Reduced oligomeric and vascular amyloid-β following immunization of TgCRND8 mice with an Alzheimer's DNA vaccine

Immunization with amyloid-β (Aβ) peptide reduces amyloid load in animal studies and in humans; however clinical trials resulted in the development of a pro-inflammatory cellular response to Aβ. Apoptosis has been employed to stimulate humoral and Th2-biased cellular immune responses. Thus, we sought to investigate whether immunization using a DNA vaccine encoding Aβ in conjunction with an attenuated caspase generates therapeutically effective antibodies. Plasmids encoding Aβ and an attenuated caspase were less effective in reducing amyloid pathology than those encoding Aβ alone. Moreover, use of Aβ with an Arctic mutation (E22G) as an immunogen was less effective than wild-type Aβ in terms of improvements in pathology. Low levels of IgG and IgM were generated in response to immunization with a plasmid encoding wild-type Aβ. These antibodies decreased plaque load by as much as 36 ± 8% and insoluble Aβ42 levels by 56 ± 3%. Clearance of Aβ was most effective when antibodies were directed against N-terminal epitopes of Aβ. Moreover, immunization reduced CAA by as much as 69 ± 12% in TgCRND8 mice. Finally, high-molecular-weight oligomers and Aβ trimers were significantly reduced with immunization. Thus, immunization with a plasmid encoding Aβ alone drives an attenuated immune response that is sufficient to clear amyloid pathology in a mouse model of Alzheimer's disease.     

Image processing in swallowing and speech research

An image processing system for application to studies of the temporal and spatial parameters of movement during swallowing and speech is described. Image sequences from videotape are digitized for computerized manipulation and analysis in an attempt to improve on conventional visual inspection. The system is “interactive” or “event-driven”: after executing a function, the computer waits for guidance from the user who controls the program through keyboard and mouse input, selecting options from menus and responding to prompts. The analyst alters image clarity by the application of filters and heightens contrast through video enhancement. A technique called “remapping” reduces head motion and provides uniform spatial scaling. Animated sequences of images are used, as opposed to frame-by-frame analysis, to preserve temporal context and increase efficiency of measurement. Low cost off-the-shelf personal computer hardware is used along with original software tailored to the application.     

Effects of a Broad-spectrum Behavioral Medicine Treatment Program on Children with Refractory Epileptic Seizures: An 8-Year Follow-Up

We present an 8 year follow-up on a group of children with refractory epileptic seizures who participated in the early 1980s in a controlled group study on the effects of a broad-spectrum behavior modification treatment program on children with refractory epileptic seizures. In the original study, 18 children were divided into three groups: behavior modification group, attention control group, and control group. The purpose was to investigate the effects of a learning-based treatment program superimposed on a regular medical treatment program. Also, the effects of professional attention were evaluated. At the 10 week and 1 year follow-ups, only the group receiving the behavior modification intervention had a significantly reduced rate of seizure index. The present study investigates these same children 8 years later using the same methods of investigation for an additional 10 week period. The results indicate that a significant reduction in seizures was obtained only for the behavior modification group at the 8 year follow-up.     

Efficiency of the ortho VITROS assay for detection of hepatitis C virus-specific antibodies increased by elimination of supplemental testing of samples with very low sample-to-cutoff ratios

The clinical significance of specimens with low sample-to-cutoff (S/Co) ratios in the Ortho VITROS chemiluminescence assay (CIA) for detection of antibodies to hepatitis C virus (HCV) was evaluated. In one study of 482 CIA-reactive samples, none of the 83 samples with S/Co ratios of < 5 was HCV RNA positive. In a subsequent study, 332 samples with S/Co ratios of between 1 and 20 were tested with the recombinant immunoblot assay (RIBA). None of the 163 samples with S/Co ratios of < 5 was RIBA positive, 83% were RIBA negative, and 28 samples (18%) were RIBA indeterminate. HCV RNA and/or clinical evidence of hepatitis was not found in the 27 indeterminate cases examined. These results show that over 99% of samples with very low S/Co ratios (< or = 5) have no evidence of HCV infection. Therefore, we suggest that the HCV antibody testing algorithm for the VITROS assay might be modified to eliminate supplemental testing of samples with very low S/Co ratios.     

Purification of thrombospondin from human platelets

Summary Thrombospondins are a rapidly growing family of adhesive proteins that have diverse activities to modulate cellular growth, motility, and gene expression. Thrombospondin-1 (TSP) was the first identified member of this family and is the major form of thrombospondin in human platelets. A method is described to prepare TSP from human platelets in biologically active form with minimal degradation or contamination with other platelet proteins.