Oct transcription factors mediate t(14;18) lymphoma cell survival by directly regulating bcl-2 expression.

Oct-1 and Oct-2 are members of the POU homeodomain family of transcriptional regulators and are critical for normal embryonic development. Gene-targeting studies showed that Oct-1 and Oct-2 are largely dispensable for B-cell development and immunoglobulin production, although both Oct-2 and Bob-1 are required for a proper immune response and germinal center formation. In these studies, we investigated the role of Oct factors in B-cell lymphomas. Recent investigations have shown increased expression of Oct-2 and Bob-1 in lymphomas, and we observed greatly increased levels of Oct-2 in lymphoma cells with the t(14;18) translocation. Decreased expression of Oct-1, Oct-2, or Bob-1 by RNA interference resulted in apoptosis and down-regulation of bcl-2 expression. Furthermore, Oct-2 induced bcl-2 promoter activity and mediated this effect through three regions in the bcl-2 P2 promoter. Although these regions did not contain canonical octamer motifs, we observed the direct interaction of Oct-2 with all three sites both in vitro by EMSA and in vivo by chromatin immunoprecipitation assay. Moreover, by mutation analysis we found that the ability of Oct-2 to activate bcl-2 required C/EBP, Cdx, and TATA-binding sites. Oct-2, therefore, acts as a cell survival factor in t(14;18) lymphoma cells by directly activating the antiapoptotic gene bcl-2.

Effect of dietary iron on the course of Plasmodium berghei malaria in young rats.

Clinical and experimental evidence suggests that iron-deficient hosts are less susceptible to severe malaria and that iron supplementation aggravates infection. In the present study, 60 weanling Wistar rats were fed standard diets with different iron concentrations: 21 mg/kg (group 1), 45 mg/kg (group 2) and 113 mg/kg (group 3). Ferrous sulfate (FeSO4 x 7H2O) was added to the normal-iron and iron-supplemented diets (groups 2 and 3, respectively). Data are reported as mean +/- SEM. After 16 days of regimen, eight rats from each group were killed to measure serum iron concentration (SI) and transferrin saturation capacity (TSC). At this moment, rats from group 1 were underweight and their dietary intake was significantly lower than that of animals from the other groups. Severe iron deficiency (SI = 49.2 +/- 4.5 micrograms/100 ml and TSC = 8.3 +/- 0.7%) was observed in rats from group 1, while the animals from the other groups were iron-sufficient (group 2: SI = 186.5 +/- 28.5 micrograms/100 ml and TSC = 27.3 +/- 3.4%; group 3: SI = 137.3 +/- 18.2 micrograms/100 ml and TSC = 21.3 +/- 2.3%). Nine animals from each group were then infected with the malaria parasite Plasmodium berghei, whereas three animals from each group were used as noninfected controls. Parasitemias (% of infected red blood cells) peaked 7 days post-infection in animals from groups 2 and 3 (mean values of 2.4% and 1.7%, respectively), but in animals from group 1 parasitemias increased until the 9th day post-infection (mean at peak, 2.3%) and parasite clearance was significantly slower than in the other groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of dietary iron on the course of Plasmodium berghei malaria in young rats

Clinical and experimental evidence suggests that iron-deficient hosts are less susceptible to severe malaria and that iron supplementation aggravates infection. In the present study, 60 weanling Wistar rats were fed standard diets with different iron concentrations: 21 mg/kg (group 1), 45 mg/kg (group 2) and 113 mg/kg (group 3). Ferrous sulfate (FeSO4 x 7H2O) was added to the normal-iron and iron-supplemented diets (groups 2 and 3, respectively). Data are reported as mean +/- SEM. After 16 days of regimen, eight rats from each group were killed to measure serum iron concentration (SI) and transferrin saturation capacity (TSC). At this moment, rats from group 1 were underweight and their dietary intake was significantly lower than that of animals from the other groups. Severe iron deficiency (SI = 49.2 +/- 4.5 micrograms/100 ml and TSC = 8.3 +/- 0.7 per cent ) was observed in rats from group 1, while the animals from the other groups were iron-sufficient (group 2: SI = 186.5 +/- 28.5 micrograms/100 ml and TSC = 27.3 +/- 3.4 per cent ; group 3: SI = 137.3 +/- 18.2 micrograms/100 ml and TSC = 21.3 +/- 2.3 per cent ). Nine animals from each group were then infected with the malaria parasite Plasmodium berghei, whereas three animals from each group were used as noninfected controls. Parasitemias ( per cent of infected red blood cells) peaked 7 days post-infection in animals from groups 2 and 3 (mean values of 2.4 per cent and 1.7 per cent , respectively), but in animals from group 1 parasitemias increased until the 9th day post-infection (mean at peak, 2.3 per cent ) and parasite clearance was significantly slower than in the other groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolism of triglyceride-rich emulsions in rats with protein malnutrition.

Knowledge of chylomicron metabolism is very important in understanding and treating protein malnutrition, since these particles are the primary carriers of dietary fat in lymph and plasma. In the bloodstream, fat transported in chylomicrons is hydrolyzed by the action of lipoprotein lipase and the resulting fatty acids and glycerol are taken up by the body tissues. Chylomicron remnants are then rapidly removed by the liver. To clarify chylomicron metabolism in protein malnutrition, triglyceride-rich emulsions known to behave metabolically like lymph chylomicrons and labeled with 14C-cholesteryl ester and 3H-triglycerides were injected intraarterially into control rats and rats fed a protein-deficient diet for 40 days. Plasma kinetics and organ uptakes of the labeled lipids were determined. Hydrolysis of the emulsion triglycerides by lipoprotein lipase was not different in the malnourished rats (TG-FCR = 0.250 +/- 0.027 m-1 vs 0.250 +/- 0.070 m-1 in controls), but plasma clearance of the resulting triglyceride-depleted emulsion remnant particles was markedly lower compared to controls (cholesteryl-ester FCR = 0.088 +/- 0.009 and 0.146 +/- 0.019 m-1, respectively, p < 0.001). These results were obtained regardless of the amount of emulsion lipid that was injected. Liver atrophy seem to account for the delayed remnant uptake in protein-depleted rats. These data provide insight into the consequences of parenteral nutrition with lipid emulsions when administered in states of protein malnutrition.

[Influence of protein malnutrition on the phagocytic function of neutrophils in rats]. / Influência da desnutrição proteica sobre a função fagocitária de neutrófilos de ratos.

A study was carried out to determine the effect of protein deficiency on the phagocytic function of blood neutrophils and of peritoneal exudate of rats. The deficient animals exhibited significantly lower leukocyte and neutrophil values, as well as NBT reduction and diminished peroxidase and bactericidal capacity. Englobement of S. aureus and latex particles was found to be normal in both groups. Alkaline phosphatase activity in the neutrophils appear to be increased in the deficient animals.

Survival of myocutaneous flaps. Experimental evaluation by intra-arterial injection of a dye.

Ninety-four myocutaneous island flaps of the pectoralis major were studied in the rabbit using sulfan blue (Disulphine-blue). In 13 cases, the dye was injected intra-arterially in the acromiothoracic artery before the flap was lifted, and 47 more were injected after the lifting of the flap. In 34 further cases, sulfan blue was injected intravenously once the flap had been lifted. In another 16 flaps, vascularization was studied by means of "diaphanization" (ie, making the tissue transparent or diaphenous in nature). In all groups, the surviving length of flap was observed to be greater than the stained length. Intra-arterial administration of sulfan blue was associated with reduced flap survival. Viable flap length was not related to the anatomy of the vascular base.