Production and characterization of astrocyte-derived human apolipoprotein E isoforms from immortalized astrocytes and their interactions with amyloid-beta.

The apolipoprotein E (apoE) genotype is an important genetic risk factor for Alzheimer's disease (AD). In the central nervous system (CNS), most apoE is produced by astrocytes and is present in unique high-density lipoprotein (HDL)-like particles that have distinct properties from apoE derived from other sources. To develop an efficient system to produce astrocyte-derived apoE in large quantities, we produced and characterized immortalized cell lines from primary astrocyte cultures derived from human APOE knock-in mice.

Notes of a policy watcher: the Medicare Drug Plan.

The Medicare Modernization Act, signed into law by President Bush in December 2003, provides for new prescription drug benefits to those enrolled in Medicare. This new benefit will provide many seniors with improved access to medications and should thereby improve outcomes of care. The benefit is complex, though, and we are currently in a transition period.

Platelet-derived growth factor C induces liver fibrosis, steatosis, and hepatocellular carcinoma.

Members of the platelet-derived growth factor (PDGF) ligand family are known to play important roles in wound healing and fibrotic disease. We show that both transient and stable expression of PDGF-C results in the development of liver fibrosis consisting of the deposition of collagen in a pericellular and perivenular pattern that resembles human alcoholic and nonalcoholic fatty liver disease. Fibrosis in PDGF-C transgenic mice, as demonstrated by staining and hydroxyproline content, is preceded by activation and proliferation of hepatic stellate cells, as shown by collagen, alpha-smooth muscle actin and glial fibrillary acidic protein staining and between 8 and 12 months of age is followed by the development of liver adenomas and hepatocellular carcinomas.

Timed motor test for wheelchair users: initial development and application in children with spinal cord injury.

Objective: The objective of this study was to describe the development and preliminary results of reliability testing of the timed motor test (TMT), a performance-based measure of functional status for children with a spinal cord injury (SCI) who use a manual wheelchair. This study will also provide pilot data using the TMT to examine the impact of thoracolumbosacral orthoses (TLSO) on function in children with a SCI.

Study Design: Cross-sectional observational study.

Breath testing in patients with respiratory disability.

The presence of chronic respiratory disease is sometimes claimed as a defence by drivers who refuse or fail a breath test. Trials have been conducted with two breath analysis instruments used in the state of Victoria, Australia in order to determine the respiratory parameters compatible with a satisfactory test. Patients with restrictive and obstructive conditions participated in the trial that was conducted in the respiratory unit of a large teaching hospital.

Drug-induced anisocoria in two detainees.

Two suspects held by the police were examined for fitness to be interviewed. It was noticed that both had a persistent unilateral dilated pupil in the absence of a history of pre-existing disease or acute head injury. They subsequently admitted to misuse of eye drops.

Continuing education programme - Victorian Institute of Forensic Medicine and Department of Forensic Medicine, Monash University.

Given the increasing requirement of the courts for forensic experts to engage in ongoing education, a continuing education programme was developed in forensic medicine at the Victorian Institute of Forensic Medicine to cater for both clinicians and pathologists. The programme consists of a series of cases which are circulated several times per year. All are actual cases and are reflective of the types of presentations experienced in forensic medicine.

Continuing education programme - Victorian Institute of Forensic Medicine and Department of Forensic Medicine, Monash University.

Given the increasing requirement of the courts for forensic experts to engage in ongoing education, a continuing education programme was developed in forensic medicine at the Victorian Institute of Forensic Medicine to cater for both clinicians and pathologists. The programme consists of a series of cases which are circulated several times per year. All are actual cases and are reflective of the types of presentations experienced in forensic medicine.

Continuing Education Programme - Victorian Institute of Forensic Medicine and Department of Forensic Medicine, Monash University.

Given the increasing requirement of the courts for forensic experts to engage in ongoing education, a continuing education programme was developed in forensic medicine at the Victorian Institute of Forensic Medicine to cater for both clinicians and pathologists. The programme consists of a series of cases which are circulated several times per year. All are actual cases and are reflective of the types of presentations experienced in forensic medicine.

Imposition of crossover interference through the nonrandom distribution of synapsis initiation complexes.

Meiotic crossovers (COs) are nonrandomly distributed along chromosomes such that two COs seldom occur close together, a phenomenon known as CO interference. We have used genetic and cytological methods to investigate interference mechanisms in budding yeast. Assembly of the synaptonemal complex (SC) initiates at a few sites along each chromosome, triggered by a complex of proteins (including Zip2 and Zip3) called the synapsis initiation complex (SIC).

A review of nursing skill-mix to optimise care in an acute trust.

The main resource of the NHS is its workforce. However, achieving the correct mix of staff is crucial if it is to provide high-quality patient care in a cost-effective manner. When an acute trust was singled out in an independent analysis as having 'too rich' a skill-mix (compared with the rest of the strategic health authority), an internal review was undertaken to determine the ratio of qualified to unqualified nursing staff, and to compare these with acuity and dependency in each clinical area.

Parotid surgery in an outpatient setting: the Vancouver Hospital experience.

Objective: The goal of the present study was to review our experience with parotid surgery in an outpatient setting. Particular attention was given to examining the demographics of the population suitable for this approach as well as to evaluating complication and readmission rates. Waiting times for surgery were reviewed.

ApoE and clusterin cooperatively suppress Abeta levels and deposition: evidence that ApoE regulates extracellular Abeta metabolism in vivo.

Apolipoprotein E (apoE) and clusterin can influence structure, toxicity, and accumulation of the amyloid-beta (Abeta) peptide in brain. Both molecules may also be involved in Abeta metabolism prior to its deposition. To assess this possibility, we compared PDAPP transgenic mice that develop age-dependent Abeta accumulation in the absence of apoE or clusterin as well as in the absence of both proteins.

In vivo assessment of brain interstitial fluid with microdialysis reveals plaque-associated changes in amyloid-beta metabolism and half-life.

Soluble amyloid-beta (Abeta) peptide converts to structures with high beta-sheet content in Alzheimer's disease (AD). Soluble Abeta is released by neurons into the brain interstitial fluid (ISF), in which it can convert into toxic aggregates. Because assessment of ISF Abeta levels may provide unique insights into Abeta metabolism and AD, an in vivo microdialysis technique was developed to measure it.

Analysis of the DNA joining repertoire of Chlorella virus DNA ligase and a new crystal structure of the ligase-adenylate intermediate.

Chlorella virus DNA ligase is the smallest eukaryotic ATP-dependent DNA ligase known; it suffices for yeast cell growth in lieu of the essential yeast DNA ligase Cdc9. The Chlorella virus ligase-adenylate intermediate has an intrinsic nick sensing function and its DNA footprint extends 8-9 nt on the 3'-hydroxyl (3'-OH) side of the nick and 11-12 nt on the 5'-phosphate (5'-PO4) side. Here we establish the minimal length requirements for ligatable 3'-OH and 5'-PO4 strands at the nick (6 nt) and describe a new crystal structure of the ligase-adenylate in a state construed to reflect the configuration of the active site prior to nick recognition.

Electronic psychosocial evaluation tool: use in a living donor organ transplant program.

Psychosocial evaluation of potential organ donors ensures that these patients are prepared for donation and that their psychosocial issues have been addressed. The determination that the decision to donate an organ has been made voluntarily by a competent individual is a primary concern for living donor transplant programs, which must work to the highest ethical standard in this unique area of medicine. Identification of potential vulnerabilities on the part of the donor permits monitoring and/or intercession both before and after donation.

Structure-based experimental confirmation of biochemical function to a methyltransferase, MJ0882, from hyperthermophile Methanococcus jannaschii.

We have determined the three-dimensional (3-D) structure of protein MJ0882, which derives from a hypothetical open reading frame in the genome of the hyperthermophile Methanococcus jannaschii. The 3-D fold of MJ0882 at 1.8 A highly resembles that of a methyltransferase, despite limited sequence similarity to any confirmed methyltransferase.

Sepsis: early detection and care.

Nurses need to be aware of the signs and symptoms of sepsis. Staff education to encourage the early identification of this life-threatening condition will be aided by a new resource kit.

The critical care outreach service and the early warning system on surgical wards.

The implementation and evaluation of a modified early warning system (MEWS) on surgical wards are described. The MEWS was found to be a useful adjunct to the outreach service. Early data have shown that MEWS can help direct critical intervention.

Clusterin promotes amyloid plaque formation and is critical for neuritic toxicity in a mouse model of Alzheimer's disease.

Studies have shown that clusterin (also called apolipoprotein J) can influence the structure and toxicity of amyloid-beta (Abeta) in vitro. To determine whether endogenous clusterin plays a role in influencing Abeta deposition, structure, and toxicity in vivo, we bred PDAPP mice, a transgenic mouse model of Alzheimer's disease, to clusterin(-/-) mice. By 12 months of age, PDAPP, clusterin(-/-) mice had similar levels of brain Abeta deposition as did PDAPP, clusterin(+/+) mice.

Plaque-associated disruption of CSF and plasma amyloid-beta (Abeta) equilibrium in a mouse model of Alzheimer's disease.

To better understand amyloid-beta (Abeta) metabolism in vivo, we assessed the concentration of Abeta in the CSF and plasma of APP(V717F) (PDAPP) transgenic mice, a model that develops age-dependent Alzheimer's disease (AD)-like pathology. In 3-month-old mice, prior to the development of Abeta deposition in the brain, there was a highly significant correlation between Abeta levels in CSF and plasma. In 9-month-old-mice, an age at which some but not all mice have developed Abeta deposition, there was also a significant correlation between CSF and plasma Abeta; however, the correlation was not as strong as that present in young mice.