ABSTRACT
Five polyurethane vascular grafts with three different chemistries were investigated in terms of device function, healing characteristics and material stability in a canine abdominal aorta model for prescheduled periods of 1 and 6 months. Corvita-reinforced grafts, with walls made of poly(carbonate urethane) (PCU) filaments, displayed a relatively thin, uniform and partially endothelialized inner capsule with good tissue in-growth. The external polyester mesh separated from the underlying PCU wall due to the degradation of the melt adhesive between these two layers. Three types of Thoratec access graft exhibited a high degree of thrombus and little tissue in-growth, and were non-adhesive to both the inner and external capsules as the solid layer beneath their lumens completely blocked any transmural communication. The microporous poly(ether urethane urea) degraded extensively. Pulse-Tec grafts at one month also demonstrated non-adhesive properties because the external skin served as a barrier to tissue in-growth. At 6 months, its poly(ether urethane) wall displayed the most severe degradation, damaging graft structural integrity and causing significant tissue deposition in the degradation areas. This study shows the importance of multiple factors in vascular prosthesis design and demonstrates that collective and comprehensive thinking will be key in the future development of creative and novel approaches.
Subject(s)
Blood Vessel Prosthesis , Polyurethanes/chemistry , Prosthesis Design , Angiography , Animals , Aorta, Abdominal/cytology , Aorta, Abdominal/diagnostic imaging , Aorta, Abdominal/physiology , Aorta, Abdominal/surgery , Calorimetry, Differential Scanning , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/metabolism , Coated Materials, Biocompatible/pharmacology , Coated Materials, Biocompatible/toxicity , Dogs , Female , Follow-Up Studies , Hematologic Tests , Mechanical Phenomena , Microscopy, Electron, Scanning , Models, Animal , Polyesters/chemistry , Polyurethanes/metabolism , Polyurethanes/pharmacology , Polyurethanes/toxicity , Porosity , Spectroscopy, Fourier Transform Infrared , Time Factors , Tissue and Organ HarvestingABSTRACT
Dendritic cells (DC) efficiently cross-present exogenous antigen on MHC class I molecules to CD8+ T cells. However, little is known about cross-presentation by Langerhans cells (LC), the DCs of the epidermis. Therefore, we investigated this issue in detail. Isolated murine LCs were able to cross-present soluble ovalbumin protein on MHC-class I molecules to antigen-specific CD8+ T cells, albeit less potently than the CD8+ DC subsets from spleen. Furthermore, LCs cross-presented cell-associated ovalbumin peptide and protein expressed by neighboring keratinocytes. Use of transporter associated with antigen processing (TAP-1)-deficient mice suggested a TAP-dependent pathway. Similar observations were made with migratory LC. Antigen expressed in the epidermis was ingested by LCs during migration from the epidermis and presented to antigen-specific T cells in vitro. Cross-presentation of ovalbumin protein by LCs induced IFN-gamma production and cytotoxicity in antigen-specific CD8+ T cells. Additionally, epicutaneous application of ovalbumin protein induced in vivo proliferation of OT-I T cells in the draining lymph nodes; this was markedly enhanced when antigen was applied to inflamed, barrier-disrupted skin. Thus, LCs cross-present exogenous antigen to CD8+ T cells and induce effector functions, like cytokine production and cytotoxicity, and may thereby critically contribute in epicutaneous vaccination approaches.
Subject(s)
Antigen Presentation , Antigens/immunology , Langerhans Cells/immunology , Skin/immunology , Animals , CD8-Positive T-Lymphocytes/immunology , Cells, Cultured , Cytokines/immunology , Cytotoxicity, Immunologic , Genes, MHC Class I , Langerhans Cells/cytology , Mice , Mice, Inbred Strains , Ovalbumin/metabolismABSTRACT
In this paper we present a web-based system for the semantic integration of biological data using a database model and an XML exchange format. The prototype developed integrates data related to enzymes.
Subject(s)
Databases, Factual , Internet , Models, Biological , Programming Languages , Software , Information Storage and Retrieval , User-Computer InterfaceABSTRACT
We have investigated the functional consequences of three P/Q-type Ca(2+) channel alpha1A (Ca(v)2.1alpha(1)) subunit mutations associated with different forms of ataxia (episodic ataxia type 2 (EA-2), R1279Stop, AY1593/1594D; progressive ataxia (PA), G293R). Mutations were introduced into human alpha1A cDNA and heterologously expressed in Xenopus oocytes or tsA-201 cells (with alpha(2)delta and beta1a) for electrophysiological and biochemical analysis. G293R reduced current density in both expression systems without changing single channel conductance. R1279Stop and AY1593/1594D protein were expressed in tsA-201 cells but failed to yield inward barium currents (I(Ba)). However, AY1593/1594D mediated I(Ba) when expressed in oocytes. G293R and AY1593/1594D shifted the current-voltage relationship to more positive potentials and enhanced inactivation during depolarizing pulses (3 s) and pulse trains (100 ms, 1 Hz). Mutation AY1593/1594D also slowed recovery from inactivation. Single channel recordings revealed a change in fast channel gating for G293R evident as a decrease in the mean open time. Our data support the hypothesis that a pronounced loss of P/Q-type Ca(2+) channel function underlies the pathophysiology of EA-2 and PA. In contrast to other EA-2 mutations, AY1593/1594D and G293R form at least partially functional channels.
