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Biomedical subjects

R J Summers

Publications and source records attributed to R J Summers.

At least 109 records · Page 6Linked to original sources
PubMed1986

Autoradiographic evidence for a heterogeneous distribution of alpha 1-adrenoreceptors labelled by [3H] prazosin in rat, dog and human kidney.

The selective alpha1-adrenoreceptor antagonist radioligand [3H] prazosin has been used to localize alpha1-adrenoreceptors in slide mounted sections of rat, dog and human kidney. The biochemical characteristics of [3H] prazosin binding to rat kidney sections were examined and found to be saturable, reversible, stereoselective, with a KD of 0.12 nM and Bmax of 6.72 +/- 0.2 fmoles/section. 3H Ultrofilm images of [3H] prazosin binding to rat, dog, and human kidney revealed binding to the vasculature but in the rat additional receptors were confined to the renal cortex. In the rat kidney autoradiography using emulsion coated coverslips showed that binding in the renal cortex was largely to proximal tubules. In all three species the autoradiographic studies support a role for alpha1-adrenoreceptors in control of renal blood flow. In the rat the location of alpha1-adrenoreceptors suggests that they can also have an important influence on fluid and electrolyte balance, gluconeogenesis and production of prostanoids.

Animals↗
PubMed1986

The influence of age and sex on cardiac, renal and caudal artery catecholamine content in spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats.

Noradrenaline (NA), adrenaline (A) and dopamine (DA) levels were measured in the heart, kidney and caudal artery of male and female SHR and WKY rats aged 6, 14 and 28 weeks, and the influence of strain, sex and age on catecholamine content determined. Levels of A were elevated in all three regions of SHR compared to WKY rats, independent of age and sex. This may represent increased A accumulation in sympathetic nerves resulting from the increased sympatho-adrenomedullary hyper-reactivity of the SHR strain. DA levels were also elevated in the heart and kidney of SHR rats, independent of sex and age. Na levels were lower in the heart of SHR rats, but this appeared to be partly a consequence of cardiac hypertrophy and partly due to strain difference between older male but not female rats. Thus a simple association between decreased cardiac NA levels and hypertension appeared unlikely. It is emphasised that further genetic studies of F2 backcross rats would be required to establish an etiological association between these differences in catecholamine levels and differences in blood pressure between the SHR and WKY strains.

Age Factors↗
PubMed1986

Autoradiographic analysis of the distribution of beta-adrenoceptors in the dog splenic vasculature.

The technique of in vitro labelling and autoradiography has been used to localize beta-adrenoceptors in sections of the splenic vascular bundle of the dog. Binding of (-)-[125I]-cyanopindolol (Cyp) to sections of splenic vascular bundle equilibrated within 150 min and slowly dissociated after addition of (-)-propranolol. The process was saturable with a dissociation constant (KD) of 40.3 +/- 4.4 pM and Bmax of 18.9 +/- 1.7 fM (in 6 sections). Binding to sections was stereoselective, the (-)-isomer of propranolol being 90 times more effective than the (+)-isomer in competing for (-)-[125I]-Cyp binding. Delineation of beta-adrenoceptor subtypes using the selective antagonists betaxolol (beta 1) and ICI 118,551 (beta 2) indicated that the receptors present were almost exclusively of the beta 2-subtype. Autoradiographic studies under the conditions evaluated in the biochemical experiments showed that beta-adrenoceptors are unevenly distributed in the dog splenic vein, artery and associated nerve bundles. High concentrations of receptors are associated with the splenic nerves and lower but still significant concentrations in the vasculature. Higher resolution studies with nuclear emulsion coated coverslips revealed concentrations of beta-adrenoceptors over cells adjacent to the lumen in veins. In arteries most beta-adrenoceptors were found associated with the medial layer with fewer receptors towards the intima or adventitia. Serial sections of either artery or vein incubated with (-)-[125I]-Cyp in the presence of (-)-propranolol showed low levels of non-localized binding.

Animals↗
PubMed1986

Changes in the innervation and catecholamine concentrations in the myometrium of pregnant and non-pregnant sheep.

The innervation of the myometrium in virgin, pregnant and post-partum ewes was examined using the SPG histofluorescence method and a high-performance liquid chromatographic catecholamine assay. In non-pregnant ewes, fluorescent axons were visible in all regions of the uterus. At 50 days of pregnancy the innervation was unchanged, but at 100 days axons were scarce over the whole uterus with the exception of the tubal extremities of the uterine horns. Noradrenaline concentrations were also significantly lower in late pregnancy, and significant variations occurred in different regions of the uterus, with the greatest concentrations present in the tubal extremities. At 13-16 weeks post partum, the density of innervation was variable, although the noradrenaline concentration was only slightly less than in virgin animals. Dopamine was also present in substantial quantities, but the mean concentrations remained unchanged during pregnancy.

Animals↗
PubMed1986

Comprehensive immunization delivery in conjunction with influenza vaccination.

All patients and employees presenting for influenza A and B vaccination were studied for the need for other immunizations or tests, based on criteria of the Immunization Practices Advisory Committee. More than 72% of patients and employees needed at least one other vaccine or test. During a 4 1/2-month period, 1,353 doses of influenza virus vaccine, bivalent, types A and B, were prescribed. Health care providers ordered doses of diphtheria and tetanus toxoids (adult) for 36.8% of these recipients, pneumococcal vaccine, polyvalent 23, for 42.1%, and a tuberculin skin test for 36.3%. Determinations of hepatitis B titers or hepatitis B vaccine doses were ordered for 140 individuals. Patients older than 60 years needed additional immunizations with greater frequency. Rates of delayed adverse reactions (35.9%) and subsequent self-medication (11.7%) were recorded. The systemic adverse reaction rate was 17.3%. Annual influenza vaccination programs are valuable public health opportunities to determine immunizations needed by patients who might not otherwise receive a comprehensive, individualized review of the status of their immunization protection.

Adolescent↗
PubMed1986

Contact urticaria to O-phenylphenate.

Contact urticaria is a form of immediate hypersensitivity reaction that is being noted with increasing frequency. This report illustrates an unusual presentation of contact urticaria in the form of an immediate reaction to a component of plaster cast material. The substance involved was ortho-phenylphenate, a preservative. It has not been previously implicated in a contact urticaria reaction.

Adult↗
PubMed1985

Light microscopic autoradiography of the distribution of [3H]rauwolscine binding to alpha 2-adrenoceptors in rat kidney.

The localization of [3H]rauwolscine binding to microscope slide mounted sections of rat kidney has been examined using the technique of in vitro labelling and autoradiography. Binding to sections equilibrated within 60 min and was reversible following the addition of 10 microM phentolamine. Saturation studies revealed a single population of high affinity (KD 4.27 nM) non-interacting sites (nH 0.97) with a density of 11.1 fmol/section. Stereoselectivity was observed with respect to the isomers of noradrenaline and the relative affinity of a series of alpha-adrenoceptor antagonists suggested binding to alpha 2-adrenoceptors. Autoradiographic studies using 3H-Ultrofilm showed that the binding is largely confined to the renal cortex. More detailed studies using emulsion coated coverslips indicates that the major concentration of binding sites is over the proximal tubules. This study provides evidence that alpha 2-adrenoceptors, known to be coupled in an inhibitory fashion to renal adenylate cyclase, are highly localized to particular structures in the kidney.

Animals↗
PubMed1985

Localization of beta-adrenoceptors in the rabbit ear by light microscopic autoradiography.

The beta-adrenoceptor antagonist [125I]cyanopindolol (CYP) was used to localize beta-adrenoceptors in sections of rabbit ear. Biochemical studies demonstrated that the binding was stereoselective, and that the beta-adrenoceptors are predominantly of the beta 2-subtype. Autoradiographic studies using 3H-Ultrofilm or nuclear emulsion coated coverslips showed high concentrations of beta 2-adrenoceptors present in the central ear artery, hyaline cartilage, nerve trunks, epithelium and sebaceous glands.

Animals↗
PubMed1985

Changes in brainstem and spinal adrenoceptor binding with ageing in spontaneously hypertensive and Wistar-Kyoto rats.

Adrenoceptor binding in membranes prepared from the brainstem and thoracic spinal cord of male spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats aged 6 and 36-40 weeks has been compared. Binding of [3H]prazosin (alpha 1-receptors), [3H]rauwolscine (alpha 2-receptors) and [3H]dihydroalprenolol (DHA: beta-receptors) fell with age in both regions in both strains. Strain, independent of age, was also a significant determinant of binding for all three ligands in brainstem and for [3H]DHA in spinal cord. The changes in receptor binding may reflect differences in noradrenergic activity with age and between SHR and WKY rats.

Aging↗
PubMed1985

alpha 2-Adrenoceptors in dog kidney: autoradiographic localization and putative functions.

The location of alpha 2-adrenoceptors has been examined in slide-mounted sections of dog kidney by using labelling in vitro with [3H]rauwolscine and autoradiography. [3H]Rauwolscine binding in dog kidney was of high affinity, saturable, and to a single population of sites. Stereoselectivity was observed for (-)-noradrenaline and the relative affinity of a series of competing antagonists indicated binding to alpha 2-adrenoceptors. Autoradiography of [3H]rauwolscine binding revealed localization to three areas: glomeruli, the intimal and adventitial surfaces of arcuate blood vessels and the medullary vascular bundles.

Animals↗
PubMed1985

The measurement of central noradrenergic activity in spontaneously hypertensive rats: a comparison of free 3,4-dihydroxyphenylethyleneglycol levels with FLA-63 induced noradrenaline depletion.

Noradrenergic activity was measured in the brainstem, hypothalamus and thoracic spinal cord of male and female spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats at 6 and 28-36 weeks of age. Two techniques were used, measurement of a major noradrenaline (NA) metabolite, free 3,4-dihydroxyphenylethyleneglycol (DHPG), and measurement of the rate of decline in brain NA levels following dopamine-beta-hydroxylase (DBH) inhibition by FLA-63. There was a good correlation between the changes with age in NA turnover measured by the two techniques. NA levels and NA turnover measured by both techniques fell with age in brainstem and thoracic spinal cord in both SHR and WKY rats. In both strains these falls in turnover were associated with increases in blood pressure. However, the increase in blood pressure in the SHR was greater than in the WKY, even though NA turnover fell to a similar extent in both strains. These data show a difference in the pattern of change in NA levels and turnover in the brainstem and thoracic spinal cord compared to other brain regions and may therefore be related to the development of higher levels of blood pressure in older rats in both strains. They do not offer a simple explanation for the much higher blood pressures seen at all ages in the SHR.

Animals↗
PubMed1985

Autoradiographic localization of beta-adrenoceptor subtypes in guinea-pig kidney.

The distribution of beta-adrenoceptor subtypes in slide-mounted sections of guinea-pig kidney has been examined by the technique of in vitro labelling combined with autoradiography. Binding of (-)-[125I]-cyanopindolol (Cyp) to kidney sections equilibrated and dissociated slowly, was saturable and stereoselective with respect to the isomers of propranolol and pindolol. These characteristics were appropriate for binding to beta-adrenoceptors. Delineation of beta-adrenoceptor subtypes was achieved by use of betaxolol (beta 1-adrenoceptors) and ICI 118,551 (beta 2-adrenoceptors) and computer assisted curve fitting techniques. Both beta 1- and beta 2-adrenoceptors were present in the proportions 1:2. 3H-Ultrofilm images of (-)-[125I]-Cyp binding to guinea-pig kidney sections showed localized patches of binding in the cortex and concentrated binding in the outer stripe of the medulla. Cortical receptors were of the beta 1 subtype and those associated with the outer stripe of the medulla were of the beta 2-adrenoceptor subtype. beta 1-Adrenoceptors were concentrated over glomeruli and beta 2-adrenoceptors over the straight portion of the proximal tubule.

Animals↗
PubMed1985

[3H]-rauwolscine binding to alpha 2-adrenoceptors in the mammalian kidney: apparent receptor heterogeneity between species.

Binding of the alpha 2-adrenoceptor antagonist [3H]-rauwolscine was characterized in membrane preparations from the kidneys of mouse, rat, rabbit, dog, and man. In all species, binding reached equilibrium within 45 min and dissociated at a single exponential rate after addition of phentolamine 10 microM. Saturation studies showed that the affinity of [3H]-rauwolscine was similar in all species (2.33-3.03 nM) except man where it was significantly higher (0.98 nM). Marked differences were seen in the density of binding sites, increasing in the order: man less than dog less than rabbit less than rat less than mouse. In all cases, Hill coefficients were not significantly different from unity. [3H]-rauwolscine binds with low affinity (KD greater than 15 nM) to membranes prepared from guinea-pig kidney. The low affinity binding is not due to the absence of particular ions in the incubation medium or to receptor occupation by endogenous agonist. The binding in all species was found to be stereoselective with respect to the isomers of noradrenaline. However, differences were seen in the characteristics of agonist interactions with the binding site both between isomers and between species. Marked differences in affinity of particular alpha-adrenoceptor antagonists were observed for alpha 2-adrenoceptors labelled by [3H]-rauwolscine. These differences were most evident with the alpha 1-adrenoceptor selective antagonist prazosin which displayed inhibition constants (Ki values) of 33.2, 39.5, 261, 570 and 595 nM in rat, mouse, dog, man and rabbit, respectively. Differences are apparent in the characteristics of alpha 2-adrenoceptors labelled by [3H]-rauwolscine between species and it is suggested that the differences observed for alpha 1-selective antagonists such as prazosin may be related to binding to additional sites in the vicinity of the alpha 2-adrenoceptor.

Adrenergic alpha-Antagonists↗
PubMed1985

A comprehensive allergen extract monograph with advice for the patient.

Interest in increased patient education regarding medications they receive is gathering momentum. An historical overview is provided as well as summaries of available patient information resources. To date little such information has been available for patients receiving immunotherapy with allergen extracts. A comprehensive draft monograph driven from multiple sources for the various products available is proposed, as well as suggested advice for patients. Comments and suggestions for revision are solicited, prior to proposed inclusion in a national patient information publication.

Allergens↗
PubMed1985

Localization of beta adrenoceptor subtypes in rat kidney by light microscopic autoradiography.

The characteristics and localization of beta adrenoceptor subtypes in rat kidney sections have been examined using [125I]cyanopindolol and in vitro labeling combined with autoradiography. Binding was stereoselective since the (-)-isomers of propranolol and pindolol were some two orders of magnitude more effective as competitors than the (+)-isomers. Competition curves obtained using the subtype selective antagonists ICI 118,551 (beta-2) and betaxolol (beta-1) had low pseudo Hill coefficients and were resolved into two distinct components representing beta-1 (63%) and beta-2 adrenoceptors (37%). Combined autoradiographic and histochemical studies using nuclear emulsion-coated coverslips and alkaline phosphatase staining showed that the majority of receptors were in the renal cortex and in the outer band of the medulla with fewer receptors associated with the inner medulla, papilla and renal blood vessels. Delineation of beta-1 and beta-2 adrenoceptor subtypes with the selective antagonists betaxolol and ICI 118,551 indicated that the highly localized receptors were predominately of the beta-1 subtype, associated with glomeruli and with tubules that from their staining characteristics and topography represent distal and cortical collecting tubules with few if any receptors associated with proximal tubules. Beta-2 adrenoceptors were more diffusely distributed in the cortex and there were minor areas of localization in the inner medulla. Although some glomerular beta adrenoceptors probably play a role in control of renin release, their distribution throughout this structure indicates that they also control other functions. The distribution of beta adrenoceptors in tubules corresponds well with the known distribution of beta adrenoceptor-stimulated adenylate cyclase in rat kidney and indicates that these receptors subserve a physiological function.

Animals↗
PubMed1984

Human hypersensitivity to a sham vaccine prepared from mosquito-cell culture fluids.

A sham vaccine, prepared with the C6/36 cell line derived from larval Aedes albopictus mosquitoes, was skin tested on 12 volunteers. Although no reactions were observed after prick tests, three immediate reactions did occur after intradermal tests. Subcutaneous administration of the C6/36 sham vaccine was initially performed on the nine subjects who did not demonstrate immediate reactions. Five of these subjects developed delayed reactions at the site of the intradermal test within 12 hr after inoculation. A Prausnitz-Küstner test was performed on the back of one unsensitized subject by use of both unheated and heated sera from three subjects who had immediate skin reactions, three who demonstrated a delayed reaction, and one who had a negative skin response. In the Prausnitz-Küstner test, immediate skin reactions were observed with all seven unheated sera but with none of the heated serum aliquots. The determination that skin reactivity was associated with a heat-labile serum factor suggested the mechanism was IgE-mediated. Under close surveillance, the C6/36 sham vaccine was administered subcutaneously to one volunteer who had previously demonstrated an immediate response. This subject developed an anaphylactic reaction characterized by hives at the site and more distantly from the site of the subcutaneous inoculation. Hypersensitivity to A. albopictus larval antigens is common and precludes the use of C6/36 cell culture as a substrate for viral vaccines.

Cells, Cultured↗