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Biomedical subjects

R F Power

Publications and source records attributed to R F Power.

46 records · Page 3Linked to original sources
PubMed1989

Autoradiographic localization of endothelin-1 binding sites in the cardiovascular and respiratory systems.

Specific high-affinity binding sites for endothelin-1 (ET-1) have been demonstrated in peripheral tissues using the technique of in vitro receptor autoradiography. Binding was time dependent and saturable and inhibited by coincubation with an excess of unlabeled ET-1 but resistant to dissociation. Binding sites were localized to blood vessels of all sizes including coronary arteries, intrapulmonary vessels, and intrarenal and intrasplenic arteries. In addition, high-affinity binding sites were identified on airway smooth muscle, over alveolar septa, and on nerve trunks. Scatchard analysis of the data revealed a Bmax of 250 amol/mm2 and a Kd of 0.1 nM for the binding of rat tracheal smooth muscle, with similar values for porcine coronary artery. The localization of binding sites is consistent with the known effects of ET-1 and suggests a direct action on specific receptors.

Animals↗
PubMed1989

Endothelin-induced contractions of tracheal smooth muscle and identification of specific endothelin binding sites in the trachea of the rat.

1. The presence of specific binding sites and the contractile activity of the novel peptide, endothelin have been investigated in rat trachea. 2. Endothelin (10(-8)-10(-5) M) induced long-lasting contraction of rat tracheal rings superfused with Krebs solution (EC50 5.4 x 10(-6) M). Contractions of the tissue to 10(-6) M endothelin were attenuated in Ca2+-free medium containing 0.1 mM EGTA but unaffected by nicardipine (10(-7) M). 3. After equilibration in Ca2+-free medium (without EGTA) a return to normal Ca2+ concentrations (2.5 mM), 30 min or 60 min following endothelin (10(-6) M), produced a sustained contraction of the tissue. 4. Specific binding sites for endothelin were identified on rat tracheal smooth muscle (KD 1.34 x 10(-10) M, maximal binding 1.2 fmol mm-2). Specific binding sites were also identified on nerve trunks. Endothelin binding was unaffected by co-incubation with nicardipine (10(-7) M) or verapamil (10(-7) M). 5. The discrepancy between the apparent KD for endothelin binding and the EC50 for endothelin-induced contraction suggests that the endothelin binding sites identified in this study may not be associated with the receptors mediating contraction. 6. These results indicate that endothelin binding sites are present on tracheal smooth muscle. The mechanism of endothelin-induced contraction, whilst being dependent on extracellular calcium, does not appear to involve binding to the dihydropyridine- or verapamil-sensitive sites on the voltage-dependent Ca2+ channel. Its long duration of action may be associated with a sustained increase in Ca2+ permeability.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1988

Markers for neuroendocrine differentiation.

Several morphological methods are currently available for the demonstration of neuroendocrine differentiation. Silver impregnation techniques to show argyrophilia or argentaffinity are reliable albeit limited tests for neuroendocrine cells. Immunocytochemistry, at the light or electron microscopic level, is now a routine technique in many histopathological departments. General neuroendocrine markers can be immunostained to define the nature of a tumour or, using antisera to specific neuroendocrine cell products, the exact type of tumour can be established. The application of a range of antisera to bioactive peptides and other derivatives of their precursors can increase the efficiency of detection and classification of neuroendocrine tumours. The latest technology available goes beyond looking at neuroendocrine cell products and investigates peptide gene expression. In situ hybridisation of DNA or mRNA species thereby adds a new dimension to the morphological analysis of neuroendocrine tumours. Used in combination with immunocytochemistry, this technique can provide information on intracellular hormone synthesis. The study of markers of neuroendocrine differentiation continues to yield information which aids not only the diagnosis of neuroendocrine tumours but also the understanding of their biology and the effects exerted by their products.

Biomarkers, Tumor↗
PubMed1988

Anatomical distribution of vasoactive intestinal peptide binding sites in peripheral tissues investigated by in vitro autoradiography.

Vasoactive intestinal polypeptide has a widespread distribution in the body, occurring in both the central and peripheral nervous systems and considerable information is available on its distribution, physiology, and pharmacological actions. Receptors for VIP have been demonstrated previously in peripheral tissues by conventional binding techniques using isolated membrane preparations. However, information on their precise localization is limited. We therefore localized binding sites in a variety of guinea pig and rat tissues by in vitro autoradiography and made a parallel study of the distribution of VIP nerves in these tissues using immunocytochemistry. [125I]VIP was prepared by the chloramine T method and shown to be pharmacologically active. After a preincubation procedure to remove endogenously bound VIP, unfixed cryostat sections were incubated with 1 nM [125I]VIP. To determine specific binding, sections were incubated in the presence or absence of 1 microM unlabeled VIP. Autoradiograms were generated by exposing the sections to LKB-Ultrofilm or emulsion-coated coverslips. Dense binding occurred in discrete locations within the gastrointestinal, respiratory, and genital tracts, correlating with known actions of VIP and, to various extents, with the distribution of VIP nerves. For example, there was precise localization to respiratory epithelium, smooth muscle of airways and blood vessels, and alveolar walls, in keeping with the effects of VIP on vascular and airway smooth muscle and mucus secretion.

Animals↗
PubMed1988

Localisation of atrial natriuretic peptide immunoreactivity in the ventricular myocardium and conduction system of the human fetal and adult heart.

Atrial natriuretic peptide immunoreactivity was found in ventricular and atrial tissues with specific antisera raised to the amino and carboxy terminal regions of the precursor molecule. In 13 developing human hearts (7-24 weeks' gestation) the immunoreactivity was concentrated in the atrial myocardium and ventricular conduction system but it was also detected in the early fetal ventricular myocardium. Immunoreactivity in five normal adults was largely confined to the atrial myocardium although it was also found in the ventricular conduction tissues of hearts removed from 10 patients who were undergoing cardiac transplantation. The ventricular conduction system is an extra-atrial site for the synthesis of atrial natriuretic peptide. In the failing heart this synthesis may be further supplemented by expression of the gene in the ventricular myocardium. It is possible that ventricular production of the peptide contributes to the raised circulating concentrations of atrial natriuretic peptide immunoreactivity found in severe congestive heart disease, particularly in patients with dilated cardiomyopathy.

Adolescent↗
PubMed1987

Transgenic mouse model: a new approach for the investigation of endocrine pancreatic B-cell growth.

The transformation and adaptation of pancreatic insulin-producing (B) cells has been studied in a transgenic mouse model using a panel of antisera recognising peptides and general neuroendocrine markers at both light and electron microscopical levels. Stages of tumour genesis in the transgenic mouse model from hyperplasia to neoplasia, have been compared with human B-cell tumours. A normal complement of peptide containing cells was seen in the transgenic mouse pancreas, but cells containing pro-insulin-derived peptides became more numerous as hyperplasia commenced. The transgenic mouse tumours were composed of B cells, although 30-35% of the tumours were also found to contain PP cells--a finding which is directly comparable with that in human insulin-producing tumours. NSE, 7B2 and chromogranin immunoreactivities were found in most cells from all the tumours examined. Antisera to PGP 9.5, a novel marker for elements of the neuroendocrine system, were found to stain hyperplastic and neoplastic B-cells intensely. In contrast, normal mouse B-cells did not show PGP 9.5 immunoreactivity thus it appears that PGP 9.5 is differentially expressed in transformed and/or growing mouse B-cells and hence may be used as an indicator in studies of early tumour growth.

Adenoma, Islet Cell↗
PubMed1987

Dual intrinsic and extrinsic origins of CGRP- and NPY-immunoreactive nerves of rat gut and pancreas.

The origins of nerves containing calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), and substance P were investigated in the rat stomach, pancreas, and colon, using immunocytochemistry combined with retrograde tracing and surgical and chemical denervation procedures. Compared with nerves containing vasoactive intestinal polypeptide (VIP) and galanin, which have primarily local origins in mammalian gut, CGRP-, NPY-, and substance P-immunoreactive nerves revealed dual extrinsic and intrinsic origins. Immunocytochemistry combined with retrograde tracing showed that the extrinsic CGRP- and substance P-immunoreactive nerves in the stomach and pancreas originate from bilateral dorsal root ganglia mainly at levels T8-T11, while those of the colon are derived from bilateral ganglia at S1 and, to a lesser extent, L1 and L6. Chemical denervations showed that neurons in these ganglia form a sensory input to the gut, and that those containing CGRP form the largest proportion. The results of combined retrograde tracing and immunocytochemistry indicated that extrinsic NPY-immunoreactive nerves originate from postganglionic sympathetic neurons lying in the coeliac and inferior mesenteric ganglia. These nerves were located mainly around blood vessels in gut and pancreas, showed sensitivity to 6-hydroxydopamine, and thus are likely to be noradrenergic. The present study provides a detailed mapping of the origins of some of the major peptide-containing nerves of the rat gastroenteropancreatic tract, thus providing further information on the anatomy of the enteric innervation.

Animals↗
PubMedDate not supplied

Ultrastructure and electron immunocytochemistry of insulin-producing B-cell tumors from transgenic mice: comparison with counterpart human tumors.

This paper reports on an ultrastructural and electron-microscopic immunocytochemical study of pancreatic B cells from normal mice, pancreatic B cells and derivative tumors from transgenic mice, and tissue from human pancreatic B-cell tumors. In normal and neoplastic B cells from both species, typical immature and mature beta-granules (with spherical cores of variable density) were observed, whereas typical beta-granules with a crystalloid core were only present in human B cells (normal and tumor). A small number of atypical granules were found in distinct neoplastic cells which contained no typical beta-granules. The atypical granules were smaller (100-200 nm diameter) than typical beta-granules (250-450 nm diameter) seen in other cells. Immunoreactivity for proinsulin was localized only to immature granules, whereas insulin and C-peptide immunoreactivities were demonstrated in atypical, immature, and mature granules. In transgenic mouse and human B-cell tumors, insulin immunoreactivity was consistently weaker than the immunostaining for C-peptide. An intragranular, topographic segregation of immunoreactive C-peptide was observed in a population of transgenic tumor cells. Our results showed similarities in antigenic distribution and only slight differences in morphology between human and mouse B cells. Therefore, the transgenic mouse system may prove to be an effective model for studying mammalian B-cell tumorigenesis.

Adenoma, Islet Cell↗