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G C Smith

Publications and source records attributed to G C Smith.

At least 289 records · Page 16Linked to original sources
PubMed1984

The masking of amine accumulation by catecholamine depletion.

6-Hydroxydopamine (2 microliter of 8 micrograms/microliter) was injected bilaterally into the lateral hypothalamus of male Sprague-Dawley rats to produce depletion of forebrain terminal fields and an accumulation of amines proximal to the site of injection. Two additional groups of animals were injected with either vehicle or were food and water intake-matched to those receiving 6-hydroxydopamine. Motor performance, food and water intake and body weight were measured in all animals for 2 days before and 6 days after injection. Animals were then sacrificed and brain tissue was prepared for biochemical assay or fluorescence histochemistry. The area of hypothalamic tissue proximal to 6-hydroxydopamine injection, that which contains the amine accumulation, was sectioned from the surrounding tissue with a biopsy punch and assayed for noradrenaline and dopamine content. The nucleus caudatus-putamen, basomedial hypothalamus, and tissue containing the olfactory tubercle and accumbens nucleus were also assayed. Fluorescent histochemical examination of tissue showed that in addition to the depletion of catecholamines in various terminal fields there was also an increase in the fluorescent amine accumulation proximal to the injection site in the impaired animals. This accumulation was not detected with the biochemical assay and is probably due to the occurrence of a masking effect by adjacent depletions. A significant rise in noradrenaline levels was seen in the basomedial hypothalamus of intake-matched controls. However, this too was not detected in 6-OHDA-treated animals and was probably due to masking by adjacent depletions in these areas.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Deficits in locomotor behaviour and thermoregulation produced by intrahypothalamic dopamine injections.

When nigrostriatal dopamine neurones degenerate, a loss of functional dopamine in the striatum occurs and is accompanied by increased dopamine in the degenerating axons which traverse the hypothalamus. While the behavioural deficits which occur after nigrostriatal degeneration have been attributed to the loss of functional dopamine neurotransmission, evidence produced by us suggests that the increased levels of amines in the degenerating axons may be neuroactive and participate in the production of these behavioural deficits. To test this hypothesis further, albino rats were injected bilaterally with 200 nmol of dopamine in a location just rostral to the diencephalon/mesencephalon border, where amine accumulation is commonly observed following lateral hypothalamic damage. The effect of these injections upon open field performance, thermoregulation and motor reflex control was determined 40 min after dopamine injection. In a second study, pargyline (15 mg/kg. i.p.) was administered 30 min before intracerebral dopamine to determine whether this treatment would increase the severity of motor and thermoregulatory deficits which occurred after dopamine injections alone. Deficits in locomotion, rearing and the ability to regulate body temperature were seen after the dopamine injections while motor reflex control in these animals was similar to that seen in vehicle-injected controls. The behavioural deficits displayed by pargyline pretreated, dopamine injected animals were slightly but not significantly more severe than those displayed by animals receiving dopamine injections alone. Fluorescent histochemical assessment of injection sites revealed that dopamine injection produced an increase in fluorescence or "amine accumulation" at the site of injection but this was considerably less than that seen after catecholamine degeneration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Ventricular, paraventricular and circumventricular structures involved in peptide-induced satiety.

Cholecystokinin, bombesin or gastrin (2 microliter of 50 ng/microliter) was injected stereotaxically into the paraventricular nucleus of the hypothalamus, the arcuate/ventromedial area, the subfornical organ, the area postrema and the cerebral aqueduct of Sprague-Dawley rats and the effects of these injections on food and water intake were studied. While the injection of cholecystokinin reduced food intake when it was injected into both hypothalamic loci, food and water intake were most severely affected by the injection of this peptide into the cerebral aqueduct. Bombesin reduced food intake after its injection into all areas except the subfornical organ and reliable reductions in water intake were seen after injection of this peptide into all areas except the paraventricular nucleus. Minor reductions in food intake were seen following gastrin injection into the paraventricular nucleus while increased water consumption was observed after this peptide was injected into the paraventricular nucleus and cerebral aqueduct. In a second study 6-hydroxydopamine injections (2 microliter of 8 micrograms/microliter were made into the five areas studied 10 days before animals were injected with 100 micrograms/kg of cholecystokinin (i.p.). All 6-hydroxydopamine-injected animals reduced their food and water intake in response to the cholecystokinin challenge as did intact controls. These results indicate that while the changes in food and water intake produced by the central injection of cholecystokinin, bombesin or gastrin may involve central catecholamine systems, those occurring after its systemic administration do not. Therefore, if the release of gastrointestinal peptides during natural feeding is part of a homeostatic mechanism regulating hunger and satiety, this mechanism may operate without directly involving central catecholamine systems.

Animals↗
PubMed1984

A role for amine accumulation in the syndrome of ingestive deficits following lateral hypothalamic lesions.

Lesions of the lateral hypothalamus produce ascending catecholamine neuron degeneration which results in terminal depletion and proximal accumulation above the lesions. The occurrence of deficits in ingestive behaviour has been attributed traditionally to the loss of functional dopamine neurotransmitter in the terminal fields. However, release of functional amines may occur in the lateral hypothalamus at areas of accumulation, to produce at least some of the behavioural symptoms characterizing the lateral hypothalamic syndrome. Recovery from behavioural deficits as a result of various pharmacological treatments, after dopamine-depleting lesions, may be mediated by changes in amine release or modified sensitivity of receptors affected by released amines. We conclude that amine accumulation should be considered when interpreting experiments implicating central catecholamine systems in the control of consumatory behaviour and the regulation of body weight.

Animals↗
PubMed1984

Effect of varying protein and energy densities in complete rations fed to cows in first lactation.

Sixty-three Holstein cows in first lactation were allotted randomly at 28 days postpartum to receive one of nine rations in a 3 X 3 factorial design. Rations had crude protein 12, 15, or 18% in each of three energy densities from ratios of forage:concentrate of 75:25, 55:45, and 35:65. Corn silage and hay crop silage were combined in a ratio of 2:1 (dry basis) in each case, and diets were offered for ad libitum intake as complete feeds for an 11-wk experimental period plus 2 wk for a digestion trial. In regression analysis as energy density increased, feed intake, milk yield, milk protein, and lactose yields increased linearly, urea nitrogen in blood plasma decreased linearly, and milk fat percent and yield decreased curvilinearly. As dietary protein increased, feed intake, fat-corrected milk, milk fat yield, and plasma urea nitrogen increased linearly, and yields of milk, solids-corrected milk, milk protein, and lactose increased curvilinearly. Actual milk yield adjusted for dry matter intake increased with greater energy density but not with higher protein concentration. Increases of energy and protein each resulted in linear increases of digestibility of dry matter, crude protein, and energy of diets. There were no interactions of energy X protein for these measurements. Cows in first lactation will increase milk production in response to increasing protein over a range of energy densities when feed intake is increased.

Animals↗
PubMed1984

Biochemical and morphological characterization of clonal AXC rat prostate cancer cells.

We used three heterogeneous parental cultures of LSC-AXC rat prostate cancer cells: LSC-AXC-C/O, cells maintained on culture medium; LSC-AXC-D/O, cells maintained on culture medium containing 10(-7) M 5 alpha-dihydrotestosterone; and LSC-AXC-T/O, cells maintained on culture medium containing 10(-7) M testosterone, to isolate clonally derived cell lines. Eleven of 15 clonal cell lines were tumorigenic when inoculated into intact male AXC rats. Eight tumorigenic clonal cell lines were selected for further evaluation, and all were found to possess features characteristic of secretory epithelium, as judged by light and electron microscopy. All parental cell lines and the eight selected clonal cell lines contained cytoplasmic and nuclear androgen receptors. Total receptor content was 131 +/- 61 (S.D.), 43 +/- 32, and 274 +/- 96 fmol/100 micrograms of DNA, respectively, for C-, D-, and T-cells. The differences were significant (p less than 0.05). Androgen receptor content of young mature or senescent AXC rat ventral prostate, respectively, is 518 +/- 58 and 266 +/- 40 fmol/100 micrograms of DNA. Since chromosomal analysis established that LSC-AXC prostate cancer cells are hypotriploid, androgen receptor content per cell in C- and T-cells is indicated to be either greater than or equal to that of senescent AXC rat ventral prostate, the tissue in which the original adenocarcinoma arose. Parental and clonal cell lines contained 5 alpha-reductase activity. There were significant differences (p less than 0.05) in both total reductase activity and metabolite distribution. Consequently, the intracellular content of testosterone metabolites was cell line specific. All characterized cell lines contained a higher concentration (p less than 0.05) of APase activity than did young mature or senescent AXC rat ventral prostate. In 6 of 11 cell lines, prostate-secretory APase concentration exceeded (p less than 0.05) that of AXC rat ventral prostate. However, the relative content of secretory APase compared to total APase in carcinoma cells consistently was less (p less than 0.05) than that of AXC rat ventral prostate. These studies document the establishment of clonal AXC rat prostate adenocarcinoma cell lines which have retained important morphological and phenotypic markers characteristic of differentiated prostate epithelium. Since these cells are tumorigenic and represent a spectrum of retained differentiated phenotypic markers, they should be particularly useful for in vivo and in vitro studies of hormonal regulation of prostate cancer cell behavior.

Acid Phosphatase↗
PubMed1983

Short-term effects of intrahypothalamic colchicine.

Colchicine was injected in the vicinity of the medial forebrain bundle to cause an accumulation of catecholamines in the lateral hypothalamus proximal to the injection site. Such injections caused severe deficits in consummatory behavior and motor performance within a few hours after injection, which were accompanied by the accumulation of catecholamines in the hypothalamus. Behavioural deficits occurring within 24 h after colchicine injection cannot be attributed to reduced synaptic transmission in the striatum or to dopamine depletion because these events do not commence until 24-48 h after colchicine administration. This study demonstrates the importance of considering all neurochemical changes which accompany catecholamine depletion when assessing the role of the catecholamine-containing system in the regulation of behaviour.

Animals↗
PubMed1983

Deficits in locomotor behaviour and motor performance after central 6-hydroxydopamine or peripheral L-DOPA.

Intracerebral injections of 6-hydroxydopamine (6-OHDA) which produce deficits in locomotor behaviour and motor performance cause localized accumulation of monoamines as well as depletion of central catecholamines (CA). To determine whether the localized increases in monoamines could be contributing to the behavioural deficits seen after intracerebral 6-OHDA injection, the behavioural and biochemical effects of peripherally administered L-DOPA were compared to those which occurred after central injections of 6-OHDA. Forty-five minutes after the injection of 40 mg/kg of L-DOPA, in animals pretreated with 50 mg/kg of R04-4602, the ability to step down, to retract a limb and to ambulate were significantly impaired. Locomotor behaviour and body temperature of L-DOPA-injected animals were similar to those displayed by animals receiving intracerebral injections of 6-OHDA. Fluorescent histochemical and biochemical assessment of diencephalic and telencephalic CA revealed that depletion of CA was not related to the severity of the motor deficits which occurred, but that increased diencephalic CA were present in impaired animals injected with either 6-OHDA or L-DOPA. These findings support the contention that increased CA in degenerating hypothalamic neurones may contribute to behavioural deficits seen after the injection of 6-OHDA.

Animals↗
PubMed1983

Peripheral DA receptor blockade facilitates behavioural recovery from nigrostriatal damage.

Animals were injected via the intraperitoneal route with the peripheral dopamine receptor blocker domperidone for three days before receiving bilateral lesions of the lateral hypothalamus. Pretreatment with domperidone significantly facilitated recovery from lesion imposed deficits in consummatory behaviour and motor reflex control. The enhanced behavioural recovery achieved with domperidone pretreatment was similar to that which occurs with other dopamine receptor blockers but such recovery has been attributed to the central effects of these compounds. The results from this study demonstrate that recovery from catecholamine depleting lesions, attributed previously to the development of striatal receptor hypersensitivity, may also be due to changes in dopamine receptors outside the blood-brain barrier.

Animals↗
PubMed1983

Neuroleptic-like anorexia produced by an extra-cerebral DA antagonist.

The effects of the DA receptor antagonists metoclopramide and pimozide on food and water intake in male Sprague Dawley rats were compared to those of domperidone, which does not cross the blood-brain barrier, in an attempt to determine whether any extracerebral DA receptors participate in neuroleptic induced anorexia. While metoclopramide caused only minor changes in food and water intake at the doses employed both pimozide and domperidone caused a significant reduction in food intake and water consumption 1 hr and 4 hr after injection during a 4 hr intake test. These results support the hypothesis that the nigrostriatal system may not be the system principally involved in the neuroleptic induced anorexia which occurs after the administration of these drugs.

Animals↗
PubMed1983

Purification and molecular anatomy of the varicella-zoster virion.

Varicella-zoster virus (VZV) infected cell cultures were harvested and sonically disrupted when cytopathic effect was advanced. Infectious cell-free virus in the sonicates, as well as that in the culture medium, was further concentrated by precipitation with 8% (w/v) polyethylene glycol in the presence of high salinity (0.5 M). The virus-enriched pellet was layered onto 15-45% linear metrizamide gradients and sedimented for 18 h at 70,000 g. Of the three visible bands (designated upper, middle and lower), the middle band at a buoyant density of 1.156-7 g/cm3 was enriched for enveloped virions. Electron microscopic enumeration of particles demonstrated a total of 10.04 log10 enveloped particles and 8.26 log10 unenveloped particles from middle bands representing the yield from a 150 cm2 VZV-infected monolayer. Fractionation of radiolabeled virion preparations by SDS-PAGE revealed 30 polypeptides between 30 and 200 kilodaltons (K) with a total mol wt of 2,240,000. Prominent structural polypeptides included the major capsid protein (155K) and three glycoproteins--62K, 98K and 118K. Certain polypeptides better labeled by [14C] amino acids than by [35S] methionine included a higher mol wt polypeptide (174K) and 45K protein comigrating with actin. Immune precipitation of a Nonidet-extracted virion fraction again demonstrated the three major glycoproteins, as well as the 155K and 45K polypeptides. Comparison of structural polypeptides with the 16 constituents of the VZV-specific immunoprecipitation profile identified at least one polypeptide (145K) which was not represented in the virion and assumed, therefore, to be nonstructural.

Capsid↗
PubMed1982

The behavioural effects of intrahypothalamic multistage versus single injections of 6-hydroxydopamine.

16 micrograms of 6-hydroxydopamine were injected bilaterally into the lateral hypothalamus of male Sprague-Dawley rats in either a single injection or in a series of multistage injections over a period of 75 days. While the single injection produced behavioural deficits typical of those seen following catecholamine depletion of the forebrain, the behaviour of animals injected incrementally with the same dose was indistinguishable from that of controls. Fluorescent histochemical assessment revealed that the animals in the multistage injection group, the behaviourally unimpaired, suffered more severe depletion of forebrain catecholamines than those in the single-stage injection group. Accumulation of amines proximal to the site of drug injection was extensive only in those animals displaying behavioural deficits, that is, the group with the lesser amount of forebrain catecholamine depletion. It is suggested that the severity of deficits in consummatory and motor behaviour occurring after hypothalamic trauma is determined by a lesion's effectiveness in producing amine accumulation rather than catecholamine depletion.

Animals↗
PubMed1982

Further studies on the effects of intravenously administered 6-hydroxydopamine on the median eminence of the rat.

6-Hydroxydopamine (6-OHDA) given i.v. in a dose of 150 mg/kg to adult male Sprague-Dawley rats produces at 24 h a complete depletion of median eminence (ME) and neurointermediate lobe (NIL) catecholamines (CA), as judged by Falck-Hillarp fluorescence histochemistry, leaving the remainder of the hypothalamus substantially unaltered. Restoration of a normal fluorescence histochemical appearance took place over 35 days, apparently due to regeneration of CA-containing terminals. Administration of desipramine prior to 6-OHDA injection modified its effect; depletion was largely confined to the midline region of the external layer of the ME and to the NIL, suggesting that these regions contain dopaminergic terminals. Microspectrofluorometric methods were used in an attempt to verify this conclusion. It is suggested that this technique provides a model for establishing the role of ME and NIL CA-containing structures in control of pituitary gland function.

Animals↗
PubMed1982

Microspectrofluorometric characterization of the fluorescent derivatives of biogenic amines produced by aqueous aldehyde (Faglu) fixation.

The fluorescent derivatives of the reaction between an aqueous aldehyde (Faglu) solution and the biogenic amines (5-hydroxytryptamine, dopamine and noradrenaline) have been examined in the order to determine the conditions required for maximal fluorescence yield. The fluorescence intensity and spectra of the final reaction products have been characterized and found to be highly dependent on the pH of the reaction mixture, Fluorophores derived from catecholamines have maximal yield and are most easily characterized when the reaction is performed at pH 7.3, whilst those derived from 5-hydroxytryptamine have maximal yield and are most readily characterized when the reaction is performed at pH 10.0. The addition of potassium ferricyanide to the Faglu further enhances the fluorescence yield of 5-hydroxytryptamine-containing models and tissues at both pH 10.0 and pH 7.3. Using the modified Faglu reaction mixture, it has been possible to demonstrate 5-hydroxytryptamine in the central nervous system without the need for pharmacological manipulation.

Animals↗
PubMed1982

Coronavirus-like particles in nonhuman primate feces.

Coronavirus-like particles were detected by electron microscopy in normal and diarrhea stool specimens from baboons, chimpanzees, macaques, and marmosets. There was a high prevalence of particles in both normal and diarrhea stools of older animals, whereas stools from nonweaned animals rarely contained these coronavirus-like particles.

Aging↗