Phosphorylation of elF-4E and initiation of protein synthesis in P19 embryonal carcinoma cells

Mitogenic stimulation of protein synthesis is accompanied by an increase in elF-4E phosphorylation. The effect on protein synthesis by induction of differentiation is less well known. We treated P19 embryonal carcinoma cells with the differentiating agent retinoic acid and found that protein synthesis increased during the first hour of addition. However, the phosphorylation state, as well as the turnover of phosphate on elF-4E, remained unchanged. Apparently, the change in protein synthesis after RA addition is regulated by another mechanism than elF-4E phosphorylation. By using P19 cells overexpressing the EGF receptor, we show that the signal transduction pathway that leads to phosphorylation of elF-4E is present in P19 cells; the EGF-induced change in phosphorylation of elF-4E in these cells is likely to be regulated by a change in elF-4E phosphatase activity. These results suggest that the onset of retinoic acid-induced differentiation is triggered by a signal transduction pathway which involves changes in protein synthesis, but not elF-4E phosphorylation. © 1995 Wiley-Liss, Inc.     

A nuclear magnetic resonance study of the glucose metabolism of Hymenolepis diminuta exposed to histamine and serotonin in vitro.

The direct effects of the inflammatory mediators, histamine (HI) and serotonin (SE), on the glucose metabolism of Hymenolepis diminuta in vitro were studied by analyzing the excretory products from culture media, containing D-1-13C-glucose and various concentrations of HI and/or SE, by 1H-nuclear magnetic resonance (n.m.r.) spectroscopy. The results revealed that HI markedly accelerated the glycolysis process by increasing the amount of lactate production. The increased glycolytic activity was reflected in a concentration-dependent increase in glucose uptake. Excretion of acetate was also stimulated by HI. A low concentration of SE significantly increased succinate, acetate and lactate excretions, whereas a high concentration had little effect on lactate production and significantly decreased succinate and acetate excretions. A combination of HI and SE treatment at a low concentration had no significant effect, but at a high concentration showed an additive effect, with an increase in lactate production, a decrease in succinate production and an increase in glucose uptake. Thus this work confirms that HI and SE directly influence, albeit differently, energy metabolism of the tapeworm H. diminuta.     

Current aspects of the short-term prognosis of meningococcal infection morbidity for the sake of epidemiological surveillance

The short-term prognosis of the epidemic situation requires the establishment of the system of constant surveillance, which takes into account the data on morbidity rates for several years, both total and in various age groups, the data on the morbidity level and its changes, induced by meningococci of the epidemic group, in the IV quarter of the year, the data on the level of carriership among the indicator groups of the population in this period, as well as the data on changes in antibody titers in the sera of donor blood samples taken in summer and in December.     

Nucleoid structure and partition in Methanococcus jannaschii: an archaeon with multiple copies of the chromosome.

We measured different cellular parameters in the methanogenic archaeon Methanococcus jannaschii. In exponential growth phase, the cells contained multiple chromosomes and displayed a broad variation in size and DNA content. In most cells, the nucleoids were organized into a thread-like network, although less complex structures also were observed. During entry into stationary phase, chromosome replication continued to termination while no new rounds were initiated: the cells ended up with one to five chromosomes per cell with no apparent preference for any given DNA content. Most cells in stationary phase contained more than one genome equivalent. Asymmetric divisions were detected in stationary phase, and the nucleoids were found to be significantly more compact than in exponential phase.     

Radioprotection après injection thérapeutique de [131I]-mIBG : données préalables à l’ouverture du protocole MIITOP-0607

IntroductionThe MIITOP-0607 protocol, studying the efficiency of administration of topotecan and myelosupressive [¹³¹I]-mIBG therapy in children affected by neuroblastoma, needed to assess irradiation risks on staff and family of children to obtain the agreement of the Autorité de sûreté nucléaire (ASN). Our aim was to quantify irradiation of the staff during preparation of the mIBG and to assay the irradiation and contamination of the accompanying persons.Patient and methodsRadiation exposure of the staff was measured during the preparation, transport and administration of the first treatment. Salivary and urinary excretions were monitored well as the atmospheric radioactivity. Radiation exposure and contamination of the accompanying persons were also measured.ResultsFinger dose of 3 mSv and whole body dose of 50 μSv were estimated for preparation of an 11.1 GBq syringe. Irradiation from urinary activity can be as low as 100 μSv if a dedicated device is used. Salivary excretion decreased rapidly during the first 24 hours. Atmospheric contamination always remained below 25 Bq m^?3. Total irradiation of the accompanying persons is about 2.35 mSv for the two consecutive injections (9,3 and 11,1 GBq). Internal contamination occurred only once and corresponded to a 27 μSv whole body irradiation and 670 μSv thyroid irradiation.ConclusionThis study shows the safety of [¹³¹I]-mIBG treatments using high activities. The involved dose is not negligible but seems to be acceptable in the specific paediatric oncology context if radioprotection instructions are met and if optimization of protocols is performed.     

Effects of glucose, tetrapyrroles and protein kinase C activators on cell proliferation in cultures of Saccharomyces cerevisiae

Abstract Saccharomyces cerevisiae was inoculated into a yeast nitrogen base with either glycerol or glucose as carbon source. Cell proliferation was followed by colony counts on agar medium. Cells in the glycerol-supplemented medium divided less than once in 10 days. When glucose, 6-deoxy-glucose or protoporphyrin IX was added, the cells had doubling times of about 24 h and increased in number to about 0.5 × 10⁶ cells ml⁻¹ Addition of either of the protein kinase C activators oleoyl-acetylglycerol or phorbol-12-myristate-13-acetate did not activate cell proliferation in the glycerol medium. However, when (i) glucose was combined with either protoporphyrin IX or chlorophyllin, or (ii) either protoporphyrin IX or chlorophyllin was combined with either of the protein kinase C activators, the cells had doubling times of about 12 h. Hence, (i) glucose can act as both a carbon source and a signalling molecule for proliferation, and (ii) two systems are involved in activating cell proliferation in S. cerevisiae : one operating through a protein kinase C system and another through a guanylate cyclase system.     

POMC gene-derived peptides activate melanocortin type 3 receptor on murine macrophages, suppress cytokine release, and inhibit neutrophil migration in acute experimental inflammation.

To investigate the relevance of adrenocorticotrophic hormone (ACTH) therapy in human gouty arthritis, we have tested the effect of several ACTH-related peptides in a murine model of experimental gout. Systemic treatment of mice with ACTH4-10 (MEHFRWG) (10-200 microgram s. c.) inhibited neutrophil accumulation without altering peripheral blood cell counts or circulating corticosterone levels. A similar effect was seen with alpha- and beta-melanocyte stimulating hormones (1-30 microgram s.c.). In vivo release of the chemokine KC-(detected in the lavage fluids before maximal influx of neutrophils) was significantly reduced (-50 to -60%) by ACTH4-10. Macrophage activation in vitro, determined as phagocytosis and KC release, was inhibited by ACTH and ACTH4-10 with approximate IC50 values of 30 nM and 100 microM, respectively. The melanocortin receptor type 3/4 antagonist SHU9119 prevented the inhibitory actions of ACTH4-10 both in vitro and in vivo. However, melanocortin type 3, but not type 4, receptor mRNA was detected in mouse peritoneal macrophages by RT-PCR. Therefore, we propose that activation of this receptor type by ACTH4-10 and related amino acid sequences attenuates KC release (and possibly production of other cytokines) from macrophages with consequent inhibition of the host inflammatory response, thus providing a notional anti-inflammatory mechanism for ACTH that is unrelated to stimulation of glucocorticoid release.     

Effects of two-vessel forebrain ischemia and of administration of indomethacin and quinacrine on Na<Superscript>+</Superscript>, K<Superscript>+</Superscript>-ATPase activity in various rat brain areas

The effect of a two-vessel forebrain ischemia (induced by occlusion of carotid arteries and hypotension), subsequent reperfusion, and administration of indomethacin and quinacrine on the Na⁺,K⁺-ATPase activity and diene conjugate content was studied in various rat forebrain fields. The most pronounced metabolic alterations were observed during ischemia and reperfusion. Under these effects, there was a statistically significant reduction of the Na⁺,K⁺-ATPase activity in the brain cortex and striatum and an increase of the diene conjugate content in the rat brain cortex in comparison with sham-operated animals. Injection of indomethacin, a cyclooxygenase inhibitor, to rats subjected to ischemia and reperfusion, resulted to a statistically significant increase of the Na⁺,K⁺-ATPase activity in the brain cortex, hippocampus, and striatum (p < 0.02) as compared with control animals. The diene conjugate content in the rat brain cortex during brain ischemia and reperfusion was statistically significantly lower in the rats injected with indomethacin. The effect of quinacrine (a blocker of phospholipase A₂) was similar to that of indomethacin in the rat cortex, whereas in the rat striatum and hippocampus, the quinacrine effect during ischemia and reperfusion was less marked than that of indomethacin. The obtained data indicate the ability of inhibitors of the arachidonic pathway of free radical formation to normalize the Na⁺, K⁺-ATPase activity during brain ischemia. There also revealed local peculiarities of metabolic disturbances in different regions of the rat forebrain during ischemia and reperfusion.Translated from Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, Vol. 41, No. 1, 2005, pp. 33–38.Original Russian Text Copyright © 2005 by Molchanova, Moskvin, Zakharova, Yurlova, Nosova, Avrova.