Tumor necrosis factor effects on ascites formation in an experimental tumor model.

In humans, treatment of malignant ascites with bolus TNF leads to resolution of the ascites. In an experimental model NMRI nude mice were inoculated intraperitoneally with human NIH-OVCAR3 adenocarcinoma cells, resulting in production of ascites and intraperitoneal tumor growth. Ascites formation and tumor growth after IP injection of recombinant human TNF was determined. Depending on the treatment schedule, a dual effect of TNF on the development of ascites was seen. Doses of TNF (1-10 micrograms/g) given once per week completely prevented ascites production, whereas the same doses of TNF given on a daily schedule induced enhanced ascites formation in an inverse TNF dose relationship. The area of tumor cell-covered peritoneal lining corresponded to these findings, indicating a correlation of tumor mass with ascites production. In an attempt to prevent renewal of ascites after drainage, neither inhibition nor enhancement in ascites production was seen when TNF was given five times per week. However, doses of 10 micrograms/g of TNF once per week led to almost complete inhibition of ascites reappearance. Histological examination of animals that received repeated TNF treatment demonstrated chronic peritonitis with strong stromal proliferation, angiogenesis, and increased adhesion of tumor cells to the peritoneum.

Flagellar structure and hyperthermophily: analysis of a single flagellin gene and its product in Aquifex pyrophilus.

The polytrichously inserted flagella of Aquifex pyrophilus, a marine hyperthermophilic bacterium growing at 85 degrees C, were isolated and purified. Electron micrographs of the 19-nm-diameter flagellar filaments show prominent helical arrays of subunits. The primary structure of these 54-kDa flagellin monomers determining the helical shape and heat stability of filaments was of particular interest. The genomic region encoding the flagellin subunit (flaA gene) and an upstream open reading frame (orf1) were cloned and sequenced. The 1,503-bp flaA and 696-bp orf1 are preceded by separate sigma 28-like promoters and ribosome-binding motifs and succeeded by palindromic transcription terminators. Both genes are actively transcribed, but the nature and function of the orf1-encoded 231-residue polypeptide remain unknown. The deduced primary structure of the 501-amino-acid flagellin encoded by flaA consists of conserved N- and C-terminal regions and a variable 246-residue central domain. In comparison to mesophilic flagellins, the thermostable A. pyrophilus flagellin is characterized by increases in aromatic residues and prolines as well as by a 7.9% +/- 3.2% increase in all hydrophobic residues that is balanced by a respective decrease in hydrophilic residues. This composition is thought to form more compact flagellin monomers and stable interface contacts between neighboring subunits in the polymer.