ABSTRACT
This paper presents a novel reeducation device for paraplegics that combines hybrid orthoses and closed-loop electrical muscle stimulation. Based on the so called Cyberthosis concept, the WalkTrainer enables an active muscular participation of the subject in the walking reeducation process by the mean of closed-loop muscle stimulation. The WalkTrainer is also equipped with a leg and pelvic orthosis, an active bodyweight support, and motorized wheels to allow true over ground deambulation. This paper will focus on the development of the WalkTrainer, the presentation of the control strategies, and also give some preliminary results of the first clinical trials.
Subject(s)
Electric Stimulation , Muscle, Skeletal/physiology , Orthotic Devices , Rehabilitation/instrumentation , Walking/physiology , Algorithms , Biomechanical Phenomena , Equipment Design , Humans , Leg/physiology , Models, Statistical , Motion , Muscle, Skeletal/innervation , Paraplegia/rehabilitation , Pelvis/physiologyABSTRACT
We earlier proposed that a human endogenous retroviral (HERV) superantigen (SAg) IDDMK(1,2)22 may cause type I diabetes by activating autoreactive T cells. Viral infections and induction of interferon-alpha (IFN-alpha) are tightly associated with the onset of autoimmunity. Here we establish a link between viral infections and IFN-alpha-regulated SAg expression of the polymorphic and defective HERV-K18 provirus. HERV-K18 has three alleles, IDDMK(1,2)22 and two full-length envelope genes, that all encode SAgs. Expression of HERV-K18 SAgs is inducible by IFN-alpha and this is sufficient to stimulate V beta 7 T cells to levels comparable to transfectants constitutively expressing HERV-K18 SAgs. Endogenous SAgs induced via IFN-alpha by viral infections is a novel mechanism through which environmental factors may cause disease in genetically susceptible individuals.
Subject(s)
Autoimmunity , Diabetes Mellitus, Type 1/virology , Endogenous Retroviruses/immunology , Interferon-alpha/pharmacology , Models, Immunological , Superantigens/genetics , Antigens, CD/biosynthesis , Antigens, CD/genetics , CD4-Positive T-Lymphocytes/immunology , CD48 Antigen , Cells, Cultured , Endogenous Retroviruses/genetics , Endogenous Retroviruses/metabolism , Environment , Gene Products, env/genetics , Gene Products, env/immunology , Humans , Leukocytes/virology , Lymphocyte Activation , Membrane Proteins , Proviruses/genetics , Proviruses/immunology , Proviruses/metabolism , RNA, Viral/biosynthesis , Superantigens/biosynthesis , Superantigens/immunology , Transfection , Virus Diseases/complicationsABSTRACT
Human papillomavirus type 18 (HPV18) capsid proteins L1 and L2, synthesised in mammalian cells using recombinant vaccinia viral expression vectors, are transported to the nucleus and assembled into virus-like particles. When 293T cells, which express SV40 T antigen, were transfected with plasmid DNAs containing an SV40 origin of replication then infected with vaccinia viral vectors encoding L1 and L2, plasmid DNA was encapsidated into the particles. The DNAs ranged in size from 5.4 to 7.9 kb. By encapsidating plasmids containing either the beta-galactosidase gene or the puromycin-resistance gene, the pseudovirions were shown to be infectious in that they could transfer beta-galactosidase activity or confer resistance to puromycin to a number of cell types, indicating that the uptake and decapsidation of HPV particles are not the main determinants of cell type specificity of HPV. Episomal HPV16 DNA in a cervical keratinocyte line could also be encapsidated. Further investigation showed that DNA encapsidation is independent of HPV DNA sequences and of T antigen-mediated plasmid DNA replication. Instead, the minor capsid protein, L2, was found to be attached to plasmid mini-chromosomes extracted from these cells, suggesting a role for L2 in encapsidation. Consistent with this, the L1 protein alone was unable to encapsidate DNA, although it was able to form virus-like particles. The results suggest that intracellular episomal DNAs of suitable size can be encapsidated by the HPV18 L1 and L2 proteins without the need of any HPV packaging signal, and reintroduced into cells.
