Human monoclonal antibodies against amyloid-beta from healthy adults

Two anti-amyloid-beta human antibody-producing cell lines were established from amyloid-beta (Abeta)-selected lymphocytes from peripheral blood of healthy adults. ELISA and Western blot analysis showed that the monoclonal antibodies bound with high affinity to the 43 amino acid-long amyloid-beta peptide. The antigen epitope of these antibodies encountered within amino acids 1-16 of the amyloid-beta peptide. The antibodies did not bind to several immunoglobulin light chain amyloids (AL) and amylin. One of the monoclonals was tested by immunohistochemistry for the binding to frozen sections of brains derived from patients with Alzheimer's disease. It specifically and intensively stained diffuse and core amyloid-beta plaques; whereas, sections from normal brains were not stained. Concomitant staining with a commercial mouse anti-amyloid-beta monoclonal antibody co-localized with that of the human antibody. Simultaneous staining with the human antibody and Congo red implied that the antibody binds primarily to an early immature form of beta-amyloid. Human monoclonal antibodies, which resemble physiologically normal non-pathogenic and possibly protective antibodies in healthy adults, might be attractive candidates for immune therapy of Alzheimer's disease.     

Microwave Spectroscopy of Myocardial Ischemia and Infarction. 2. Biophysical Reconstruction

The proposed dielectrical relaxation model of the myocardium in the microwave spectrum has been verified both on test solutions and on normal canine myocardium. Furthermore, the model was utilized to reconstruct the changes in tissue properties (including myocardial bulk resistance and water content) following myocardial acute ischemia and chronic infarction. It was shown that the reconstructed myocardial resistance and water content correlate dynamically with the process of the development of acute myocardial ischemic injury. In chronic cases the reconstructed resistance and water content of infarcted myocardium are significantly different from that of normal myocardium: the resistance is lower and water content is higher than in normal myocardium. © 2000 Biomedical Engineering Society. PAC00: 8764-t, 8719Xx     

Adjuvant-dependent modulation of Th1 and Th2 responses to immunization with beta-amyloid

The role of adjuvant on the T(h)1 and T(h)2 immune responses to Abeta-immunotherapy (Abeta(42 )peptide) was examined in wild-type mice. Fine epitope analysis with overlapping oligomers of the Abeta(42) sequence identified the 1-15 region as a dominant B cell epitope. The 6-20 peptide was recognized only weakly by antisera from mice administrated with Abeta(42) peptide formulated in complete Freund's adjuvant (CFA), alum or TiterMax Gold (TMG). However, mice immunized with Abeta(42) mixed with QS21 induced a significant antibody response to the 6-20 peptide. The only T cell epitope found was within the 6-28 sequence of Abeta(42). QS21 and CFA induced the strongest humoral response to Abeta, alum was intermediate, and TMG the weakest adjuvant. Analysis of antibody isotypes specific for Abeta indicates that alum induces primarily T(h)2-type immune response, whereas TMG, CFA and QS21 shift the immune responses toward a T(h)1 phenotype. Stimulation of splenocytes from Abeta-immunized mice with Abeta(40) peptide induced strikingly different cytokine expression profiles. QS21 and CFA induced significant IFN-gamma, IL-4 and tumor necrosis factor-alpha expression, whereas alum induced primarily IL-4 production. As T(h)1-type immune responses have been implicated in many autoimmune disorders, whereas T(h)2-type responses have been shown to inhibit autoimmune disease, the choice of adjuvant may be critical for the design of a safe and effective immunotherapy for Alzheimer's disease.     

Solving the Faddeev-Merkuriev Equations in Total Orbital Momentum Representation via Spline Collocation and Tensor Product Preconditioning

The computational approach for solving the Faddeev-Merkuriev equations in total orbital momentum representation is presented. These equations describe a system of three quantum charged particles and are widely used in bound state and scattering calculations. The approach is based on the spline collocation method and exploits intensively the tensor product form of discretized operators and preconditioner, which leads to a drastic economy in both computer resources and time.     

Prevalence,risk factors and preventive strategies in work‐related musculoskeletal disorders among Israeli physical therapists

Background and Purpose . Although physical therapists (PTs) have extensive knowledge of body mechanisms and injury prevention, work‐related musculoskeletal disorders (WRMD) are quite common in this population. The purposes of this study were: to determine the prevalence and impact of WRMD among Israeli PTs; to investigate WRMD risk factors and to identify preventive strategies used by PTs; and to compare the risk of injuries in two professional settings: rehabilitation centres (RCs) and outpatient clinics (OPCs). Method . A validated, modified Cromie questionnaire, translated into Hebrew, was distributed to the PTs at their workplaces. The relationship between WRMD symptoms and professional settings was analysed by Pearson chi‐square. The risk models were developed by logistic regression. One hundred and twelve PTs working in OPCs and RCs who defined themselves as healthy individuals were the subjects of this study. Results . Lifetime prevalence of WRMD was 83%. The highest prevalence of WRMD was in the lower back area (80%). Rehabilitation treatment was associated with an increased risk of lower back (odds ratio [OR] = 1.05) and shoulder symptoms (OR = 1.04); manual treatment was associated with an increased risk of wrist/thumb symptoms (OR = 1.11). Discussion . Work in RCs was associated with an increased prevalence of lower back/shoulder symptoms, whereas work in OPCs was associated with an increased prevalence of thumb/wrist symptoms. PT's used different strategies to reduce risk of WRMD, including altering practice technique. The respondents recommended administrative and ergonomic changes in the workplace. Conclusion . Workplace‐specific interventions to reduce WRMD in PTs should be developed and tested in future studies. Copyright © 2009 John Wiley & Sons, Ltd.