Informing patient contacts about iatrogenic Creutzfeldt-Jakob disease.

The unanticipated diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) in a patient after previous neurosurgery can lead to difficult decisions regarding informing contacts. A patient developed sCJD 3 years after neurosurgery. There were 29 potential contacts and 26 were contacted.

Exploring the role of knowledge of condition and psycho-social profiles of young people with epilepsy during transition.

Transitioning from paediatric to adult care can be a particularly challenging time for young people with epilepsy and research has shown that there are a range of factors which may influence a young person's ability to successfully cope with this difficult time. The following study aimed to explore the psychosocial characteristics of this transitioning population, as well as investigate how knowledgeable the young person and their parent/carer are of their own condition throughout transition. Young people with epilepsy were recruited from two specialist epilepsy clinics in the North West and allocated to one of three groups; Group 1 pre-transition, Group 2 transitioning, and Group 3 post-transition.

The ROAM/EORTC-1308 trial: Radiation versus Observation following surgical resection of Atypical Meningioma: study protocol for a randomised controlled trial.

Background: Atypical meningiomas are an intermediate grade brain tumour with a recurrence rate of 39-58 %. It is not known whether early adjuvant radiotherapy reduces the risk of tumour recurrence and whether the potential side-effects are justified. An alternative management strategy is to perform active monitoring with magnetic resonance imaging (MRI) and to treat at recurrence.

Adipocyte size and cellular expression of caveolar proteins analyzed by confocal microscopy.

Caveolae are abundant in adipocytes and are involved in the regulation of lipid accumulation, which is the main volume determinant of these cells. We have developed and applied a confocal microscopic technique for measuring individual cellular expression of the caveolar proteins cavin-1 and caveolin-1 along with the size of individual adipocytes. The technique was applied on collagenase isolated adipocytes from ad libitum fed Sprague-Dawley rats of different age (4-26 wk) and weight (103-629 g).

MURC/Cavin-4 and cavin family members form tissue-specific caveolar complexes.

Polymerase I and transcript release factor (PTRF)/Cavin is a cytoplasmic protein whose expression is obligatory for caveola formation. Using biochemistry and fluorescence resonance energy transfer-based approaches, we now show that a family of related proteins, PTRF/Cavin-1, serum deprivation response (SDR)/Cavin-2, SDR-related gene product that binds to C kinase (SRBC)/Cavin-3, and muscle-restricted coiled-coil protein (MURC)/Cavin-4, forms a multiprotein complex that associates with caveolae. This complex can constitutively assemble in the cytosol and associate with caveolin at plasma membrane caveolae.

The behavioral consequences of exposure to antiepileptic drugs in utero.

The aim of the study was to examine the behavior of 242 children, aged between 6 and 16 years, born to mothers with epilepsy. Exposure to sodium valproate (VPA) in utero was associated with high levels of parental stress induced by the child's maladaptive behavior. These children were also poorer for daily living skills and skills relating to socialization.

Adiponectin and its response to thiazolidinediones are associated with insulin-mediated glucose metabolism in type 2 diabetic patients and their first-degree relatives.

Patients with type 2 diabetes (T2D) and their first-degree relatives (FDRs) are characterized by hypoadiponectinaema and insulin resistance. In T2D patients, plasma adiponectin and insulin sensitivity (SI) increase in response to thiazolidinediones (TZDs). These findings suggest a role for adiponectin in the regulation of SI.

Dysmorphic features: an important clue to the diagnosis and severity of fetal anticonvulsant syndromes.

Background: In utero exposure to antiepileptic drugs (AEDs) can result in several different teratogenic effects including major malformations, dysmorphic facial features, and learning and behavioural problems. It is estimated that there is a 2-3-fold increase in the risk of malformations compared with the general population. The risk of cognitive impairment and behavioural problems is less clear.

Identification of a major protein on the cytosolic face of caveolae.

Cav-p60, a specific and ubiquitous caveolar protein, was immunoprecipitated from solubilized rat adipocyte plasma membranes and identified as similar to a GeneBank entry annotated mouse polymerase transcript release factor (PTRF) by MALDI-TOF and MS-MS of major fragments. Cloning and virtual translation of the corresponding rat adipocyte cDNA sequence revealed 98.7% identity with mouse PTRF.

Neuropsychological effects of exposure to anticonvulsant medication in utero.

Objective: To investigate the long-term differential drug effects on cognitive functioning in school-aged children exposed to antiepileptic drugs (AEDs) in utero.

Methods: Mothers with epilepsy were recruited from specialist epilepsy clinics and obstetric clinics from the Liverpool and Manchester region. The mothers and their children were recruited without prior knowledge of their AED treatment during pregnancy or the health of the offspring.

The longer term outcome of children born to mothers with epilepsy.

Objectives: To determine the prevalence of cognitive delay and possible associated dysmorphic features in children exposed to antiepileptic drugs (AEDs) in utero.

Design: Retrospective study of children born to mothers with epilepsy.

Setting: Regional epilepsy clinics in Liverpool and Manchester, UK.

Common antiepileptic drugs in pregnancy in women with epilepsy.

Background: The potential adverse effects of antiepileptic drug (AED) exposure in pregnancy have been well recognised but the relative risks of specific antiepileptic drug exposures remain poorly understood.

Objectives: To assess the adverse effects of commonly used antiepileptic drugs on maternal and fetal outcomes in pregnancy in women with epilepsy. Comparison of outcomes following specific antiepileptic drug exposures in utero to unexposed pregnancies in the general population or women with epilepsy are described.

Caveolae, caveolin and cav-p60 in smooth muscle and renin-producing cells in the rat kidney.

Aims: In vascular smooth muscle cells caveolae are important for signalling mechanisms regulating vascular contraction. In smooth muscle layer of the renal afferent arteriole juxtaglomerular cells (JG cells) are non-contractile renin producing cells that have the capacity to change their phenotype into smooth muscle cells and back again by metaplastic transformation. Signalling mechanisms in JG cells are not fully understood and we therefore investigated if caveolae were present, and thereby could be involved as integrators of cellular signalling in both of these phenotypes of smooth muscle cells.

Immunopurification and characterization of rat adipocyte caveolae suggest their dissociation from insulin signaling.

Adipocytes play an important role in the insulin-dependent regulation of organismal fuel metabolism and express caveolae at levels as high or higher than any other cell type. Recently, a link between insulin signaling and caveolae has been suggested; nevertheless, adipocyte caveolae have been the subject of relatively few studies, and their contents have been minimally characterized. With the aid of a new monoclonal antibody, we developed a rapid procedure for the immunoisolation of caveolae derived from the plasma membrane of adipocytes, and we characterized their protein content.

Proteome analysis reveals phosphorylation of ATP synthase beta -subunit in human skeletal muscle and proteins with potential roles in type 2 diabetes.

Insulin resistance in skeletal muscle is a hallmark feature of type 2 diabetes. An increasing number of enzymes and metabolic pathways have been implicated in the development of insulin resistance. However, the primary cellular cause of insulin resistance remains uncertain.

Clinical lipoatrophy in HIV-1 patients on HAART is not associated with increased abdominal girth, hyperlipidaemia or glucose intolerance.

Objective: To compare information on body fat changes from questionnaire and clinical examination and to study lipoatrophy in HIV-1 patients on highly active antiretroviral therapy (HAART).

Methods: The study was cross-sectional within a randomized trial. One hundred and sixty-eight male HIV-1 patients were examined by questionnaire and clinical examination.

Cholesterol depletion disrupts caveolae and differentially impairs agonist-induced arterial contraction.

Objective: This study assessed the role of cholesterol-rich membrane regions, including caveolae, in the regulation of arterial contractility. Methods and Results- Rat tail artery devoid of endothelium was treated with the cholesterol acceptor methyl-beta-cyclodextrin, and the effects on force and Ca2+ handling were evaluated. In cholesterol-depleted preparations, the force responses to alpha1-adrenergic receptors, membrane depolarization, inhibition of myosin light chain phosphatase, and activation of G proteins with a mixture of 20 mmol/L NaF and 60 micro mol/L AlCl3 were unaffected.

Indirect evidence for decreased hypothalamic somatostatinergic tone in anorexia nervosa.

Objective: In animals, somatostatin (SRIH) and growth hormone (GH)-releasing hormone (GHRH) increase feeding via a common neural mechanism. Furthermore, SRIH counteracts the suppressive action of corticotrophin-releasing hormone (CRH) on food intake. Hypothetically, SRIH could be involved in the central feeding mechanism in anorexia nervosa (AN).

cav-p60 expression in rat muscle tissues. Distribution of caveolar proteins.

Caveolae are plasmalemmal invaginations of uncertain function. In view of the large number of hypotheses on caveolar functions, it is important to identify which components of caveolae are tissue specific and which are general. The only well-characterized major protein of caveolae is caveolin, which exists in three tissue-specific isoforms: caveolin-1, -2, and -3.

A 60-kDa protein abundant in adipocyte caveolae.

To search for caveolar proteins, mice were immunised with rat adipocyte membranes. Hybridoma supernatants were screened for antibodies to proteins on the cytosolic face of caveolae by indirect immunoelectron microscopy of immunogold-labelled adipocyte plasma membrane sheets adsorbed on electron-microscope (EM) grids. One of the hybridoma supernatants (2F11) produced a specific labelling of caveolae which was much more intense than that obtained with caveolin-1 antibodies.

The nicotinic acid analogue acipimox increases plasma leptin and decreases free fatty acids in type 2 diabetic patients.

The effect of 3 days of intensive treatment with acipimox, an antilipolytic nicotinic acid derivative, on plasma leptin levels was studied in eight patients with Type 2 diabetes mellitus in a double-blind, placebo-controlled, cross-over study. Acipimox reduced plasma free fatty acids (FFA) markedly and lowered plasma triglycerides, glucose and insulin. Plasma leptin levels were elevated in all eight patients during 3 days of acipimox treatment (mean increase+/-s.

Involvement of PI 3-kinase and activated ERK in facilitating insulin-stimulated triacylglycerol synthesis in hepatocytes.

Triacylglycerol synthesis was studied in hepatocytes isolated from fasted/refed rats by EDTA perfusion. Insulin induced a 1.5-fold increase in glucose incorporation into triacylglycerol.