Ultrastructural cytochemical demonstration of peroxidase-positive monocyte granules: an additional method for studying the origin of mononuclear cells in encephalitic lesions.

Unlike lymphocytes, blood monocytes possess in their cytoplasm peroxidase-positive (azurophil) granules (ppg) which largely correspond to the homonymous organelles of neutrophil granulocytes. We tested whether ppg, demonstrated cytochemically at the submicroscopic level, could serve as markers of monocyte-derived reactive mononuclear cells in encephalitic lesions. Samples of cerebrocortical tissue from adult albino mice with experimental yellow fever virus encephalitis were incubated in a medium containing diaminobenzidine and H2O2 for localization of peroxidatic activity. Mononuclear cells exhibiting ppg were found (1) in the lumen of brain venules, (2) in different stages of migration through the walls of such vessels, (3) in perivascular areas, (4) in the glioneuropil, either loosely scattered or forming small clusters, (5) in a satellite position to neurons, and (6) in leptomeningitic inflitrates. Several mononuclear elements harboring ppg had assumed an elongated, rod cell-like outline. Amongst the peroxidase-negative mononuclears were fully developed brain macrophages and elements showing morphologic features characteristic of activated lymphocytes. Most mononuclear cells without ppg resembled the peroxidase-reactive ones. The results of this study provide direct evidence in favor of a monocytic origin of, at least, numerous reactive mononuclear elements in encephalitic lesions. The approach followed in the present study is not suitable for quantitative investigations of the histogenesis of mononuclear cells responding to brain injuries, since emigrated blood monocytes rapidly lose their ppg, particularly, when they display enhanced phagocytic activity.

[Ultrastructure of intracellular storage materials in an autopsy case of adult-onset metachromatic leucodystrophy (MLD) (author's transl)]. / Ultrastruktur des intracellulären Speichermaterials bei einem Autopsiefall von adulter metachromatischer Leukodystrophie (MLD).

Formalin-fixed samples from the demyelinated frontal white matter of an autopsy case of adult-onset MLD were studied by electron microscopy. The intracellular storage materials exhibited the following types of structural patterns: (I) ordinary myelin figures; (II) pleated myelin figures; (III) narrow stacks of lamellar discs which were most likely components of formerly compact "prismatic" inclusions; (IV) paired lamellae, either arranged in loose parallel arrays or scattered about in random directions; (V) piles of parallel lamellae with alternating electron-dense and electron-lucent inter-spaces; and (VI) collections of structures resembling fragments of so-called pentalaminar membranes. Types I to IV have already been described in early-onset as well as late-onset forms of MLD, but types V and VI have not. Postmortem autolysis had possibly altered the structural organization of some cytoplasmic deposits and given rise to the formation of those lamellar patterns which were hitherto not known to occur in MLD.

[Cerebral toxoplasmosis complicating Hodgkin's disease in the adult. Light and electron-microscopic findings (author's transl)]. / Cerebrale Erwachsenen-Toxoplasmose bei Morbus Hodgkin. Licht- und elektronenmikroskopische Befunde.

A male patient with a history of Hodgkin's disease of 11 years duration died at age 41 with signs of progressive cerebral involvement. The blastomatous process had been treated with X-rays, cytostatic agents, and corticosteroids. Autopsy revealed isolated lymphogranulomatous lesions in the chest walls and multiple foci of necrosis in the brain. In the latter, Toxoplasma could be detected by light and electron microscopy. The inflammatory response elicited by the protozoan parasite was strikingly slight. This indicated that the patient had had some immunologic impairment. Pathomorphologic and clinical aspects of cerebral toxoplasmosis in the adult are discussed. It is emphasized that patients suffering from chronic malignant disorders, particularly Hodgkin's disease, are preferentially affected by toxoplasmosis of the brain.

Follow-up study of a case of generalized ceroidlipofuscinosis of childhood with special reference to the finding of an abnormal serum lecithin fatty acid pattern.

In quest of a more precise and stringent diagnosis for a case of generalized ceroidlipofuscinosis the patient was reexamined and additional laboratory tests were performed. For the third time myeloperoxidase activity was normal. On two separate occasions the serum lecithin fatty acid pattern was found to be abnormal and to resemble closely the pattern reported to be characteristic of polyunsaturated fatty acid lipidosis. The tau fraction was measured on one occasion and found to be normally present. Head circumference was confirmed to be normal. Pigmentary retinal changes were observed by fundoscopic examination. The child had prominent epileptic activity in form of myoclonic jerks. The case does not fit exactly into the picture reported recently for children with polyunsaturated fatty acid lipidosis. Doubt is voiced that these children have other than an infantile type of generalized ceroidlipofuscinosis. Thus, for the time being we regard ours as a case of generalized ceroidlipofuscinosis of infantile onset with an abnormal serum lecithin fatty acid composition. Furthermore, it seems to us that the infantile form, in the same manner and to the same extent as the late infantile and juvenile forms, does not constitute an entirely homogeneous group within the ceroidlipofuscinoses.

[The neuronal Torres bodies in experimental yellow fever encephalomyelitis. An additional example of the heterogeneous nature of Cowdry type A intranuclear inclusions]. / Die neuronalen Torres-Körperchen bei der experimentellen Gelbfieber-Encephalomyelitis. Ein weiteres Beispiel für die uneinheitliche Natur der Kerneinschlüsse vom Typ A nach Cowdry

In experimental yellow fever virus encephalomyelitis of adult albino mice, the occurrence of intranuclear inclusions within nerve cells, in particular, within spinal and bulbar motoneurons, is a constant finding. The light microscopic features of these so-called neuronal Torres bodies correspond entirely to the criteria laid down by Cowdry for the type A intranuclear inclusions. At the ultrastructural level, these karyoplasmic formations consist of haphazardly distributed patches of an essentially amorphous material of various density. Unlike the Cowdry type A intranuclear inclusions characteristic of several herpesvirus and paramyxovirus infections, neuronal Torr-s bodies do not contain any viral structures. The frequency with which neuronal Torres bodies, certain nucleolar alterations and severe tigrolytic changes occur together, possibly indicates that this sort of type A intranuclear inclusion developes as a consequence of a virus induced disturbance of the cell nucleic acid and/or protein anabolism.

Fenestrated blood capillaries in rat cranio-spinal sensory ganglia.

Several fenestrated capillaries were seen in the endoneurium of trigeminal and dorsal root ganglia from two young adult albino rats treated with tetraethylthiuram disulfide. The finding is regarded as normal, although the possibility exists that intoxication with tetraethylthiuram disulfide may have enhanced the intensity and/or rate of this cytologic specialization of some isolated endothelial cells.

Intracisternal A and C particles in mouse neurons: a thin-section study of normal trigeminal ganglion and C1300 neuroblastoma.

Trigerminal ganglia of 4 adult albino mice of the NMRI outbred stock were examined by electron microscopy. In all animals, about 10% of the neurons contained intracisternal A particles. Isolated structures resembling intracisternal A particles could be detected in atleast 50% of the nerve cells and in a few Schwann cells. Budding at the cell surface and/or extracellular type-C particles were not observed. An intracerebrally transplanted mouse C1300 neuroblastoma was likewise studied. Most tumor cells exhibited large numbers of intracisternal A particles having the same ultrastructure as the particles in trigeminal neurons. In addition, budding and extracellular type-C particles were occasionally observed.

Cytosome morphology and distribution of generalized ceroidlipofuscinosis in a twenty-eight month old boy with normal myeloperoxidase activity.

A brain biopsy obtained from a twenty-eight month old boy with ceroidlipofuscinosis was studied by light and electron microscopy. There were widespread intracellular deposits of autofluorescent material taking the fat stains. Cytoplasmic inclusions were plentiful in neurons, astrocytes, oligocytes, M cells and vascular elements. Their substructure ranged from that of variably dense aggregates of essentially homogeneous or granular appearance to that of miscellaneous collections of lamellar pairs and/or tubular structures of variable length. Stacks of 2 to 4 linear profiles with a curved outline were rarely seen and then almost exclusively inside cytosomes of endothelial cells. Similar observations were made in peripheral nerve, skin and liver biopsies. The granules of peripheral blood neutrophilic leukocytes were unremarkable. A small percentage of lymphocytes contained granular cytoplasmic bodies not unlike those known to be an ordinary feature of some lymphocytes of the average blood sample. However, a certain resemblance between these bodies and some of the cytosomes seen in the patient's tissues was also apparent. Myeloperoxidase activity was tested with paraphenylenediamine and was found to be normal on two occasions. The patient's age, cytosome morphology and distribution and results of peroxidase assay add special interest to this case of generalized ceroidlipofuscinosis. However, none of these features, either singly or in combination, warrants creation of a distinct subtype within this group of disorders. Myeloperoxidase deficiency is probably just another phenotypical marker of some patients with generalized ceroidlipofuscinosis rather than the genetic defect of Batten disease.

Organized inclusions in astrocytic and amorphous inclusions in neuronal mitochondria of human frontal brain tissue.

Brain tissue specimens were obtained early post mortem from the frontal lobe of seven unselected elderly subjects known to have been free of neurologic disease. Electron microscopically, two types of intramitochondrial inclusions were seen in four of seven cases. In two cases a few astrocyte mitochondria of the gyral white matter showed dense, elongated inclusions with an ordered linear substructure. These inclusions were, as a rule, accompanied by a row of prismatic cristae. In three cases some nerve cell mitochondria contained amorphous material of medium density and compact appearance. The globular masses often occupied the whole width of the mitochondrion. A relationship between the observed finding and a particular disease or morbid condition was not apparent. The inclusions are regarded as the morphologic substrate of a nonspecific metabolic change or degenerative process of the mitochondrion.

Virions and virus-associated structures within dendrites in an experimental flavovirus encephalomyelitis.

In experimental yellow fever virus encephalomyelitis of adult albino mice, virions, and virus-associated structures were observed not only inside neuronal perikarya but also within dendrites of varied size. The finding permits the following explanations: (1) either the viral agent is synthesized in the nerve cell bodies and transported intradendritically in a proximodistal direction; or (2) virus morphogenesis takes place in neuronal perikarya and dendrites as well; or (3) both possiblities are equally valid. Some incidental findings were suggestive of virus release at postsynaptic dendrite membranes. They are discussed with reference to a hypothetical long-distance pathway of viral dissemination involving endocytosis of the agent by presynaptic axon terminals, intraaxonal virus decoating, and retrograde axoplasmic transport of the infectious nucleic acid to the cell soma.