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  • 1
    ISSN: 1432-0533
    Keywords: Metachromatic leukodystrophy ; Peripheral nerve ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The ultrastructural findings in nerve biopsies from two cases of late onset metachromatic leukodystrophy were compared with those in cases of late infantile and juvenile onset. Hypertrophic changes and regenerating clusters were more evident in the late onset cases, in which macrophages were less frequent, presumably reflecting the chronicity of the disorder in this form. Inclusions within Schwann cells and endoneurial macrophages were similar in all four cases. Myelin figures, in which the periodicity of major dense lines was 8 nm, were present in Schwann cells associated with myelinated axons. The electron lucent zones between the major dense lines were bisected by lines of lesser electron density. These inclusions were probably related to myelin breakdown. All other inclusions displayed a periodicity of 5.8 nm and consisted of zebra bodies, vacuoles containing irregularly orientated lamellar material and stacks of flattened discs. These inclusions represented the metachromatic sulphatide deposits. Occasional inclusion bodies were observed within axons.
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  • 2
    ISSN: 1432-0533
    Keywords: Experimental allergic neuritis ; Suppression ; Bovine dorsal root ; Lewis rat ; Resistance to reinduction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The injection of bovine dorsal root antigen in complete Freund's adjuvant can be used to produce experimental allergic neuritis (EAN) in rats. In this study attempts were made to prevent the development of the disease by prior injections of antigen. It was found that eight intradermal (i.d.) injections of antigen in either incomplete Freund's adjuvant or in saline failed to suppress EAN. A single intraperitoneal (i.p.) injection of antigen in saline produced only minimal protection against the disease. However, it was found that rats which had been given a primary course of EAN were subsequently completely unresponsive to a second injection of antigen.
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  • 3
    ISSN: 1432-0533
    Keywords: Peripheral nerve ; Experimental diabetes ; Intramembranous particles
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Freeze-fracture studies have been made on the sciatic nerve of rats with chronic streptozotocin-induced diabetes mellitus. The density of intramembranous particles was reduced in both the P and E faces of the axolemma of myelinated and unmyelinated axons, in myelin and in the perineurial cells. This may reflect a general reduction in protein synthesis, or excessive protein degradation, related to the diabetic state. The perineurial cells also showed gap junctions which are not normally present in adult rat peripheral nerve. These may represent a reaction to changes in perineurial activity consequent to alterations in the endoneurial tissue fluid.
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  • 4
    ISSN: 1432-0533
    Keywords: Diabetic neuropathy ; Perineurium Basal lamina ; Endoneurial capillaries
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Measurements were made of the thickness of the basal lamina of perineurial cells in the sural nerve in a series of patients with diabetic neuropathy and compared with a group of patients with type I hereditary motor and sensory neuropathy (HMSN) and with organ donor control cases. The thickness was significantly greater in the diabetic patients as compared both with the HMSN cases and the organ donor controls. This was most obvious for the intermediate layers of the perineurium. Perineurial basal laminal thickness was only slightly greater in the HMSN cases than in the organ donor controls and the difference was not statistically significant. The thickening of the perineurial cell basal laminae was compared with the thickening of the basal laminal zone around the endoneurial microvessels. No significant correlation was found either for the diabetic neuropathy or HMSN cases or for the organ donor controls. As had been observed previously, the basal laminal zone around the endoneurial capillaries was of increased thickness both in the diabetic neuropathy and the HMSN cases and, although it was greater for the diabetic neuropathy patients, the difference was not statistically significant. Taken together, these findings indicate that the thickening of the basal lamina of the perineurial cells in a more characteristic feature of diabetic neuropathy than is thickening of the basal laminal zone around the endoneurial capillaries. The results suggest that the causative mechanisms are likely to differ, a conclusion supported by the morphological appearances: the basal laminal thickening around the perineurial cells is uniform, whereas that around the capillaries consists of basal laminal reduplication. Atrophy and necrosis of perineurial cells were observed in patients with diabetic neuropathy but rarely in the cases with HMSN and not in the organ donor cases. This may be similar to the degeneration of endoneurial fibroblasts that has been described as a non-specific finding in neuropathies.
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  • 5
    ISSN: 1432-0533
    Keywords: Diabetic neuropathy ; Axonal regeneration ; Nerve growth factor receptors ; Schwann cells ; Basal lamina
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Observations were made on myelinated fibre regeneration in diabetic sensory polyneuropathy assessed in sural nerve biopsy specimens. These confirmed that regenerative clusters initially develop within abnormally persistent Schwann cell basal laminal tubes. The number of regenerating fibres, identified by light microscopy, was found to decline in proportion to the reduction in total myelinated fibre density. The relative number of regenerating fibres was significantly greater in patients with insulin-dependent as compared with those with non-insulin-dependent diabetes after correction for age. There was a slight negative correlation between the relative proportion of regenerating fibres and age, but this was not statistically significant. The progressive reduction in the number of regenerating fibres with declining total fibre density indicates that axonal regeneration fails with advancing neuropathy. The production of nerve growth factor (NGF) and NGF receptors by denervated Schwann cells is likely to be important for axonal regeneration. To investigate whether the failure of axonal regeneration could be related to a lack of NGF receptor production by Schwann cells, we examined the expression of p75 NGF receptors by Büngner bands immunocytochemically. In comparison with other types of peripheral neuropathy, p75 NGF receptor expression appeared to take place normally. It is concluded that failure of axonal regeneration constitutes an important component in diabetic neuropathy. Its explanation requires further investigation.
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  • 6
    ISSN: 1432-0533
    Keywords: Key words Diabetic polyneuropathy ; Nodes of ; Ranvier ; Paranodes ; Axoglial dysjunction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Observations have been made on the structure of the paranodal region at nodes of Ranvier in the sural nerve of patients with diabetic sensory polyneuropathy. The structure of the paranodes was examined with particular attention to the definition and assessment of axoglial dysjunction, which has been claimed to be a characteristic feature of both human and experimental diabetic neuropathy and which has been related to paranodal swelling. In the present series of cases it was not possible to confirm that axoglial dysjunction is a distinctive feature of diabetic polyneuropathy in fibres not undergoing active demyelination or wallerian-type degeneration, neither was excessive paranodal enlargement found.
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  • 7
    ISSN: 1432-0533
    Keywords: Chronic relapsing experimental allergic neuritis ; Thymectomy ; Splenectomy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Experimental allergic neuritis (EAN) was induced in Lewis rats aged 4 months by the inoculation of whole bovine dorsal root with Freund's complete adjuvant. Prolonged follow-up demonstrated that a relapsing course is a regular feature of the disorder in animals at this age. Although the initial disease episode was the most severe, clinical recovery from subsequent relapses was less satisfactory, this probably being related to persistent morphological abnormalities in the peripheral nervous system. Antecedent thymectomy, splenectomy, or the two combined, had little effect on the clinical course of the disorder, apart from reducing the duration of relapses. This was only statistically significant following combined thymectomy/splenectomy. Histological abnormalities, however, tended to be less severe in the operated as compared with normal control or sham-operated animals with EAN. The animals must have attained an immunocompetent state at the time of thymectomy and/or splenectomy. The capacity to develop EAN presumably resides in the draining lymph nodes and the occurrence of relapses is due to the continuing presence of antigen at the injection sites.
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  • 8
    ISSN: 1432-0533
    Keywords: Painful diabetic neuropathy ; Insulin treatment ; Nerve regeneration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A case of acute painful diabetic neuropathy that followed the establishment of strict glycaemic control using continuous subcutaneous insulin infusion is described. Sural nerve biopsy shortly after the onset of the acute painful syndrome showed no evidence of active nerve fibre degeneration; instead, the appearances were those of a chronic neuropathy with prominent regenerative activity. The suggestion is made that adequate diabetic control promoted regeneration and that the pain may have been related to the ectopic generation of impulses in regenerating axon sprouts.
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  • 9
    ISSN: 1432-0533
    Keywords: Key words Diabetic neuropathy ; Axonal regeneration ; Nerve growth factor receptors ; Schwann cells ; Basal lamina
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Observations were made on myelinated fibre regeneration in diabetic sensory polyneuropathy assessed in sural nerve biopsy specimens. These confirmed that regenerative clusters initially develop within abnormally persistent Schwann cell basal laminal tubes. The number of regenerating fibres, identified by light microscopy, was found to decline in proportion to the reduction in total myelinated fibre density. The relative number of regenerating fibres was significantly greater in patients with insulin-dependent as compared with those with non-insulin-dependent diabetes after correction for age. There was a slight negative correlation between the relative proportion of regenerating fibres and age, but this was not statistically significant. The progressive reduction in the number of regenerating fibres with declining total fibre density indicates that axonal regeneration fails with advancing neuropathy. The production of nerve growth factor (NGF) and NGF receptors by denervated Schwann cells is likely to be important for axonal regeneration. To investigate whether the failure of axonal regeneration could be related to a lack of NGF receptor production by Schwann cells, we examined the expression of p75 NGF receptors by Büngner bands immunocytochemically. In comparison with other types of peripheral neuropathy, p75 NGF receptor expression appeared to take place normally. It is concluded that failure of axonal regeneration constitutes an important component in diabetic neuropathy. Its explanation requires further investigation.
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  • 10
    ISSN: 1432-0533
    Keywords: Key words Diabetic neuropathy ; Collagen ; Extracellular matrix ; Nerve regeneration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The pattern of collagenisation in peripheral nerve in diabetic polyneuropathy was examined in nerve biopsy specimens from patients with diabetic polyneuropathy in comparison with organ donor control nerves and disease controls (other neuropathies). There was increased endoneurial collagenisation both in the diabetic polyneuropathy cases and the disease controls, this predominantly involving types I and III. Type II collagen was not detected in organ donor control nerves or in the diabetic and the disease control nerves. There was a relative increase in type VI collagen in the endoneurium in the diabetic nerves immediately surrounding groups of Schwann cells. This was not a feature in the other neuropathies. The quantity of types IV, V and VI collagen was increased around the endoneurial microvessels in the diabetic patients and, to a lesser extent, in those with hereditary motor and sensory neuropathy (HMSN). Increased deposition of types IV and V collagen was observed in the perineurium in the diabetic nerves, the latter being most evident in the innermost lamellae where the amount of laminin was possibly also increased. The diameter of the general endoneurial collagen fibrils was greater in the diabetic nerves, although this was not more than in a disease control (HMSN). The collagen fibrils that were present within the basal laminal tubes that had surrounded degenerated myelinated fibres in the diabetic nerves, and those within the onion bulbs of the HMSN cases, were of the normal endoneurial calibre. The expression of laminin by Büngner bands in diabetic neuropathy did not differ from that in disease control nerves, nor were any differences detected for fibronectin. Whether the changes observed are important for the impaired regenerative capacity in diabetic neuropathy requires further investigation.
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