ABSTRACT
INTRODUCTION: Microinfarcts, small ischaemic foci common in ageing brain, are associated with dementia and gait dysfunction. We determined their relationship with dementia, mobility and cerebrovascular disease in an older population-representative brain donor cohort. These data on microinfarcts were evaluated in relation to pathological assessments of clinically significant cerebral small vessel disease (SVD). METHODS: Microinfarcts were assessed in the MRC Cognitive Function and Ageing Study (n = 331). Nine brain areas were staged according to the number of areas affected. RESULTS: 36% of brains showed at least 1 microinfarct. Higher cortical microinfarct stage was associated with dementia at death (OR 1.41, 95% CI 1.02; 1.96, P = 0.038), whilst cortical and subcortical microinfarct stages were associated with impaired mobility (OR 1.36, 95% CI 1.05-1.74; P 0.018) and falls (OR 1.96, 95% CI 1.11-3.43; P = 0.02). Adding data on microinfarcts to a definition of SVD, based on white matter lesions (WMLs), lacunes and significant arteriosclerosis, were assessed by comparing area under ROC curve (AUC) with and without microinfarcts. SVD was significantly related to dementia status with or without inclusion of microinfarcts. Modelling potential pathological definitions of SVD to predict dementia or impaired mobility indicated optimal prediction using combined assessment of WMLs, lacunes and microinfarcts. CONCLUSION: Cortical (dementia) and subcortical microinfarcts (impaired mobility) are related to diverse clinical outcomes. Optimal pathological assessment of significant SVD in brain ageing is achieved based on WMLs, lacunes and microinfarcts and may not require subjective assessment of the extent and severity of arteriosclerosis.
Subject(s)
Brain Infarction/epidemiology , Brain/pathology , Cerebral Small Vessel Diseases/pathology , Aged , Aged, 80 and over , Autopsy , Cohort Studies , Dementia/epidemiology , Dementia/pathology , Female , Humans , Male , Mobility Limitation , PrevalenceABSTRACT
Lafora disease is characterized by pathognomonic inclusions, Lafora bodies (LB), in neurons and other cell types. In skin, LB have been reported in either eccrine sweat glands or in apocrine sweat glands. The disease is caused by mutations in either the EPM2A gene or in a second yet-unknown gene. Here the authors determine whether a genotype-phenotype correlation exists between the genetic form of the disease and the skin cell type affected by LB formation. Also is described an important source of false positivity in the use of axillary biopsies for disease diagnosis.
Subject(s)
Lafora Disease/diagnosis , Skin/pathology , Adolescent , Child , False Positive Reactions , Female , Genotype , Humans , Lafora Disease/genetics , Lafora Disease/pathology , Pedigree , Phenotype , Protein Tyrosine Phosphatases/genetics , Protein Tyrosine Phosphatases, Non-Receptor , Skin/cytologyABSTRACT
OBJECTIVE: To assess normal-appearing white matter (NAWM) characteristics by magnetic resonance spectroscopy (MRS) and diffusion-weighted imaging (DWI) in elderly subjects. METHODS: The authors studied 60 volunteers (mean age 72.6 years; SD 4.7; range 64 to 84 years) without signs of neurologic illness. They used DWI and spectroscopic imaging to investigate whether there were changes in the NAWM that related to the presence of white matter hyperintensities (WMH). RESULTS: The authors found a correlation (p < 0.001) between the apparent diffusion coefficient in the NAWM and the total volume of WMH. The metabolite ratios N-acetylaspartate/creatine and N-acetylaspartate/choline of the NAWM also correlated significantly with total WMH volume. These correlations were independent of age. CONCLUSIONS: Damage associated with WMH is detectable in NAWM.
Subject(s)
Aspartic Acid/analogs & derivatives , Brain Diseases/diagnosis , Brain Diseases/metabolism , Brain/metabolism , Diffusion Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Aged , Aged, 80 and over , Aspartic Acid/metabolism , Brain/pathology , Choline/metabolism , Creatine/metabolism , Cross-Sectional Studies , Diffusion , Female , Humans , Image Processing, Computer-Assisted , Male , Middle Aged , Reference Values , Water/metabolismABSTRACT
The success of synthetic polymers as biomaterials depends upon their interfacial properties and resultant interactions with cells and biological fluids in vivo. A useful experimental approach to defining requirements for biocompatibility is to study the mechanisms by which synthetic substrata influence eukaryote cell behaviour in culture. Here we present an overview of the relationships between physical and chemical substratum properties and cell behaviour on a range of synthetic polymers. We relate our results to theories of in vivo tissue compatibility.
Subject(s)
Biocompatible Materials , Polymers , Animals , Cell Adhesion , Cells, Cultured , Cricetinae , Humans , Rats , Surface PropertiesABSTRACT
We have investigated the topography of polyHEMA coated culture substrates by scanning electron microscopy, and quantitatively assessed their effect upon the spreading activity of mammalian cells. Results indicate a clear correlation between cell spreading activity and polymer film discontinuity. Preparation of polyHEMA films on modified tissue culture substrates has allowed direct investigation of the role of the underlying substrate in regulating cell spreading, and confirms that apparent modulation of cell spreading by polyHEMA reflects increasing expression of the coated surface. We have further employed a spinning technique by which films of precise thickness, down to 0.01 micron, may be produced on coverslips. All polyHEMA coatings prepared in this way are smooth and complete. They do not allow cell attachment at any thickness. We conclude that polyHEMA is non-adhesive for mammalian cells.
