Pathophysiological effects of human TNF-alpha-producing tumor xenografts in immunosuppressed mice.

Groups of CBA mice immunosuppressed with anti-thymocyte serum (ATS) treatment were xeno-transplanted with either HeLa human cervical carcinoma cells or genetically modified cells expressing the human tumor necrosis factor-alpha (TNF) gene (All cells). Both cell lines were highly resistant to the cytotoxic effects of TNF. If 3 x 10(6) tumor cells were inoculated s.c. into female mice, HeLa cells grew progressively into large tumors and killed 74% of the recipients, while TNF-expressing All cells caused fatal tumor growth only in 22% of the mice. 3 x 10(6) or 1.5 x 10(7). All cells produced progressive tumor growth and lethality in all male recipients. In sera of all the A11-cell-transplanted mice, biologically active TNF was detected shortly (4.5 h) after tumor inoculation (6 39 U/ml), decreasing to below detection level in the circulation by day 3. In recipients of 15 million A11 cells, circulating TNF reappeared and reached high levels (12-1000 U/ml) 3 to 7 weeks later, when the animals bore large tumors (14-23 mm). Generally, such mice became cachectic, severely anemic, hypothermic, and soon died. On account of calcium mobilization from bones, their serum Ca levels were high. Electron microscopy revealed severe liver damage, but there were no signs of chronic arthritis. These results suggest that ATS-treated mice xenotransplanted with TNF-gene-transfected A11 human tumor cells provide a new model for studying the pathophysiological and anti-tumor effects of TNF.

Childhood rhabdomyosarcoma in otorhinolaryngology.

Two cases of childhood rhabdomyosarcoma with otorhinolaryngological localization are reported and the literature of this rare malignancy is reviewed. The prognostic importance of localization, early diagnosis and combined surgical, irradiation and cytostatic treatment are emphasized.

[Regeneration of the proximal kidney tubules after sublimate-induced necrosis in the rate. Scanning electron microscopic studies]. / A proximális csatornák szublimátnekrózist követo regenerációja patkányvesében. Scanning elektron-mikroszkópos vizsgálatok.

Necrosis of the proximal tubules of the kidney in white rats has been produced by a relative small doses (1,5 mg/kg) of sublimate. Necrosis of the epithelial cells and their regeneration was studied during 10 days by scanning electron microscopy. Parallelism of the various regressive and regenerative processes was noted, attention was paid to the correlation existing between them. Periodicity of normal and necrotic segments was also observed. As a sequal of the necrosis the basement membranes became denuded, later in the first period of the regeneration flattened epithelial cells--having no microvilluses--covered them. On the surface of the latter, in a very short period (several hours) gradually microvilluses, regular brush-border and interdigitation of the cells were formed. In 10-17 days the regenerated epithelium could hardly be distinguished by scanning electron microscopy from the normal one.

Regeneration of proximal tubules of the rat kidney following sublimate necrosis. A scanning electron microscopic study.

Necrosis of the proximal tubules of the rat kidney was induced by low (1.5 mg/kg) doses of sublimate. Epithelial necrosis and regeneration were followed by scanning electron microscopy for 10 days. Regressive and regenerative processes were observed simultaneously. The naked basement membrane is first invaded by flat epithelial cells lacking microvilli. Within a few hours microvilli appear followed by the formation of regular brush-border and interdigitations cells. After 7--10 days the newly formed epithelium cannot be distinguished from the intact one.