Distribution of cortical interneurons in grey matter heterotopia in patients with epilepsy.

Purpose: Grey matter heterotopia are well-defined malformations of the cortex often associated with severe epilepsy. Defects have been identified in genes, including DCX and FLN1, that influence radial migration of postmitotic cells from the ventricular zone to the cortical plate. A proportion of cortical gamma-aminobutyric acid (GABA)-containing interneurons may arise from the ganglionic eminence of the ventral telencephalon.

Interaction of antigen presenting cells with mycobacteria.

The interaction of mycobacteria with antigen presenting cells is a key feature in the pathogenesis of tuberculosis and the outcome of this interaction is pivotal in determining whether immunity or disease ensues. Human and mouse macrophages and dendritic cells (DC) have been shown to become infected with mycobacteria and to produce a response to infection that reflects their suggested role in immunity. Thus, macrophages elicit anti-microbial mechanisms for elimination of mycobacteria and DC up-regulate expression of molecules that aid their stimulation of T lymphocytes.

The evolution and maintenance of delayed implantation in the mustelidae (mammalia: carnivora).

Diapause, the temporary cessation of development at an early life-history stage, is widespread among animals and plants. The range of taxa exhibiting various forms of diapause indicates its enormous ecological significance and highlights its value as a model for examining life-history trait evolution. However, despite the impact of diapause on species ecology, there is little understanding of its adaptive value in many groups.

GABA(B1a), GABA(B1b) AND GABA(B2) mRNA variants expression in hippocampus resected from patients with temporal lobe epilepsy.

The aim of this study was to investigate the mRNA expression of the two GABA(B1) receptor isoforms and the GABA(B2) subunit, in human postmortem control hippocampal sections and in sections resected from epilepsy patients using quantitative in situ hybridisation autoradiography. Utilising human control hippocampal sections it was shown that the oligonucleotides employed were specific to the receptor. Hippocampal slices from surgical specimens obtained from patients with hippocampal sclerosis and temporal lobe epilepsy were compared with neurologically normal postmortem control subjects for neuropathology and GABA(B) mRNA expression.

Major vault protein, a marker of drug resistance, is upregulated in refractory epilepsy.

Purpose: The molecular basis of drug resistance in epilepsy is being explored. Two proteins associated with drug resistance in cancer, P-glycoprotein and multidrug resistance-associated protein 1, are upregulated in human epileptogenic pathologies. Other proteins associated with resistance in cancer include major vault protein (MVP) and breast cancer resistance protein (BCRP).

Cajal-Retzius cells, inhibitory interneuronal populations and neuropeptide Y expression in focal cortical dysplasia and microdysgenesis.

Focal cortical dysplasia (FCD) and microdysgenesis (MD) are likely to represent abnormalities of radial neuronal migration during cortical development. We investigated the distribution of reelin-positive Cajal-Retzius cells, known to be important in the later stages of radial neuronal migration and cortical organization, in 12 surgical cases of both MD and FCD. Quantitation revealed significantly higher numbers of these cells in MD cases compared to controls.

Sudden and unexpected death in epilepsy (SUDEP): evidence of acute neuronal injury using HSP-70 and c-Jun immunohistochemistry.

Post-mortem and neuropathological examination in sudden and unexpected death in epilepsy (SUDEP) shows no specific lesions and the exact cause and mechanism of death in these cases remains undetermined. There is clinical evidence to support the fact that SUDEP is a seizure-mediated event, and patients with poorly controlled seizures are at higher risk. We aimed to identify any evidence of acute neuronal injury in SUDEP cases at post-mortem to support that a recent seizure had occurred.

Widespread upregulation of drug-resistance proteins in fatal human status epilepticus.

Purpose: Accumulating evidence implicates drug-transporter proteins ABCB1 and ABCC1 in resistance to multiple antiepileptic drugs (AEDs) in refractory epilepsy. These proteins are upregulated in surgically resected human brain tissue containing epileptogenic pathologies, including cortical dysplasia. In surgically resected cases, no upregulation is seen in normal adjacent tissue, suggesting that neither seizures nor prolonged exposure to AEDs need induce ABCB1 or ABCC1 expression.

Abnormalities of grey and white matter [11C]flumazenil binding in temporal lobe epilepsy with normal MRI.

In 20% of potential surgical candidates with refractory epilepsy, current optimal MRI does not identify the cause. GABA is the principal inhibitory neurotransmitter in the brain, and GABA(A) receptors are expressed by most neurones. [(11)C]Flumazenil (FMZ) PET images the majority of GABA(A) receptor subtypes.

Studies of GABA(B) receptors labelled with [(3)H]-CGP62349 in hippocampus resected from patients with temporal lobe epilepsy.

1 The aim of this study was to investigate the binding of a novel GABA(B) receptor radioligand, [(3)H]-CGP62349, to human post-mortem control and epileptic hippocampal sections using quantitative receptor autoradiography. Utilizing human control hippocampal sections it was shown that [(3)H]-CGP62349 bound with high affinity (K(D) 0.5 nM) to this tissue.

Abnormal expression of cdk5 in focal cortical dysplasia in humans.

Focal cortical dysplasia (FCD) is an important cause of refractory epilepsy in humans. The origin of its pathognomonic abnormal cell types and the links between abnormal cell morphology and epileptogenicity remain unknown. The developmentally-regulated kinase cdk5 and its neuronal activator p35 are known to be central to a number of key components in neuronal development, cellular morphology, cytoskeletal function, synaptic plasticity and neurodegeneration.

Cytoarchitectural abnormalities in hippocampal sclerosis.

Hippocampal sclerosis (HS) is the most common pathological substrate for temporal lobe epilepsy with a characteristic pattern of loss of principle neurons primarily in CA1 and hilar subfields. Other cytoarchitectural abnormalities have been identified in human HS specimens, including dispersion of dentate granule cells and cytoskeletal abnormalities in residual hilar cells. The incidence of these features, their relationship to the severity of HS and potential indication of underlying hippocampal maldevelopment is unverified.

Bilateral isolated hippocampal malformation in temporal lobe epilepsy.

Hippocampal malformations in patients with epilepsy usually are reported in the context of widespread cortical malformations. Isolated hippocampal malformations are more rarely identified in MRI studies with little documentation of their pathologic appearance. Postmortem examination revealed abnormal position and complex convolutional malformations isolated to the hippocampal formation in an adult with temporal lobe epilepsy in whom MRI demonstrated bilateral hippocampal abnormalities.

Diffusion tensor imaging in refractory epilepsy.

Diffusion tensor imaging is an imaging method that is sensitive to the molecular movement of water, which indicates cellular integrity and pathology. A patient with refractory epilepsy and normal conventional MRI was examined with diffusion tensor imaging. An area of abnormal diffusion in the right frontal lobe was identified and surgically resected.

Drug resistance in epilepsy: human epilepsy.

The basis of drug resistance in human epilepsy is not understood. Parallels with resistance in cancer suggest that drug resistance proteins may have a role. To examine this possibility, we have studied human brain tissue containing pathologies capable of causing refractory epilepsy.

Ammon's horn sclerosis: a maldevelopmental disorder associated with temporal lobe epilepsy.

Ammon's horn sclerosis (AHS) is the major neuropathological substrate in patients with temporal lobe epilepsy (TLE). Histopathological hallmarks include segmental loss of pyramidal neurons, granule cell dispersion and reactive gliosis. Pathogenetic mechanisms underlying this distinct hippocampal pathology have not yet been identified and it remains to be resolved whether AHS represents the cause or the consequence of chronic seizure activity and pharmacoresistant TLE.

Development of an ELISA for bovine IL-10.

The objective of the study was to develop an assay for bovine IL-10 that could be applied to analyses of immune responses and advance understanding of a variety of diseases of cattle. Recombinant bovine IL-10 (rbo IL-10) was transiently expressed in Cos-7 cells and shown to inhibit the synthesis of IFN gamma by bovine cells stimulated with antigen in vitro. Mice were immunised with a plasmid containing a cDNA insert encoding rbo IL-10 and inoculated with rbo IL-10.

Mitochondrial dysfunction associated with neuronal death following status epilepticus in rat.

Status epilepticus (SE) in humans and animal models results in significant cerebral damage and an increased risk of subsequent seizures, associated with a characteristic pattern of neuronal loss particularly affecting the hippocampus. Seizure related cell death is considered to be excitotoxic, but studies have been limited, concentrating on terminal events rather than initial mechanisms. We have studied the biochemical events in the first few days following SE.

Progesterone receptors are expressed with higher frequency by optic nerve sheath meningiomas.

Optic nerve sheath meningiomas are infrequent neuropathological specimens as conservative management of these benign tumors is often adopted. It is established that progesterone receptor expression in meningiomas may be of functional significance in the growth of these neoplasms and is related to the tumor grade and likelihood of recurrence. In addition, progesterone receptor expression can be indicative of a potential response of surgically less accessible meningiomas to hormonal treatments.

Drug resistance in epilepsy: expression of drug resistance proteins in common causes of refractory epilepsy.

Epilepsy is resistant to drug treatment in about one-third of cases, but the mechanisms underlying this drug resistance are not understood. In cancer, drug resistance has been studied extensively. Amongst the various resistance mechanisms, overexpression of drug resistance proteins, such as multi-drug resistance gene-1 P-glycoprotein (MDR1) and multidrug resistance-associated protein 1 (MRP1), has been shown to correlate with cellular resistance to anticancer drugs.

Infundibulohypophysitis in a man presenting with diabetes insipidus and cavernous sinus involvement.

Infundibulohypophysitis is an unusual inflammatory condition that affects the infundibulum, the pituitary stalk, and the neurohypophysis and may be part of a range that includes lymphocytic hypophysitis. Lymphocytic hypophysitis occurs mainly in women and most often presents in the later stages of pregnancy. Infundibulohypophysitis usually presents with diabetes insipidus and the cause remains unclear.

Microdysgenesis in temporal lobe epilepsy. A quantitative and immunohistochemical study of white matter neurones.

Microdysgenesis is a microscopic cortical malformation considered to act as a substrate for seizures in some patients with generalized epilepsy. It is also recognized to involve the temporal lobe in a proportion of patients with intractable temporal lobe epilepsy, but the incidence of this abnormality, its relationship to mesial temporal lobe sclerosis and relevance to epileptogenesis remain unknown. This is partly due to a lack of well-defined quantitative pathological diagnostic criteria.