Multiple system atrophy: laminar distribution of the pathological changes in frontal and temporal neocortex--a study in ten patients

OBJECTIVE: To determine the distribution of the pathological changes in the neocortex in multiple-system atrophy (MSA). METHOD: The vertical distribution of the abnormal neurons (neurons with enlarged or atrophic perikarya), surviving neurons, glial cytoplasmic inclusions (GCI) and neuronal cytoplasmic inclusions (NI) were studied in alpha-synuclein-stained material of frontal and temporal cortex in ten cases of MSA. RESULTS: Abnormal neurons exhibited two common patterns of distribution, viz., density was either maximal in the upper cortex or a bimodal distribution was present with a density peak in the upper and lower cortex. The NI were either located in the lower cortex or were more uniformly distributed down the cortical profile. The distribution of the GCI varied considerably between gyri and cases. The density of the glial cell nuclei was maximal in the lower cortex in the majority of gyri. In a number of gyri, there was a positive correlation between the vertical densities of the abnormal neurons, the total number of surviving neurons, and the glial cell nuclei. The vertical densities of the GCI were not correlated with those of the surviving neurons or glial cells but the GCI and NI were positively correlated in a small number of gyri. CONCLUSION: The data suggest that there is significant degeneration of the frontal and temporal lobes in MSA, the lower laminae being affected more significantly than the upper laminae. Cortical degeneration in MSA is likely to be secondary to pathological changes occurring within subcortical areas.

Multiple system atrophy (MSA): Topographic distribution of the alpha-synuclein-associated pathological changes

To study the topographic distribution of the pathology in multiple system atrophy (MSA). Pattern analysis was carried out using a-synuclein immunohistochemistry in 10 MSA cases. The glial cytoplasmic inclusions (GCI) were distributed randomly or in large clusters. The neuronal inclusions (NI) and abnormal neurons were distributed in regular clusters. Clusters of the NI and abnormal neurons were spatially correlated whereas the GCI were not spatially correlated with either the NI or the abnormal neurons. The data suggest that the GCI represent the primary change in MSA and the neuronal pathology develops secondary to the glial pathology.

A simple, sensitive and selective quantum-dot-based western blot method for the simultaneous detection of multiple targets from cell lysates

Quantum dots (Qdots) are fluorescent nanoparticles that have great potential as detection agents in biological applications. Their optical properties, including photostability and narrow, symmetrical emission bands with large Stokes shifts, and the potential for multiplexing of many different colours, give them significant advantages over traditionally used fluorescent dyes. Here, we report the straightforward generation of stable, covalent quantum dot-protein A/G bioconjugates that will be able to bind to almost any IgG antibody, and therefore can be used in many applications. An additional advantage is that the requirement for a secondary antibody is removed, simplifying experimental design. To demonstrate their use, we show their application in multiplexed western blotting. The sensitivity of Qdot conjugates is found to be superior to fluorescent dyes, and comparable to, or potentially better than, enhanced chemiluminescence. We show a true biological validation using a four-colour multiplexed western blot against a complex cell lysate background, and have significantly improved previously reported non-specific binding of the Qdots to cellular proteins.

Development and validaton of an indicator to compare antibiotic usage in secondary care in England

The use of antibiotics was investigated in twelve acute hospitals in England. Data was collected electronically and by questionnaire for the financial years 2001/2, 2002/3 and 2003/4. Hospitals were selected on the basis of their Medicines Management Self-Assessment Scores (MMAS) and included a cohort of three hospitals with integrated electronic prescribing systems. The total sample size was 6.65% of English NHS activity for 2001/2 based on Finished Consultant Episode (FCE) numbers. Data collected included all antibiotics dispensed (ATC category J01), hospital activity FCE's and beddays, Medicines Management Self-assessment scores, Antibiotic Medicines Management scores (AMS), Primary Care Trust (PCT) of origin of referral populations, PCT antibiotic prescribing rates, Index of Multiple Deprivation for each PCT. The DDD/FCE (Defined Daily Dose/FCE) was found to correlate with the DDD 100beddays (r = 0.74 psecondary care antibiotic prescribing rates for the same referral population or between the weighted mean IMD 2000 for each hospital's referral population and the hospital antibiotic prescribing rate.