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Biomedical subjects

A Chadwick

Publications and source records attributed to A Chadwick.

At least 19 recordsLinked to original sources
PubMed2000

Functional reconstruction of the hippocampus: fetal versus conditionally immortal neuroepithelial stem cell grafts.

Late fetal CA1 hippocampal grafts and stem cell grafts from the conditionally immortal MHP36 clonal line derived from the H-2Kb-tsA58 transgenic mouse neuroepithelium both improved spatial deficits in rats with ischaemic CA1 damage induced by four-vessel occlusion (4VO). However, the distribution of fetal and MHP36 grafts differed. Fetal cells lodged in clumps around the implant sites and along the corpus callosum, whilst MHP36 grafts infiltrated the area of CA1 ischaemic damage, achieving apparent architectural reconstruction of the hippocampus. The migration of MHP36 cells is damage-dependent. Few cells were found in intact brain; after 15 min of 4VO cells repopulated only the discrete area of CA1 cell loss, whereas with more extensive damage after 30 min occlusion cells migrated to all hippocampal fields and to cortex. A higher proportion of grafted MHP36 cells differentiated into neurons in the host CA1 field than grafts of striatal or cortical expanded cell populations. Cortical population grafts were as effective as MHP36 grafts in improving water maze learning, whereas striatal or ventral mesencephalic cells were ineffective, indicating a degree of stem cell specificity. The efficacy of MHP36 cells extends to primates. In marmosets with profound impairments in conditional discrimination tasks after lesions of the CA1 field, MHP36 cells improved performance as effectively as fetal grafts and migrated evenly through the CA1 field, in contrast to clustered fetal cells. These findings suggest that MHP36 stem cell grafts are as effective as fetal grafts in functional repair of hippocampal damage, and that their preference for areas of cell loss and adoption of appropriate morphologies is consistent with a point-to-point repair mechanism.

Animals↗
PubMed2000

Conditionally immortal neuroepithelial stem cell grafts reverse age-associated memory impairments in rats.

In order to investigate the effects of stem cell grafts on water maze deficits in aged (22-month-old) rats, three groups of aged rats, assigned by pre-training latency scores to unimpaired, impaired control and impaired grafted groups, were compared with young (five-month-old) controls, six to eight weeks after implantation of cells from the conditionally immortal Maudsley hippocampal stem cell line, clone 36 (MHP36 stem cell line), in the cortex, striatum and hippocampus. Grafted rats were substantially superior to their matched impaired aged controls, and learned to find the platform as rapidly as unimpaired aged rats, although young controls were more efficient than all aged groups in several measures of spatial search during training. On the probe trial, however, aged rats with grafts showed significantly better recall of the precise position of the platform than any other group, including young controls, possibly indicating some perseveration. A further comparison found that groups of unimpaired and moderately impaired aged rats showed far less improvement from water maze pre-training to acquisition phases than young controls, indicative of progressive deficits over time. Histological investigation showed that beta-galactosidase-positive MHP36 cells migrated widely from the implantation sites to infiltrate the striatal matrix, all hippocampal fields and areas of the cortex. Grafted cells showed both astrocytic and neuronal morphologies, with cells of pyramidal and granular appearance in appropriate hippocampal strata.Taken together, these results indicate that neuroepithelial stem cell grafts extensively colonize the aged rat brain and substantially reverse progressive cognitive decline associated with ageing.

Aging↗
PubMed1997

Recovery of spatial learning by grafts of a conditionally immortalized hippocampal neuroepithelial cell line into the ischaemia-lesioned hippocampus.

Transient global cerebral ischaemia in rats causes relatively circumscribed and specific damage to the CA1 pyramidal cells of the dorsal hippocampus, along with a cognitive deficit manifest as difficulties in the performance of a range of spatial learning and memory tasks. Our previous studies have shown that restoration of behavioural performance in ischaemic rats by neural grafts taken relatively late in fetal development occurs only after local replacement of cells homotypic to those lost through the ischaemic insult. This lesion-plus-behaviour model therefore offers a powerful means for establishing whether multipotent embryonic neuroepithelial cells will engraft the damaged CA1, develop into appropriate neuronal phenotypes and produce behavioural recovery. Here we report that, in rats subjected to 15 min of global cerebral ischaemia, intrahippocampal implants of a conditionally immortal, multipotent cell line, directly derived from the embryonic day 14 hippocampal neuroepithelium of the H-2Kb-tsA58 transgenic mouse, selectively repopulated the lesioned CA1 pyramidal layer and restored ischaemia-induced deficits in acquisition of a hidden platform location in the Morris water maze.

Animals↗
PubMed1996

Lewy bodies are located preferentially in limbic areas in diffuse Lewy body disease.

Lewy bodies (LBs)are found throughout the brain stem, limbic and neocortical areas in Parkinson's disease. Lewy bodies are also associated in these areas with dementia and the substrate of 'dementia with Lewy bodies' is thought to include Lewy body pathology in limbic and neocortical areas with or without Alzheimer-type changes. In order to determine whether dementia with Lewy bodies is characterised primarily by cortical or limbic LB pathology, we have measured the density of Lewy bodies, neuritic plaques and neurofibrillary tangles in 12 neocortical, limbic and brain stem sites in 10 patients who were pathologically diagnosed with diffuse Lewy body disease (DLBD) (64.7 +/- 2.7 years). The mean LB density in limbic areas (3.00 +/- 0.61/mm2) was significantly greater than that of neocortical areas (1.13 +/- 0.22/mm2, P < 0.001). The greatest density of LBs was found in the amygdala (4.1 +/- 0.7/mm2) and the lowest in the occipital cortex (0.3 +/- 0.1/mm2). In limbic areas, LB formation positively correlated with neuritic plaque formation (r = 0.51, P < 0.01) but not with neurofibrillary tangle densities. These data indicate that dementia with Lewy bodies is characterised primarily by limbic, and secondly by neocortical, LB pathology. It remains to be determined why limbic areas are selectively vulnerable to LB pathology in dementia with Lewy bodies.

Aged↗
PubMed1995

Influence of the presence of chicks on the ability to resume incubation behavior in domestic hens (Gallus domesticus).

In this study, hormonal and behavioral changes associated with nest deprivation in the absence or in the presence of chicks (replaced every day or not) were investigated in incubating hens. Prolactin levels decreased, whereas LH and E2 levels increased following nest deprivation. Surprisingly, the presence of chicks had no effect on prolactin changes. However, the presence of chicks significantly limited increases in plasma LH and estradiol. Furthermore, this inhibitory effect was greater when day-old chicks were replaced every day. On the other hand, the presence of chicks induced the emergence of specific maternal behavior, while, surprisingly, one-third of the nest-deprived hens without chicks continued to incubate. After a 3-day deprivation period, readiness to renest was maintained for a percentage of hens. Thus more than 2/3 of hens deprived of the nest for 3 days in the presence of chicks returned to their nests during the first day of being allowed to do so, versus less than 1/3 of hens without chicks among those that previously disrupted incubation behavior. Plasma prolactin concentrations of these renesting hens increased rapidly and reached again levels characteristic of incubating hens. We conclude that, under our experimental conditions, presence of chicks maintains readiness to incubate without maintaining high levels of plasma prolactin.

Animals↗
PubMed1993

Beta A4 protein deposition in familial Alzheimer's disease with the mutation in codon 717 of the beta A4 amyloid precursor protein gene and sporadic Alzheimer's disease.

Beta A4 protein immunoreactivity in the neocortex and hippocampus of familial Alzheimer's disease (AD) including the case with the beta A4 amyloid precursor protein (APP) gene mutation in codon 717 (APP717 Val-->Ile) and sporadic cases of AD is described. A semi-automatic image analysis system was used to quantify beta A4 protein load in the isocortex of the frontal and temporal lobes and in subfields of the hippocampus. Immunoreactivity was measured in ten cases of sporadic AD and in five cases of familial AD including one in which the APP717 Val-->Ile mutation was present. Beta A4 protein load, as measured by square microns of immunoreactivity per square millimetre of cortex, was similar in the frontal and temporal isocortex in both sporadic and familial AD. There was greater variation in beta A4 protein load in subfields of the hippocampus but these differences were not significant between sporadic and familial cases. In the case with the APP717 Val-->Ile mutation. Beta A4 protein load in isocortex was greater than the mean for familial and sporadic cases of AD but less than the most severe cases of beta A4 protein deposition which were found in sporadic AD. In addition, the case with the APP717 Val-->Ile mutation has the same cytoskeletal pathology as sporadic cases of AD. The mechanism by which normal and mutant APP is processed to produce amyloidogenic fragments remains to be determined.

Aged↗
PubMed1993

Respective effects of chicks and nest on behavior and hormonal concentrations of incubating domestic hens.

Removal of incubating hens from their nestboxes or substitution of chicks for eggs disrupt incubation; prolactin levels decrease whereas luteinizing hormone and gonadal steroid concentrations tend to rise. The present experiment was undertaken to determine the relative influence of removing the nest (nest-deprived hens), adding chicks (maternal hens), or both (maternal nest-deprived hens), on the behavior and hormone concentrations of incubating hens. The results confirm that nest removal, as well as adding chicks, stops incubation. No differences were found between maternal and maternal nest-deprived hens' behavioral responses or hormonal concentrations. These results do not support the hypothesis that the drop of plasma prolactin observed in maternal hens is the consequence of the nest abandonment. In contrast, nest-deprived hens presented lower concentrations of prolactin and higher concentrations of estradiol than maternal and maternal nest-deprived hens. Moreover, the nest-deprived hens presented lower concentrations of prolactin and higher concentrations of LH and estradiol than the hens given chicks. We assume that physical contact with chicks, during brooding bouts, slows down the decrease of prolactin secretion and inhibits LH and estradiol release at the end of incubation.

Animals↗
PubMed1992

Astrocytosis, beta A4-protein deposition and paired helical filament formation in Alzheimer's disease.

Alzheimer's disease (AD) temporal cortex (Brodmann area 22) was investigated using stains for astrocytes (GFAP immunohistochemistry), paired helical filaments (Gallyas silver impregnation) and beta A4-protein deposition (beta A4-protein immunohistochemistry). Paired helical filament formation (PHF), as demonstrated by neurofibrillary tangle (NFT) and neuritic plaque (NP) density, was greatest in the pyramidal cell layers III and V. beta A4-protein deposition was greatest in layer III but was present in all neocortical layers. In a regression analysis, astrocyte density was significantly correlated with beta A4-protein deposition (R2 = 0.35, P = 0.02). Astrocyte density was also positively correlated with PHF formation as measured by NFT (R2 = 0.16, P = 0.14) and NP (R2 = 0.25, P = 0.06) density, but this was less significant. This quantitative study demonstrates that both beta A4-protein deposits and PHF formation are positively correlated with the severity of astrocytosis and that damage to the brain parenchyma in temporal cortex in AD may be slightly more strongly associated with beta A4-protein deposition than paired helical filament formation. These results demonstrate the close association of astrocytes with beta A4-protein deposition and neuritic change in AD.

Aged↗
PubMed1991

beta-Amyloid protein load is relatively uniform throughout neocortex and hippocampus in elderly Alzheimer's disease patients.

beta-Amyloid protein immunoreactivity in neocortex and hippocampus of Alzheimer's disease and control brains has been measured using an automatic image analysis system. Successive fields from the pial surface to white matter in 4 neocortical sites, parahippocampal gyrus and along the pyramidal cell layer in the hippocampus have been measured using a number of variables including: area fraction or load, counts per unit area and deposit size. In Alzheimer's disease beta-amyloid protein load in neocortex and hippocampus was significantly greater than in non-demented age-matched controls. beta-Amyloid protein load, as measured by size variables, was relatively uniform throughout the neocortex in elderly Alzheimer's disease patients. However, greater variability in deposition was measured in parahippocampal gyrus and hippocampus than in neocortex. Size and density variables used to measure beta-amyloid protein deposition were not correlated with age although there was a tendency for the cortical load to decrease with age beyond 80 years.

Aged↗
PubMed1990

Incubation and maternal behaviour in domestic hens: influence of the presence of chicks on circulating luteinising hormone, prolactin and oestradiol and on behaviour.

1. The consequences of the adoption of chicks and their subsequent removal on behaviour and plasma hormone concentrations of incubating hens were investigated. Birds were divided into two group: in group A, incubating hens were given chicks for 11 d; in group B chicks were left with the hens for 3 d only. 2. Incubating hens given chicks immediately showed maternal responses. The introduction of chicks induced a gradual nest desertion. Their removal stopped nest desertion temporarily on day 4 in group B hens. 3. Plasma prolactin concentrations fell one day after introduction of chicks and continued to decline for about one week in group A hens, although there was no further significant decrease in group B hens. Circulating prolactin tended to decrease with time in both groups. 4. Plasma luteinising hormone (LH) concentrations increased concurrently with the decrease of prolactin. The increase was more abrupt in group B hens. 5. Plasma oestradiol concentrations decreased slightly on the day chicks were introduced. The decline was arrested by removal of chicks in group B; in group A the tendency was reversed about 10 days after chick introduction. 6. Irrespective of group, before chick removal hens which deserted their nest rapidly had less contact with chicks and lower prolactin concentrations.

Analysis of Variance↗
PubMed1989

Effect of estrogen on calcium homeostasis and pituitary hormones in the growing chick.

An experiment was carried out to investigate the effect of a range of estradiol (E2) doses (0.1-6.5 micrograms/g body wt/day) on vitamin D metabolism and the plasma levels of growth hormone (GH) and prolactin (PRL) in the growing chick. Doses of 0.5-0.7 microgram/g E2, which are insufficient to raise the plasma calcium level, did induce an increase in growth rate, an increase in 25-hydroxyvitamin D 1 alpha-hydroxylase (1-hydroxylase) and 24-hydroxylase activities, and an increase in plasma GH level. These parameters leveled off or fell over the dose range 1-2 micrograms/g E2 but there was evidence of a second peak in 1-hydroxylase activity at 6 micrograms/g E2. At this high dose rate, the plasma Ca level rose to 8 mM, as it does in the laying hen; 24-hydroxylase activity, growth rate, and plasma GH and plasma PRL levels all decreased. It was concluded that the dose response to estrogen in the growing chick is not linear and, in the case of 1-hydroxylase activity, may even be biphasic.

Animals↗
PubMed1988

Tendency to display spontaneous incubation does not affect maternal responsiveness in the domestic hen.

Induction of maternal behavior was performed in 63-week-old hens of the JV15 (or "Vedette") strain which had previously exhibited brief incubating phases during the preceding egg-laying period to discover if their maternal behavior differed from that induced in hens who had no previous record of incubating. The degree of maternal behavior exhibited showed large variation among individuals. However, hens with a history of one or more spontaneous, brief incubation bouts and hens without such histories showed similar responsiveness toward chicks and similar levels of general activity. In most of the subjects, the establishment of maternal behavior was accompanied by a significant long-term fall in the plasma levels of luteinizing hormone whereas the plasma levels of prolactin appeared to be unaffected.

Animals↗
PubMed1987

Induction of maternal behavior in incubating and non-incubating hens: influence of hormones.

Maternal responses and variations in plasma levels of prolactin and testosterone have been studied in incubating and in non-incubating, non-laying hens during forced adoption experiments. The results demonstrate the ability of incubating hens to display complete maternal behavior as early as the 10th day of incubation after being exposed to stimulation by chicks during one night. Maternal responses also emerged in non-laying hens but more gradually. In both groups, a decline in plasma testosterone occurred after the introduction of the chicks and, in the incubating hens, prolactin levels fell as they abandoned their nests.

Animals↗
PubMed1986

Plasma levels of arginine vasotocin, prolactin, aldosterone and corticosterone during prolonged dehydration in the domestic fowl: effect of dietary NaCl.

Three groups of White Plymouth Rock laying hens were adapted to three levels of dietary NaCl: low-NaCl food with tap water (LOW), high-NaCl food (1% NaCl w/w added) with tap water (HT), and high-NaCl food with 0.5% NaCl for drinking (HS). The birds were subjected to water deprivation (dehydration) for 18 days. Blood sampling was done at 2-4 day intervals. Plasma concentrations of arginine vasotocin (AVT), prolactin (PRL), aldosterone (ALDO) and corticosterone (CS) were determined by radioimmunoassay. Plasma osmolality, sodium, chloride, and potassium were also determined. In the normally hydrated hens fully adapted to the diets, there was a stepwise increase from LOW to HS in plasma osmolality (305, 315, 332 mOsm, for LOW, HT and HS, respectively), [Na+] (144, 153, 161 mM) and [Cl-] (109, 119, 127 mM) as well as in [AVT] (6, 14, 18 pg/ml) and [PRL] (16, 24, 34 ng/ml). Regressing [AVT] on osmolality gave a slope of 0.30 pg . ml-1/mOsm and a threshold of 273 mOsm. The slope of [PRL] on osmolality was 0.73 ng . ml-1/mOsm. The correlation coefficient of [AVT] and [PRL] was 0.67. LOW had high [ALDO] (165 pg/ml) which was suppressed to low levels in HT and HS (5-8 pg/ml), while [CS] was the same in all groups (0.9-1.1 ng/ml). Plasma [K+] was decreased in the high-NaCl groups (5.8 mM in LOW, 4.4 and 4.7 mM in HT and HS). Dehydration resulted within 2 days generally in a sharp (5-15%) increase in osmolality, [Na+] and [Cl-], which thereafter increased more slowly during the remaining 16 days in all groups, with the slowest increase in LOW. The levels of osmolality [Na+] and [Cl-] were 5% lower in LOW than in HT and HS, which showed the same levels during the dehydration period. Plasma [AVT] and [PRL] increased 2-4 fold within 2 days of dehydration; [AVT] reached a plateau at 29 pg/ml in all groups, but [PRL] continued to rise in all groups, fastest in LOW, reaching similar levels in all groups after 14-18 days of dehydration, about 85 ng/ml. The correlation coefficient of [AVT] and [PRL] was decreased by half (to 0.32) during dehydration. Plasma [ALDO] increased in all groups with dehydration, 1.7 fold in LOW and 3-6 fold in HT and HS, but the levels reached in HT and HS were only 15-30% of that seen in LOW.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Cortex Hormones↗
PubMed1986

Osmotic stimuli and NaCl-intake in the fowl; release of arginine vasotocin and prolactin.

White Plymouth Rock hens were fed a high- and a low-NaCl content of the diet. The two groups were exposed to moderate dehydration, to intra-arterial hyperosmotic NaCl-loading, or to injection of physiological doses of arginine vasotocin (AVT). The plasma levels of AVT and prolactin were measured by accurate and sensitive radioimmunoassay and the osmolality and Na, K (and Cl) concentrations also measured for 48 h after dehydration, and for 60-90 min after NaCl-loading or AVT-injection. The plasma concentration of AVT after a given increase of plasma osmolality was in all experiments found higher in the low- as compared to the high-NaCl diet group. The average difference was 0.2 pg/ml X mOsm. The intra-arterial injection of AVT resulted in a strictly mono-exponential fall over the next hour with an average half-life of 6.3 min without any difference between the high- and the low-NaCl diet groups. It is concluded (a) that the release of prolactin after osmotic stimulation is most likely caused by a direct effect of osmolality (or Na concentration) and not by AVT, (b) that the release of AVT is influenced by the NaCl-intake in a direction which tends to maintain extracellular volume.

Animals↗
PubMed1985

Effects of putative neurotransmitters on release of prolactin from pituitary glands of the domestic fowl co-incubated with hypothalamic tissue.

Pituitary glands and hypothalami from broiler fowl heads were incubated alone or together with histamine, gamma-aminobutyric acid (GABA) or acetylcholine (ACh) as well as with catecholamines or neurotransmitter antagonists. Histamine and ACh stimulated, whereas GABA inhibited, the hypothalamus-induced release of prolactin, responses blocked by their specific antagonists. The dopamine antagonist pimozide, but not adrenergic (both alpha and beta), serotoninergic or cholinergic antagonists, prevented the actions of histamine and GABA. None of the antagonists except the cholinergic blocker, atropine, affected ACh-induced release of prolactin. Neither histamine nor ACh prevented inhibition of prolactin release by dopamine or stimulation of prolactin release by noradrenaline. GABA did not affect the response to noradrenaline. Furthermore, histamine, GABA and ACh had no effects on thyrotrophin releasing hormone-stimulated release of prolactin directly at the pituitary level. These results suggest that histamine and GABA affect prolactin release from chicken pituitaries in vivo by modifying the activity of the dopaminergic system. Acetylcholine may stimulate the secretion of prolactin releasing factor from the hypothalamus.

Acetylcholine↗
PubMed1985

The time sequence of adaptive changes to dietary phosphorus deficiency in the chick.

Ten-day old chicks were divided into 6 groups which were fed a low phosphorus (P) diet for periods of 0, 0.5, 1, 3, 7 or 11 days before killing at 3 weeks old. Labelled calcium (47Ca) was injected intraperitoneally into some birds 18 hours before killing. A marked fall in growth rate, plasma phosphorus level, plasma growth hormone level and renal 24-hydroxylase activity levels had occurred by 12 hours after the experimental diet had started. After one day on the diet, the rate of duodenal Ca absorption had risen and continued to rise up to the 11th day. During this period, the renal 25-hydroxyvitamin D-1-hydroxylase activity rose slightly while the 24-hydroxylase activity rose towards the control level. At 24 hours, the 47Ca level in the bone was markedly lower than in the control group and remained low. It was concluded that the first adaptive response of the chick to dietary P insufficiency was to suppress growth. Subsequent adaptive responses were to increase the rate of Ca and P absorption from the gut and mobilisation from the bone but despite these measures, the growth rate only recovered slightly and the plasma P level continued to fall.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗