Biomedical subjects

D B Clarke

Publications and source records attributed to D B Clarke.

At least 19 recordsLinked to original sources

PubMed2006

Target-derived neurotrophins may influence the survival of adult retinal ganglion cells when local neurotrophic support is disrupted: Implications for glaucoma.

Following target innervation, developing and neonatal retinal ganglion cells (RGCs) depend on neurotrophic factors from their target tissue for survival. This dependence is reduced for adult RGCs which rely primarily on trophic support from their local environment; however, some findings indicate that target tissue may play a role in the long-term survival of RGCs. We propose that a deficiency in neurotrophic factors from the target tissue may influence the survival of RGCs when local neurotrophic support is disrupted. Furthermore, we propose that this hypothesis may explain, at least in part, the progressive loss of RGCs in optic neuropathies such as glaucoma. Neurotrophic factors are present in the adult superior colliculus and they are trafficked to the retina; however, removal or lesioning of the adult target tissue results in little or no RGC loss for up to several months. In vitro, adult RGCs will survive when maintained by co-culturing these neurons with their target tissue. As well, the timing and pattern of adult RGC loss is consistent with that seen in glaucoma and in reports of delayed RGC loss following target-removal. Our hypothesis can be tested by selectively disrupting local neurotrophic support and evaluating RGC survival when target-derived neurotrophic support is maintained and when it is disrupted. Specifically, intravitreal injection of blocking antibodies could be used to disrupt local neurotrophic signaling, while aspiration of the superior colliculus will eliminate retrograde transport from the primary target tissue in rodents. The results of these experiments would provide valuable information concerning the influence of target-derived neurotrophic support when local neurotrophin signaling is disrupted. Specifically, this research could verify whether deficiencies in target-derived neurotrophic support play a role in RGC loss during glaucoma. A further understanding of this mechanism may lead to the development of effective neuroprotective strategies for treating glaucoma.

Adult↗

PubMed2006

Brain & chiasmal herniations into sella after medical treatment of prolactinoma.

BACKGROUND: Dopamine agonists are widely used in the treatment of pituitary prolactinomas. We report a case of inferior mesial frontal lobe (gyrus rectus) and chiasmal herniations into an enlarged sella following successful medical treatment of a pituitary macroadenoma. METHOD: A 71-year-old healthy man presented to medical attention with visual complaints. On examination, he was found to have bitemporal hemianopsia. Endocrine evaluation revealed an elevated prolactin level. He was treated medically with a dopamine agonist (bromocriptine). RESULTS: Evaluation after one year of medical treatment revealed stabilization of the patient's vision, with a significant bitemporal field loss. Serum prolactin levels normalized (5.16 ng/ml). The MRI of the sella showed almost complete disappearance of the tumor, resulting in right mesial frontal lobe herniation inferiorly into an enlarged sella with associated chiasmal deformation. CONCLUSIONS: We report a case where successful medical treatment of a large pituitary prolactinoma has resulted in inferior frontal lobe and chiasmal herniatons into an enlarged sella.

Aged↗

PubMed2005

The role of heat shock proteins Hsp70 and Hsp27 in cellular protection of the central nervous system.

Heat shock proteins (Hsps) are highly conserved and under physiological conditions act as molecular chaperones and/or have anti-apoptotic activities. Expression in the brain of two heat shock proteins, the70 kDa Hsp (Hsp70) and the 27 kDa Hsp (Hsp27), is notable because both proteins are highly inducible in glial cells and neurons following a wide range of noxious stimuli including ischemia, epileptic seizure and hyperthermia. In the central nervous system, constitutive expression of Hsp27 is limited to many (but not all) sensory and motor neurons of the brain stem and spinal cord, while there is little or no constitutive expression of Hsp70. However, inducible expression of both Hsp70 and Hsp27 is present in many areas of the brain and retina and is associated with cellular resistance to a variety of insults. The potential for manipulating the expression levels of Hsps for therapeutic advantage in neurodegenerative diseases such as Alzheimer's disease, stroke and glaucoma will be explored.

Animals↗

PubMed2004

Determination of unusual soya and non-soya phytoestrogen sources in beer, fish products and other foods.

Fish and fish products (14 samples), Indian foods and meals (10 samples), spices (30 samples) and beers (10 samples) were analysed for their phytoestrogen content, and a number of significant non-soya sources of dietary phytoestrogens were identified. No isoflavones were detected in unprocessed, farmed or ocean fish, but some samples of processed fish products contained soya isoflavones, which are assumed to come from coatings or protein addition. Additionally, some processed fish products contained, genistein glycocongugates not derived from soya. Genistein was detected in Indian meals such that, for example, a single portion of a vindalooo curry contained 11 mg genistein. The origin was most likely from the spices used, since the analysis of curry powders, chilli powder, crushed red chillies, garam masala and tandoori powder revealed that some contained genistein at more than 100 mg kg(-1). Cumin was the most likely source material, although not all individual samples of cumin tested contained high levels of genistein. Prenylnaringenin phytoestrogens were determined in UK hop-based beers at mean concentrations of 0.21 mg(-1) 6-prenylnaringenin and 0.06mg(-1) 8-prenylnaringenin. The beers also contained traces of daidzein, genistein and biochanin A. The significance of 'hidden soya' in processed foods and these non-soya sources of phytoestrogens is that UK dietary intake of phytoestrogens must be assumed to be higher than estimated previously and that some sources of phytoestrogens remain poorly characterized.

Beer↗

PubMed2004

Dietary exposure estimates of isoflavones from the 1998 UK Total Diet Study.

The phyto-oestrogen contents of the 1998 UK Total Diet Study (TDS) food group composites were determined. Each TDS set consisted of composite samples, one for each of the 20 designated food groups. These composites then represented the average consumption of all the individual food elements in each group, processed into the form in which they were consumed. In the TDS, individual composites of the bread, processed meat and fish food groups contained >5 mg kg(-1) of the individual isoflavones (daidzein, genistein and glycitein). Individual composites from the groups, miscellaneous cereals, other vegetables, fruit products and nuts contained >1 mg kg(-1). After weighting for average consumption of food from each TDS food group, an estimated daily intake of 3 mg day(-1) of combined isoflavone aglycones was obtained from the TDS sample collection model for the average (adult) consumer. The UK dietary intake of phyto-oestrogens is higher than previously estimated due in part to the use of soya in processed foods.

Bread↗

PubMed2003

Administration of brain-derived neurotrophic factor suppresses the expression of heat shock protein 27 in rat retinal ganglion cells following axotomy.

Optic nerve transection results in the apoptotic cell death of the majority of retinal ganglion cells by 14 days. The neurotrophin brain-derived neurotrophic factor (BDNF) enhances survival of retinal ganglion cells. In addition, the small heat shock protein Hsp27, with its anti-apoptotic effects, may be important for neuron survival following axotomy or trophic factor withdrawal. We recently reported the induction and expression of Hsp27 in a subset of retinal ganglion cells following axotomy. Here we have examined the effect of BDNF administration on the expression of Hsp27 in axotomized adult rodent retinal ganglion cells. Retinal ganglion cells were pre-labeled with Fluorogold prior to optic nerve transection and concomitant intraocular injection of BDNF or vehicle. Hsp27 immunofluorescence was examined in retinal sections from 4 to 28 days following injury. Consistent with previous survival studies, the number of Fluorogold-labeled retinal ganglion cells declined from 100% at 4 days to approximately 15% by 14 days following axotomy and vehicle injection. In contrast, with BDNF administration, retinal ganglion cell survival was maintained at 100% to 7 days following axotomy. We report that the number of Hsp27-positive injured retinal ganglion cells, as detected by immunohistochemical staining, was decreased by 50% in BDNF-treated retinas, when compared with vehicle-treated controls. This decreased expression of Hsp27 in response to BDNF treatment was seen both at early (4 days) and delayed (14 days) times. BDNF following optic nerve transection significantly reduced the expression of Hsp27 in retinal ganglion cells. These results indicate that BDNF may down-regulate alternate cell survival pathways, including the stress-induced expression of Hsp27, and may help to explain the failure of chronic neurotrophin treatment to maintain long-term retinal ganglion cell survival.

Animals↗

PubMed2002

Injury to retinal ganglion cells induces expression of the small heat shock protein Hsp27 in the rat visual system.

Optic nerve transection results in apoptotic cell death of most adult rat retinal ganglion cells that begins at 4 days and leaves few surviving neurons at 14 days post-injury [Berkelaar et al. (1994) J. Neurosci. 14, 4368-4374]. The small heat shock protein Hsp27 has recently been shown to play a role in sensory neuron survival following peripheral nerve axotomy [Lewis et al. (1999) J. Neurosci. 19, 8945-8953]. To investigate the role of Hsp27 in injured CNS sensory neurons, we have studied the induction and cell-specific expression of Hsp27 in rat retinal ganglion cells 1-28 days after optic nerve transection. Immunohistochemical results indicate that Hsp27 is not present at detectable levels in the ganglion cell layer of control (uninjured) or sham-operated control rats. In contrast, Hsp27 is detected in retinal ganglion cells from 4 to 28 days following axotomy. Furthermore, the percentage of surviving retinal ganglion cells that are Hsp27-positive increased over the same time period. Hsp27 is also detected in glial fibrillary acidic protein-positive astrocytes in the optic layer of the superior colliculus from 4 to 28 days after optic nerve transection. These experiments demonstrate that transection of the optic nerve results in the expression of Hsp27 in three distinct regions of the rat visual system: sensory retinal ganglion cells in the eye, glial cells of the optic tract, and astrocytes in the optic layer of the superior colliculus. Hsp27 may be associated with enhanced survival of a subset of retinal ganglion cells, providing evidence of a protective role for Hsp27 in CNS neuronal injury.

Animals↗

PubMed2002

Verification of the findings of acrylamide in heated foods.

We report here the first confirmation of the recent Swedish findings of acrylamide in heated foods. The verification exercise used an LC-MS/MS method developed for the purpose as well as an established GCMS method for acrylamide analysis. LC-MS/MS was suitable for the direct determination of acrylamide in aqueous extracts of foods by isotope dilution mass spectrometry (IDMS) using triply deuterated acrylamide. Some food matrices were not suited to the new method and mixed-mode solid-phase extraction (SPE) was used to clean these extracts. The foods tested included UK versions of some of the key food groups analysed in Sweden. Also tested were some foods heated under home-cooking conditions. There was good agreement between the LC-MS/MS results and the GC-MS results and the levels of acrylamide found here were similar to those reported for the corresponding foods analysed in the Swedish study. The analyses confirmed that acrylamide is absent from the raw or boiled foods but present at significant levels in fried, grilled, baked and toasted foods. The highest result was 12000 microg kg(-1) acrylamide in overcooked oil-fried chips.

Acrylamide↗

PubMed2001

Meningeal melanocytoma of the planum sphenoidale. Case report and review of the literature.

Meningeal melanocytoma is a rare benign primary melanotic tumor of the meninges, most commonly found in the spinal canal and the posterior fossa. The authors report the 19th published case of a supratentorial meningeal melanocytoma and the first reported case in which the tumor arose from the planum sphenoidale. The patient's presenting symptoms were characteristic of a large bifrontal lesion and included headaches, personality change, lethargy, and urinary and fecal incontinence. Computerized tomography and magnetic resonance imaging studies revealed an extraaxial lesion arising from the planum sphenoidale. The patient underwent successful gross total removal of the tumor without neurological sequelae. Based on the findings shown in this case report, meningeal melanocytoma should be included in the differential diagnosis of extraaxial lesions arising from the area of the planum sphenoidale.

Female↗

PubMed2000

Endovascular treatment of a "blister-like" aneurysm of the internal carotid artery.

BACKGROUND: "Blister-like" aneurysms of the supraclinoid internal carotid artery have recently been recognized as having unique pathological and clinical features. Little is known regarding their optimal treatment modality. METHODS: We report a case of a "blister-like" aneurysm of the internal carotid artery treated with Guglielmi detachable coil (GDC) embolization. CASE REPORT: A 55-year-old man presented with a Hunt & Hess grade II subarachnoid hemorrhage. Computed tomography revealed diffuse subarachnoid blood. Cerebral angiography demonstrated a broad-based bulge on the medial wall of the right distal internal carotid artery. The patient was taken to the operating room and underwent a right pterional craniotomy and wrapping of this unclippable aneurysm. On postoperative day 11, he developed signs of vasospasm, and repeat angiography showed remarkable growth of the aneurysm. The aneurysm was believed to be amenable to endovascular therapy and was treated by GDC embolization. The patient recovered well and remained neurologically intact on follow-up examinations. Repeat cerebral angiography was performed three and nine months following his initial presentation and revealed a significant aneurysm neck remnant. This neck remnant was treated by repeat GDC embolization 13 months following his subarachnoid hemorrhage. CONCLUSIONS: "Blister-like" aneurysms of the internal carotid artery are important to recognize and are difficult to manage using traditional surgical approaches. Early repeated cerebral angiography is indicated and, where appropriate, endovascular therapy should be considered in the management of these patients.

Carotid Artery, Internal↗

PubMed1998

Prolonged administration of NT-4/5 fails to rescue most axotomized retinal ganglion cells in adult rats.

The survival of axotomized RGCs was increased by intravitreal NT-4/5 given by repeated injections or osmotic minipumps, but the effects were less complete than predicted. Compared to a single injection of the neurotrophin on day 0, second injections on days 3 or 7 only sustained an additional 10-20% of the RGCs on day 10. Minipumps augmented RGC survival up to 4-fold (50%) at 2 weeks but most RGCs were lost by 1 month. Thus, specific neurotrophins can rescue many RGCs soon after injury but long-term neuronal survival may require a better understanding of changes in neurotrophin receptors and interactions with other molecules.

Animals↗

PubMed1998

Meningeal melanocytoma. Report of a case and a historical comparison.

Meningeal melanocytomas are rare tumors of the central nervous system that are found almost exclusively in the posterior fossa and spinal cord and whose natural history is poorly defined. In this report, the authors review the clinical presentation, radiological appearance, operative findings, and histological features in two cases of meningeal melanocytoma: one cranial and one spinal. Two women, aged 21 and 30 years, were admitted to the hospital 60 years apart: the first because of progressive paraplegia and the second because of slowly progressive hearing loss. The first patient had an extradural tumor that was treated by laminectomy, subtotal resection, and postoperative radiotherapy in 1936. Her symptoms recurred 16 years later and she underwent reoperation of the residual tumor, which was found to have an intradural component. The authors' patient, who presented 60 years later, underwent plain and enhanced computerized tomography and magnetic resonance imaging that demonstrated a large posterior fossa lesion indicative of either an acoustic neuroma or a meningioma. She underwent posterior fossa decompression but only partial excision of the tumor could be accomplished because vigorous bleeding limited the extent of the resection. Surgery was followed by radiotherapy. The residual tumor enlarged despite these measures and required repeated resection 6 months later. At the second operation the tumor was much less vascular, perhaps reflecting the effects of radiotherapy, and was removed almost entirely. The patient died 6 months later from an anticoagulant-related cerebellar hemorrhage. In both cases the lesions were jet black, and histological examination revealed melanin-containing hypercellular tumors with rare mitotic figures. Meningeal melanocytomas are being diagnosed with increased frequency in parallel with improvements in neuroimaging and clarification of histological features. Clinical presentation of patients with these tumors typically occurs in their fifth decade and women are affected twice as often as men. The posterior fossa lesions can mimic acoustic neuromas and meningiomas in location and radiological appearance; however, the internal auditory canal is normal. In the spine, meningeal melanocytomas present with the clinical features of myeloradiculopathy. Diagnosis is made intraoperatively from the gross, jet-black appearance of the tumor and from histological examination. Vascularity, size, and location may render complete resection unfeasible. Because of the tumor's propensity to recur, radiotherapy has been recommended but its role remains to be elucidated.

Adult↗

PubMed1996

Brain-derived neurotrophic factor and neurotrophin-4/5 stimulate growth of axonal branches from regenerating retinal ganglion cells.

To investigate the influences of growth factors on axonal regeneration in the mammalian CNS, we used intracellular tracers to quantitate the effects of brain-derived neurotrophic factor (BDNF), neurotrophin (NT)-4/5, or NT-3 on individual retinal ganglion cell (RGC) axons in the retinas of adult rats after optic nerve transection. A single injection of BDNF or the prolonged administration of NT-4/5 by mini-pump increased axon branch median lengths by eightfold but had no effect on the number of branches formed by the RGC axons. NT-3 did not significantly influence axonal regrowth. These specific in vivo effects of BDNF and NT-4/5 on axonal regeneration from injured RGCs may be used to promote growth and expand the abnormally small terminal arbors observed when RGCs regrow into their CNS targets.

Animals↗

PubMed1996

Crystallization of experimental bioactive glass compositions.

Crystallization kinetics studies for six experimental glass formulations in the system Na2O-CaO-SiO2-P2O5 synthesized by wet chemistry were conducted by means of differential thermal analysis. These glasses had CaO/P2O5 and SiO2/ (CaO + Na2O) ratios ranging from 8.74-3.38 and 0.92-3.03, respectively. Samples of each glass (n = 30 were heated from 23 to 1250 degrees C under N2 atmosphere at heating rates ranging from 10 to 50 degrees C/min. Glass-ceramics were obtained after heat treating the initial glasses at temperatures determined from their DTA exotherms. The activation energy of crystallization for each glass composition was calculated from an expression-relating log-heating rate and the reciprocal of the exothermic peak temperature. The compositions of the six glasses were significantly different (p = 0.05). The activation energy of crystallization (Q) values ranged from 196 to 782 kJ/mole. A correlation was obtained between Q and CaO/P2O5 and between Q and the Young's modulus (P < 0.001). Two of the six glasses exhibited bulk crystallization. X-ray diffraction studies showed that four of the six glasses exhibited different proportions of crystalline phases following heat treatment. These phases were wollastonite (CaSiO3), Na2CaSi3O9, combeite [Na4Ca3SI6O16(OH)2], and some unidentifiable phases. Two of the six bioceramic materials had a mixture of unknown crystalline phases.

Biocompatible Materials↗

PubMed1996

Effects of neurotrophins on the survival and regrowth of injured retinal neurons.

The focus of this short review is the role of certain neurotrophins and their receptors on the survival and regrowth of retinal ganglion cells (RGCs) whose axons are damaged in the optic nerve. Initial experiments in our laboratory documented patterns of RGC death after axotomy. Subsequent studies were designed to investigate the distribution of high-affinity neurotrophin receptors in neurons and glial cells of the retina and optic nerve. This information was used both in vitro and in vivo to study the effects of specific trophic molecules on the survival and regrowth of injured RGCs. During the course of experiments involving neurotrophin administration, an endogenous source of trophic support--independent of the exogenous administration of growth factors--was found within the eye. Several experiments were subsequently undertaken to define further this survival effect and determine its nature and source within the eye. Finally, anatomical techniques that help visualize fine axonal processes within the retina have provided insights into the specific effects of neurotrophins on the growth and branching of injured CNS axons.

Animals↗

PubMed1996

Surgical treatment of epilepsy: the problem of lesion/focus incongruence.

BACKGROUND: This study suggests an alternative surgical strategy for treating patients with intractable epilepsy in whom a lesion, visualized by imaging, is found to be at a distance from the maximal electroencephalographic abnormality (focus). METHODS: Sixty patients (divided into three groups of 20), all of whom have had surgical resection for intractable epilepsy, are reviewed. Group A patients, representing the most common situation of a congruent electroencephalographic focus and structural lesion, underwent resection of the lesion/focus. Group B patients, in whom the focus and the lesion are incongruent, underwent resection of the focus only. Group C patients are those where the focus and lesion are incongruent; in this group, the lesion only was resected. RESULTS: Group A patients underwent resection of the lesion/focus (sites: 13 temporal, six frontal, and one parietal) with excellent results. Group B patients, in whom the focus only was resected (lesion sites: 14 temporal, four parietal, and two occipital) obtained poor results. Group C patients had excellent results following resection of the lesion only (lesion sites: 12 temporal, seven frontal, and one parietal). The superior surgical outcome in seizure control of group C is comparable to that seen in group A (Chi2 contingency test; Chi2 = 3.27 p > .05, 3 degrees of freedom) and is in contrast to the poor results seen in group B (Chi2 = 20.59 p < .001, 3 degrees of freedom). CONCLUSION: In those patients where a choice between a focus and a lesion is imperative, the lesion detected by imaging should be given priority in surgical resection.

Brain Diseases↗

PubMed1994

Effects of ocular injury and administration of brain-derived neurotrophic factor on survival and regrowth of axotomized retinal ganglion cells.

Optic nerve transection in adult rats results in the death of approximately 50% of the axotomized retinal ganglion cells (RGCs) by 1 week and nearly 90% by 2 weeks after injury. The capacity of brain-derived neurotrophic factor (BDNF) to prevent this early, severe loss of RGCs was investigated in vivo by intravitreal injections of BDNF [5 micrograms in 5 microliters of bovine serum albumin/phosphate-buffered saline (BSA/PBS)] or vehicle (5 microliters of BSA/PBS). Using quantitative anatomical techniques, we show that (i) all RGCs survived 1 week after a single injection of BDNF at the time of axotomy. (ii) RGC densities decreased in the BDNF-treated retinas by 2 weeks but remained significantly greater than in the untreated controls. (iii) An enhanced RGC survival was obtained with single injections of BDNF from 6 days before to 5 days after axotomy. (iv) Repeated injections resulted in greater numbers of surviving RGCs, an effect that declined to undetectable levels by 6 weeks. (v) There were indications for an endogenous local source of trophic support whose expression was triggered by ocular injury, particularly to the anterior part of the eye. (vi) With multiple BDNF injections, there was profuse axonal sprouting around the optic disc. This remarkable intraretinal growth was not, however, reflected in increased RGC innervation of the peripheral nerve grafts, which are known to facilitate regeneration when used as optic nerve substitutes.

Animals↗

PubMed1994

Newborn apnea caused by a neurofibroma at the craniocervical junction.

The authors report, for the first time, the finding by magnetic resonance imaging of a neurofibroma at the craniocervical junction with upper cervical cord and lower brainstem compression causing complete apnea from birth. Subsequent subtotal resection of the neurofibroma resulted in the successful extubation of a previously ventilator-dependent patient. After a two month period of breathing spontaneously, the newborn developed an upper respiratory tract infection and was reintubated. The patient, unable to be weaned off of the respirator, was extubated and expired shortly thereafter, at the age of five months. The authors suggest that in newborns with unexplained apnea, MRI of the cranio-cervical junction is indicated. Certain patients may be discovered who have less compromised cervico-medullary function and are afflicted by less aggressive forms of neurofibromatosis type 1. These patients may benefit permanently from a surgical decompression.

Apnea↗