Search

α2-Macroglobulin (A2M) is a proteinase inhibitor found in association with senile plaques (SP) in Alzheimer's disease (AD). A2M has been implicated biochemically in binding and degradation of the amyloid β(Aβ) protein which accumulates in SP. We studied the relationship between Alzheimer's disease and a common A2M polymorphism, Val1000 (GTC)/lle1000 (ATC), which occurs near the thiolester active site of the molecule. In an initial exploratory data set (90 controls and 171 Alzheimer's disease) we noted an increased frequency of the G/G genotype from 0.07 to 0.12. We therefore tested the hypothesis that the G/G genotype is over-represented in Alzheimer's disease in an additional independent data set: a group of 359 controls and 566 Alzheimer's disease patients. In the hypothesis testing cohort, the G/G genotype increased from 0.07 in controls to 0.12 in Alzheimer's disease (P < 0.05, Fisher's exact test). The odds ratio for Alzheimer's disease associated with the G/G genotype was 1.77 (1.16-2.70, P < 0.01) and in combination with APOE4 was 9.68 (95% CI 3.91-24.0, P < 0.001). The presence of the G allele was associated with an increase in Aβ burden in a small series. The A2M receptor, A2M-r/LRP, is a multifunctional receptor whose ligands include apolipoprotein E and the amyloid precursor protein. These four proteins have each been genetically linked to Alzheimer's disease, suggesting that they may participate in a common disease pathway

Alzheimer's disease, frontotemporal dementia, dementia with Lewy bodies, and prion diseases are age-related neurodegenerative disorders associated with a progressive decline of cognitive brain functions. Due to the increase in prevalence rates, and the rising costs associated with clinical and social care, treatments designed to prevent or reverse these diseases are urgently needed. The most common major biochemical characteristic of these neurodegenerative diseases is the deposition of abnormal protein aggregates in brain. The decryption of the mechanisms of aggregation and associated neurotoxicity may reveal new therapeutic targets, which will enable treatment for these devastating conditions.

Einleitung: Die Tyrosinkinaseinhibitoren Dasatinib, Nilotinib, Gefitinib und Erlotinib sind als zielgerichtete Therapeutika für verschiedene Tumorentitäten etabliert. Diese Studie untersucht den Einfluss dieser Inhibitoren auf die EGFR- bzw. VEGFR1/2-Expression in HPV-positiven und -negativen Plattenepithelkarzinomzellen. Methoden: Mittels ELISA wurde die Änderung der Proteinexpression von EGFR und VEGFR1/2 in den HPV-negativen Zelllinien HNSCC 14C und 11A sowie in der HPV-positiven CERV196-Linie nach Inkubation mit Dasatinib, Nilotinib, Gefitinib oder Erlotinib mit einer Konzentration von 5-20 µmol/l bestimmt und mit einer chemonaiven Kontrolle verglichen. Die Inkubationszeiten betrugen 24-96 Stunden. Ergebnisse: Alle getesteten Substanzen bewirkten eine signifikante (p, GMS Current Posters in Otorhinolaryngology - Head and Neck Surgery; 12:Doc104

Aims: To ensure that all Alzheimer centres across Europe are capable of using a similar method of data collection. Information about the patient assessment tools used by each participating centre was obtained and normal clinical practice in each EADC centre was documented by collecting data from routine new patient consultation. Methods: Twenty new consecutive patients with objective memory impairment were recruited in each Alzheimer centre over 6 months. Each patient consultation was carried out according to routine clinical practice. Patient data were recorded using the anonymous patient protocol (demographic, diagnosis, MMSE score, patient assessment scales, and most prominent behavioural problem). Information about neuropsychological assessment tools used in each centre was take to account to harmonise research practice for future multicentre collaboration. Results: Seven hundred and four patients from 36 memory clinics in 13 countries across Europe participated in the study. [M:F ratio 0.67. Mean age 75.4 SD 9.3 (51-102) Mean MMSE 21 SD 6 (0-30)] Five hundred and fifty-five patients had a clinical diagnosis of dementia [Alzheimer's disease (68.5%), vascular dementia (10.3%), frontal lobe dementia (5.6%), Lewy body dementia (4.1%), mixed dementia (5.6%)]. Duration of symptoms: 0-6 months 6.5%; 6-12 months 16.1%; 1-2 years 30.5%; 2-5 years 46.9%. Assessment scales used: Clinical Dementia Rating (CDR) 48.9%, Reisberg's Global Deterioration Scale (GDS) 38.6%, ADL/IADL (Lawton and Brody, 1969) 37.5%, Neuropsychological Inventory (NPI) 28.6%, Geriatric Depression Scale 22%, ADL (Katz et al., 1963) 19.2%, ADAS-Cog 14.9%, Cornell Scale for Depression 12.9%, Grober and Bushke Selective Reminding Test 11.5%, ADCS/ADL 7.7%. 64.8% of the patients experienced behavioural symptoms: apathy 13.6%; anxiety 12.8%; dysphoria 9.9%; irritability 7.8%; agitation 5.5%; hallucinations 3.6%; delusions 3.6%, sleep disorder 2.4%; desinhibition 2%. Conclusions: The most common type of cognitive decline was Alzheimer's disease followed by mild cognitive impairment and vascular dementia. CDR, GDS Reisberg, and ADL/IADL were used widely (40-50%). The NPI, geriatric depression scale and ADL (Katz, 1963) were only used in 20% of the centres. We verified large differences in the tools use in the EADC centres to evaluate patients with dementia across Europe. There is a need for a consensus in the use of assessment tools for dementia in Alzheimer's centres in Europe.

Background. Use of intravenous (IV) immunoglobulin (Ig) to obtain panel reactive antibody (PRA) A reduction in sensitized patients has been widely reported. Because no IVIg preparation is formulated specifically for this purpose, the authors have sought to determine whether, through laboratory testing, they could guide the rational choice of product for clinical use. Methods. Using a flow cytometric approach, the authors have quantitatively determined the capacity of 22 different IVIg preparations to cause PRA reduction. Results. IVIg preparations showed considerable variability in their individual capacity to reduce serum PRA. Protein-A pretreatment of IVIg preparations was found to reduce their capacity to cause PRA reduction. Conclusion. Laboratory screening of IVIg preparations provides a rational basis for the selection of product for administration to patients in whom the aim is to produce a PRA reduction. Experiments involving protein-A treatment of IVIg preparations indicate that immunoglobulin G is the principal factor involved in the abrogation of serum reactivity.

We examine the use of ordinary steel and concrete strain gauges to monitor the dynamic response of reinforced concrete (RC) slabs excited in non-destructive vibrational testing. Plots of measured dynamic strains in the embedded steel reinforcement bars and on the concrete surface, as well as of mid-span deflection, are presented at different levels of load-induced damage. The plots show unique strain and deflection signatures that vary with the internal state of the slab, and could be used for condition monitoring and residual strength identification. It is feasible that the techniques outlined could be used in AI-based evaluation tools for RC slabs and other RC structures.