Reinhard L. Friede

The Cytogenetic Basis for Classifying Ependymomas

The phylogeny of ependymal cells and astrocytes can be traced to a single primitive progenitor the ependymoglia or the tanycyte, respectively. Ependymoglia cells have ependymal perikarya having astrocyte-like processes that terminate subpially in primitive glial footplates. Such cells prevail in primitive nervous systems, but they also persist regionally in the mature mammalian brain. Their fine structure has been studied in many species. An electronmicroscopic study of 8 ependymomas reveals that the neoplastic cells possess features characteristic of primitive ependymoglia; in particular they possess cell processes filled with glial filaments, terminating submesenchymally in a primitive, piston-shaped footplate. The perivascular pseudorosettes of ependymomas are the equivalents of these cell poles. The dominant phenomenon of ependymoma structure appears to be a reversion of cellular organization to the stage of primitive ependymoglia cells. On reviewing 43 ependymomas and 71 astrocytomas 11 neoplasms were found having a tissue structure reminiscent of the evolution of piloid astrocytes from ependymoglia or tanycytes, respectively. These features correspond to transitional stages seen in normal primitive brains. Tumors of this type may be characterized as a tanycytic variant of ependymomas. They appear to be relatively common in the spinal cord and present a source of confusion with piloid astrocytomas.

Responses of thymidine labeling of nuclei in gray matter and nerve following sciatic transection

SummaryThe effect of sectioning the sciatic nerve on rates of cell proliferation was studied in rats, using autoradiographic demonstration of the incorporation of tritiated thymidine into the nuclei. Preparation of the spinal cord with the nervesin toto permitted a bilateral survey of the number of labeled cells in the cord, ganglia, and nerves. Proliferation of glia cells occurred in the cord within 24 to 48 hours after sectioning the nerve, with a maximum by the 3rd day, and was confined sharply to the affected segments. The increase in labeled capsule cells in spinal ganglia was only a fraction of that in the cord, with a maximum by the 4th day.Nearly equal increases in the number of labeled cells occurred initially in both stumps of the nerve, but increase after the fourth day continued only in the proximal stump. Cell labeling in Wallerian degeneration started markedly later than that in the stumps, that is, by the 4th day, and reached levels equal to those in the distal stump by the 6th day. There was a slow and lasting increase in the number of mast cells in the distal nerve, but not in the stumps.These data indicate individual and characteristic patterns of cell proliferation for each of the affected regions, suggesting the existence of multiple control mechanisms of cell proliferation.ZusammenfassungDie Wirkung der Durchschneidung des N. ischiadicus auf die Rate der Zellvermehrung wurde bei Ratten mittels autoradiographischem Nachweis des Einbaus von H3-Thymidin in die Kerne untersucht. Die Herstellung von Präparaten des Rückenmarks mit den Nervenin toto ermöglichte die beidseitige Feststellung der Zahl markierter Zellen im Rückenmark, Ganglien und Nerven. Die Ganglienzellvermehrung trat im Rückenmark innerhalb von 24–48 Std nach der Nervendurchschneidung auf, erreichte ein Maximum am 3. Tag und beschränkte sich scharf auf die affizierten Segmente. Der Anstieg von markierten Kapselzellen in den Spinalganglien betrug nur einen Bruchteil jenes im Rückenmark und erreichte am 4. Tag ein Maximum.Ein nahezu gleicher Anstieg der Zahl markierter Zellen trat anfänglich in beiden Nervenstümpfen auf, hielt aber nach dem 4. Tag nur im proximalen Stumpf weiter an. Die Zellmarkierung bei der Wallerschen Degeneration begann deutlich später als die in den Stümpfen, d. h. um den 4. Tag, und erreichte ein gleiches Ausmaß wie die im distalen Stumpf um den 6. Tag. Es erfolgte auch ein langsamer und anhaltender Anstieg der Zahl von Mastzellen im distalen Nerv aber nicht in den Stümpfen.Diese Befunde weisen auf individuelle und charakteristische Muster der Zellvermehrung in jeder der affizierten Region hin, welche das Vorhandensein mehrfacher Kontrollmechanismen der Zellvermehrung nahelegt.

Accumulation of axoplasmic organelles in swollen nerve fibers

Abstract The density of axoplasmic organelles in swollen fibers was determined with a method of line sampling and was correlated with the degree of axonal swelling. A linear relation was found between axon swelling and the density of axoplasmic organelles. The latter occupied less than 9% of the axoplasm in normal nerve fibers and approximately 30% in excessively swollen fibers. The total combined volume of organelles per maximally swollen fiber was approximately 12 times normal, enough to fill the entire axis cylinder before the onset of swelling. The same correlation was found between the degree of swelling and the increase in organelle density in myelinated and non-myelinated fibers. This indicates that the primary events responsible for axonal swelling occurred within the axoplasm, and that the process of sheath expansion was only incidental to these primary axonal changes. The changes in the density of axoplasmic organelles corresponded to their reorientation between neurofilaments and microtubules. In normal axons, mitochondria and smooth endoplasmic reticulum were aligned in succession within ‘cytoplasmic streets’ between the bundles of neurofilaments and microtubules, all with their long axes parallel to the fiber. In moderately swollen fibers, the ‘streets’ were enlarged and crowded with organelles. Markedly swollen fibers showed a loss of neurofilamentous material and a lack of alignment of organelles. The identification of axoplsmic organelles, theories of axonal flow, and mechanism producing reactive axonal swelling are discussed.

Myelin phagocytosis in Wallerian degeneration of peripheral nerves depends on silica-sensitive,bg/bg-negative and Fc-positive monocytes

Previous experiments with nerves enclosed in millipore diffusion chambers had shown that myelin degradation during Wallerian degeneration depends on invasion by non-resident cells. The present study was aimed at a more precise identification of the invading cell population. Monoclonal antibody studies of degenerating nerves showed many cells with the Fc marker; cells having the Lyt-1, Lyt-2, Ia or Mac-1 markers were sparse or absent. Nerves transplanted into mice of the Chediak-Higashi bg/bg strain were invaded by cells lacking the bg/bg marker (giant lysosomes), while cotransplanted muscle tissue was invaded by cells with the bg/bg marker. Blocking monocytes with silica reduced both cell invasion and myelin degradation in degenerating nerves. These observations show that Wallerian degeneration of peripheral nerve fibers involves a subset of monocytes which are silica-sensitive and have Fc receptors but no bg/bg giant lysosomes.

Metastatic lesions in the sella turcica and pituitary gland

The sella turcica with adjacent osseous tissues was examined histologically in 60 cases of carcinoma which came to postmortem examination in the course of one year. Forty‐nine of the specimens were also examined by roentgenography. Sixteen contained metastatic lesions, 9 of which originated from the breast. Statistical analysis showed that the incidence of sellar metastases was significantly higher for carcinoma of the breast than for all other neoplasms. Involvement of the sella was positively correlated with other skeletal metastases. X‐ray examination was found to be a relatively insensitive method for detecting metastatic lesions in the sella.

Analysis of the process of sheath expansion in swollen nerve fibers

Abstract 1. Reactive axon swellings in the proximal stumps of rat sciatic nerves were studied at 1–8 days after transection of the nerves. Sheath thickness and axon circumference were measured in plastic-embedded 1 μm sections; the axon circumference, the number of turns of myelin lamellae in the sheath and the interperiod width were determined in electron micrographs. Measurements in 1 μm sections were a reliable implement for the analysis of pathological fiber population. All data were subjected to statisticak regression analysis by computer. 2. Reconstruction of fibers from serial 1 μm sections showed that reactive axon swellings did not develop in the terminal stump of the fiber, but, rather, at some distance from the stump; the portion distal to the zone of swelling was continuous with the rest of the fiber, and the sheaths were collapsed. 3. Swelling of the axon was accompanied by an increase in axon circumference, a reduction in the number of turns of myelin lamellae, and by an unaltered interperiod width. These data constitute proof of slippage of myelin lamellae. Excessive slippage resulted in denudation of the axon. 4. The changes in fiber structure resulting from different degrees of axonal swelling were calculated; these calculated changes agreed with actual measurements in swollen fibers. Accordingly, the number of turns of myelin lamellae and the axon circumference of a swollen fiber permit determination of the degree of axonal swelling. An estimate of the dimension of the fiber before the onset of swelling is also possible. 5. Fibers with marked slippage of the sheath showed islands of cytoplasm underneath an intact basement membrane. These were interpreted as resulting from sequestration by tearing of the outer mesaxon, which presumably cannot be displaced with the same speed as the myelin leaflets in the sheath can slip. 6. The expansion of the sheath and the denudation of excessively swollen fibers was an acute process, occurring mostly during the first 4 days after cutting; thereafter, the majority of fibers showed normal proportions between axon and sheath, or they were denuded because of excessive swelling. 7. A new technique, using plastic-embedded 1 μm sections, was developed for the demonstration of oxidative enzyme activity in mitochondria. This technique showed swelling of the fiber to correspond to a progressive increase in mitochondrial density in the axoplasm. Maximum mitochondrial density was found in excessively expanded or denuded fibers.

TOPOGRAPHIC DETERMINATION OF ZINC IN HUMAN BRAIN BY ATOMIC ABSORPTION SPECTROPHOTOMETRY

Atomic absorption spectroscopy was used for measuring the zinc content, in ppb (μg/1), of brain tissue. A new method for determining the correction factor of atomic absorption interference is described.

Fine Structure of Arachnoid Cysts

Recent studies of the fine structure of the cranial meanings of laboratory animals and man have shown that there is no subdural space. The latter is formed artificially by the tendency of meningeal tissues to cleave along a collagen-free zone, the dura-arachnoid interface layer. This layer is composed of an outer zone of dural border cells and an inner arachnoid barrier layer. The fine structure of nine arachnoid cysts was studied to determine the derivation of the cysts wall from the various components of normal human meanings. A cleaved dura-arachnoid interface layer covered only the dome of the cyst where the latter had abutted the dura mater. The interface layer did not partake in forming the cysts wall. The dominant phenomenon of the cysts wall was an absence of the normal trabeculation of the subarachnoid space, the trabecules being replaced by tightly packed collagen fibrils and a few scattered cells in between. Some cells were layered discontinuously at the inner face of the cyst wall, but there was no organized inner lining. No evidence was found for either a tight sealing of the extracellular spaces in the cysts wall, nor for the existence of an active transcellular fluid movement.

Dating the development of human cerebellum

SummaryA histological study of normal cerebella in 72 human autopsies allowed defining several readily identifiable landmarks by which cerebellar development was dated for vermis and for hemispheres respectively: Disappearance of the lamina dissecans at 28 and 32 weeks gestation; Purkinje cells first discernible at the same age for both; onset of growth of inner granular layer at 30 and 32 weeks; sharp boundary between inner granular layer and white matter at approximately 36 weeks and about term; onset of marked growth of molecular layer at 30 and 38 weeks; adult thickness of molecular layer at approximately the 8th postnatal month for both; and accelerated involution of outer granular layer between the 2nd and 4th postnatal months, remnants persisting up to 9 and 13 months. Nests of matrix cells in the cerebellar nuclei were found in 28% of the cases less than 4 months old. These cell nests appear to undergo involution by the 4th month—that is, at the same time as the outer granular layer. The significance of these developmental events for the interpretation of pathological alterations in the developing cerebellum is discussed.

Entry of labeled monocytic cells into the central nervous system

SummaryThe entry of circulating blood cells into the brain was studied by injecting radioactively labeled cells from the bone marrow of donor animals into recipient animals. The cells were labeledin vitro orin vivo, using H3 thymidine or H3 uridine. Labeled cells having features of monocytes or macrophages were shown to enter normal brain tissue and to aggregate at various types of brain lesions. There was indication that these cells later returned to the spleen.ZusammenfassungDer Eintritt zirkulierender Blutzellen in das Gehirn wurde mittels radioaktiv markierter Zellen aus dem Knochenmark von Spender-auf Empfängertiere untersucht. Die Zellen wurden in vitro oder in vivo mittles H3-Thymidin oder H3-Uridin markiert. Die markierten Zellen vom Charakter der Monocyten oder Makrophagen dringen nach den erhobenen Befunden in normales Hirngewebe ein und sammeln sich in verschiedenartigen Hirnläsionen an. Es ergaben sich Hinweise dafür, daß diese Zellen später in die Milz zurückkehren.