Flavone-8-acetic acid augments systemic natural killer cell activity and synergizes with IL-2 for treatment of murine renal cancer

The investigational drug flavone-8-acetic acid (FAA) potently augments NK activity in the spleen, liver, lungs, and peritoneum in a dose-dependent manner after i.v. or i.p. administration. Augmented NK activity peaks by 24 h after FAA injection and returns to normal after 6 days. Combined treatment of established murine renal cancer with FAA and rIL-2 results in up to 80% long term survival whereas FAA or rIL-2 alone were unable to induce any long term survivors. The optimal dose of rIL-2 required for use with FAA was in the range of 10,000 to 30,000 U/day. Further studies demonstrated that the regimen of FAA plus rIL-2 administration that was effective in treating established murine renal cancer also induced a more potent augmentation of NK activity than did either FAA or rIL-2 alone. Subsequent studies revealed that the therapeutic effectiveness of FAA plus rIL-2 was significantly reduced when tumor-bearing mice were treated with anti-asialo GM1 serum. These results are consistent with a role for augmented NK activity in the therapeutic effects of FAA plus rIL-2 murine renal cancer. In addition, these studies demonstrate that FAA and rIL-2 is a useful approach for cancer treatment in that subtoxic doses of rIL-2 can be used and significant anti-tumor efficacy occurs even without accompanying adoptive immunotherapy.     

Microbial populations and activity in two soils of Tanzania as influenced by mercury

Summary The influence of mercury on microbial populations and activity of two soils from Tanzania was studied. Aretan (2-methoxyethylmercury chloride) slightly affected the microbial population of the Morogoro (Oxisol) soil, which was 10⁷ c.f.u./g in control soil and 10⁶ c.f.u./g in the presence of 2000 mg Hg/kg soil. Mercuric chloride at >8 mg Hg/kg soil increased the population slightly, with a sharp decrease at >100 mg Hg/kg soil, dropping ultimately to 10³ c.f.u./g at 2000 mg Hg/kg soil. In the Arusha (Andept) soil, the microbial response to the two mercury compounds was the opposite of that for the Morogoro soil. Aretan sharply reduced the nitrogenase activity of aerobically incubated Morogoro soils at Hg levels >24 mg/kg, resulting in very low activity at >50 mg Hg/kg soil. Mercuric chloride increased the activity, which showed a peak at 24 mg Hg/kg soils, followed by a sharp drop at 30 mg Hg/kg and remained low thereafter. In the Arusha soil, the activity was reduced gradually by both Aretan and HgCl₂. The response of the activity under anaerobic incubation in the Morogoro soil was the opposite of that under aerobic incubation, in that it was Aretan which at first increased the activity. In the Arusha soil the activity under anaerobic incubation decreased gradually over the entire range of added Hg. Nitrification was decreased by HgCl₂ atlevels of <2 and <10 mg Hg/kg soil in the Arusha and Morogoro soils, respectively. The tolerance to Hg by microorganisms in this study was in the order: total population > nitrogen fixers > nitrifiers. This may be explained in terms of species diversity of the microorganisms, which may be expected to follow the same sequence.

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Population et activités microbiennes dans deux sols de Tanzanie sous l'influence du mercure

Résumé On étudie l'influence du mercure sur les populations et les activités microbiennes de deux sols en provenance de Tanzanie. L'Aretan (chlorure de 2-méthoxyéthylmercure) n'affecte que faiblement la population microbienne du sol de Morogoro (oxisol), qui compte 10⁷ individus par g dans le sol témoin et 10⁶ individus en présence de 2000 mg de mercure par kg de sol. Le chlorure mercurique, à une dose supérieure à 8 mg de mercure par kg de sol, augmente quelque peu la population. Celle-ci décroît brutalement au delà de 100 mg de mercure par kg de sol, pour tomber finalement à 10³ individus par g à 2000 mg de mercure par kg de sol. Dans le sol d'Arusha (Andept), la réponse microbienne aux deux composés mercuriels est l'inverse de celle obtenue avec le sol de Morogoro. L'Aretan réduit fortement l'activité de la nitrogénase de sols de Morogoro incubés en aérobiose à des teneurs en mercure au delà de 24 mg par kg. L'activité devient très faible au delà de 50 mg de mercure par kg de sol. Le chlorure mercurique augmente cette activité, avec un pic de 24 mg de mercure par kg de sol, suivi d'une chute sévère à 30 mg de mercure par kg. L'activité demeure faible aux doses plus fortes. Dans le sol d'Arusha, l'activité est réduite progressivement tant par l'Aretan que par HgCl₂. La réponse de l'activité en incubation anaérobie dans le sol de Morogoro est l'inverse de celle en incubation aérobie en ceci que c'est l'Aretan, cette fois-ci, qui augmente d'abord l'activité. Dans le sol d'Arusha, l'activité en incubation anaérobie décroît progressivement sur l'échelle entière des concentrations d'ajout de mercure. La nitrification est réduite par HgCl₂ à des seuils au dessous de 2 et 10 mg de mercure par kg de sol, respectivement pour les sols d'Arusha et de Morogoro. La tolérance des microorganismes au mercure dans cette étude est dans l'ordre: population totale > fixateurs d'azote > nitrificateurs. Ceci peut être expliqué en termes de diversité des espèces de microorganismes qui suit vraisemblablement la même séquence.

     

The effects of phorbol ester on mouse blastomeres: a role for protein kinase C in compaction?

The effects of phorbol myristate acetate (PMA) and other activators of protein kinase C on the cytoskeletal organization of mouse oocytes and early embryos have been examined. The effects observed depended on the developmental stage on exposure to PMA. PMA had little effect on the cytoskeletal or microvillous organization of unfertilized oocytes. Interphase cells from embryos prior to compaction showed limited disruption and loss of microvilli when exposed to PMA and foci of polymerized actin remained visible in the cytocortex of embryos up to the early 8-cell stage. When compacted late 8-cell embryos were exposed to PMA, most microvilli were lost and little polymerized actin remained in the cytocortex. PMA also caused loss of microtubules from compact 8-cell embryos under some experimental conditions. Intercellular flattening was both prevented and reversed. The relevance of these observations to the rearrangement of cell-cell contacts and cytoskeletal organization seen during compaction at the 8-cell stage is discussed and a possible role for protein kinase C in the generation of cell polarity proposed.     

Transmucosal triglyceride transport rates in proximal and distal rat intestine in vivo.

Transmucosal transport rates for triolein in proximal and distal intestine were compared in unanesthetized rats. Emulsified [1-14-C] triolein together with bile and pancreatic juice from donor rats was infused for 6 hr into either the duodenum or the midpoint of the small intestine at such a rate that absorption was essentially complete in both regions of the intestine. Lymph was collected from the thoracic duct during triolein infusion and for an additional 6-hr period. The decrease in the rate of lymphatic output of labeled fat was found to follow a simple exponential function in all animals. This rate of decrease (decay rate) was used to calculate the half-times of lipid turnover through the intestinal wall and the fractional output rates. Distal intestine transported lipid 40% more slowly than proximal intestine, and the difference was associated with a greater accumulation of triglyceride in the distal intestinal wall. Chylomicron synthesis and/or release is the rate-limiting step for distal lymphatic fat transport in vivo, whereas fat uptake from the lumen is rate limiting for proximal intestine.