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The Onderstepoort strain of canine distemper virus (CDV) which has been adapted to newborn Swiss mice was used in a study in weanling mice. Intracerebral inoculation of newborn mice with either the parent or mouse-adapted virus strain led to mortality in 100% of the animals. In weanling mice the parent virus produced less than 10% mortality, whereas the mouse-adapted strain killed approximately 40% of the animals and this was not dose-dependent. Although a meningitis was observed in the surviving mice, the occurrence of viral antigens was less widespread in the brain of weanling mice than in the brain of newborn mice, and could not be detected more than 5 months after infection. In long-term experiments two phenomena were observed. At 4 to 6 months post-infection up to 30% of the mice became obese; however, no viral antigens were detected in the brains. At 13 to 17 months post-infection a number of mice became paralysed and virus antigen could be detected in the brain and lymph glands; however, infectious virus could not be isolated. These observations are discussed in relation to neurological infection and metabolic disease.

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An experimental study on acute Hexachlorophene (HCP) neurotoxicity is reported in mice and baboons: - by light microscopy, a severe spongiform lesion of the central nervous system is localized in the white matter without myelin breakdown or cellular reaction; - by electron microscopy, the myelin alteration is characterized by the presence of vacuolation of "splitting" in the intralamellar spaces of compact sheaths; myelinated axons are occasionally involved. The changes described are discussed according to various reports on HCP neurotoxicity in humans and experimental animals. The effects of this chemical agent on the central nervous system is related to the percentage of HCP in talcum powder or solution for topical use. The toxicity of very low dosage level is demonstrated in baboons. Therefore HCP use cannot be recommended for young infants.

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A study on hexachlorophene encephalopathy in mice and baboons is reported. By light microscopy, a severe spongiform lesion of the central nervous system (CNS) was localized in the white matter, without myelin breakdown or cellular reaction. By electron microscopy, the myelin alteration was characterized by wide intralamellar spaces or "splitting" developed in the intraperiod line of compact sheaths. The acute changes described were induced by administration of the drug by the digestive or cutaneous routes at various dosage levels in an aqueous solution or in talcum powder. The toxic effects depended on the age of the animals, the survival times and the concentrations of hexachlorophene, i.e., 6%, 3%, and 0.5%. The findings are compared with previous reports on the neurotoxicity of hexachlorophene and other chemicals in human and experimental animals. Hexachlorophene cannot be recommended for use in young infants because of its neurotoxicity in very low doses as demonstrated in the present report.

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Induction of synthesis of the viral antigens T and V during polyoma virus infection was studied in primary Mouse and Hamster kidney and brain cultures, as well as in various types of human cells. The results show that: (1) Despite a very low percentage of positive cells by immunofluorescence, Hamster brain cells produced more viral antigen than kidney cells, as opposed to what was found in Mouse brain cells. (2) Most human cells produced neither T nor V antigens. Conversely, a large number of brain cells synthesized the T antigen very early after infection.

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The morphological characteristics of three clones of hamster brain cells transformed in vitro by polyoma virus and of the tumors obtained after subcutaneous grafting of these cells in syngenic animals are reported. These clones appeared to be glial in nature by light and electron microscopy. The initial tumors induced by the three clones presented astrocytic features both by electron microscopy and immunohistochemistry. Analysis of the subsequent in vivo passages showed a decrease in cell differentiation, which was accompanied by a decrease in the latency period; after 2 years of serial transplantation, the tumors seemed poorly differentiated gliomas. A control cell line of hamster cerebellar cells evolved similarly.

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Primary cultures of whole brain and cortex cells origination from 14-day-old A/Jax or C3H mouse fetuses were treated with benzo(a)pyrene (B(a)P) for 24 h. After 7 to 8 passages a malignant transformation was observed in the chemically treated whole brain and cortex cultures. Control cultures of cortex remained non-transplantable during the whole experiment (up to 14 passages) whereas in the control cultures originating from whole brain a spontaneous transformation appeared after 11 passages. With horseradish peroxidase-labelled antibody, the specific glial fibrillary acidic protein (GFAP) was detected in both control and transformed total brain and cortex cultures, and in the tumors initiated by the in vitro transformed cells. This finding shows that glialike cells persisted after a long in vitro maintanance and transformation.

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An ultrastructural study was performed on normal and Benzo(a)-pyrene(B(a)P)-transformed fetal mouse brain cells. Early subcultures of a strain initiated from whole brain presented three cell types in vitro: astroglial, poorly differentiated glial, and spongioblastic types. After B(a)P-treatment, there was an exclusive transformation and the growth of neuroglia sometimes without gliofibrillary maturation, but with the presence of glial fibrillary acidic protein (GFAP) in the cytoplasm. Early subcultures of another strain initiated from cortex only presented poorly differentiated neuroglial cells. After transformation, cell maturation as evidenced by gliofibrillogenesis and GFAP production by these cells was observed. In both cases, the potentiality of glial differentiation after in vitro malignant transformation by a chemical carcinogen seemed preserved.

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One case of meningiothelial meningioma with "hyaline inclusions" (colloid-bodies or pseudopsammomas) as noted by Cushing and Eisenhardt (1938) and by Kepes (1961-1975) is reported by light and electron microscopy. Two types of these structures, either homogeneous or polymorphic, surrounded by microvilli are described and regarded as signs of secretory differentiation of tumor cells. In addition to Kepes' description, the authors show, at high magnification, the polymorphic material including homogeneous component, lamellar structures, microvesicles and dense bodies. The endocellular overproduction of the various types of "hyaline inclusions" and the nature of their material are discussed.

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The transformation of cultivated hamster brain cells by polyoma virus is reported. The transformed cell line contained polyoma virus-specific nuclear, surface and transplantation antigens. Subcutaneous and intracranial inoculations revealed high tumorigenicity of the cells. Brain-specific S 100 protein was found in these tumors with immuno-peroxidase staining, suggesting that they were of a nervous nature. Both in vivo and in vitro, the cells had glial features as studied by phase contrast, light and electron microscopy. Type-H virus-like particles were found in the tumor cells and might have played a role in the viral transformation.

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Using primary cultures originating from 14 day old fetal Hamster brain, we have obtained a cell line with glial morphology. These cell remain non transplantable during the first year of in vitro culture, but undergo spontaneous transformation during the second year. Following prolonged contact of the glial-like cells with 25 to 50 microgram/ml of methylnitrosourea (MNU), a malignant transformation is observed 5 months after the treatment. The lowest concentrations of (MNU) do not cause malignant transformation, but seem to inhibit (or postpone) the spontaneous transformation. After MNU treatment, cells retain their glial nature.

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A cell line called HCxPy was obtained in vitro by transformation of dissociated hamster brain cell cultures by polyoma virus. The first foci of transformed cells became evident 90 to 120 days after viral infection. This cell line is now at the 46th passage. The cells appear tumorigenic for hamsters after subcutaneous and intracerebral injection. They carry the polyoma virus T and cell surface antigens. Good evidence for astrocytic differentiation can be found by morphological examination of the tumours and of the cultured cells.

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The authors report electron-microscopic observations upon a primitive cerebral haemangiopericytoma. The vascular appearance of the tumour is due to the presence of abundant extracellular material which has a structure like that of vascular basement membranes. The fact that the tumour cells are pericytes is confirmed by the existence of intracytoplasmic microfilaments of 60-80 A in diameter, sometimes gathered into osmiophilic aggregations and forming simple cellular junctions (zonulae adherentes). Stress is laid upon the importance of differentiating this rare tumour from an angioblastic meningioma; the haemangiopericytoma is more rapidly growing and carries a more serious prognosis.

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One case of malignant tumour of the left nasal cavity is reported in a woman 56 year old, affected by the disease 24 years. Numerous recurrences appeared and various histological diagnoses were performed. At the last surgery, the tumour invaded the ethmoid and was a typical olfactory esthesioneurocytoma. By electron microscopy, mature ganglion cells with dense cored vesicles (neurosecretory granules) were densely packed. Neuritic processes with microtubules were rarely normal in size and their content was most often abnormal; furthermore dystrophic axons were noted in great number.

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The authors report premilinary results of an experiment on permeability of the blood-brain barrier (BBB) to anti-tumor virus-induced immunological factors in the polyoma virus/Syrian Hamster system. The animals were protected by subcutaneous or intracranial injections with virus before challenge with polyoma virus transformed cells by both routes. BBB seemed to be permeable to the efferent part of the subcutaneously induced immune reaction. On the contrary, antigenic information introduced in the central nervous system was trapped inside the BBB. Thus the BBB might offer a "one-way" permeability in this system.

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