A transgenic mouse model for studying the clearance of blood-borne pathogens via human complement receptor 1 (CR1)

Complement receptor 1 (CR1) on the surface of human erythrocytes facilitates intravascular clearance of complement-opsonized pathogens. The need for complement activation can be circumvented by directly coupling the organism to CR1 using a bispecific monoclonal antibody heteropolymer (HP). Lack of a functional homologue to CR1 on mouse erythrocytes has made it difficult to study HP-dependent clearance of pathogens in small animals. We have developed a transgenic mouse that expresses human CR1 on erythrocytes. CR1 antigen is of appropriate size and in a clustered distribution as confirmed by immunoblotting and fluorescence microscopy, respectively. HP that immobilized bacteriophage ΦX174 prototype pathogen to erythrocyte CR1 of the transgenic mice increased the rate of clearance of the virus compared with HP that bound bacteriophage, but not CR1. This transgenic mouse model will allow evaluation of different HPs for their in vivo efficacy and potential as human therapeutics

Increased deposition of C3b on red cells with low CR1 and CD55 in a malaria-endemic region of western Kenya: Implications for the development of severe anemia

<p>Abstract</p> <p>Background</p> <p>Severe anemia due to <it>Plasmodium falciparum </it>malaria is a major cause of mortality among young children in western Kenya. The factors that lead to the age-specific incidence of this anemia are unknown. Previous studies have shown an age-related expression of red cell complement regulatory proteins, which protect erythrocytes from autologous complement attack and destruction. Our primary objective was to determine whether in a malaria-endemic area red cells with low levels of complement regulatory proteins are at increased risk for complement (C3b) deposition <it>in vivo</it>. Secondarily, we studied the relationship between red cell complement regulatory protein levels and hemoglobin levels.</p> <p>Methods</p> <p>Three hundred and forty-two life-long residents of a malaria-holoendemic region of western Kenya were enrolled in a cross-sectional study and stratified by age. We measured red cell C3b, CR1, CD55, and immune complex binding capacity by flow cytometry. Individuals who were positive for malaria were treated and blood was collected when they were free of parasitemia. Analysis of variance was used to identify independent variables associated with the %C3b-positive red cells and the hemoglobin level.</p> <p>Results</p> <p>Individuals between the ages of 6 and 36 months had the lowest red cell CR1, highest %C3b-positive red cells, and highest parasite density. Malaria prevalence also reached its peak within this age group. Among children ≤ 24 months of age the %C3b-positive red cells was usually higher in individuals who were treated for malaria than in uninfected individuals with similarly low red cell CR1 and CD55. The variables that most strongly influenced the %C3b-positive red cells were age, malaria status, and red cell CD55 level. Although it did not reach statistical significance, red cell CR1 was more important than red cell CD55 among individuals treated for malaria. The variables that most strongly influenced the hemoglobin level were age, the %C3b-positive red cells, red cell CR1, and red cell CD55.</p> <p>Conclusion</p> <p>Increasing malaria prevalence among children >6 to ≤ 36 months of age in western Kenya, together with low red cell CR1 and CD55 levels, results in increased C3b deposition on red cells and low hemoglobin. The strong contribution of age to C3b deposition suggests that there are still additional unidentified age-related factors that increase the susceptibility of red cells to C3b deposition and destruction.</p

Computational Intelligence in Electrophysiology: Trends and Open Problems

“The original publication is available at www.springerlink.com”. Copyright Springer. [Full text of this item is not available in the UHRA]This chapter constitutes mini-proceedings of the Workshop on Physiology Databases and Analysis Software that was a part of the Annual Computational Neuroscience Meeting CNS*2007 that took place in July 2007 in Toronto, Canada (http ://www.cnsorg.org). The main aim of the workshop was to bring together researchers interested in developing and using automated analysis tools and database systems for electrophysiological data. Selected discussed topics, including the review of some current and potential applications of Computational Intelligence (CI) in electrophysiology, database and electrophysiological data exchange platforms, languages, and formats, as well as exemplary analysis problems, are presented in this chapter. The authors hope that the chapter will be useful not only to those already involved in the field of electrophysiology, but also to CI researchers, whose interest will be sparked by its contents