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1.
J Med Eng Technol ; 43(1): 1-7, 2019 Jan.
Article in English | MEDLINE | ID: mdl-31033365

ABSTRACT

For surgical reconstruction of the medial patello-femoral ligament (MPFL) a variety of techniques are used for fixation of the graft to the medial border of the patella. The bone bridge or V-shaped tunnel technique utilises two tunnels drilled from the medial aspect of the patella that converge centrally creating a tunnel through which the graft is threaded. This technique has advantages: it avoids hardware (bone anchors) and their associated complications, creates a broad attachment of the ligament approximating normal anatomy and the tunnel does not breach the lateral cortex of the patella reducing the risk of patella fracture. In current practice the bony tunnels are created using freehand techniques. These rely on estimation of the patella centre by the surgeon and is subject to wide variation. Additionally this technique can be inefficient, inaccurate and time consuming. To address these disadvantages a new drill-guide device was developed. A prototype drill-guide was constructed using CAD and 3D printing methods. The device was designed to allow the surgeon to accurately and efficiently drill the required v-shaped bone tunnel. To assess the efficacy of the prototype drill guide, an experiment designed to assess a group of ten surgeons with an average of 4.2 years experience performing the task of creating a v-shaped bone tunnel using a free-hand technique and the drill-guide. To determine the accuracy of the tunnel placement, the angle between drill holes, distance from centre of the patella and the amount of over-drill were measured. Procedure duration was also compared. The results revealed that the prototype drill-guide created a more accurate bone bridge than the traditional free hand method. The root mean square error for the distance from centre was 0.50 mm vs 2.12 mm and the angle between tunnels was 2.6O vs 15.9O for the prototype and traditional methods respectively. There was a mean of 8.9 mm over-drill with the traditional method, which was negated when using the guide. Surgeons using the guide were approximately 25% faster than using the traditional free-hand technique. The prototype drill-guide improved the accuracy, reduced the variability, and reduced procedure duration compared to the traditional free-hand technique.


Subject(s)
Femur/surgery , Ligaments, Articular/surgery , Patella/surgery , Plastic Surgery Procedures/instrumentation , Humans
2.
Surg Radiol Anat ; 40(8): 891-897, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29632965

ABSTRACT

PURPOSE: Gold standard recipient arteries in head and neck free flap microvascular reconstruction are currently branches of the external carotid. However, these arteries can be compromised by neck dissection or radiotherapy, resulting in 'vessel-depleted neck' and 'frozen neck' respectively. In such cases, the transverse cervical artery (TCA) may be a suitable recipient artery. METHODS: The origin, course and diameter of the TCA were determined in 46 sides of neck from 23 cadavers. The distances from the origin of the TCA to the angle of the mandible, floor of the mouth and mandibular symphysis were measured to determine the pedicle length required for free flap anastomosis. RESULTS: The TCA was present bilaterally in all subjects investigated and its course across the posterior triangle of the neck was constant between individuals. The mean distances from the origin of the TCA to the angle of mandible, floor of mouth and mandibular symphysis were 10.0, 9.2 and 12.6 cm, respectively. There were no significant differences in these distances between the left and right sides of the neck (p > 0.05 for all comparisons). The distances from the TCA origin to the angle of the mandible and floor of the mouth were significantly longer in males than in females (p = 0.004) and correlated directly with the greater height of males compared to females (p = 0.0004). The mean diameter of the TCA measured 2 cm from its origin was 2.2 mm. CONCLUSION: The TCA is a suitable and reliable recipient artery for free flap microvascular reconstruction, when branches of the external carotid artery are unavailable.


Subject(s)
Carotid Artery, External/surgery , Free Tissue Flaps/transplantation , Head and Neck Neoplasms/surgery , Microsurgery/methods , Plastic Surgery Procedures/methods , Aged , Aged, 80 and over , Anastomosis, Surgical/methods , Cadaver , Female , Free Tissue Flaps/blood supply , Humans , Male , Neck/blood supply , Neck/surgery
3.
Clin Anat ; 31(3): 409-416, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29082561

ABSTRACT

Core Surgical Trainees (CST) in the London (UK) Postgraduate School of Surgery receive clinical anatomy teaching in their first year of training, and, in their second year, give 30 sessions of anatomy teaching to medical and other students. This study set out to investigate the role of demonstrators from the perspective of the trainees. A focus group was convened to ascertain trainees' perspectives on demonstrating anatomy and to identify problems and improvement strategies to optimize their ability to enhance students' learning. A questionnaire was formulated and all second-year CST (n = 186-from two cohorts) in the London Postgraduate School of Surgery were invited. A total of 109 out of 186 trainees completed the questionnaire. A high percentage (98%) of trainees that completed the questionnaire responded that demonstrating was an invaluable part of their training. Sixty-two per cent responded that anatomy teaching they received in their first year of core surgical training helped them in their teaching role and 80% responded that it helped them prepare for surgical training. The study also revealed the need for improved communication between trainees and the London Postgraduate School of Surgery/Medical Schools/National Health Service Trusts to address issues such as trainees' perceived difficulty in fulfilling their teaching session requirement. The stakeholders have acknowledged and addressed the outcomes to improve the experience for both surgical trainees and students. The results indicate that anatomy demonstrating delivers important benefits to early surgical trainees, in addition to those received by the students that they teach. Clin. Anat. 31:409-416, 2018. © 2017 Wiley Periodicals, Inc.


Subject(s)
Anatomy/education , General Surgery/education , Teaching/psychology , Humans
4.
J Anat ; 228(1): 15-23, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26612592

ABSTRACT

The Anatomical Society's core syllabus for anatomy (2003 and later refined in 2007) set out a series of learning outcomes that an individual medical student should achieve on graduation. The core syllabus, with 182 learning outcomes grouped in body regions, referenced in the General Medical Council's Teaching Tomorrow's Doctors, was open to criticism on the grounds that the learning outcomes were generated by a relatively small group of anatomists, albeit some of whom were clinically qualified. We have therefore used a modified Delphi technique to seek a wider consensus. A Delphi panel was constructed involving 'experts' (n = 39). The revised core syllabus of 156 learning outcomes presented here is applicable to all medical programmes and may be used by curriculum planners, teachers and students alike in addressing the perennial question: 'What do I need to know ?'


Subject(s)
Anatomy, Regional/education , Curriculum/standards , Education, Medical, Undergraduate/methods , Delphi Technique , Humans , Societies, Medical
5.
J Anat ; 225(5): 492-501, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25181319

ABSTRACT

Changes that occur in astroglial populations of the nucleus ambiguus after recurrent (RLN) or superior (SLN) laryngeal nerve injury have hitherto not been fully characterised. In the present study, rat RLN and SLN were lesioned. After 3, 7, 14, 28 or 56 days of survival, the nucleus ambiguus was investigated by means of glial fibrillary acidic protein (GFAP) immunofluorescence or a combination of GFAP immunofluorescence and the application of retrograde tracers. GFAP immunoreactivity was significantly increased 3 days after RLN resection and it remained significantly elevated until after 28 days post injury (dpi). By 56 dpi it had returned to basal levels. In contrast, following RLN transection with repair, GFAP immunoreactivity was significantly elevated at 7 dpi and remained significantly elevated until 14 dpi. It had returned to basal levels by 28 dpi. Topographical analysis of the distribution of GFAP immunoreactivity revealed that after RLN injury, GFAP immunoreactivity was increased beyond the area of the nucleus ambiguus within which RLN motor neuron somata were located. GFAP immunoreactivity was also observed in the vicinity of neuronal somata that project into the uninjured SLN. Similarly, lesion of the SLN resulted in increased GFAP immunoreactivity around the neuronal somata projecting into it and also in the vicinity of the motor neuron somata projecting into the RLN. The increase in GFAP immunoreactivity outside of the region containing the motor neurons projecting into the injured nerve, may reflect the onset of a regenerative process attempting to compensate for impairment of one of the laryngeal nerves and may occur because of the dual innervation of the posterior cricoarytenoid muscle. This dual innervation of a very specialised muscle could provide a useful model system for studying the molecular mechanisms underlying axonal regeneration process and the results of the current study could provide the basis for studies into functional regeneration following laryngeal nerve injury, with subsequent application to humans.


Subject(s)
Astrocytes/metabolism , Glial Fibrillary Acidic Protein/metabolism , Medulla Oblongata/metabolism , Recurrent Laryngeal Nerve Injuries/pathology , Animals , Apoptosis , Cell Proliferation , Denervation , Male , Nerve Regeneration , Rats, Sprague-Dawley , Recurrent Laryngeal Nerve Injuries/metabolism
6.
Brain Res Bull ; 79(5): 288-95, 2009 Jun 30.
Article in English | MEDLINE | ID: mdl-19480989

ABSTRACT

Growing evidence suggests that the arcopallium/posterior pallial amygdala plays a major role in the control of fear behaviour in birds. This brain region comprises several subdivisions, but no direct evidence is available about its functional parcellation. The aim of the present study was to investigate the relative involvement of two subdivisions of the arcopallium/posterior pallial amygdala complex in four classical tests of fear in quail: the presentation of a novel object, the 'hole-in-the-wall', 'open-field' and tonic immobility tests. Bilateral electrolytic lesions damaging the posterior part of the arcopallium/posterior pallial amygdala resulted in an increase in fear behaviour in the 'open-field' test, whereas quail with lesions damaging the anterior part of the arcopallium displayed a decrease in an 'overall fear score', compared to quail with bilateral nidopallium or sham lesions. The differential involvement of the anterior and posterior parts of the arcopallium/posterior pallial amygdala in fear behaviour is discussed in view of the known connections between the arcopallium/posterior pallial amygdala complex and brain regions considered to be limbic in nature.


Subject(s)
Amygdala/physiology , Behavior, Animal/physiology , Coturnix/physiology , Fear/physiology , Amygdala/anatomy & histology , Amygdala/injuries , Animals , Male , Neuropsychological Tests
7.
J Neuroendocrinol ; 21(7): 648-56, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19453825

ABSTRACT

There is a transient fall in hypothalamic serotonin (5-hydroxytryptamine; 5-HT) activity in the second week post partum in male but not female rats. When this fall is masked by administration of the 5-HT(2) agonist (-) 2,5-dimethoxy-4-iodophenyl]-2-aminopropane hydrochloride [(-)DOI], over days 8-16 post partum, males are feminised in adulthood. To investigate whether the effect of 5-HT is mediated by dopamine and whether testosterone exerts its masculinising effect by reducing 5-HT and dopamine activity, male pups were treated with (-)DOI alone or together with the dopamine antagonist, haloperidol, over days 8-16 post partum, whereas females were treated with testosterone propionate on day 2 post partum. In adulthood, the volumes of the anteroventral periventricular nucleus (AVPV), sexually dimorphic nucleus of the preoptic area (SDN-POA) and arcuate nucleus (ARC) were determined, together with the number of tyrosine hydroxylase-immunoreactive (TH-ir) cells and fibres within them. The concentrations of 5-HT, dopamine and their metabolites were also measured. (-)DOI treatment increased the volume of the AVPV, decreased that of the SDN-POA and increased the number of TH-ir cells in the AVPV. These feminising effects were antagonised by concurrent haloperidol treatment. Neonatal testosterone propionate masculinised the volumes of the female AVPV and SDN-POA and reduced the number of TH-ir cells in the AVPV. Dopamine and 5-HT turnover in the AVPV was greater in female compared to male rats and neonatal testosterone propionate reduced dopamine concentration in the female AVPV. Neonatal (-)DOI had no effect on dopamine and 5-HT activity in the AVPV but increased both in the ARC. The findings that TH-ir neurone number and dopamine activity are greater in the female AVPV; the feminising effect of 5-HT is prevented by a haloperidol; and the masculinising effect of testosterone propionate is accompanied by a decrease in TH-ir neurone number and dopamine concentration in the female AVPV, suggest that dopamine is involved in hypothalamic sexual differentiation and may mediate the effect of 5-HT.


Subject(s)
Dopamine Antagonists/pharmacology , Haloperidol/pharmacology , Hypothalamus/drug effects , Hypothalamus/growth & development , Serotonin/metabolism , Sex Characteristics , Amphetamines/pharmacology , Animals , Animals, Newborn , Central Nervous System Agents/pharmacology , Dopamine/metabolism , Female , Male , Neurons/drug effects , Neurons/metabolism , Postpartum Period , Random Allocation , Rats , Rats, Wistar , Serotonin 5-HT2 Receptor Agonists , Serotonin Receptor Agonists/pharmacology , Testosterone Propionate/pharmacology , Tyrosine 3-Monooxygenase/metabolism
8.
Hip Int ; 18(1): 7-10, 2008.
Article in English | MEDLINE | ID: mdl-18645967

ABSTRACT

Accurate positioning of the acetabular component in total hip arthroplasty is essential to minimise the risk of dislocation and preserve the range of movement of the hip. It also affects polyethylene wear and the rate of osteolysis. Although there are many tools available to the surgeon to aid placement of the acetabular component, errors still occur, especially in version. We conducted a study of 14 cadaveric hips to investigate whether the transverse acetabular ligament can be used to align implanted cups with the correct degree of anteversion. Radiographic measurement revealed that all of the implanted cups were found to lie within the 'safe zone' for anteversion, when aligned with the ligament.


Subject(s)
Acetabulum/anatomy & histology , Acetabulum/surgery , Arthroplasty, Replacement, Hip/instrumentation , Hip Prosthesis , Ligaments, Articular/anatomy & histology , Acetabulum/physiopathology , Aged , Arthroplasty, Replacement, Hip/methods , Cadaver , Female , Hip Dislocation/etiology , Hip Dislocation/prevention & control , Humans , Ligaments, Articular/diagnostic imaging , Male , Prospective Studies , Prosthesis Failure , Radiography
9.
Eur J Neurosci ; 27(9): 2473-80, 2008 May.
Article in English | MEDLINE | ID: mdl-18445234

ABSTRACT

Masculinization of the brain is dependent upon a perinatal surge in testosterone. It also requires a transient decrease in hypothalamic 5-HT concentration and turnover and an increase in androgen receptor (AR) expression during the second postnatal week. We have previously shown that increasing 5-HT activity over this period in male or androgenized female rats feminizes their adult behaviour and also feminizes the size of their anteroventral periventricular nucleus (AVPV) and sexually dimorphic nucleus of the preoptic area (SDN-POA). To investigate the role of 5-HT in sexual differentiation of the brain, 5-HT activity was raised over postnatal days 8-16 in male, female and androgenized female rats by daily administration of the 5-HT(2) receptor agonist (-)[2,5 dimethoxy-4-iodophenyl]-2-amino propane hydrochloride [(-)DOI]. By postnatal day 18, the size of the AVPV and SDN-POA was sexually dimorphic; their sizes were feminized by (-)DOI treatment. In the absence of (-)DOI treatment, there were significantly more AR-immunoreactive cells in the AVPV of males, and in the SDN-POA of males and androgenized females, than in those of females on postnatal day 18. (-)DOI treatment reduced the number of AR-immunoreactive cells in the AVPV and SDN-POA of males and androgenized females, but not of females, by postnatal day 18. These results suggest that 5-HT(2) receptor activation can influence sexual differentiation of the brain by controlling AR expression.


Subject(s)
Midline Thalamic Nuclei/metabolism , Preoptic Area/metabolism , Receptors, Androgen/biosynthesis , Receptors, Serotonin, 5-HT2/metabolism , Sex Characteristics , Amphetamines/pharmacology , Animals , Animals, Newborn , Female , Immunohistochemistry , Male , Midline Thalamic Nuclei/drug effects , Midline Thalamic Nuclei/growth & development , Preoptic Area/drug effects , Preoptic Area/growth & development , Rats , Serotonin Receptor Agonists/pharmacology
10.
Metab Brain Dis ; 22(3-4): 353-73, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17828620

ABSTRACT

Sepsis is a major clinical challenge that is associated with encephalopathy and multi-organ dysfunction. Current therapeutic interventions are relatively ineffective and the development of novel treatments is hampered by the lack of a well-characterised animal model. Therefore, the behavioural, metabolic, physiological and histological changes resulting from 'through and through' caecal ligation and puncture (CLP) in the rat were investigated to determine its suitability as an animal model of human sepsis. CLP resulted in bacteraemia, characterised by the presence of multiple enteric species within 18-20 h. Locomotor activity was reduced within 4 h of CLP and this reduction increased with time. Pyrexia was evident 4-5 h after CLP and was followed by hypothermia beginning 17 h after intervention. CLP resulted in reduced white blood cell and platelet counts and an increased neutrophil: lymphocyte ratio within 18-20 h. It also resulted in decreased blood glucose, but not lactate levels. CLP caused histopathological changes in the cerebral cortex, liver, lungs and vascular system indicative of multi-organ dysfunction. Therefore, CLP in the rat mimics the cardinal clinical features of human sepsis and the subsequent development of multi-organ dysfunction. It appears to be the best available animal model currently available, in which to investigate the underlying pathophysiology of sepsis and identify therapeutic targets.


Subject(s)
Disease Models, Animal , Multiple Organ Failure/etiology , Sepsis/etiology , Animals , Blood Glucose/analysis , Body Temperature , Body Weight , Cecum/surgery , Eating , Humans , Lactic Acid/blood , Leukocyte Count , Ligation , Male , Motor Activity , Platelet Count , Punctures , Rats
11.
Reproduction ; 133(2): 331-59, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17307903

ABSTRACT

This review summarizes current knowledge of the genetic and hormonal control of sexual differentiation of the reproductive system, brain and brain function. While the chromosomal regulation of sexual differentiation has been understood for over 60 years, the genes involved and their actions on the reproductive system and brain are still under investigation. In 1990, the predicted testicular determining factor was shown to be the SRY gene. However, this discovery has not been followed up by elucidation of the actions of SRY, which may either stimulate a cascade of downstream genes, or inhibit a suppressor gene. The number of other genes known to be involved in sexual differentiation is increasing and the way in which they may interact is discussed. The hormonal control of sexual differentiation is well-established in rodents, in which prenatal androgens masculinize the reproductive tract and perinatal oestradiol (derived from testosterone) masculinizes the brain. In humans, genetic mutations have revealed that it is probably prenatal testosterone that masculinizes both the reproductive system and the brain. Sexual differentiation of brain structures and the way in which steroids induce this differentiation, is an active research area. The multiplicity of steroid actions, which may be specific to individual cell types, demonstrates how a single hormonal regulator, e.g. oestradiol, can exert different and even opposite actions at different sites. This complexity is enhanced by the involvement of neurotransmitters as mediators of steroid hormone actions. In view of current environmental concerns, a brief summary of the effects of endocrine disruptors on sexual differentiation is presented.


Subject(s)
Brain/embryology , Gonadal Steroid Hormones/physiology , Sex Differentiation/physiology , Urogenital System/embryology , Animals , Brain/physiology , Disorders of Sex Development/embryology , Endocrine Disruptors/adverse effects , Environmental Pollutants/adverse effects , Female , Gene Expression Regulation, Developmental , Genes, sry , Humans , Male , Urogenital System/physiology
12.
AJR Am J Roentgenol ; 188(1): W37-43, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17179325

ABSTRACT

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.


Subject(s)
Esophagus/anatomy & histology , Image Enhancement/methods , Magnetic Resonance Imaging/methods , Mediastinum/anatomy & histology , Aged , Aged, 80 and over , Cadaver , Esophagectomy , Esophagus/surgery , Female , Humans , In Vitro Techniques , Mediastinum/surgery
13.
Eur J Neurosci ; 19(2): 387-95, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14725633

ABSTRACT

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.


Subject(s)
Animals, Newborn/physiology , Brain/metabolism , Luteinizing Hormone/metabolism , Serotonin/physiology , Sex Characteristics , Testosterone/pharmacology , Animals , Brain/drug effects , Female , Gonadal Steroid Hormones/metabolism , Gonadal Steroid Hormones/pharmacology , Male , Pregnancy , Rats , Rats, Wistar , Serotonin/metabolism , Serotonin Receptor Agonists/pharmacology , Testosterone/metabolism
14.
Neurobiol Dis ; 14(1): 89-97, 2003 Oct.
Article in English | MEDLINE | ID: mdl-13678670

ABSTRACT

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.


Subject(s)
Amyloid beta-Protein Precursor/genetics , Brain/metabolism , Membrane Proteins/genetics , Mutation , tau Proteins/metabolism , Adult , Age Factors , Aged , Aged, 80 and over , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Amyloid beta-Protein Precursor/metabolism , Animals , Brain/pathology , Humans , Membrane Proteins/metabolism , Mice , Mice, Transgenic , Middle Aged , Phosphorylation , Presenilin-1 , Transgenes/physiology , tau Proteins/genetics
15.
Br J Cancer ; 87(6): 621-3, 2002 Sep 09.
Article in English | MEDLINE | ID: mdl-12237771

ABSTRACT

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.


Subject(s)
Adenocarcinoma/metabolism , Aquaporins/metabolism , Astrocytoma/metabolism , Brain Neoplasms/metabolism , Brain/metabolism , Adenocarcinoma/secondary , Aquaporin 1 , Astrocytes/metabolism , Astrocytes/pathology , Astrocytoma/pathology , Blood Group Antigens , Blood-Brain Barrier/physiology , Brain/pathology , Brain Edema/pathology , Brain Neoplasms/pathology , Brain Neoplasms/secondary , Gene Expression Regulation, Neoplastic , Glial Fibrillary Acidic Protein/analysis , Humans , Immunoenzyme Techniques , Microcirculation/pathology , Neoplasm Staging , Neovascularization, Pathologic , Prognosis , Up-Regulation
16.
J Anat ; 200(6): 639-46, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12162731

ABSTRACT

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.


Subject(s)
Astrocytoma/pathology , Blood-Brain Barrier , Brain Edema/microbiology , Brain Edema/pathology , Brain Neoplasms/pathology , Endothelium, Vascular/ultrastructure , Sepsis/pathology , Aquaporin 4 , Aquaporins/metabolism , Astrocytoma/metabolism , Brain Edema/metabolism , Brain Neoplasms/metabolism , Endothelium, Vascular/metabolism , Humans , Membrane Proteins/metabolism , Occludin , Sepsis/metabolism , Tight Junctions/metabolism
17.
J Anat ; 200(Pt 2): 169-83, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11895115

ABSTRACT

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.


Subject(s)
Chickens/anatomy & histology , Nerve Fibers/ultrastructure , Superior Colliculi/anatomy & histology , Animals , Golgi Apparatus/chemistry , Golgi Apparatus/ultrastructure , Immunohistochemistry , Microscopy, Immunoelectron , Nerve Fibers/chemistry , Superior Colliculi/chemistry , gamma-Aminobutyric Acid/analysis
18.
Brain Res Bull ; 57(3-4): 537-41, 2002.
Article in English | MEDLINE | ID: mdl-11923024

ABSTRACT

Neuroanatomical data suggest that the lizard striato-amygdaloid transition area is homologous with the mammalian central amygdala. In order to investigate possible functional similarities, tonic immobility was induced in adult lizards and its duration recorded. Each lizard was then randomly assigned to one of three treatments: (1) bilateral striato-amygdaloid transition area lesions, (2) bilateral dorsal cortex lesions or (3) untreated controls. Three days after trial 1, each lizard was subjected to a second trial and the tonic immobility duration recorded. The mean tonic immobility duration in lizards with striato-amygdaloid transition area lesions was significantly shorter (80.5%; p < 0.0033) in trial 2 than in trial 1. There were no inter-trial differences within dorsal cortex-lesioned lizards or untreated controls. There was a significant treatment effect on tonic immobility duration in trial 2 (p < 0.0001). The mean tonic immobility duration of lizards with striato-amygdaloid transition area lesions was significantly shorter than that of dorsal cortex-lesioned lizards (72.2%; p < 0.01) or untreated controls (78.2%; p < 0.01). There was no significant difference in mean tonic immobility duration between dorsal cortex-lesioned lizards and untreated controls. Tonic immobility is considered to be an anti-predator behaviour that reflects the underlying state of fear. Therefore, the reduced tonic immobility duration in lizards with striato-amygdaloid transition area lesions reflects a reduction of fear. These results provide the first data to indicate a functional similarity between the lizard striato-amygdaloid transition area and the mammalian central amygdala.


Subject(s)
Amygdala/physiology , Behavior, Animal/physiology , Corpus Striatum/physiology , Fear/physiology , Lizards/physiology , Movement/physiology , Animals , Time Factors
19.
J Neurol Neurosurg Psychiatry ; 72(2): 262-5, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11796780

ABSTRACT

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.


Subject(s)
Aquaporins/analysis , Astrocytoma/pathology , Brain Edema/pathology , Brain Neoplasms/pathology , Adenocarcinoma/pathology , Adenocarcinoma/secondary , Adult , Aged , Aquaporin 4 , Astrocytes/pathology , Blood-Brain Barrier/physiology , Brain/pathology , Brain Neoplasms/secondary , Capillary Permeability/physiology , Female , Glial Fibrillary Acidic Protein/analysis , Humans , Male , Microcirculation/pathology , Middle Aged , Water-Electrolyte Balance/physiology
20.
Eur J Morphol ; 40(2): 101-13, 2002 Apr.
Article in English | MEDLINE | ID: mdl-12854048

ABSTRACT

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.


Subject(s)
Neurons/pathology , Neurons/ultrastructure , Optic Nerve/ultrastructure , gamma-Aminobutyric Acid/metabolism , Animals , Biotinylation , Cell Nucleus/ultrastructure , Chickens , Dendrites/pathology , Dextrans/chemistry , Golgi Apparatus/metabolism , Golgi Apparatus/ultrastructure , Immunohistochemistry , Microscopy, Electron , Models, Anatomic , Synapses , Time Factors
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