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Biomedical subjects

C B Smith

Publications and source records attributed to C B Smith.

At least 145 records · Page 8Linked to original sources
PubMed1984

Attempts to combine 2-deoxyglucose autoradiography and tyrosine hydroxylase immunohistochemistry.

The possibilities were analysed to combine the 2-deoxyglucose technique and indirect immunofluorescence histochemistry using tyrosine hydroxylase antiserum, with the aim to study functional activity in immunohistochemically characterized single neurons. Since the product measured with the 2-deoxyglucose method is water soluble and since immunohistochemistry requires that sections repeatedly run through aqueous media, the 2-deoxyglucose method was carried out before fixation and immunohistochemistry. The routine rapid thaw-mounting at + 60 degrees C of sections for 2-deoxyglucose autoradiography was found not to be compatible with immunohistochemistry. Instead a new mounting technique based on "gluing" the sections on to the object slide with a mixture of a standard mounting medium (Permount) and xylene was used to avoid diffusion at this stage. Two procedures were outlined, both starting with unfixed brains cut on a cryostat. In Method I autoradiographic sheet film was used. After autoradiographic exposure, the section was immersion-fixed in formalin, processed for immunohistochemistry, analysed and photographed in a fluorescence microscope and the results compared with the autoradiographic distribution patterns on the film. However, only the low resolution of the routine 2-deoxyglucose technique was obtained, which did not allow analysis of activity in single cells. In Method II, liquid emulsion applied by the loop technique was used. After exposure, autoradiographic developing and fixation, dehydration, mounting, analysis and photography of autoradiographs in the light microscope, the cover-slip was removed, the sections rehydrated and processed for indirect immunofluorescence histochemistry. With this procedure single autoradiographically labeled cells were observed, some of which contained tyrosine hydroxylase. Thus, with Method II it may in the future be possible to monitor functional activity in single immunohistochemically identified neuronal cell bodies. In order to obtain a useful and reliable method for this purpose, however, further extensive work with regard to, for example, quantification will be required.

Animals↗
PubMed1984

Evaluation of cost-effectiveness and rationale for use of a selective culture plate for isolation of Staphylococcus aureus from stool specimens.

An assessment was made of the necessity of performing routine screening for Staphylococcus aureus in stool specimens. A total of 527 stool specimens were evaluated. Because of the rare incidence of staphylococcal enterocolitis and the high ($2.50) screening cost, the results of this evaluation suggest that such a screening need not be performed routinely.

Adult↗
PubMed1984

Birth weights of fetuses exposed to diagnostic ultrasound.

The birth weights of newborns routinely subjected to diagnostic ultrasound antenatally are compared with the birth weights of infants delivered by the same physician over a similar span of time seven years earlier, when diagnostic ultrasound was not available. They are also compared with the birth weights of infants delivered by a physician in the same rural community who requested diagnostic ultrasound for less than 10 per cent of his pregnant patients. There is no apparent difference between the average weights of the infants subjected to diagnostic ultrasound and those who were not.

Birth Weight↗
PubMed1984

Comparison of alpha 2 adrenoreceptors on arterial smooth muscle and brain homogenates from spontaneously hypertensive and Wistar-Kyoto normotensive rats.

Alpha 2 adrenoreceptors are located on vascular smooth muscle of the rat tail artery. In the present study this receptor was studied in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Adrenergic agonists were used to produce isometric contractions of helically-cut tail artery strips from SHR and WKY. Clonidine and guanabenz, alpha 2 agonists, were more potent in the SHR than in the WKY (e.g. clonidine: EC50 SHR = 3.5 +/- 0.6 X 10(-8) M; EC50 WKY = 17.0 +/- 0.2 X 10(-8) M; P less than 0.0005). There was no difference in potency between the alpha 1 agonists, phenylephrine and methoxamine. Yohimbine, an alpha 2 antagonist, was more potent in inhibiting the clonidine-induced contraction in the SHR (pA2 = 7.66 versus 7.14). To determine the number of alpha 2 adrenoreceptors, the specific binding of 3H-clonidine to homogenates of tail artery and of five brain areas was also measured. The maximum number of high-affinity sites on the tail artery was threefold greater in SHR than in WKY (31 +/- 5 versus 11 +/- 3 fmol/mg protein, P less than 0.0005). No differences in the number or affinity of alpha 2 receptor sites was found in the hypothalamus, hippocampus, locus coeruleus or parietal cortex of the two strains of rat. There was a difference in the amygdala (SHR: 163 +/- 16 versus WKY: 108 +/- 14, P less than 0.05). The larger number of alpha 2 adrenoreceptors on the vascular smooth muscle in SHR may provide an explanation for the supersensitivity of SHR to adrenergic agonists.

Animals↗
PubMed1984

Stimulation of protein synthesis and glucose utilization in the hypoglossal nucleus induced by axotomy.

The metabolic responses of rat hypoglossal nuclei to unilateral section of the 12th cranial nerve have been studied. Changes in the rates of protein synthesis and glucose utilization in the regenerating nucleus were determined with two quantitative autoradiographic techniques, the L-[1-14C]leucine method and the [14C] deoxyglucose method, respectively. The results show that both of these processes increase in the nucleus ipsilateral to the sectioned nerve and are unaffected in the contralateral nucleus as compared with sham-operated animals. The time courses of these metabolic changes have been compared with that of the return of functional innervation of the tongue. An increase in glucose utilization is first detected 24 hr postaxotomy. It is maximal between 1 and 3 days postaxotomy and constitutes an 84% increase over the rate in the contralateral control nucleus. The increase in protein synthesis is of smaller magnitude than that of glucose utilization. It is maximal at 48 hr after axotomy and constitutes a 25% increase over the rate in the contralateral nucleus. The increases in both of these metabolic processes persist even after functional recovery of the tongue at 21 days postaxotomy. Protein synthesis and glucose utilization return to normal levels between 24 and 35 days postaxotomy. Although the time courses of the changes in protein synthesis and glucose utilization are similar, the magnitude of the increase in glucose utilization is too large to be accounted for by the energy requirements of the relatively small increase in protein synthesis and probably reflects other processes as well, including altered function of the soma-dendritic membrane of regenerating neurons.

Animals↗
PubMed1983

Improved resolution of the 2-deoxy-D-glucose technique.

It was attempted to improve the resolution of the 2-deoxyglucose method. Two principle changes in the procedure were introduced: the gluing of the sections on to the object slide at--20 degrees C and the application of the emulsion with the loop technique. With this approach autoradiographs with grain accumulations over single cell bodies could be observed in many brain regions in addition to a diffuse activity over neuropil.

Animals↗
PubMed1983

Platelet alpha 2 adrenoreceptors in chronic congestive heart failure.

Patients with chronic congestive heart failure (CHF) are known to have elevated plasma concentrations of norepinephrine. Although this elevation of catecholamines in plasma may facilitate myocardial contractility, it may also be toxic to the myocardium in the long term. The alpha 2 adrenoreceptor located on noradrenergic nerve terminals regulates neuronal norepinephrine release by feedback inhibition. This receptor is also located on human blood platelets. This study determines the status of platelet alpha 2 adrenoreceptors in 16 patients with CHF (class I and II in 7 and class III and IV in 9) and in 26 normal volunteers. Specific high-affinity binding of the alpha 2 agonist 3H-clonidine and the alpha 2 antagonist 3H-yohimbine was used to determine the number (Bmax) of alpha 2 receptors and the dissociation constant (KD) for the 2 ligands. In the control population, the Bmax (in fmol/mg protein) for 3H-clonidine was 33 +/- 2 and for 3H-yohimbine was 165 +/- 12. There was a 25% difference in the maximum number of specific binding sites for 3H-clonidine in the class III/IV group (Bmax 24 +/- 2, p less than 0.05) and a 43% difference in the maximum number of specific binding sites for 3H-yohimbine (Bmax 94 +/- 9; p less than 0.005). There was a smaller but nonsignificant difference in the number of receptors on platelets from patients in the class I and II group. The KD's were similar in all 3 groups. These differences correlated well with the increases in plasma norepinephrine levels between the normal group (273.8 +/- 44.1 pg/ml) and the class III/IV group (1333.5 +/- 244.9, p less than 0.0005). This study supports the hypothesis that increased levels of circulating norepinephrine in CHF lead to a decrease in platelet alpha 2 adrenoreceptors. Further studies should be performed to determine whether pharmacologic stimulation of these receptors might lead to a decrease in the neuronal release of that norepinephrine which might be toxic to the myocardium. Monitoring of platelet alpha 2 adrenoreceptor number may provide a guide to therapy of CHF.

Adult↗
PubMed1983

Changes in alpha2 adrenoreceptors in various areas of the rat brain after long-term administration of "mu" and "kappa" opiate agonists.

Clonidine, an alpha 2 adrenoreceptor agonist, is used to treat opiate dependent individuals who are experiencing the signs and symptoms of withdrawal. Changes in the apparent number of alpha 2 adrenoreceptors in specific areas of the rat brain have been observed after chronic morphine administration. In the present study, the effects of chronically administered morphine sulfate upon alpha 2 adrenoreceptors were compared to those of UM-1072, (+/-)-5,9-alpha-dimethyl-2-hydroxy-2-tetrahydro-furfuryl-6, 7-benzomorphan HCl, a "kappa" agonist which does not produce typical morphine-like dependence. The maximum number of specific binding sites (Bmax) and dissociation constants (KD's) for 3H-clonidine were measured with neural membranes isolated from saline or drug-treated rats. Rats were injected with saline, morphine or UM-1072, i.p., every 8 hr for 14 days. Doses of morphine ranged from 10 mg/kg, t.i.d., on the first three days to 100 mg/kg, t.i.d., on the last two days. Doses of UM-1072 covered a similar range. In control experiments, the Bmax's for specific binding of 3H-clonidine were (in fmoles/mg protein): hypothalamus, 142 +/- 7; amygdala, 141 +/- 3; brainstem, 70 +/- 2; parietal cortex, 130 +/- 4; hippocampus, 94 +/- 2; and caudate nucleus, 62 +/- 3. After chronic morphine treatment, the Bmax's were decreased significantly in all areas except the hippocampus. After chronic UM-1072 treatment, the Bmax's were decreased significantly in all areas studied. Neither treatment altered appreciably the KD's for 3H- clonidine. This study suggests that "mu" and "kappa" agonists might have similar actions upon noradrenergic systems in the brain.

Animals↗
PubMed1983

Androgen metabolism by human prostatic tumours in organ culture.

Metabolism of testosterone and 5 alpha-dihydrotestosterone were investigated in benign and malignant human prostatic tumours maintained for 48 hr in organ culture. When tritiated testosterone was used as substrate there were significant differences between the metabolic pathways of the two types of tumour. Whilst the benign tumour had a predominantly reductive pathway leading to the formation of 5 alpha-reduced metabolites of testosterone, an oxidative pathway producing androstenedione was found to be the major pathway operative in the intermediate and poorly differentiated malignant specimens studied. In contrast to these differences observed in the metabolic pathway of testosterone when tritiated 5 alpha-dihydrotestosterone was used as substrate, no significant differences in the pattern of radiometabolites were observed.

Androstenedione↗
PubMed1983

Platelet alpha 2 adrenoreceptors are decreased in number after antidepressant therapy.

Specific binding of 3H-clonidine to alpha 2 adrenoreceptors upon human blood platelet membranes is increased in patients with major depressive disorder (endogenous depression). Specific binding of 3H-yohimbine to the platelet adrenoreceptor is not altered in endogenously depressed patients. Other psychiatric disorders are not associated with alterations in the specific binding of either 3H-clonidine or 3H-yohimbine. In patients with severe congestive heart failure or with symptomatic coronary artery disease the number of platelet alpha 2 adrenoreceptors is actually decreased. Treatment of endogenously depressed patients with tricyclic antidepressants, lithium salts or electroconvulsive therapy results in a decrease in the number of alpha 2 adrenoreceptors on blood platelet membranes. These studies suggest that a supersensitivity of the alpha 2 adrenoreceptor might exist in patients with endogenous depression and that effective forms of therapy lead to a decrease in the number of neural alpha 2 adrenoreceptors which is reflected by a decrease in the number of these receptors upon blood platelet membranes.

Animals↗
PubMed1983

Zomepirac: preclinical narcotic abuse liability evaluation.

5-(4-Chlorobenzoyl)-1,4-dimethyl-1H-pyrrole-2-acetate dihydrate (Zomepirac, Zomax) was assessed in a variety of preparations in which narcotic agonists and antagonists have distinctive profiles. Zomepirac failed to displace tritiated etorphine significantly at concentrations up to 200 mumol/l. It was active (3-7 X 10(-5) mol/l) on both the electrically stimulated guinea pig ileum and mouse vas deferens but was less efficacious than morphine; these effects were not reversed by narcotic antagonists. Zomepirac was inactive in some analgesic assays in mice: tail-flick (1-30 mg/kg s.c.); hot plate (1-100 mg/kg s.c.); Nilsen (1-50 mg/kg s.c.); it was also inactive (1-10 mg/kg s.c.) as an antagonist of morphine in the tail-flick assay. It was, however, active in the paraphenylquinone writhing assay; this action was not reversed by naloxone (1-10 mg/kg) Zomepirac (2.5-10 mg/kg s.c.) failed to suppress signs of withdrawal produced by morphine deprivation in dependent rhesus monkeys. The intraperitoneal infusion of high doses of zomepirac (50 mg/kg/24 h or more) in rats produced toxicity. However, lower doses failed to induce narcotic-like dependence over a 6-7-day infusion period. The compound failed to maintain intravenous drug self-administration responding in rhesus monkeys over a range of doses (0.1-3.2 mg/kg) although codeine did so. In rhesus monkeys trained to discriminate narcotic agonists (etorphine or ethylketazocine) from saline, zomepirac (1-10 mg/kg i.m.) failed to produce drug-appropriate responding. Thus, zomepirac appears to possess few, if any, of the characteristic actions of narcotics that are associated with their abuse liability.

Analgesics, Opioid↗
PubMed1983

Alpha-2 adrenoreceptors on arterial smooth muscle: selective labeling by [3H]clonidine.

The specific binding of [3H]clonidine was used to characterize alpha-2 adrenoreceptors on rat tail artery smooth muscle membranes. At 24 degrees C binding of 8 nM [3H]clonidine was rapid T 1/2 of association = 2.1 min) and reversible (T 1/2 of dissociation = 0.7 min). The binding sites for the [3H]clonidine showed the specificity required for the alpha-2 adrenoreceptor. The rank order of potency of inhibitors of [3H]clonidine binding for agonists was clonidine greater than phenylephrine greater than methoxamine and for antagonists was yohimbine and piperoxan much greater than prazosin. Scatchard analysis of the binding data indicated the existence of a single population of binding sites with the maximum number of binding sites, Bmax, equal to 33.5 +/- 0.3 fmoles/mg of protein and the dissociation constant, KD, equal to 7.3 +/- 0.4 nM. There was no evidence for cooperativity (Hill coefficient = 0.96). The inhibition constants, Ki values, of various adrenergic agonists and antagonists for the displacement of [3H]clonidine from tail artery membranes were well correlated with Ki values determined for the displacement of this ligand from rat hippocampal membranes. Similar correlations were found with the potencies of these same agents in producing contractions of isolated tail artery strips. This study confirms the presence of alpha-2 adrenoreceptors on arterial smooth muscle and suggests that these receptors might be important in vascular function.

Adrenergic alpha-Agonists↗