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  • 1
    Keywords: proliferation ; SYSTEM ; DISEASE ; PROTEIN ; MICE ; PATIENT ; MARKER ; ANTIGEN ; ANTIGENS ; T cell ; T cells ; T-CELL ; T-CELLS ; culture ; antibodies ; antibody ; MOUSE ; NERVOUS-SYSTEM ; LESIONS ; NUMBER ; COMPONENT ; DAMAGE ; cytoskeleton ; NETHERLANDS ; CD8(+) ; CENTRAL-NERVOUS-SYSTEM ; pathology ; AMYOTROPHIC-LATERAL-SCLEROSIS ; MULTIPLE-SCLEROSIS ; INTERFERON-GAMMA ; inflammation ; CD4(+) T-CELLS ; AUTOIMMUNE ENCEPHALOMYELITIS ; SERUM ; AUTOIMMUNITY ; IMMUNIZATION ; CYTOKINE ; RECOMBINANT ; RE ; SERUM ANTIBODIES ; LEVEL ; multiple sclerosis ; USA ; animal model ; central nervous system ; DEGENERATION ; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS ; correlates ; SENSORY NEURONOPATHY ; axonal damage ; MS LESIONS ; neurofilament light ; PROGRESSIVE MULTIPLE-SCLEROSIS ; spastic paresis
    Abstract: Axonal damage is the major cause of irreversible neurologic disability in patients with multiple sclerosis. Although axonal damage correlates with antibodies against neurotilament light (NF-L) protein, a major component of the axonal cytoskeleton, the possible pathogenic role of autoirnmunity to axonal antigens such as NF-L has so far been ignored. Here we show that Biozzi ABH mice immunized with NF-L protein develop neurologic disease characterized by spastic paresis and paralysis concomitant with axonal degeneration and inflammation primarily in the dorsal column of the spinal cord. The inflammatory central nervous system lesions were dominated by F4/80' macrophages/microglia and relatively low numbers of CD4(+) and CD8(+) T-cells. In splenocyte cultures, proliferation to NF-L was observed in CD4(+) T-cells accompanied by the production of the proinflammatory cytokine interferon-gamma. Elevated levels of circulating antibodies recognizing recombinant mouse NF-L were present in the serum, and immunoglobulin deposits were observed within axons in spinal cord lesions of mice exhibiting clinical disease. These data provide evidence that autoimmunity to NF-L protein induces axonal degeneration and clinical neurologic disease in mice, indicating that autoimmunity to axonal antigens, as described in multiple sclerosis, may be pathogenic rather than acting merely as a surrogate marker for axonal degeneration
    Type of Publication: Journal article published
    PubMed ID: 17413320
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  • 2
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Although there are clear parallels between apoptosis and epidermal terminal differentiation it is unclear whether terminal differentiation of keratinocytes is a form of apoptosis. We found that apoptosis was rare in adherent cultures of normal keratinocytes, even when growth factors were removed. When keratinocytes were placed in suspension for 24-96 h the majority of cells were induced to undergo terminal differentiation, as assessed by involucrin expression and cornified envelope assembly, but few cells underwent apoptosis, as assessed by morphological examination, TUNEL labelling and by DNA laddering. Withdrawal of serum and growth factors stimulated apoptosis of suspended keratinocytes but led to some reduction in the number of cells that underwent terminal differentiation. At 96 h the majority of cells retained their nuclei in the presence or absence of serum and growth factors. In normal epidermis only occasional cells within the granular layer had apoptotic nuclei, determined by TUNEL labelling and light and electron microscopy. In affected epidermis of psoriasis, Darier's disease and pityriasis rubra pilaris, diseases characterized by perturbation of growth, differentiation or adhesion, light microscopy revealed no higher proportion of apoptotic nuclei than in normal epidermis. However, the majority of viable epidermal layers in diseased skin were positive by TUNEL labelling, suggesting that TUNEL is not always a specific marker of apoptosis in keratinocytes. We conclude that in vivo and in culture keratinocyte terminal differentiation and apoptosis are distinct cellular events, subject to different stimuli.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 0897-3806
    Keywords: nerve regeneration ; muscle grafts ; peripheral nerve ; distal factors ; basement membrane ; Life and Medical Sciences ; Miscellaneous Medical
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Nerve fiber regeneration into sciatic nerve branches was investigated in rats after repairing a 1 cm gap with freeze-thawed autogenous muscle grafts in two configurations. “Prejunctional” grafts were introduced in the main trunk proximal to branching, while Y-shaped “junctional” grafts replaced and reconstructed the site of division of the sciatic nerve into its tibial and peroneal branches. In addition to assessing functional and electrophysiological recovery, myelinated fibers in whole nerve cross sections were counted (i) in the sciatic nerve proximal to the site of transection, (ii) within the grafts themselves proximal to branching, and (iii) in individual tibial, peroneal, and sural branches.Fibers regenerated into all three branches but eventual relative and absolute fiber counts differed between the two graft types, and these in turn from values in these nerves in unoperated controls. Thus, any specific influences directing appropriate fibers into particular branches that might exist did not exert a marked effect on regeneration in vivo. Differences in fiber counts at successively more distal cross-sectional levels were described in terms of elongation, branching, or regression of regenerating fibers. In either graft type, fiber branching coincided with close anatomical relationship with more than one distal stump, and was particularly marked 150-300 days after graft implantation with junctional grafts. However, subsequent penetration of such fibers into the three major branches was more effective if the anatomy of the original branch site was preserved, by using prejunctional grafts. The implications of these findings to clinical nerve repair involving large nerve territories is discussed.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 0897-3806
    Keywords: minifascicles ; perineurium ; compartmentation in muscle grafts ; Life and Medical Sciences ; Miscellaneous Medical
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: This paper describes the morphological appearances of long-term nerve repair using freeze-thawed, coaxially aligned autogenous skeletal muscle grafts in rats. The presence of minifascicles (compartmentation) within the muscle grafts confirms earlier reports of compartmentation whenever nerve regeneration occurs in a nonnerural environment. However, in contrast to the reports in the literature, there was no evidence of a loss of compartmentation at long intervals after nerve repair. It was found that a number of minifascicles became enclosed by a further proliferation of perineural cell to form distinct minifascicular groups. The term “midfascicle” is used to describe these larger perineural defined groups of minifascicles. The role of the perineurium is discussed.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1573-7381
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Nerve regeneration through grafts of basement membrane matrix, prepared by freezing of autogenous muscle followed by thawing in distilled water, was investigated in Sprague-Dawley rats. Electrophysiological evidence of recovery in distal nerve was observed at 51 days after implantation of treated grafts whose basement membrane tubes were coaxial with the proximal and distal ends of the transected sciatic nerve. This correlated with histological findings of well-developed myelinated nerve fibres within both grafts and distal nerve. However, whereas normal axon numbers were achieved in the grafts by 3 months, the regenerating nerve in these muscle grafts took 6 months to 1 year to recover normal axon diameter and myelination. Recovery was delayed through grafts whose basement membrane tubes were at right angles to the nerve fibres and through grafts of untreated muscle coaxially aligned. It is concluded that successful repopulation of the distal stump and functional recovery can follow nerve regeneration through treated muscle autografts. The rate of regeneration is dependent on the availability of empty basement membrane tubes. If these are unavailable or inappropriately orientated, regeneration can still occur but is significantly delayed.
    Type of Medium: Electronic Resource
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