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Biomedical subjects

C Simoens

Publications and source records attributed to C Simoens.

18 recordsLinked to original sources

In vitro interaction between ecteinascidin 743 (ET-743) and radiation, in relation to its cell cycle effects.

Ecteinascidin 743 (ET-743) is a new marine-derived agent with promising activity against a number of solid tumours. In four human tumour cell lines, the interaction between ET-743 and radiation was investigated in relation to the effects of ET-743 on the cell cycle, in vitro. Cell survival was measured based on quantitative staining of cellular protein by sulforhodamine B. A 24 h treatment with ET-743 before radiation resulted in a moderate increase in radiosensitivity in three out of four cell lines. Dose enhancement factors > or =1.8 were observed for concentrations resulting in 52, 46 and 30% cell kill in ECV304, H292 and CAL-27, respectively, whereas in A549 no radiosensitisation was observed (no significant increase in radiosensitivity). According to the combination index analysis, synergism was observed only in ECV304 and CAL-27 cells. A 24 h incubation with ET-743 resulted in a concentration-dependent G2/M block, which might explain the moderate radiosensitising effects in ECV304 and H292. The lack of radiosensitisation in A549 might be due to the S phase delay preceding the G2/M block at the moment of radiation, which only occurred in this cell line. In conclusion, ET-743 has moderate cell line-dependent radiosensitising properties; however, only when cytotoxic concentrations of ET-743 are used. In one of the four cell lines tested, no radiosensitisation was observed.

Antineoplastic Agents, Alkylating↗

Retroperitoneoscopic lumbar sympathectomy with balloon dissection: clinical experience.

PURPOSE: To describe our technique and clinical experience of retroperitoneoscopic lumbar sympathectomy with balloon dissection. PATIENTS AND METHODS: From 1995 to 1999, 23 procedures were performed. RESULTS: No complications were noted. The median hospital stay was 4 days. Of the 23 attempts, 2 had to be converted to open technique. Histologic examination demonstrated interruption of the sympathetic chain in 22 of the 23 cases and absence of nervous tissue in 1. CONCLUSIONS: Once the technique is mastered, it can be performed fast, and it offers patients the benefits of a minimally invasive approach without the inconsistent therapeutic results of chemical sympathectomy.

Aged↗

Effect of sublethal doses of cadmium, inorganic mercury and methylmercury on the cell morphology of an insect cell line (Aedes albopictus, C6/36).

The effect of CdCl2 (44 microM), HgCl2 (3.7 microM), and MeHgCl (2 microM) on the morphology of Aedes albopictus C6/36 cells was studied at the light microscopical level. Treatment times and metal concentrations were in the sublethal range as determined by a fluorometric dye exclusion test. The three metal species had profound effects on the cell morphology. MeHgCl treatment induced the development of a large number of short, actin-supported, tangled filopodia. Both CdCl2 and HgCl2 induced long extensions. Pretreatment with colchicine but not with cytochalasin B prevented formation of these extensions which suggests that they were supported by microtubules. This was confirmed by immunostaining for microtubules. The extensions were relatively stable towards colchicine post-treatment. To authors' knowledge, this effect has not yet been described for heavy metals. The similarity with 20-hydroxyecdysone-treated cells and the occurrence of cytoplasmic feet in insect cells is discussed.

Actins↗

Recent developments in lipid emulsions: relevance to intensive care.

For years, intravenous lipid supply has been considered as a means of providing an efficient fuel to many tissues of the body and of preventing or correcting essential fatty acid deficiency. The potential for lipid emulsions to modulate cell function via their content of specific fatty acids and of liposoluble vitamins has not received much attention yet. Soybean [long-chain triglycerides (LCT)] emulsions provide a valuable source of energy, but they are excessively rich in omega-6 essential fatty acids (FAs). Their infusion is associated with an accumulation of linoleate and a reduction of long-chain (> or = C20) omega-6 and omega-3 fatty acids in cell membrane phospholipids, as well as with a depletion of antioxidant status, associated with a reduction of alpha-tocopherol in plasma lipoproteins. Infusions of the mixed medium-chain triglycerides (MCT)/LCT (50%:50%; wt:wt) largely bypass these disadvantages. In addition, plasma elimination of MCT/LCT is faster than that of LCT. Recent advances indicate a great potential for omega-3 FAs incorporated into membrane phospholipids to modulate cell response to various stimuli and to influence several intracellular metabolic processes. Furthermore, some of these FA directly influence the production and the action of important mediators, the eicosanoids. In practical terms, an increased intake of omega-3 FAs may reduce inflammatory and thrombotic responses while protecting tissue microperfusion and immune defenses. Such properties may find interesting applications in several types of intensive care unit patients, provided that omega-3 FA incorporation takes place promptly. We recently had the opportunity to study in vitro and in vivo the metabolism of emulsions made of a mixture of MCT, soybean LCT, and fish oil triglycerides. Plasma elimination of such preparations appeared to be very fast, and their infusion was not associated with a prolonged residence of emulsion particles. In addition, uptake of remnants enriched with omega-3 FAs and liposoluble vitamins was fairly fast and occurred in several types of cells, leading to an efficient incorporation of omega-3 FAs in cell membranes within a few hours. The understanding that remnant uptake plays a significant role in the delivery of components included in lipid emulsions opens new areas of investigation and is likely to find several conditions of applications for new types of preparations.

Antioxidants↗

Manipulation of tissue fatty acid profile by intravenous lipids in dogs.

This study was undertaken to determine the effects on the fatty acid (FA) composition of various dog tissues of 4 different lipid emulsions (a 100% long-chain triacylglycerol (LCT) derived from soya bean oil emulsion, a mixed 50% medium-chain triacylglycerol (MCT)/50% LCT emulsion as well as both these emulsions supplemented with 10% fish oil (FO) triacylglycerols), when daily infused over 15 days as a substantial component of total parenteral nutrition. Lipids represented 55% of the non-protein energy. Blood samples as well as biopsies from liver, muscle and adipose tissue were taken 15 days before, and again immediately after TPN. In addition, the spleen was also removed immediately after TPN. Tissue FA composition was analysed by gas liquid chromatography of each lipid component after separation by thin layer chromatography. No differences in either safety or tolerance were detected between the different TPN preparations. In particular, infusion over 2 weeks of fat emulsions containing 10% fish oil was tolerated as well as conventional LCT and MCT/LCT emulsions. Relative linoleate content of tissue triacylglycerol (TG) was markedly increased in animals that received the LCT emulsions (e.g. from 22.6 +/- 2.5% to 32.2 +/- 0.6% in the liver), this effect being markedly reduced with MCT/LCT preparations. n-3FA were slightly incorporated into liver TG (from 0.0 +/- 0.0% to 2.3 +/- 0.7% and 1.2 +/- 0.4% for eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) respectively, with LCT + FO), but remained undetectable in extrahepatic tissue TG. Of interest, medium chain FA were found in tissue TG after infusion of the mixed MCT/LCT emulsions. As expected, changes of tissue phospholipid (PL) composition involved only long-chain FA. Infusion of soya bean oil emulsion was associated with an increased content of linoleate in liver PL (from 13.6 +/- 0.4% to 17.7 +/- 0.4%), but not in other tissues. MCT/LCT did not markedly affect PL/FA pattern in any tissue. Supplementation with fish oil was associated with an efficient incorporation of n-3FA into tissue PL, particularly in the liver (from 0.4 +/- 0.1% to 2.5 +/- 0.3% for EPA and from 3.9 +/- 0.8% to 9.1 +/- 0.4% for DHA, with the LCT + FO emulsion).

Journal Article↗

Genetic engineering in plants.

Until now most research, and its funding, has been focused on animal and human health care as well as simple microbiological model systems such as Escherichia coli and yeast. Molecular plant studies have generally lagged behind, often simply adapting discoveries from the animal field to plants. Clearly, good health and the efficient tackling of diseases is crucial for the well-being of humans, and good remedies have a high economic value for the pharmaceutical industry. However, one should not forget that plants are an essential component of the large ecosystem that is our planet. They are not only the basic food producers but they are also necessary for a balanced atmosphere (oxygen production) and stable and viable climates. Especially in this period of demographic explosion and growing environmental deterioration, there is a need to rebuild our agricultural systems. Plants also have a wide variety of 'non-food' uses, for instance as energy sources, construction materials, or cosmetics. Last, but not least, they produce a lot of chemicals that can be used as pharmaceuticals. The growing awareness of the importance of plants has coincided with the development of plant molecular biology. Specific features make them ideally suited for gene engineering and genetic studies in general.

Biotechnology↗

Inflorescence-specific genes from Arabidopsis thaliana encoding glycine-rich proteins.

Genomic and cDNA clones for three inflorescence-specific genes from Arabidopsis thaliana were isolated and characterized. The genes are tandemly organized in the genome on a 10 kb fragment. The expression of these genes is coordinately regulated in a developmental and organ-specific pattern. They are expressed predominantly in anthers at the later stage of flower development. The primary structure of the encoded gene products exhibits comparable features consisting of a hydrophobic domain at the N-terminal region followed by repeated glycine-rich motifs. Little homology is observed either between the glycine-rich domain of the three genes or with previously described glycine-rich proteins from other plant species.

Amino Acid Sequence↗

Use- and frequency-dependent blockade by UL-FS 49 of the if pacemaker current in sheep cardiac Purkinje fibres.

The mechanism by which the bradycardiac agent UL-FS 49 blocks the if pacemaker current was investigated in sheep Purkinje fibres using the two microelectrode voltage-clamp technique. If was activated by 1 s pulses applied between -30 mV and -120 mV at 0.4 Hz in a modified Tyrode solution containing BaCl2 and MnCl2, and with TRIS replacing most of the Na+. UL-FS 49 caused an exponential decline of the if current amplitude during a train of pulses. Both the rate and extent of the if reduction increased with drug concentration, without there being a resting blockade. Recovery from blockade followed a single exponential time course during prolonged hyperpolarizations. The recovery rate was extremely slow and increased with more negative voltages, as did the extent of steady state recovery from blockade. A frequency-dependent reduction of the diastolic depolarization rate resulted from a use-dependent blockade of the pacemaker current.

Animals↗

[Efficacy of percutaneous caffeine in the treatment of apnea in the premature infant].

In 18 prematures (gestational age less than 32 weeks), an aqueous monohydrated caffeine colloidal gel was administered topically. High plasma levels were rapidly obtained with a loading dose divided in 4 applications by massaging, 1 ml of gel per kg body weight, at 12 hour intervals (18 mg caffeine base/kg). Maintenance was then instituted with a dose of 0.5 ml/kg/day. Treatment was initiated before 8 days of life, in children under assisted ventilation but without severe pulmonary involvement, during the period of weaning from the respirator. A good local and general tolerance was invariably observed and remarkable therapeutic efficacy was obtained.

Administration, Cutaneous↗

Effect of acute suppression of acid secretion by omeprazole on postprandial gastrin release in conscious dogs.

The effect of acute suppression of acid secretion induced by administration of a single dose of omeprazole (2 mg/kg body wt) on postprandial gastrin release was studied in 10 conscious dogs. In omeprazole-treated dogs, a sustained gastrin release was observed during a 10-h period after feeding, although greater than 95% of the meal had left the stomach after 4 h. This sustained gastrin release could be inhibited by acidification of the gastric lumen, by somatostatin, and by atropine. Insulin and bombesin induced considerable gastrin release in omeprazole-treated dogs, but plasma gastrin concentrations returned almost to basal values after 3 h. Omeprazole administered alone had no significant effect on basal gastrin levels. These data indicate that, in dogs, when acid secretion is suppressed by omeprazole a meal induces a sustained gastrin release lasting for up to 10 h. This gastrin release is probably related to the fact that food has been in contact with the gastric lumen, as neither vagal nor bombesin stimulation induced such a sustained activity of the G cells.

Animals↗

Effect of cimetidine, ranitidine and omeprazole on postprandial gastrin and somatostatin release in conscious dogs.

During a first series of experiments, the gastrin responses to a meal were measured and compared to the responses seen after administration of cimetidine (2.5 mg/kg/h) or omeprazole (2 mg/kg). During a second series of experiments the effects of cimetidine (2.5 mg/kg/h), ranitidine (0.5 mg/kg/h) and omeprazole (2 mg/kg) on post-prandial gastrin and somatostatin release were determined in experiments during which the intragastric pH was maintained close to 6.4. During a third series of experiments, the effects of cimetidine (2.5 mg/kg/h) and omeprazole (2 mg/kg) on basal gastrin and somatostatin release were estimated. Postprandial gastrin release was increased by cimetidine and by omeprazole. When acidification of the gastric content was prevented by intragastric titration, postprandial gastrin release was increased by about 100%. No further increase was observed when the animals were concomitantly treated with cimetidine, ranitidine or omeprazole. Intragastric titration did not alter postprandial somatostatin release. Concomitant administration of H2 blockers decreased the somatostatin response to the meal, while concomitant administration of omeprazole did not alter this release. No significant changes were observed in basal gastrin or somatostatin levels after administration of cimetidine or omeprazole.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of vagotomy and atropine on plasma somatostatin response to a meal in conscious dogs.

In 4 conscious dogs with gastric fistulas the somatostatin responses to a meal were measured and compared to the responses seen after i.v. infusion of atropine sulfate (20 and 50 micrograms.kg-1.h-1) or cimetidine (8 mg.kg-1.h-1). The experiments were repeated after truncal vagotomy. The somatostatin responses to bombesin (0.5 micrograms.kg-1.h-1) were also measured before and after vagotomy. Vagotomy decreased basal and postprandial somatostatin levels and reduced the somatostatin responses to feeding during the first 30-min period following the ingestion of the meal but not during subsequent periods. Bombesin-induced somatostatin release was increased after vagotomy. Atropine decreased the somatostatin responses to the meal before and after vagotomy. Cimetidine had no significant effect. These studies suggest that, in conscious dogs, somatostatin released into the circulation is partly under vagal control and that, as for gastrin release, vagal pathways for stimulation and inhibition are present. Our studies also suggest that cholinergic mechanisms are involved in the control of postprandial somatostatin release.

Animals↗

High meiotic stability of a foreign gene introduced into tobacco by Agrobacterium-mediated transformation.

Two lines of transgenic Nicotiana tabacum transformed to kanamycin resistance by means of a binary Agrobacterium vector containing a nos-npt gene were investigated over three generations. Southern hybridization and crossing analyses revealed that a single copy of T-DNA had integrated in each line and that the kanamycin resistance was regularly transmitted to the progeny as a monogenic dominant trait. Homozygous transgenic plants were fully fertile, morphologically normal and did not significantly differ from wild-type plants in the quantitative characters examined (plant height, flowering time). The two lines showed very low, but significantly different levels of meiotic instability: kanamycin-sensitive plants occurred among backcross progeny from homozygous transgenic plants with frequencies of 6/45,000 and 25/45,000, respectively. The sensitive plants arose independently of each other and thus resulted from meiotic rather than mitotic events. These findings demonstrate for the first time that integrated foreign genes can be transmitted to progeny with the high degree of meiotic stability required for commercial varieties of crop plants. They emphasize the importance of non-homologous integration and of avoiding co-integration of inactive gene copies for achieving meiotically stable transformants.

Genetic Vectors↗

A binary vector for transferring genomic libraries to plants.

The transformation of mutant plants with a complete recombinant library derived from wild-type DNA followed by assay of transformed plants for complementation of the mutant phenotype is a promising method for the isolation of plant genes. The small genome of Arabidopsis thaliana is a good candidate for attempting this so-called shotgun transformation. We present the properties of an A. thaliana genomic library cloned in a binary vector, pC22. This vector, designed to introduce genomic libraries into plants, contains the oriV of the Ri plasmid pRiHR1 by which it replicates perfectly stably in Agrobacterium. Upon transfer of the library from E. coli to A. tumefaciens large differences in transfer efficiencies of individual recombinant clones were observed. There is a direct relation between transfer efficiency and stability of the recombinant clones both in E. coli and A. tumefaciens. The stability is independent of the insert size, but seems to be related to the nature of the insert DNA. The feasibility of shotgun transformation and problems of statistical sampling are discussed.

Cloning, Molecular↗

Acute pneumoperitoneum without peritonitis. A case report.

An uncommon case of pneumoperitoneum without peritonitis, related to small bowel diverticulosis is presented. Pneumoperitoneum is usually a life-threatening incident, most frequently attributed to a perforated viscus and generally requiring emergency surgery. Non surgical pneumoperitoneum, however, is known to be caused by a variety of pathological and non pathological entities. Small bowel diverticulosis is an extremely rare cause of chronic pneumoperitoneum without peritonitis. In the presence of mechanical bowel obstruction, the latter kind of pneumoperitoneum can suddenly become impressively increased. A conservative attitude is generally advocated in the presence of such a benign pneumoperitoneum. However, laparoscopic exploration may be helpful for the diagnosis.

Acute Disease↗

Recurrent gastrointestinal blood loss of obscure origin: report of an exceptional case.

A 66-year old tailor was admitted because of venous insufficiency of the left lower leg. During the hospital course, recurrent severe gastrointestinal blood loss developed. A classical approach was extended by enteroscopy and radionuclide scanning, followed by exploratory laparatomy with removal of two intra-abdominal sewing needles and a jejunal leiomyoma. After surgery, bleeding did not recur. This case illustrates the difficult diagnostic work-up of obscure gastrointestinal bleeding. It also shows that intra-abdominal sewing needles may migrate in the intestinal tract and remain silent during many years, eventually causing gastrointestinal bleeding.

Abdomen↗