Biomedical subjects
Publications and source records attributed to H D Webster.
Explore the source record for details and available documents.
A quantitative double blind procedure is described to test the myelinotoxicity of cerebrospinal fluid (SSF) by using optic nerves of Xenopus tadpoles as an in vivo model of a myelinated CNS tract. Only 0.5 ml of unconcentrated CSF is needed for a test and the result is known in 5 days. Groups of 8-10 Xenopus tadpoles received a subcutaneous injection of 12-13 muL of a coded CSF sample or of a saline control solution around the right optic nerve. After 48 h, whole mounts of the right optic nerves were prepared and the slides were randomized before using a differential-interference contrast microscope to count the myelin lesions. The myelinotoxicity of a CSF sample was considered positive (+) when it produced significantly higher (P less than 0.01) counts than the saline control. When P was less than 0.05, the counts were recorded as borderline (+/-) and it was negative (-) when P was greater than 0.05.
To investigate the myelinotoxicity of cerebropsinal fluid in multiple sclerosis, we used an in vivo model of the myelinated central-nervous-system tract of tadpoles for quantitative double-blind tests of 46 cerebrospinal-fluid samples. Groups of xenopus tadpoles were injected with cerebrospinal fluid near the optic nerve. Forty-eight hours later, whole mounts of optic nerves were prepared, and a differential interference microscope was used to count myelin lesions. Cerebrospinal-fluid samples from 60 per cent of the patients with an acute attack of definite multiple sclerosis had myelinotoxic activity. This activity correlated best with the severity and duration of the disease, rather than with gamma-globulin or total protein concentrations. Activity was negative in 85 per cent of cerebrospinal-fluid samples from a control group with other neurologic diseases. This assay is a useful method for investigating myelinotoxic factors of cerebrospinal fluid in patients with multiple sclerosis, but was not helpful diagnostically.
The permeability of Xenopus tadpole optic nerves to macromolecules was studied in order to evaluate the usefulness of this system for studying mechanisms of serum-induced CNS demyelination in vivo. Single injections of either horseradish peroxidase (HRP), ferritin or fluorescein-conjugated human IgG were injected around the right optic nerve and tadpoles were then sacrificed between 15 min and 48 h. Each of the tracers had penetrated the nerve parenchyma by 30 min. Entry of HRP and ferritin occurred mainly via extracellular clefts between adjacent astrocytic endfeet in the glia limitans region. A similar mode of passage was suggested for IgG. Once within the nerve, the tracers became rapidly associated with myelinated axons. HRP was also seen in the periaxonal space but did not directly penetrate the myelin sheath. By 24 h, extracellular localization of tracer was virtually absent with nearly all of the tracer now being concentrated in vesicles within astrocytic processes and perikarya. The distribution of the tracers was not confined to the optic nerve on the injected side; some was seen in adjacent cranial peripheral nerves and surrounding extraocular musculature. Also, tracers eventually penetrated the pial sheath of the contralateral optic nerve. The results of this study indicate that tadpole optic nerves are permeable to a wide range of macromolecules. Furthermore, the distribution of these tracers to nearby cranial peripheral nerves may provide an important opportunity for testing the differential effect of various substances on central and peripheral myelin sheaths.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
In rat sciatic nerves, a small bundle of fibers was identified in which myelin sheaths were absent at birth, appeared within 3 days, and grew rapidly for 2 wk. During this interval, nerves were removed from littermates and were sectioned serially in the transverse plane. Alternating sets of thin and thick sections were used to prepare electron micrograph montages in which single myelinating axons could be identified and traced distally. During the formation of the first spiral turn, the mesaxon's length and configuration varied when it was studied at different levels in the same Schwann cell. The position of the mesaxon's termination shifted while its origin, at the Schwann cell surface, remained relatively constant. Along myelin internodes composed of two to six spiral turns, there were many variations in the number of lamellae and their contour. Near the mesaxon's origin, longitudinal strips of cytoplasm separated the myelin layers. Thicker sheaths were larger in circumference, more circular in transverse sections, and more uniform at different levels. Irregularities were confined to the paranodal region, and separation of lamellae by cytoplasm occurred at Schmidt-Lantermann clefts. Approximate dimensions of the bundle, its largest fibers, and their myelin sheaths were measured and calculated. The myelin membrane's transverse length and area increased exponentially with time; the growth rate increased rapidly during the formation of the first four to six spiral layers and remained relatively constant during the subsequent enlargement of the compact sheath.
Explore the source record for details and available documents.
Experimental allergic neuritis (EAN) was produced in rats by the intradermal injection of an emulsion of peripheral nerve in Freund's adjuvant. Early lesions in perfused sciatic nerves were studied by phase, light, and electron microscopy at intervals up to 15 days following immunization. Circulating lymphocytes attached focally to the inner surface of blood vessels, primarily venules, to initiate parenchymal lesion formation. Attached cells had the hand mirror configuration typical of the motile lymphocyte. They subsequently flattened against the endothelial surface and then traversed the vascular wall by sinking into and passing through the cytoplasm of endothelial cells. The transgressor and transgressed cell membranes were intact and both cells retained their integrity. Lymphocytes began to transform and divide intravascularly; these events accelerated extravascularly. Although the migrating cells became larger and more pleomorphic in the perivascular regions, their essential character was in keeping with an origin from circulating lymphocytes. In many lesions, there was fluid with protein, possibly produced by the transformed extravascular cells. The described cellular events precede tissue damage and are likely instrumental in the myelin destruction which follows
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.