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Biomedical subjects

D C Davies

Publications and source records attributed to D C Davies.

At least 19 recordsLinked to original sources
PubMed2007

High-resolution MRI in evaluation of the surgical anatomy of the esophagus and posterior mediastinum.

OBJECTIVE: The purpose of this study was to use high-resolution MRI to evaluate the surgical anatomy of the posterior mediastinum, in particular the esophagus and its relation to the surrounding structures. The aim was to familiarize radiologists with the appearance of structures considered important in planning surgical resection of the esophagus. MATERIALS AND METHODS: The thoraces of two cadavers were imaged with a 1.5-T magnet using a high-resolution T2-weighted sequence. Axial cadaveric sections of the posterior mediastinum were cut with a band saw at levels determined from the MR images, and histologic whole-mount sections of the esophagus and surrounding tissue were prepared from the cadaveric sections. The appearance of structures identified on the MR images was compared with the findings on corresponding gross anatomic and histologic whole-mount sections. RESULTS: The MR images depicted the esophagus and structures in close anatomic relation: the pleural reflections and pericardium. The technique enabled visualization of structures to our knowledge not previously described on cross-sectional imaging: the individual layers of the esophageal wall, the thoracic duct, a connective tissue layer attaching the esophagus to the anterior wall of the aorta, and a fascial plane passing between layers of the right and left parietal pleura posterior to the esophagus. CONCLUSION: High-resolution MRI of the posterior mediastinum provides detailed anatomic information, delineating structures not visible on other forms of cross-sectional imaging. It can provide important information for planning surgical intervention.

Aged↗
PubMed2004

Neonatal 5HT activity antagonizes the masculinizing effect of testosterone on the luteinizing hormone release response to gonadal steroids and on brain structures in rats.

Hypothalamic 5HT concentrations are transiently lower in male compared to female Wistar rats in the second week post partum (pp) and our previous findings have shown that pharmacologically potentiating 5HT activity over this period feminizes certain aspects of sexually differentiated behaviours in adult males and androgenized females. In order to investigate whether neonatal testosterone and 5HT interact to influence physiological and morphological brain sexual differences, females, androgenized females and males were treated with the 5HT2 agonist (-) [2,5 dimethoxy-4-iodophenyl]-2-amino propane HCl [(-) DOI], over days 8-16 pp. In androgenized females (250 microg testosterone proprionate, day 2 pp) (-) DOI prevented the delay in vaginal opening, but did not prevent the androgen-induced constant oestrus in females treated with 100 microg TP, day 2 pp. (-) DOI overcame the neonatal androgen effect in suppressing the positive feedback of ovarian steroids in a few males and androgenized females. (-) DOI had a feminizing effect on the volume of the anteroventral periventricular nucleus (normally smaller in males), by significantly increasing its volume in male and androgenized females. It also had a significant antagonistic effect on the testosterone-induced increase in the volume of the sexually dimorphic nucleus of the preoptic area in males and androgenized females. These findings support the view that raised 5HT activity in the second week of life antagonizes the masculinizing effect of neonatal testosterone.

Animals↗
PubMed2003

Hyperphosphorylated tau and paired helical filament-like structures in the brains of mice carrying mutant amyloid precursor protein and mutant presenilin-1 transgenes.

Senile plaques composed mainly of beta-amyloid (Abeta) and neurofibrillary tangles principally composed of hyperphosphorylated tau are the major pathological features of Alzheimer's disease (AD). Despite the fact that increased expression of amyloid precursor protein (APP) and presenilin-1 (PS1) transgenes in mice lead to increased Abeta deposition in plaquelike structures in the brain, little is known about the nature and distribution of tau in these mice. Therefore the relationship between Abeta and hyperphosphorylated tau was investigated in mice carrying mutant APP and mutant PS1 transgenes using both light (LM) and electron microscopy (EM) with immunocytochemistry. LM immunocytochemistry revealed cerebral Abeta deposits to be present from 8 weeks of age, whereas hyperphosphorylated tau was not detected until 24 weeks of age, when it appeared as punctate deposits in close association with the Abeta deposits in the cortex and hippocampus. However, dystrophic neurites were not as heavily immunolabeled as they are in AD brain. EM revealed that aggregations of straight filaments (10-12 nm wide) were present in some cellular processes at the periphery of Abeta plaques in 8-month-old APP/PS1 mice. In one such mouse, single filaments and paired filaments showing a helical configuration (50-55 nm half-period, 25 nm max. width) were present in a dark, atrophic hippocampal neuron. Immunogold labeling of APP/PS1 mouse brain revealed hyperphosphorylated tau epitopes in some dystrophic neurites from 24 weeks of age that were similar to those present in AD. These results suggest that hyperphosphorylated tau appears in APP/PS1 mouse brain after the onset of Abeta deposition and although it is associated with Abeta deposits, its distribution is not identical to that in AD.

Adult↗
PubMed2002

Increased aquaporin 1 water channel expression in human brain tumours.

Aquaporin 1 is a water channel protein. There was little aquaporin 1 immunoreactivity in normal brain parenchyma. In astrocytomas, aquaporin 1 was expressed in microvessel endothelia and neoplastic astrocytes. In metastatic carcinomas, aquaporin 1 was present in microvessel endothelia and reactive astrocytes. Aquaporin 1 may participate in the formation of brain tumour oedema.

Adenocarcinoma↗
PubMed2002

The ramification and connections of retinal fibres in layer 7 of the domestic chick optic tectum: a golgi impregnation, anterograde tracer and GABA-immunogold study.

Layer 7 is one of the retinorecipient layers of the avian optic tectum. However, little information is available about the neuronal organization of this layer and its implications for visual function. Golgi impregnation was used to investigate the retinal input to and the neuronal architecture of layer 7 of the chick optic tectum, which forms a narrow band between the two cell-dense layers 6 and 8. Anterograde tracers were also used to investigate the afferent and efferent connections of layer 7, in both the light and the electron microscope, together with GABA immunogold labelling. Three types of radial neuron were defined according to the origin and course of their axons. The perikarya of these neurons were situated in tectal layers 10-11. The principal dendrites of these radial neurons ascended to the tectal surface and gave rise to dendritic side-branches in layer 7. These dendritic side-branches received asymmetric synapses from the terminations of retinal fibre arborisations. Type 2 radial neurons, whose axons arose from the deep pole of the perikaryon or occasionally from a basal dendrite, were shown to project to the nucleus isthmi pars magnocellularis, which has previously been demonstrated to be GABAergic and to project to glomerulus-like complexes in tectal layers 4-5. In these layers, the dendritic branches of layer 13 neurons that project to the nucleus rotundus have previously been shown to receive retinal fibre input. Therefore, the retinal input to layer 7 may be able to modulate the transmission of information to the visual thalamus, by way of a feed-back loop to layers 4-5 of the tectum involving the nucleus isthmi pars magnocellularis.

Animals↗
PubMed2002

Blood-brain barrier breakdown in septic encephalopathy and brain tumours.

Septic encephalopathy is associated with breakdown of the blood-brain barrier and cerebral oedema. These features are also common properties of brain tumours. Perimicrovessel oedema, disruption of associated astrocyte end feet and neuronal injury occur in a porcine model of acute septic encephalopathy. The adrenergic system has been implicated in the inflammatory response to sepsis and may play a role in controlling blood-brain barrier permeability, since the beta2-adrenoceptor agonist dopexamine inhibits perimicrovessel oedema formation whereas the alpha1-adrenoceptor agonist methoxamine provokes it. Electron microscopy revealed tight junction opening in high-grade astrocytoma microvessels. Expression of the tight junction protein occludin is reduced in these microvessels and this reduction is inversely correlated with the degree of cerebral oedema. Normal astrocytes secrete factors that induce barrier properties in endothelial cells, whereas high-grade astrocytomas secrete vascular endothelial growth factor, which stimulates angiogenesis, down regulates occludin and increases endothelial cell permeability. The water channel protein aquaporin-4 is normally expressed in astrocyte foot processes around cerebral microvessels. Its expression is massively up-regulated in high-grade astrocytoma and around metastatic adenocarcinoma. There is a significant correlation between aquaporin-4 expression and the degree of cerebral oedema, but it is not clear whether increased aquaporin-4 expression enhances oedema formation or clearance. These results suggest that the pathophysiology of brain oedema is multifactorial, but that there may be common processes operating regardless of the aetiology.

Aquaporin 4↗
PubMed2002

The intrinsic neuronal organisation of the nucleus of the basal optic root in the domestic chicken; a light and electron microscopic study using anterograde tracers and postembedding GABA-immunostaining.

The intrinsic neuronal organisation in the nucleus of the basal optic root of chickens was investigated. The divergent connections with various areas and the functional complexity of the nucleus require a complex intrinsic structural arrangement. Therefore, an analysis of Golgi impregnated material, ultrastructure, GABA-immunocytochemistry and biotinylated dextran-amine anterograde tracer analysis of the nucleus was carried out. In the Golgi analysis, a characteristic dendritic ramification pattern of two types of putative projection neurons was observed. These neurons form dendritic nests with their overlapping dendritic terminal sections, that develop synaptic fields with the optic fibre terminals. These synaptic fields were confirmed by electron microscopy. GABA-immunopositive terminals synapse with distinct loci of the dendritic trees of projection neurons; they may therefore play an important role in the inhibitory-modulatory system of the nucleus of the basal optic root. The GABA-immunopositive terminals derive from small and/or elongated local circuit neurons which receive retinal afferents, and from myelinated fibres afferents to the nucleus of unknown origin.

Animals↗
PubMed2002

Aquaporin-4 expression is increased in oedematous human brain tumours.

Aquaporin-4 (AQP4) is a highly conserved water channel protein. In rats, AQP4 is expressed in astrocyte foot processes and is important in brain water homeostasis. AQP4 expression has not been investigated in non-neoplastic human brain or oedematous brain tumours, where water homeostasis is disrupted. Therefore, immunohistochemistry was used to study AQP4 expression in non-neoplastic and neoplastic human brain and blood-brain barrier permeability was assessed using contrast enhanced computed tomograms. AQP4 was present around microvessels in five specimens of non-neoplastic brain and five low grade (Daumas-Duport I or II) astrocytomas. AQP4 was massively upregulated in four and absent in one high grade (Daumas-Duport III or IV) astrocytoma. Massive upregulation of AQP4 was also found in reactive astrocytes in five metastatic adenocarcinomas. There was significant (p<0.0001) correlation between blood-brain barrier opening and upregulated AQP4 expression. Increased AQP4 expression in high grade astrocytomas and adenocarcinomas may facilitate the flow of oedema fluid.

Adenocarcinoma↗
PubMed2001

Enlargement of the fornix in early-onset schizophrenia: a quantitative MRI study.

Abnormalities of temporal lobe structure and frontal lobe function occur in schizophrenia. There have been few studies of young people with schizophrenia and little is known about temporo-frontal connectivity in the disease. Therefore, the cross-sectional area of the body of the fornix was measured on MR images from 17 young people with schizophrenia, nine with other serious psychiatric illnesses and eight without illness. The mean age of each group was 16-17 years. The mean cross-sectional fornix area in subjects with schizophrenia was significantly larger than that in subjects without illness ( approximately 40%) and psychiatric controls ( approximately 26%). There was no such significant difference between subjects without illness and psychiatric controls. The nature of the larger fornix in early-onset schizophrenia, whether it persists and whether it occurs in schizophrenia presenting in adulthood, remain to be elucidated.

Adolescent↗
PubMed2001

Conditional immortalization of freshly isolated human mammary fibroblasts and endothelial cells.

Reports differ as to whether reconstitution of telomerase activity alone is sufficient for immortalization of different types of human somatic cells or whether additional activities encoded by other "immortalizing" genes are also required. Here we show that ectopic expression of either the catalytic subunit of human telomerase (hTERT) or a temperature-sensitive mutant (U19tsA58) of simian virus 40 large-tumor antigen alone was not sufficient for immortalization of freshly isolated normal adult human mammary fibroblasts and endothelial cells. However, a combination of both genes resulted in the efficient generation of immortal cell lines irrespective of the order in which they were introduced or whether they were introduced early or late in the normal proliferative lifespan of the cultures. The order and timing of transduction, however, did influence genomic stability. Karyotype analysis indicated that introduction of both transgenes at early passage, with hTERT first, yielded diploid cell lines. Temperature-shift experiments revealed that maintenance of the immortalized state depended on continued expression of functional U19tsA58 large-tumor antigen, with hTERT alone unable to maintain growth at nonpermissive temperatures for U19tsA58 large-tumor antigen. Such conditional diploid lines may provide a useful resource for both cell engineering and for studies on immortalization and in vitro transformation.

Adult↗
PubMed2001

Neurodegenerative changes associated with beta-amyloid deposition in the brains of mice carrying mutant amyloid precursor protein and mutant presenilin-1 transgenes.

Mutations of amyloid precursor protein (APP) and presenilin-1 (PS1) lead to an increase in beta-amyloid (Abeta) production. Despite the fact that a number of transgenic mice develop cerebral Abeta plaques, few have been subjected to ultrastructural investigation and the sequence of events leading to Abeta plaque formation is unclear. We therefore investigated the doubly transgenic (mutant APP(K670N,M671L)-mutant PS1(M146L)) mouse, which develops Abeta deposits much earlier than singly transgenic littermates. Widespread Abeta plaques with or without a distinct core were found in gray matter. Abeta plaques were also present in white matter. Astrocytosis was greater around gray matter plaques than around white matter plaques. In some plaques, Abeta cores were associated with cell profiles containing prominent endoplasmic reticulum and a homogeneous cytoplasm that appeared to be neuronal. The morphology and location of other profiles indicated them to be microglia or oligodendrocytes. Some Abeta fibrils appeared to lie within these profiles, but they may have been simply surrounded by the cell profile since the profile membrane was not always visible. Dark atrophic neurons, whose morphology suggested that they were apoptotic, were present around gray matter plaques. Cerebrovascular Abeta deposition was also observed in the brains of APP/PS1 transgenic mice. Thus, the amyloid deposition and neuropathology observed in APP/PS1 mouse brain are similar to those in Alzheimer's disease and they appear to develop earlier and become more severe than in the other transgenic models currently available.

Aging↗
PubMed2001

Occludin expression in microvessels of neoplastic and non-neoplastic human brain.

The tight junction protein occludin 'glues' normal, adjacent brain microvessel endothelial cells together. Malignant brain tumours cause cerebral oedema because they have leaky endothelial tight junctions, which allow plasma fluid to enter the brain from the microvessel lumen. In order to identify molecular abnormalities in tumour endothelial tight junctions, we investigated occludin expression in microvessels from adult human non-neoplastic brain tissue using immunohistochemistry and immunoblotting. The proportions of microvessels immunolabelling for occludin were >2/3 in 5/5 non-neoplastic brain tissue samples, >1/3 in 5/5 low grade (Daumas-Duport I or II) astrocytomas and <1/3 in 5/5 high grade (III or IV) astrocytomas and 6/6 metastatic adenocarcinomas. Six non-neoplastic brain tissue immunoblots gave a 55-kDa occludin band, three low-grade astrocytomas gave 55-kDa and 60-kDa bands, 13 high-grade astrocytomas gave 60-kDa or no band and four adenocarcinomas did not give an occludin band. Expression of 55-kDa occludin inversely correlated with the presence of contrast enhancement on computed tomograms (P < 0.001). Electron microscopy showed open endothelial tight junctions in 0/2 non-neoplastic human brain specimens and 2/2 high-grade astrocytomas. We suggest that loss of 55-kDa occludin expression in human brain tumours may contribute to endothelial tight junction opening. Characterizing the molecular pathology of brain endothelial tight junctions may facilitate the design of novel drugs against cerebral oedema.

Adenocarcinoma↗
PubMed2001

Emerging molecular mechanisms of brain tumour oedema.

A common property of brain tumours is their ability to cause oedema in the surrounding brain. Oedema forms as a result of a leaky blood-tumour barrier and persists when the brain fails to clear the excess fluid. It is a significant source of morbidity and mortality. The principal anatomical component of the blood-brain barrier is the endothelial tight junction which opens in glioma microvessels. Multiple tight junction proteins have recently been identified, such as occludin, claudin, ZO-1, ZO-2 and ZO-3. We propose a model to explain tight junction opening in gliomas based on vascular endothelial growth factor secretion and loss of tight junction inducing factor production by tumour cells. The level of expression of the water channel aquaporin-4 in peritumoural astrocytes may determine the rate of oedema fluid clearance. The identification of the molecular mechanisms of brain tumour oedema may allow the design of novel anti-oedema medications.

Animals↗
PubMed2000

Comparison of methyl anthranilate and denatonium benzoate as aversants for learning in chicks.

Methyl anthranilate (MeA) has been widely used as a taste aversant for domestic chicks in the one-trial passive avoidance learning (PAL) task. However, MeA has a strong smell that may be aversive to chicks. Therefore, odourless denatonium benzoate (DB) has been suggested as an alternative taste aversant in PAL. The present study was designed to compare the efficacy of MeA and DB as aversants in the one-trial PAL task. In this task, young chicks peck a visually conspicuous bead coated with a taste aversant and in a single trial learn to avoid a similar, but uncoated bead at subsequent presentation. In Experiment 1, chicks were trained using a silver-coloured bead coated with 100% MeA, 0.5% DB or distilled water. After 3 h, MeA-trained, but not DB-trained chicks, exhibited significantly higher avoidance of the test bead than water-trained chicks. In Experiment 2, three pre-training presentations of an uncoated red bead preceded training with the silver bead. MeA-trained chicks showed significantly higher avoidance of the test bead than water-trained chicks. The numbers of water- and DB-trained chicks that avoided pecking the test bead were low and not significantly different from each other. However, DB-trained chicks exhibited significantly longer latencies to peck the test bead than water-trained chicks, indicating that they had retained some memory of the task. Thus, 0.5% DB is a weaker aversant than MeA and it does not induce high levels of learning in the one-trial PAL task. However, DB may prove useful for investigating weakly reinforced learning.

Animals↗
PubMed2000

Distribution of CGRP-like immunoreactivity in the chick and quail brain.

Calcitonin gene-related peptide (CGRP)-containing neurones have been implicated in the transmission of visceral sensory information to the cortex and in the control of arterial blood pressure in mammals. However, little is known about its function in other vertebrates. As a first step toward investigating the function of CGRP in birds, its distribution was studied in the domestic chick and quail brain by means of immunocytochemistry, by using antibodies against rat CGRP. The distribution of CGRP immunoreactivity in the chick and quail central nervous system was found to be similar. CGRP-immunoreactive (CGRPi) perikarya were not present in the telencephalon. In the diencephalon, CGRPi perikarya were present mainly in the shell of the thalamic nucleus ovoidalis, the nucleus semilunaris paraovoidalis, the nucleus dorsolateralis posterior thalami, and in the hypothalamic nucleus of the ansa lenticularis. In the brainstem, CGRPi perikarya were present in the nucleus mesencephalicus nervi trigemini, the nucleus tegmenti ventralis, the locus coeruleus, the nucleus linearis caudalis and in the parabrachial region. In addition CGRPi perikarya were found in the motor nuclei of the III, IV, V, VI, VII, IX, X, and XII cranial nerves. The telencephalon contained CGRPi fibres within the paleostriatal complex (mainly in the ventral paleostriatum), parts of the neostriatum and ventral hyperstriatum, parts of the archistriatum, and the septum. In the diencephalon, the densest plexus of CGRPi fibres was observed in the dorsal reticular thalamus. A less dense CGRPi innervation was present in some dorsal thalamic nuclei and in the medial and periventricular hypothalamus. The pretectum and midbrain tegmentum also contained CGRPi fibres, whereas the optic tectum was virtually devoid of immunolabelling. Scattered CGRPi fibres were observed in the central grey and neighbouring pontine areas. Some of the sensory fibres of the trigeminal, vagal, glossopharyngeal, and spinal nerves were also CGRPi. The results of comparative studies indicate that the presence of CGRP in some thalamo-telencephalic projections is a primitive feature of the forebrain of amniotes. Therefore, the brain areas giving rise to and receiving such a projection in different vertebrates, are likely to be homologous.

Animals↗
PubMed2000

Synaptic deficit in the temporal cortex of partial trisomy 16 (Ts65Dn) mice.

Down syndrome results from triplication of human chromosome 21. The distal end of mouse chromosome 16 shares a large region of genetic homology with the Down syndrome 'critical region' of human chromosome 21. Therefore, a partially trisomic mouse (Ts65Dn) that possesses a triplication of the distal region of chromosome 16 has been developed as a putative model for Down syndrome. Ts65Dn mice display learning and memory deficits. However, despite the importance of preserved synaptic integrity for learning and memory, the ultrastructure of neural connectivity has not yet been studied in Ts65Dn mice. Therefore, the density and apposition zone length of synapses in the temporal cortex of aged Ts65Dn mice (n=4) were compared with those in diploid controls (n=4), using quantitative electron microscopy. There were significantly less (30%) asymmetric synapses in the temporal cortex of Ts65Dn mice than in controls (t=-5.067; p=0.023). However, there was no significant difference between the mean density of symmetric synapses in Ts65Dn mice and control mice. In addition, the mean synaptic apposition lengths of both asymmetric (15%; t=9.812, p<0.0001) and symmetric (11%; t=5. 582; p<0.0001) synapses were significantly larger in Ts65Dn mice than in controls. These results suggest that excitatory synapses are preferentially affected in Ts65Dn mice and that there is an attempt to compensate for the deficit of asymmetric synapses by increasing the contact zone area of existing synapses. The results may also reveal the morphological basis for the learning and memory deficits observed in Ts65Dn mice and have a bearing on the cognitive deficits in Down syndrome in old age.

Animals↗
PubMed2000

CD7 expression distinguishes subsets of CD4(+) T cells with distinct functional properties and ability to support replication of HIV-1.

Enrichment of a subset of CD4(+)CD45R0(+)CD7(-) T cells has been observed in HIV-infected individuals. We have investigated the ability of CD7(+) and CD7(-) T cells to support replication of HIV and show that virus replicates preferentially in CD7(+) cells. Several possible mechanisms that may underlie such differences in susceptibility to HIV were studied. Our data demonstrate that mitogen stimulation induces poor expression of CD25 and IL-2 in CD7(-) compared with CD7(+) cells. We also show that uninfected CD7(-) cells are more resistant to mitogen-induced apoptosis than CD7(+) cells. Our data support the view that the CD7(-) subset is inherently resistant to HIV replication and that this is due in part to reduced CD25 expression and IL-2 production.

Acquired Immunodeficiency Syndrome↗