ABSTRACT
Gene therapy is an attractive method for the treatment of cardiovascular disease. However, using current strategies, induction of gene expression at therapeutic levels is often inefficient. In this study, we show a novel electroporation (EP) method to enhance the delivery of a plasmid expressing an angiogenic growth factor (vascular endothelial growth factor, VEGF), which is a molecule previously documented to stimulate revascularization in coronary artery disease. DNA expression plasmids were delivered in vivo to the porcine heart with or without coadministered EP to determine the potential effect of electrically mediated delivery. The results showed that plasmid delivery through EP significantly increased cardiac expression of VEGF compared with injection of plasmid alone. This is the first report showing successful intracardiac delivery, through in vivo EP, of a protein expressing plasmid in a large animal.
Subject(s)
Coronary Artery Disease/therapy , DNA/administration & dosage , Electroporation/methods , Gene Transfer Techniques , Genetic Therapy/methods , Vascular Endothelial Growth Factor A/genetics , Animals , DNA/genetics , Genetic Vectors , Heart , Plasmids/administration & dosage , Plasmids/genetics , Protein Biosynthesis/genetics , Swine , Vascular Endothelial Growth Factor A/biosynthesisABSTRACT
BACKGROUND: The aim of this study was to evaluate the usefulness of colloidal gold probes widely used in histochemistry and electronic microscopy for the serologic diagnosis of syphilis. METHODS: One hundred eighty-nine sera which had been submitted to the traditional fluorescent trigenemic absorption (FTA-ABS) test and had later been tested with the new colloidal gold probe method (IAT-ABS). RESULTS: Out of a total of 103 positive samples by FTA-ABS all were positive when tested by gold immunoprobes (sensitivity 100%). Eighty-six samples which were negative by immunofluorescence were all negative by IAT-ABS (specificity 100%). CONCLUSIONS: The new method of colloidal gold probes with the current microscopy is useful for confirming serologic diagnosis of syphilis.
Subject(s)
Antibodies, Bacterial/blood , Gold Colloid , Syphilis Serodiagnosis/methods , Treponema pallidum/immunology , Adolescent , Adult , Humans , Sensitivity and SpecificityABSTRACT
The immune repertoire is characterized by a complex and dynamic organization. Here I suggest, based on the presence of well-defined immune reactivity patterns (RP) analyzed using a linguistic analogy, that the B cell repertoires could possess a fractal structure. A simple estimation method of the fractal dimension (D) for a given immune B repertoire was developed, and D demonstrated to be an useful tool to define what complexity is regarding the immune repertoire, and to evaluate the complexity level of the immune B repertoire among age-structured groups of mice sensitized with the hemagglutinin (HA) molecule of influenza virus. Also, since a fractal-linguistic point of view, considerations are made about the ontogeny, connectivity, chaotic regimes, and size of the immune repertoire. Fractal analysis indicates that the immune repertoire shows a Zipf-like scaling behavior, a statistical property of natural languages. This result suggests that immune repertoire is structured like a powerful language.
Subject(s)
B-Lymphocytes/immunology , Fractals , Models, Biological , Animals , Antibodies, Viral/biosynthesis , Antibody Diversity , Hemagglutinins, Viral/immunology , Immunization , Mice , Mice, Inbred BALB C , Nonlinear Dynamics , Orthomyxoviridae/immunologyABSTRACT
The Zipf law, an approach to analyzing linguistic texts, was applied to study the Cytotoxic T Lymphocytes (CTL) repertoire, one of the major components of the immune system. A Zipf-scaling behavior was observed in those CTL repertoires obtained in normal or conventional mice. In contrast, CTL repertoires from irradiated chimeric animals, showed a non-scaling statistical behavior when tested by the Zipf analysis, suggesting that normal repertoires work like a structured biological language. The fractal dimension (D) was derived from the Zipf plots, and correlates well with the nature of the repertoires: high, D > 0.8, in conventional mice. Non-fractal, D > 1, in chimeric animals, and low, D < 0.3, in athymic mice. Then, D seems to be an useful tool to characterize the current status of the immune system.