Upregulation of osteopontin and alpha B crystallin in the normal-appearing white matter of multiple sclerosis: an immunohistochemical study utilizing tissue microarrays

Tissue microarrays assembled from control and multiple sclerosis (MS) brain tissue have been used to assess the expression patterns and cellular distribution of two antigens, the proinflammatory cytokine osteopontin and the inducible heat shock protein alpha B -crystallin, which have previously been implicated in MS pathogenesis. Tissue cores were taken from paraffin-embedded donor blocks containing chronic active or chronic inactive plaques and normal-appearing white matter (NAWM) in seven MS cases, and white matter (WM) in five control cases. Expression patterns of both proteins were assessed against myelin density and microglial activation in the different tissue categories. Both proteins showed increased expression in all categories of MS tissue compared with control WM. The results indicate progressive up-regulation of expression of osteopontin with increased plaque activity, while elevation of alpha B-crystallin expression in MS tissue was independent of demyelination. In MS NAWM a significant correlation was observed between high levels of expression of osteopontin and alpha B -crystallin. Osteopontin expression was predominantly confined to astrocytes throughout MS tissues. alpha B -crystallin was expressed on astrocytes, oligodendrocytes and occasionally on demyelinated axons. Taken together, these data indicate a wider distribution of osteopontin and alpha B -crystallin in MS tissues than previously described and support their proposed role in MS pathogenesis.

Exploiting a priori time constant ratio information in difference equation two-thermocouple sensor characterisation

The characterization of thermocouple sensors for temperature measurement in varying-flow environments is a challenging problem. Recently, the authors introduced novel difference-equation-based algorithms that allow in situ characterization of temperature measurement probes consisting of two-thermocouple sensors with differing time constants. In particular, a linear least squares (LS) lambda formulation of the characterization problem, which yields unbiased estimates when identified using generalized total LS, was introduced. These algorithms assume that time constants do not change during operation and are, therefore, appropriate for temperature measurement in homogenous constant-velocity liquid or gas flows. This paper develops an alternative ß-formulation of the characterization problem that has the major advantage of allowing exploitation of a priori knowledge of the ratio of the sensor time constants, thereby facilitating the implementation of computationally efficient algorithms that are less sensitive to measurement noise. A number of variants of the ß-formulation are developed, and appropriate unbiased estimators are identified. Monte Carlo simulation results are used to support the analysis.

Family-based investigation of the C677T polymorphism of the methylenetetrahydrofolate reductase gene in ischaemic heart disease

Background: Elevated homocysteine is associated with ischaemic heart disease (IHD). The C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene results in reduced MTHFR enzyme activity and reduced methylation of homocysteine to methionine resulting in mild hyperhomocysteinaemia. Case-control association studies of the role of the C677T MTHFR polymorphism in IHD have produced conflicting results. We therefore used newly described family-based association tests to investigate the role of this polymorphism in IHD, in a well-defined population. Methods: A total of 352 individuals from 129 families (discordant sibships and parent-child trios) were recruited. Linkage disequilibrium between the polymorphism and IHD was tested for using the combined transmission disequilibrium test (TDT)/sib-TDT and pedigree disequilibrium test (PDT). Homocysteine levels were measured. Results: Both the TDT/sib-TDT and PDT analyses found a significantly reduced transmission of the T allele to affected individuals (P=0.016 and P=0.021). There was no significant difference in homocysteine levels between affected and unaffected siblings. TT homozygotes had mean homocysteine levels significantly higher than those of TC heterozygotes (P

The impact of curricular change on medical students' knowledge of anatomy

Background: In recent years, following the publication of Tomorrow's Doctors, the undergraduate medical curriculum in most UK medical schools has undergone major revision. This has resulted in a significant reduction in the time allocated to the teaching of the basic medical sciences, including anatomy. However, it is not clear what impact these changes have had on medical students' knowledge of surface anatomy. Aim: This study aimed to assess the impact of these curricular changes on medical students' knowledge of surface anatomy. Setting: Medical student intakes for 1995-98 at the Queen's University of Belfast, UK. Methods: The students were invited to complete a simple examination paper testing their knowledge of surface anatomy. Results from the student intake of 1995, which undertook a traditional, 'old' curriculum, were compared with those from the student intakes of 1996-98, which undertook a new, 'systems-based' curriculum. To enhance linear response and enable the use of linear models for analysis, all data were adjusted using probit transformations of the proportion (percentage) of correct answers for each item and each year group. Results: The student intake of 1995 (old curriculum) were more likely to score higher than the students who undertook the new, systems-based curriculum. Conclusion: The introduction of the new, systems-based course has had a negative impact on medical students' knowledge of surface anatomy.