Use of apomorphine to test for dopamine responsiveness in Wilson's disease.
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Apomorphine↗
Biomedical subjects
A Hughes
Publications and source records attributed to A Hughes.
Specific binding of 125I SCH 23982, a selective dopamine (D1) receptor ligand to plasma membranes derived from human kidney cortex.
Binding of the selective D-1 dopamine receptor ligand 125I SCH 23982 was studied using crude plasma membranes derived from human renal cortex. 125I SCH 23982 bound saturably to a single high affinity site (Kd = 650 pM, Bmax = 19 fmol/mg protein). Binding at 37 degrees was rapid and reversible with forward and reverse rate constants of 5.79 x 10(8) min-1 m-1 and 0.156 min-1 respectively. Antagonist and agonist competition for 125I SCH 23982 binding was also consistent with the existence of a single site possessing pharmacological characteristics similar to a D-1 dopamine receptor. It is suggested that this site may represent a D-1 (or DA1) dopamine receptor present in human renal cortex.
Benzazepines↗
Knowledge of AIDS, use of condoms and results of counselling subjects with asymptomatic HIV2 infection in The Gambia.
A questionnaire administered to subjects seen during a serological survey in The Gambia revealed that knowledge of AIDS and HIV infection was limited. Males, those with a secondary education and people who lived in urban areas had a better understanding but only 17% of women seen in rural areas had any knowledge of the condition. Only 8% of the subjects seen had used condoms in the preceding 12 months; during this time half of them had done so on less than five occasions. Subjects with a secondary education were more likely to have used condoms. A counsellor met 31 asymptomatic seropositive subjects identified during this survey on two occasions. In the majority, the information given caused anxiety rather than modification of behaviour and, at the time of the second interview, only one subject had discussed the situation with the partner and begun using condoms. Some of the cultural factors which may affect the outcome of counselling in an African society are discussed in the light of these findings.
Acquired Immunodeficiency Syndrome↗
Blind and partial sight registration in Avon.
All blind and partially sighted registration forms for the county of Avon for a two-year period were analysed, and the findings are presented. Comparisons with the national figure published by Sorsby over 20 years ago show there has been no marked change in the rates of blind registration per 100,000 population with the exception of those for cataract, which show a large reduction. Diabetic registrations have remained similar, but this may represent an encouraging trend in view of the significant increase in the size of the diabetic population. Glaucoma may show some improvement in the future when time has elapsed for beta blockers and trabeculoplasty to be fully assessed. There has been an increase in the rate of registration from aging macular degeneration.
Adolescent↗
Thermal resistance of Listeria monocytogenes in sausage meat.
The heat resistance of a mixture of 10 different strains of Listeria monocytogenes inoculated into ground meat and ground meat plus cure was examined. D-values for ground meat ranged from 1.01 min at 62 degrees C to 13.18 min at 56 degrees C. The D-values obtained for ground meat plus cure were approximately 5-8 fold times higher than those for ground meat alone. These results imply that rare meats and possibly some cooked fermented meats may not be heated adequately to inactivate Listeria.
Food Microbiology↗
Envelope cross-reactivity in Western blot for HIV-1 and HIV-2 may not indicate dual infection.
Serological identification of infection with human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) by western blot alone may not be sufficient to diagnose dual infection. Extensive cross-reactions (eg, to envelope glycoprotein antibody) are seen on heterologous western blots. The use of other techniques, in this case competitive enzyme-linked immunosorbent assays, indicates that blot patterns previously thought to demonstrate simultaneous dual infections should be interpreted with caution.
Acquired Immunodeficiency Syndrome↗
Bromine-80m radiotoxicity and the potential for estrogen receptor-directed therapy with auger electrons.
While theoretically feasible, estrogen receptor (ER)-directed radiotherapy of hormone-dependent cancers has not been realized because no ER-seeking ligand with an appropriate radiotoxic potential has been identified. Since an appropriate nuclide is a key component we studied the 4.4-h half-life, Auger electron-emitting nuclide bromine-80m. When incorporated into DNA this nuclide was radiotoxic to cells in culture and caused substantial chromosomal damage, while similar concentrations of bromine-80m as bromide or bromoantipyrine were without effect. The mean lethal dose for bromine-80m was 45 atoms per nucleus which is consistent with use in receptor-positive cancers with limited numbers of ER.
Animals↗
Bromine-80m-labeled estrogens: Auger electron-emitting, estrogen receptor-directed ligands with potential for therapy of estrogen receptor-positive cancers.
To assess their possible use for estrogen receptor (ER)-directed radiotherapy of estrogen receptor-containing cancers, two estrogens were synthesized with the Auger electron-emitting nuclide bromine-80m and administered to immature female rats. Both the triphenylethylene-based estrogen, [80mBr]-2-bromo-1,1-bis(4-hydroxyphenyl)phenylethylene (Br-BHPE) and the steroidal estrogen [80mBr]17 alpha-bromovinylestradiol, showed substantial diethylstilbestrol-inhibitable localization only in the estrogen target tissues, the uterus, pituitary, ovaries, and vagina and, except for the liver and intestines, generally lower concentrations in all other tissues at both 0.5 and 2 h. The [80mBr]Br-BHPE (specific activity, 8700 Ci/mmol), was shown to bind specifically to the low salt extractable ER of the rat uterus. Comparing i.p., i.v., and s.c. administration of [80mBr]BHPE the i.p. route was found to be particularly advantageous to effect maximum, DES-inhibitable concentrations of radiobromine in the ER-rich target organs in the peritoneal cavity. When the tissue distribution of the [80mBr]Br-BHPE was compared with that of sodium bromide-80m, it was apparent that no substantial amounts of radiobromine were released from the bromoestrogen prior to its target tissue localization. The substantial concentration of these bromine-80m-labeled estrogens in ER-rich tissues, combined with previously reported evidence for the effective radiotoxicity of Auger electron-emitting nuclides within cell nuclei suggest a good potential for such ligands for therapy of ER positive cancers.
Animals↗
Estrogen receptor binding affinity and uterotrophic activity of triphenylhaloethylenes.
Radiohalogenated estrogens have considerable potential for estrogen receptor-directed imaging and therapy for cancers which contain such receptors. In an effort to evaluate the potential of the triphenyl ethylene structure for such purposes we have synthesized 3 series of 2-halosubstituted triphenylethylenes containing oxygen functions in the 4 position of both aromatic rings attached to carbon 1 of the ethylene and tested their uterotrophic activity and competition for rat uterine low salt extractable, "cytosol" estrogen receptor. Most active, both as competitors for estradiol binding to estrogen receptors and by their ability to stimulate uterine growth are the 1,1-bis-4-hydroxyphenyl derivatives although the 1,1-bis-4-acetoxyphenyl derivatives also show good receptor affinity and demonstrate uterotrophic activities. However, since uterine cytosol contains enzymes which hydrolyze the acetates to the free phenols even during the incubation in the cold used for the competitive binding studies, a significant portion of the competition shown by the diacetates is probably due to their hydrolysis products, the free phenols. The 1,1-bis-4-methoxyphenyl derivatives are weak competitive binders and demonstrate uterotrophic activity only when administered at the higher, 20 micrograms, doses. Comparing the relative activities of various halogens at the 2 position, in each series the bromo and chloro derivatives generally were of similar activity and significantly more active than the corresponding iodo derivative. The non-halogen substituted derivatives were very good competitors for estrogen receptor binding but less active with regard to uterine growth stimulation, providing evidence that in vivo the vinyl halides would appear to be relatively stable to simple dehalogenation. Since they show reasonably good apparent affinities for the estrogen receptor and apparent in vivo stability, reflected by estrogenic activity, these halogen substituted triphenylethylene derivatives appear to be promising substrates for investigations of estrogen receptor directed imaging and therapy.
Animals↗
Direct effect of alpha-human atrial natriuretic peptide on human vasculature in vivo and in vitro.
1. The effect of a alpha-human atrial natriuretic peptide (1-28) (ANP) on human vasculature was investigated in vivo and in vitro. Possible involvement of vascular dopamine receptors and the renin-angiotensin system in the response to ANP was also studied in vivo. 2. Forearm blood blow was measured by venous occlusion plethysmography. Isolated human blood vessels were studied using conventional organ bath techniques. 3. ANP (0.1-1 microgram/min, intra-arterially) produced a dose-dependent increase in forearm blood flow, corresponding to a 163% increase in net forearm blood flow in the study arm. This action of ANP was not antagonized by (R)-sulpiride (100 micrograms/min, intra-arterially), a selective vascular dopamine receptor antagonist, or 50 mg of oral captopril, an inhibitor of angiotensin-converting enzyme. 4. ANP (1 nmol/l-1 mumol/l) produced concentration-dependent relaxation of isolated human arteries, including brachial artery, but was without effect on isolated human saphenous vein. 5. ANP produces vasodilatation in vivo and relaxes isolated human arterial smooth muscle. This action of ANP may contribute to its reported hypotensive effects in vivo.
Adult↗
Action of dopamine on isolated human saphenous veins.
We have investigated the subtype of alpha-adrenoceptor responsible for the contractile effect of dopamine using isolated human saphenous vein. Lengths of saphenous vein were obtained surplus to coronary artery bypass graft operations and studied as intact rings using a conventional organ bath technique. Contractile responses to dopamine (10(-7)-10(-3) M) in the presence of propranolol, cocaine, and 17 beta oestradiol were competitively antagonised by the alpha 2-selective adrenoceptor antagonist yohimbine (10(-8)-10(-6) M) but unaffected by the alpha 1 selective adrenoceptor antagonist doxazosin (10(-8)-10(-6) M), whereas the response to norepinephrine (NE) (10(-8)-10(-3) M) was antagonised by doxazosin (10(-8)-10(-6) M), thus demonstrating the presence of alpha 1-adrenoceptors in this preparation. We conclude that the contractile effects of dopamine in isolated human saphenous vein are mediated predominantly by an action on alpha 2-adrenoceptors.
Aged↗
Hospice care: a model for caring for the person with AIDS.
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Acquired Immunodeficiency Syndrome↗
Bilateral spontaneous concurrent rupture of the patellar tendon in the absence of associated local or systemic disease.
A 26-year-old man incurred bilateral spontaneous rupture of the patellar ligament. This may be the eighth case in previously healthy individuals reported in the literature. Further review of other case reports suggested various etiological factors. Surgical repair generally produces excellent results.
Adult↗
The interaction of infant formula with macrophages: effect on phagocytic activity, relationship to expression of class II MHC antigen and survival of orally administered macrophages in the neonatal gut.
The effect of infant formula on human peritoneal and breast milk macrophages has been investigated. The ability of peritoneal macrophages to subsequently ingest and degrade immune complexes was slightly impaired, but breast milk cells were not affected. However, the cells were found to have bound antigenically intact casein and beta-lactoglobulin, although little, if any, alpha-lactalbumin was bound. Furthermore, a positive correlation was found between binding of these proteins and expression of HLA-DR antigen. Labelled macrophages fed to newborn mice survived for at least 4 hr in the gastrointestinal tract and, in some cases, localized in the mucosal tissue. In one case a labelled cell was found in the spleen. These findings indicate that breast milk macrophages may be able to perform immunological functions in the gut, and suggest that binding of cows' milk proteins by macrophages may constitute a first step in the sensitization of the neonate to cow's milk proteins. Human milk macrophages may also play a protective role by acting as antigen-presenting cells in the local immune response of the gut.
Animals↗
Developing neuronal populations of the cat retinal ganglion cell layer.
An improved flat-mount procedure demonstrates that the developing ganglion cell layer of the cat retina contains two morphologically distinct populations of presumed neurons at all ages between embryonic day 36 (E36) and adulthood. One population resembles the adult "classical neurons" composing the ganglion cells and bar-cells of Hughes, while the remaining cells, which are smaller and possess much less Nissl substance, presumably correspond to precursors of the adult microneurons. Although the total neuron population of the retinal ganglion cell layer remains quite constant at all studied ages, its component subpopulations alter significantly during prenatal development; some 50% of classical neurons disappear before birth and the microneuron population doubles during the same period. An obvious centroperipheral gradient exists for classical neurons by stage E47, but the microneuron density gradient only becomes apparent at birth. A 2:1 centroperipheral ratio for the total neuron population is also apparent at E47. Centroperipheral neuronal density gradients continue to increase during postnatal growth. Loss of classical neurons during prenatal life as a result of cell death or transformation into microneurons, has been postulated as a mechanism for determining neuron density gradients. Cell death does occur in the ganglion cell population but it is not yet established whether microneurons of the ganglion cell layer originate from ganglion cell transformation or migrate as a differentiated class from the ventricular layer. However, it can be concluded that not all microneurons originate from ganglion cell transformation, because the total loss of classical neurons is less than the increase in microneuron numbers during development. The population magnitudes of both neuronal classes in the ganglion cell layer stabilise after birth. However, it is during the postnatal period that the adult cruciate density topography is achieved by both populations. It is concluded that differential areal growth is the prime mechanism for postnatal cell redistribution.
Animals↗
Role of cell death in the topogenesis of neuronal distributions in the developing cat retinal ganglion cell layer.
The neurons of the developing and adult ganglion cell layer of the cat retina may be morphologically divided into two major populations. One population, the classic neurons, is mainly composed of ganglion cells, and of a small percentage of displaced amacrines, the bar cells. The remaining neurons are microneurons, which make up the majority of the displaced amacrine population. The loss of ganglion cells during the development has been attributed to cell death. It has alternatively been suggested that some ganglion cells may lose their axon and be transformed into displaced amacrine cells, without degeneration of the cell soma. Reexamination of foetal and postnatal cat retinas confirms the presence of degenerating cells in the ganglion cell layer. Their number appears to be at a maximum on embryonic day (E) 57 but declines rapidly until birth. The peak of cell death thus coincides with the decline in optic nerve fibre counts and classical neuron or ganglion cell numbers. Some cells in early stages of degeneration resemble classical neurons, but the original morphology of those advanced stages of degeneration could not be identified, nor was it possible to identify pyknotic microneurons at any stage. Substantial degeneration of the microneurons is not suggested but if it occurs, it is masked by an overall increase in the population of these cells before birth. Cell death in the microneuron population thus cannot yet be ruled out. It has been argued in the literature that fragments of degenerating cells in developing neural tissue are cleared by microglia within 10-14 hours. In order to test the hypothesis that operation of cell death can alone account for the observed loss of classical neurons in the foetal cat retina, we have modelled the effect of various presumed clearance times on corresponding neuronal population magnitudes. It is found that a constant clearance time of 10-24 hours would be consistent with the observed loss of classical neurons before birth. If this is true, then no ganglion cells would remain for transformation into amacrine cells. The absolute density of degenerating or pyknotic cells is found to be relatively constant across the retina. However their density expressed as a percentage of the local population of classical neurons is markedly higher in peripheral than central retina. In the former region, they compose more than 10% of classical neurons at stage E57. On the same day, the percentage distribution maps define an elongated central area containing only 3-5% pyknotic profiles. This region corresponds to the location of the future visual streak.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Regulation of estrogen and progestin receptor concentrations in an experimental rat prostatic carcinoma by estrogen, antiestrogen, and progesterone.
In order to assess prostatic tissue as a target for receptor-mediated estrogen action, we have examined the regulation of estrogen (ER) and progestin receptors (PgR) by estrogen, antiestrogen, and progesterone in cytosolic and nuclear fractions of the R3327H (Dunning) prostatic adenocarcinoma of the rat. Twenty micrograms diethylstilbestrol (DES) with or without 800 micrograms tamoxifen (Tam) were injected s.c. in oil 5 times weekly for 2 weeks. Controls were given oil only. Estrogen receptor assays were carried out using [3H]estradiol and a hydroxylapatite exchange method. Progestin receptors were assayed using [3H]R5020 and dextran-coated charcoal to separate free and bound steroid. All binding data were evaluated by using Scatchard analysis. Treatment with DES depleted cytosolic ER, promoted association of ER with the nuclear fraction, and concomitantly increased PgR concentrations in amounts proportional to nuclear ER. Treatment with Tam alone resulted in higher nuclear ER concentrations than treatment with DES, but induced only one-fifth the amount of PgR. Treatment with DES plus Tam resulted in similar nuclear ER concentrations as with Tam alone, but PgR concentrations were intermediate between those observed with DES alone and Tam alone. Thus Tam exhibited both estrogenic and antiestrogenic properties. In this experiment, the same cytosolic and nuclear extracts were also assayed for ER by using monoclonal antibodies to the receptor in an enzyme immunoassay. No significant differences were observed between the results obtained by the radioligand and enzyme immunoassay methods in the cytosol and nuclear fractions from the control and DES-treated tumors. However in both Tam-treated groups, the ER values obtained by the enzyme immunoassay method were significantly higher than those obtained by the radioligand method in both cytosolic and nuclear fractions. This confirms the observations made by others in female target organs, that monoclonal antibody to ER reacts differently with the Tam-bound ER complex than with the estradiol-bound ER complex. In a separate experiment, administration of progesterone with DES decreased the concentration of nuclear ER to less than one-half that observed after administration of DES alone, with proportional decreases in both cytosolic and nuclear PgR. All these observations indicate that the control of ER and PgR concentrations in this prostatic tumor is identical to that observed in female rat target organs. Use of an immunohistochemical method for the detection of ER in frozen sections indicated that the receptor was localized in the glandular epithelium in both control and DES-treated tumors.
Animals↗
The morphology, number, and distribution of a large population of confirmed displaced amacrine cells in the adult cat retina.
The presence of a large population of some 730,000 displaced amacrines is confirmed in the ganglion cell layer of the cat retina. These cells correspond to the microneurons of Hughes and Wieniawa-Narkiewicz (Nature 284:468-470, '80) and the bar-cells of Hughes (J. Comp. Neurol. 197:303-339, '81): a population of profiles of which the majority had previously been presumed to be glia (Stone: J. Comp. Neurol. 12:337-352, '65; J. Comp. Neurol 180:753-772, '78; Hughes: J. Comp. Neurol. 163: 107-128, '75). A sample of such nonganglion cells was identified by Nissl criteria in an area of retina subsequently subjected to serial sectioning and electron microscopy. Such cells form synapses with other processes in the inner plexiform layer. Members of each morphological subclass were found to bear synapses. In some instances, synapses occurred both onto and from the soma and processes of a cell, which is strong evidence for their being displaced amacrines, or preferably, "amacrines of the ganglion cell layer." In confirmation of their amacrine nature, it was established that the microneurons and bar-cells survive optic nerve section for up to 2.5 years. Ganglion cells underwent retrograde degeneration and completely disappeared in a much shorter time. Injection of kainic acid, a neurotoxin, into an eye whose optic nerve had been cut over 2 years previously resulted in the pyknosis of all morphologically classified microneurons and bar-cells without influence on conventional glial cells. These results further support the conclusion that microneurons and bar-cells are neurons and that they collectively form the displaced amacrine population of the cat ganglion cell layer. The topographic distribution of the displaced amacrines resembles that of the ganglion cells in form; their density peaks at 4,500-5,000 cells mm-2 in the area centralis and falls to less than 1,000 mm-2 in peripheral retina. A ganglion cell distribution map based on the latest morphological criteria derived from this study confirms that there are 170,000 ganglion cells in the cat retina. Displaced amacrines form some 80% of the total neuron population of the cat ganglion cell layer. The large population magnitude of these confirmed displaced amacrines implies their nonectopic origin and now provides a fresh insight into the ontogeny of the cat retinal ganglion cell layer.
Animals↗