Remyelination and recovery of conduction in cat optic nerve after demyelination by pressure.

Pressure has been applied to the optic nerve of cats sufficient to block conduction in the large (Y) nerve fibers. The pressure block produces a mixture of axotomy and demyelination. By means of implanted electrodes, recovery of conduction in these fibers was monitored. There is a short-term recovery starting about 2 weeks after block induction and finishing at about 4 weeks. A later recovery starts at about 6-7 weeks and finishes at about 10-11 weeks. The remyelination has been monitored in the electron microscope by measurement of the myelin thickness and axon diameter of the large fibers. The remyelination follows a time course similar to the late phase of conduction recovery. By reference to the work of others, we surmise that the early recovery of conduction is due to the reorganization of microtubules disorganized by the pressure.

Astrovirus and adenovirus associated with diarrhea in children in day care settings.

The relative importance of astrovirus and adenoviruses as etiologic agents of diarrhea among children in day care was examined. Stool specimens from this prospective study were screened for both astrovirus and adenovirus hexon with two new indirect double-antibody assays and for enteric adenoviruses with an EIA specific for serotypes 40 and 41. Astrovirus was detected in a significantly greater percentage of children with diarrhea (4%, 21/524) than of those without (less than 1%, 1/138) (P less than .05); however, no difference between such such children with adenovirus infections was found (8%, 43/565, and 8%, 10/129, respectively). Overall, 30% (13/43) of all adenovirus hexon-positive specimens were enteric serotypes, and by extrapolation, enteric adenoviruses were identified in an equal percentage of children (2%) with and without diarrhea. This study documents the presence of astrovirus and enteric adenoviruses among children in day care in the United States, associates astrovirus with diarrhea in this setting, and suggests that viral agents may be the most common enteric pathogens among children with diarrhea in day care.

Schwann cells divide in a demyelinating lesion of the central nervous system.

A demyelinating lesion was induced in the rat central nervous system (CNS) by the microinjection of lysophosphatidylcholine into the spinal cord. Animals were given a single dose of tritiated thymidine 6-72 h before perfusion fixation. Correlative light microscope autoradiography and electron microscopy revealed many labeled Schwann cell nuclei that were associated with demyelinated axons in 1-3 week lesions. Myelinating Schwann cells were rarely labeled. The results indicate that Schwann cells proliferate in the CNS. They appear to divide on contact with demyelinated axons and to stop dividing when they form myelin.

Pattern of Schwann cell remyelination in a spinal cord lesion.

Intraspinal injection of mitomycin C into the rat dorsal columns produced extensive demyelination, axonal degeneration and glial cell death. Five weeks post-injection Schwann cell remyelinated fibers were present along the surface of the dorsal columns and around blood vessels within the lesions. Axons near these sites either were enclosed within a Schwann cell but not myelinated or were completely devoid of any cellular ensheathment. Schwann cells were associated only with those blood vessels which no longer retained astroglial end-feet. It is concluded that Schwann cells migrate into spinal cord lesions along such vessels. The marked sub-pial and perivascular distribution of Schwann cell remyelinated fibers may reflect a failure of Schwann cells to disperse quickly elsewhere within the lesion.

Demyelination induced by serum from patients with Guillain-Barré syndrome.

Sera from 16 patients with acute Guillain-Barré syndrome (GBS) and 14 healthy control subjects were injected into rat sciatic nerve and assessed for demyelinating activity by electrophysiological and histological techniques. Only fresh GBS serum, and not GBS serum stored at -20 degrees C or -70 degrees C, blocked conduction to a significantly greater extent than did fresh control serum. Conduction block developed gradually, starting within 24 hours of injection and reaching a maximum between days 3 and 6. Recovery of conduction commenced thereafter, and conduction returned to normal by day 33. Quantitative histological studies on day 6 showed that fresh GBS serum produced significantly more widespread demyelination than did stored GBS serum (p less than 0.01). Stored GBS serum showed residual demyelinating activity when compared with fresh control serum (p less than 0.01). Fresh serum obtained from 4 patients after recovery from GBS did not produce conduction block, despite it having done so during the acute phase of the disease.

Autonomic neuropathy in the trembler mouse.

There is little detailed histological information concerning the autonomic nervous system in hereditary demyelinating neuropathies in man. An opportunity was therefore taken to study the autonomic nervous system of the trembler mouse which suffers from a dominantly inherited peripheral neuropathy. Schwann cell myelination in trembler vagus and splanchnic nerves was abnormal. Morphometric analysis of myelinated and unmyelinated fibres in these nerves showed a marked reduction in myelinated fibre density distribution, whilst unmyelinated fibre densities were within the control range. The trembler vagus contained increased numbers of large diameter unmyelinated fibres probably as a result of trembler Schwann cell failure to form myelin around axons of the appropriate diameter for myelination. The trembler splanchnic nerve, however, contained increased numbers of small diameter unmyelinated fibres, possibly postganglionic fibres which fail to achieve their expected diameters.

Remyelination by cells introduced into a stable demyelinating lesion in the central nervous system.

Schwann cells from an autogeneic peripheral nerve source were injected into an established demyelinating lesion produced by the direct micro-injection of diphtheria toxin into the cat spinal cord. In control diphtheria toxin lesions, which were not injected with Schwann cells, demyelination and some oligodendrocyte remyelination was seen but Schwann cell remyelination was not observed. In diphtheria toxin lesions which were wholly confined to the posterior columns, Schwann cell myelin was not seen before 3 weeks after cell injection. The Schwann cell myelinated fibres occurred singly or in small groups within the posterior columns and were considered to have been myelinated by injected Schwann cells. By one month Schwann cell myelinated fibres had thick myelin sheaths but many demyelinated axons remained. By contrast, in more extensive diphtheria toxin lesions there was widespread Schwann cell remyelination of central axons at all stages examined after cell injection. The Schwann cell myelinated fibres were grouped in large numbers around the damaged dorsal root entry zones, the likely source of Schwann cells in these lesions. It is concluded that CNS remyelination may be improved by the injection of peripheral Schwann cells although the extent of remyelination is limited. One facet limiting remyelination may be the concentration of Schwann cells that it is possible to inject with present techniques. Functional recovery remains to be investigated.

The spinal cord-ventral root junction in the trembler mouse.

The Trembler mouse suffers from an hereditary demyelinating neuropathy. Schwann cell myelination of peripheral nerve fibres in the Trembler mouse is abnormal. Myelination of central nerve fibres in the deeper layers of white matter of the spinal cord is normal. At the junction between the peripheral nervous system and the central nervous system in the ventral roots in the Trembler mouse central-type nerve fibres are abnormally thinly myelinated. It is suggested that the normal process of myelination of central nerve fibres in this region is affected by abnormalities of the Schwann cell in the peripheral nervous system.

Increased pyroglutamic acid levels in patients on artificial diets.

Increased plasma and urine levels of pyroglutamic acid were found in 4 patients being fed the low-lactose food Nutramigen. Pyroglutamic acid was detected and estimated by a variety of methods, and the merits of the techniques used and their application in a screening programme are discussed.

Remyelination after transient compression of the spinal cord.

Transient mild compression of the spinal cord produces a lesion in which demyelination with preservation of axon continuity is the predominant nerve fibre change. This damage is repaired by oligodendrocytes which produce complete though abnormally thin and short internodes of myelin along demyelinated stretches of axons. When compression is more severe, this damage is also repaired by Schwann cells which migrate into the spinal cord from nearby root entry zones and form complete segments of peripheral nervous system-type myelin around demyelinated central axons.