined in these patients and compared to the response in patients receiving the analogues as first choice of treatment. Oestrogen therapy was found to suppress basal and stimulated gonadotropins and testicular androgens. Cyproterone therapy only partially reduced basal hormone concentrations and the response to the LHRH analogue was delayed. Orchidectomy resulted in elevated gonadotropins and an exaggerated response to the analogue. As patients who relapse while failing conventional therapy, may subsequently be treated by further endocrine manipulation, precise determination of their endocrine status should predict any expected benefit. Patients previously treated with stilboestrol are unlikely to respond to orchidectomy or LHRH analogue.

Adenocarcinoma↗
PubMed1984

The nerves of the juxtaglomerular apparatus of man and other mammals contain the potent peptide NPY.

The juxtaglomerular apparatus, a neuroendocrine unit located in the vascular pole of the glomerulus and influencing blood pressure by the secretion of renin, is known to have a rich supply of monoaminergic nerve fibres. Neuropeptide Tyrosine (NPY), a newly discovered, potent, vasoconstrictor peptide of 36 amino acids, has been found by immunocytochemistry to be present in a dense plexus of fibres around the juxtaglomerular apparatus of man, monkey, mouse, hamster, rat and guinea pig. NPY-immunoreactivity was markedly depleted after chemical sympathectomy by 6-hydroxydopamine. The concentration of NPY within the whole mouse kidney was 29.6 +/- 6.8 pmol/g and fractionation of the extracts demonstrated that the NPY-like immunoreactivity co-eluted from the column in the same position as the porcine NPY standard. The role of this peptide in renal physiology and pathology now needs urgent investigation.

Animals↗
PubMed1984

Peptide-immunoreactive nerves in the mammalian female genital tract.

Vasoactive intestinal polypeptide, substance P, neuropeptide Y and peptide histidine isoleucine immunoreactivities have been demonstrated in the female genitalia of rat, cat, mouse and guinea-pig using immunocytochemistry and radioimmunoassay. They were localized to nerves. Each type of immunoreactive nerve showed a distinct pattern of distribution, though all were associated to some degree with blood vessels and smooth muscle. Vasoactive intestinal polypeptide-immunoreactive and neuropeptide Y-immunoreactive nerves were the most abundant. Higher concentrations of peptides were detected in the female genitalia of the mouse than those of the other species studied. Vasoactive intestinal polypeptide-immunoreactive nerves were particularly concentrated in the cervix (89.1 +/- 17.2 pmol/g, mean +/- S.E.M.) and the uterus (57.4 +/- 14.8 pmol/g) of the mouse, while neuropeptide Y immunoreactivity was more abundant in the Fallopian tube of the mouse (31.6 +/- 11.8 pmol/g) and the vagina of the rat (38.6 +/- 4.8 pmol/g) than in other regions. Separate populations of ganglion cells in the paracervical ganglia were found to contain vasoactive intestinal polypeptide and neuropeptide Y immunoreactivities. Peptide histidine isoleucine-immunoreactive and vasoactive intestinal polypeptide-immunoreactive nerves were similarly distributed, but the former were much less frequent. Substance P-immunoreactive nerves were seen mainly beneath the epithelium of the vagina and were, in general, more numerous in the guinea-pig than in other species. The significance of these peptide-immunoreactive nerves in the female genital organ remains to be determined.

Animals↗
PubMed1984

Elevation of neuropeptide Y (NPY) in substantia innominata in Alzheimer's type dementia.

Concentrations of neuropeptide Y (NPY) have been determined in 12 areas of control brains and compared to those found in brains from patients with Alzheimer's type dementia (ATD). The distribution of NPY in the control brains was compared with those reported previously. Highest concentrations were identified in the subcortical structures, in particular, nucleus accumbens (203 +/- 21.7 pmol/g), amygdala (136.7 +/- 15.8 pmol/g), and substantia innominata (109.0 +/- 12.6 pmol/g). A significant elevation in NPY concentrations was identified in the region of the substantia innominata of Alzheimer brains (controls: 109.0 +/- 12.6 pmol/g, ATD: 206 +/- 28.2 pmol/g, P less than 0.001). This change in NPY concentration was similar to the increase in somatostatin concentration in this region of ATD brain. In contrast, although cortical concentrations of somatostatin were reduced in ATD, no change was found in the concentrations of NPY in the 4 regions of cerebral cortex and the remaining subcortical areas examined.

Aged↗
PubMed1984

Peptide-containing nerves in human urinary bladder.

Nerves containing immunoreactive vasoactive intestinal polypeptide (VIP), substance P and two newly discovered peptides, neuropeptide tyrosine (NPY) and PHI (peptide having N-terminal histidine and C-terminal isoleucine), have been found in the human urinary bladder by immunocytochemistry and radioimmunoassay. Somatostatin immunoreactivity was detected by radioimmunoassay. The VIP-immunoreactive nerves were widely distributed in all regions, but were particularly dense beneath the epithelium and in the muscle layer. Scattered intramural ganglia were found to be reactive to VIP antiserum. Higher concentrations of extractable VIP were detected in the trigone than in the dome. VIP- and PHI-immunoreactive nerves were similarly distributed, the latter being less numerous. NPY-immunoreactive nerves were seen mainly in the muscle layer, particularly in the trigonal area. The distribution patterns of VIP- and NPY-immunoreactive nerves resembled those of the previously reported cholinergic and adrenergic nerves, respectively. Many blood vessels were found to be innervated by both types of immunoreactive nerves. Scattered substance P-immunoreactive fibers were occasionally seen, being present in the submucosa and around the detrusor muscles. The significance of these nerves remains to be elucidated.

Fluorescent Antibody Technique↗
PubMed1984

Radioimmunoassay of neuropeptide Y.

The development of a radioimmunoassay to the newly isolated peptide, neuropeptide Y is described. Four separate antisera have been developed using different immunisation schedules. Two of these antisera (YNI and YNIO) are directed to the C-terminal region of the peptide and cross-react with the related peptide PYY, whereas YN7 is specific being directed to the N-terminal region of NPY, YN6 is similarly specific for NPY, but is unable to bind the available fragments. These four antisera provide similar results for determination of NPY immunoreactivity within porcine brain extracts, however YN6 consistently undervalues all extracts from the other species examined (human, rat, guinea pig, cat and mouse). Chromatographic analysis by means of reverse phase high pressure liquid chromatography (HPLC) shows that NPY immunoreactivity of human extracts elutes in an earlier position than the porcine standard. It seems likely therefore that human and porcine NPY differ in their amino acid sequences.

Animals↗