Bax-inhibiting peptide protects cells from polyglutamine toxicity caused by Ku70 acetylation.

Polyglutamine (polyQ) diseases, such as Huntington's disease and Machado-Joseph disease (MJD), are caused by gain of toxic function of abnormally expanded polyQ tracts. Here, we show that expanded polyQ of ataxin-3 (Q79C), a gene that causes MJD, stimulates Ku70 acetylation, which in turn dissociates the proapoptotic protein Bax from Ku70, thereby promoting Bax activation and subsequent cell death. The Q79C-induced cell death was significantly blocked by Ku70 or Bax-inhibiting peptides (BIPs) designed from Ku70.

Phenotypic characterization of OmpX, an Ail homologue of Yersinia pestis KIM.

The goal of this study was to characterize the Yersinia pestis KIM OmpX protein. Yersinia spp. provide a model for studying several virulence processes including attachment to, and internalization by, host cells.

Discontinuation of antiepileptic drugs after pediatric epilepsy surgery.

In children with medically intractable seizures, epilepsy surgery is now a widely accepted option. Successful discontinuation of antiepileptic drugs after epilepsy surgery has been reported in adults, but rarely in children. Surgical outcome and need for antiepileptic drugs after temporal and extratemporal lobe resection were retrospectively reviewed for 80 pediatric patients from the Comprehensive Epilepsy Program at the University of Alberta.

Role of antineutrophil cytoplasmic antibodies and glomerular basement membrane antibodies in the diagnosis and monitoring of systemic vasculitides.

Systemic vasculitis, although rare, is often diagnosed late and long after the onset of symptoms. The small vessel vasculitides are recognized clinically by their multisystem presentation, markers of inflammation and evidence for an acute glomerulonephritis (GN), with the most apparent organ involved directing referral to secondary care. Routine laboratory tests are usually non-specific in systemic vasculitis but the use of anti-neutrophil cytoplasmic antibodies (ANCAs) and glomerular basement membrane (GBM) antibodies can aid diagnosis, treatment and monitoring decisions.

Absence epilepsy in childhood: electroencephalography (EEG) does not predict outcome.

Absence epilepsy is a form of generalized epilepsy commonly seen in children. The clinician is often presented with a patient whose electroencephalogram does not fit the typical absence pattern. The purpose of this study is to more closely examine both typical and atypical absence variants and their outcome.

The role of nuclear architecture in genomic instability and ageing.

Eukaryotes come in many shapes and sizes, yet one thing that they all seem to share is a decline in vitality and health over time--a process known as ageing. If there are conserved causes of ageing, they may be traced back to common biological structures that are inherently difficult to maintain throughout life. One such structure is chromatin, the DNA-protein complex that stabilizes the genome and dictates gene expression.

Caloric restriction and life span determination of yeast cells.

The diet known as caloric restriction (CR) has been known for 70 yr to extend the life span of rodents (1). CR can also extend life span in a broad range of other species as well, from unicellular organisms (2,3), to invertebrates (4) and most likely primates, as well (5). The budding yeast Saccharomyces cerevisiae is a useful model for the study of pathways that determine life span in response to dietary intake.

The pink gene encodes the Drosophila orthologue of the human Hermansky-Pudlak syndrome 5 (HPS5) gene.

Hermansky-Pudlak syndrome (HPS) consists of a set of human autosomal recessive disorders, with symptoms resulting from defects in genes required for protein trafficking in lysosome-related organelles such as melanosomes and platelet dense granules. A number of human HPS genes and rodent orthologues have been identified whose protein products are key components of 1 of 4 different protein complexes (AP-3 or BLOC-1, -2, and -3) that are key participants in the process. Drosophila melanogaster has been a key model organism in demonstrating the in vivo significance of many genes involved in protein trafficking pathways; for example, mutations in the "granule group" genes lead to changes in eye colour arising from improper protein trafficking to pigment granules in the developing eye.

Emergency medicine: A practice prone to error?

The last decade has witnessed a rapidly growing public and academic interest in medical error, an interest that has culminated in the emergence of the science of error prevention in health care. The impact of this new science will be felt in all areas of medicine but perhaps especially in emergency medicine (EM). The emergency department's unique operating characteristics make it a natural laboratory for the study of error.

How lab staff and the estimation of free light chains can combine to aid the diagnosis of light chain disease.

The diagnosis and monitoring of free light chain abnormalities and disease has always been a challenging area for laboratory and clinical staff because urine electrophoresis is often overlooked in the investigations requested. We present here three case reports which illustrate first, the role of the laboratory staff and second, the use of serum free light chain estimations in the diagnosis and monitoring of patients with light chain paraproteinaemia and myeloma.

The enzyme CD38 (a NAD glycohydrolase, EC 3.2.2.5) is necessary for the development of diet-induced obesity.

Obesity is one of the major health problems of our times. Elucidating the signaling mechanisms by which high-fat caloric diet induces obesity is critical for the understanding of this condition and for the development of therapeutic strategies for its treatment. Here, we demonstrate a novel role for protein CD38 as a regulator of body weight during a high-fat diet.

SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis.

A progressive loss of neurons with age underlies a variety of debilitating neurological disorders, including Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), yet few effective treatments are currently available. The SIR2 gene promotes longevity in a variety of organisms and may underlie the health benefits of caloric restriction, a diet that delays aging and neurodegeneration in mammals. Here, we report that a human homologue of SIR2, SIRT1, is upregulated in mouse models for AD, ALS and in primary neurons challenged with neurotoxic insults.

Perceptual reasons for resistance to change in the emergency department use of holding chambers for children with asthma.

Study Objective: We explore perceptions surrounding use of portable inhalers and holding chambers (spacers) for delivery of beta-agonist respiratory medications to children in the emergency department (ED) and factors influencing practice change.

Methods: This was a qualitative study guided by principles of grounded theory. Data were collected through focus groups and individual interviews at 2 sites in eastern Canada: Hospital A, where inhalers and holding chambers are used routinely; and Hospital B, where prevailing practice is the use of nebulization.

Challenges in multisource feedback: intended and unintended outcomes.

Context: Multisource feedback (MSF) is a type of formative assessment intended to guide learning and performance change. However, in earlier research, some doctors questioned its validity and did not use it for improvement, raising questions about its consequential validity (i.e.

Sirtuins in mammals: insights into their biological function.

Sirtuins are a conserved family of proteins found in all domains of life. The first known sirtuin, Sir2 (silent information regulator 2) of Saccharomyces cerevisiae, from which the family derives its name, regulates ribosomal DNA recombination, gene silencing, DNA repair, chromosomal stability and longevity. Sir2 homologues also modulate lifespan in worms and flies, and may underlie the beneficial effects of caloric restriction, the only regimen that slows aging and extends lifespan of most classes of organism, including mammals.

Can an ELISA replace immunofluorescence for the detection of anti-nuclear antibodies?--The routine use of anti-nuclear antibody screening ELISAs.

The aim of this study was to evaluate a commercially available ELISA assay for anti-nuclear antibodies (ANA) screening in a large routine laboratory setting. The detection of ANA is a commonly requested test by clinicians for patients suspected of rheumatic disease and other connective tissue diseases. Detection is part of the diagnostic criteria of rheumatic diseases such as SLE and can be important for monitoring purposes.

Strategies for managing a busy emergency department.

In a time of increased patient loads and emergency department (ED) exit block, the need for strategies to manage patient flow in the ED has become increasingly important. In March 2002 we contacted all 1282 members of the Canadian Association of Emergency Physicians and asked them to delineate strategies for enhancing ED patient flow and ED productivity without increasing stress levels, reducing care standards or compromising patient safety. Thirty physicians responded.

Benign epilepsy of childhood with rolandic spikes: typical and atypical variants.

Clinical course and outcome were compared for 126 children with typical and atypical features of benign epilepsy of childhood with rolandic spikes (BECRS). A retrospective case series design was used, in the setting of a tertiary-care pediatric hospital. The subjects were subdivided into two groups, based on clinical presentation.

Approaches to the quaternary stereocentre and to the heterocyclic core in diazonamide A using the Heck reaction and related coupling reactions.

In model studies towards the quaternary centre at the heart of diazonamide A (early structure 2; revised structure 1), cyclisations of the alkene-substituted iodoaryls 4, 13, 18 and 23, under Heck reaction conditions, were shown to lead to the corresponding benzodihydrofuran 5, benzofuranone 14 and the oxindoles 19 and 24 respectively, in 50-80% yield. Further manipulation of the benzodihydrofuran 5 then led to the intermediates 30, 33 and 39, which make up parts of the oxazole-indole heterocyclic core in diazonamide A. Attempts to perform a corresponding 13-exo-trig Heck cyclisation from the precursor 46a, prepared from 44 and 45, leading to 47 were not successful.

Clinical significance of photic stimulation during routine EEGs of adult patients.

Intermittent photic stimulation (IPS) is an activating procedure meant to elicit or accentuate epileptiform discharges during an EEG. There is insufficient clinical data to advocate IPS in the routine EEGs of all adult patients. We therefore sought to address the clinical significance of routine IPS in the adult population.

Data collection on patients in emergency departments in Canada.

Objective: Relatively little is known about the ability of Canadian emergency departments (EDs) and the federal, provincial and territorial governments to quantify ED activity. The objectives of this study were to determine the use of electronic patient data in Canadian EDs, the accessibility of provincial data on ED visits, and to identify the data elements and current methods of ED information system (EDIS) data collection nationally.

Methods: Surveys were conducted of the following 3 groups: 1) all ED directors of Canadian hospitals located in communities of >10,000 people, 2) all electronic EDIS vendors, and 3) representatives from the ministries of health from 13 provincial and territorial jurisdictions who had knowledge of ED data collection.