Cellular localization of responses to catecholamines in brain tissue.
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Biomedical subjects
Publications and source records attributed to S M John.
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Elastosis perforans serpiginosa (EPS) is a rare entity belonging to the group of primary perforating dermatoses. A 13-year-old male patient with Down's syndrome developed reddish hyperkeratotic papules in a serpiginous and ellipsoid configuration on the face. Histological examination revealed transepidermal elimination of thick coarse elastic fibres from the papillary dermis. The dermal infiltrate showed an immunohistological pattern consistent with an acute cell-mediated immune response. It consisted mainly of activated T-lymphocytes, with a predominance of CD4-positive cells. Considerable numbers of CD1-positive cells were also present. Inflammatory macrophages of the 27E10 phenotype were found in considerable numbers, whereas 25F9-positive resident macrophages were almost completely absent. The role of a cell-mediated immune response in the mechanism of transepithelial elimination is discussed.
The present studies investigated the use of microdialysis for the infusion of catecholamines into the brain in studies of immediate early gene (IEG) activation. c-Fos like immunoreactivity was examined histochemically in cortical tissue surrounding a dialysis probe implanted in the medial prefrontal cortex. No c-fos reactivity was observed at 48 h post implantation in control animals not probe-infused or infused 2 h earlier with Ringer's buffer. Marked reactivity was found in animals infused with a solution of norepinephrine (NE). The latter was blocked by coinfusion of the beta adrenoceptor antagonist, timolol. It is concluded that direct infusion of NE by dialysis can induce c-fos expression in cells of the cerebral cortex and that this effect is primarily via beta-adrenoceptors. Microdialysis therefore represents a useful technique in studies of IEG responses to brain catecholamines.
The present experiments were designed to clarify the cellular localization of postsynaptic beta-receptors in the rat cortex by studying the cellular source and pharmacological characteristics of in vivo cAMP responses to catecholamines. The method used to study in vivo cAMP responses in the brain involved microdialysis both to deliver catecholamines to cerebral tissue and to sample cAMP released in response to local beta-receptor activation. It was found that selective blockade of the metabolism of glial cells by fluorocitrate infusion produced a virtually complete (90%) inhibition of the cortical cAMP response to norepinephrine (NE). Selective damage of neurons by kainic acid infusion had little effect on the response. Pharmacological experiments showed that the response was selectively antagonized by a beta 1-receptor blocker which also selectively antagonized the cAMP response to NE in brain slices known to be localized in glial cells. These results support the hypothesis that beta-adrenoceptors of the rat cortex are predominantly localized on glial cells and therefore strongly suggest that these cells are an important target of the locus coeruleus noradrenergic system.
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The results of the European Working Party for Hypertension in the Elderly Study showed that treatment of high blood pressure reduced the morbidity and mortality from strokes and myocardial infarction and reduced the incidence of heart failure in elderly patients. The largest number of hypertensive patients are elderly, and it is in this group of patients that the maximum benefit of treatment might be expected. The present study was designed to study in detail the efficacy and tolerability of ketanserin in an elderly population. Seventeen elderly (greater than 70 years) patients with a lying systolic blood pressure of 160 mmHg and/or a diastolic blood pressure of greater than or equal to 90 mmHg were included in the study. For the 12 patients who completed the study, the mean blood pressure was significantly reduced on ketanserin compared with placebo (p less than 0.001) in the supine and erect positions. The mean net changes in blood pressure after 8 weeks were 21/17 mmHg and 23/16 mmHg erect. Heart rate was also significantly reduced (p less than 0.001) by a mean of 8 beats/min lying and 9 beats/min erect. Analysis of ambulatory 24-hour ECG tapes showed no significant effect of ketanserin on heart rhythms. Ketanserin therapy had no significant effect on routine hematology, plasma electrolytes, biochemistry, or urinalysis. Total exchangeable sodium and potassium and body weight were also unchanged. On ketanserin treatment, the overall quality of life score was significantly improved (p = 0.002; analysis of variance on log transformed data) compared with the placebo phase.
Microdialysis measurement of extracellular cyclic AMP (cAMP) in the cerebral cortex of conscious rats was evaluated as a method for assessing central beta-adrenoceptor function in vivo. Extracellular levels of the nucleotide were found to average 3 pmol/ml under baseline conditions. Local infusion of the beta-agonists norepinephrine (NE) and isoproterenol produced rapid (3 min) and marked (three- to sevenfold) dose-dependent increases in extracellular cAMP, which were potentiated by the phosphodiesterase inhibitor rolipram, and blocked by the beta-antagonist timolol. Responses to both catecholamines underwent rapid desensitization (6-9 min) and recovered within several hours. Time-course studies revealed that the baseline cAMP level underwent a gradual increase and then a decrease over the course of a single 8-h run, and peaked at 24 h postimplantation. Responses to NE were stable for the first 24 h after implantation, then increased at 48 and 120 h. The causes of the latter changes may include reactions to novelty, local inflammatory responses, and/or reactions of adjacent glial cells to implantation. Overall, the results indicate that the microdialysis-cAMP method can be extended to nonanesthetized animals and may be a useful tool for studying neurotransmission at central adenylate cyclase-coupled membrane receptors during various behavioral states.
A "divided naevus" (or "kissing naevus") is defined as a congenital melanocytic naevus that occurs on adjacent parts of the upper and lower eyelid and may give the appearance of a single lesion when the eye is closed. We report on four cases of this rare naevus. Two of these were examined histologically and showed the features of compound naevi. The unique occurrence in nature of the divided naevus allows conclusions on the site and time of origin not only of the divided naevus, but possibly also of other congenital melanocytic naevi. The divided naevus must originate at the latest during the period of lid fusion, between the 9th and 20th week of gestation. The fact that the fusion involves only epithelial tissue suggests an epithelial origin of congenital melanocytic naevi, which may later develop secondarily into compound or intradermal naevi by way of "dropping-off".
To test the validity of the current andrologic classification system, we performed cluster analysis in 317 andrologic patients involuntarily barren for more than 1 year. For cluster analysis, the spermatologic parameters sperm density, motility, and morphologic features were used since only these parameters contributed significantly to group identification, as revealed by stepwise discriminant function analysis. The optimal number clusters determined by calculation of the variance criterion was five. The resulting five groups partly correspond to the prevailing descriptive classification system as far as the extreme groups of "high-grade oligoteratoasthenozoospermia" and "polyzoospermia" are concerned. Surprisingly, cluster analysis distinguished between two groups of normozoospermia that differed in their mean sperm density. Cluster analysis may prove to become a powerful tool for andrologic classification.
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Certain drugs used to treat the elderly are known to precipitate hypothermia. In this study, the effects of chlormethiazole and thioridazine in producing postural hypotension were compared. In a study of hypothermia in the elderly the effects of chlormethiazole, thioridazine and lormetazepam were examined. Only three patients showed a postural drop following chlormethiazole, while 11 showed a postural drop following thioridazine. Chlormethiazole showed little variation from the control group in the hypothermia study, while thioridazine and lormetazepam caused a fall in temperature. For behaviour control in the elderly and for a short course as a hypnotic, chlormethiazole seems to be safer than thioridazine or lormetazepam.
Using the model of isolated acini the effect of cytochalasin D (CD) on rat pancreatic secretion in vitro was studied. The influence of CD (0.01-10 micrograms/ml = 0.02-19.7 microM) on amylase secretion and 3H-pulse-labelled protein release was measured under two sets of conditions: (a) basal, and (b) stimulated by 77pM caerulein. Basal secretion was not altered, but stimulated secretion of amylase and 3H-labelled proteins were similarly inhibited by up to 45%. It is concluded that CD affects only exocytosis of zymogen granules and not intracellular transport.
Studies were undertaken to determine the cellular localization of the cyclic adenosine monophosphate (cAMP) response of various forebrain regions to beta-adrenoceptor stimulation. Using brain slices, it was found that the gliotoxin, fluorocitrate (FC), which blocks metabolism selectively in glial cells, virtually abolished the cAMP response to beta-receptor stimulation whereas the neurotoxin, kainic acid (KA), was without effect. FC was confirmed by electrophysiological recording to be selective for glial cells in the brain slices. Similar results were found for these agents on in vivo brain cAMP responses to beta-receptor stimulation using a new microdialysis technique to measure in vivo responses. It is concluded that the cAMP response to beta-adrenoceptor stimulation in various regions of the forebrain occurs predominantly in glia. To determine if this could be correlated with a second biochemical response to beta-receptor stimulation, preliminary studies were undertaken on the localization of the immediate early gene, c-fos, produced in the brain after in vivo stimulation of beta-receptors. It was found that unlike the cAMP responses the c-fos response to beta-receptor stimulation occurs predominantly in neurons. The possible relationship of these two responses is discussed.