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Biomedical subjects

F Thomas

Publications and source records attributed to F Thomas.

At least 37 records · Page 2Linked to original sources

Near-infrared spectroscopy: does it function in functional activation studies of the adult brain?

Changes in optical properties of biological tissue can be examined by near-infrared spectroscopy (NIRS). The relative transparency of tissues including the skull to near-infrared light is the prerequisite to apply the method to brain research. We describe the methodology with respect to its applicability in non-invasive functional research of the adult cortex. A summary of studies establishing the 'typical' response in NIRS vascular parameters, i.e. changes in the concentration of oxygenated and deoxygenated haemoglobin, over an activated area is followed by the validation of changes in the cytochrome-oxidase redox state in response to a visual stimulus. Proceeding from these findings a rough mapping of this metabolic response over the motion-sensitive extrastriate visual area is demonstrated. NIRS measures concentration changes in deoxygenated haemoglobin [deoxy-Hb] which are assumed to be the basis of fMRI BOLD contrast (blood oxygenation level-dependent). The method is therefore an excellent tool to validate assumptions on the physiological basis underlying the fMRI signal, due to its high specificity as to the parameters measured. Questions concerning the concept of 'activation'/'deactivation' and that of the linearity of the vascular response are discussed. To challenge the method we finally present results from a complex single-trial motor paradigm study testing the hypothesis, that premotor potentials (contingent negative variation) can be examined by functional techniques relying on the vascular response. Some of the work described here has been published elsewhere.

Adult↗

Are there pros as well as cons to being parasitized?

The diversity of ways in which parasites reduce the fitness of their hosts has been documented during the past decades, and clearly indicates that parasites can often be considered as direct agents of selection. In natural systems, however, the outcome of a host-parasite interaction might be strongly determined by other ecological factors. Parasites can be detrimental to host fitness in one environment, whereas they can be beneficial to it in another. From an evolutionary perspective, this phenomenon is of considerable importance for understanding the dynamics of coevolution among geographically structured populations evolving under different ecological pressures. Here, Frédéric Thomas and colleagues review several ecological situations in which parasitized individuals enjoy a selective advantage over unparasitized conspecifics.

Animals↗

New advances in pharmacogenomics.

In the years to come, pharmacogenomics will make an impact on the development of new drugs. Numerous publications have shown that gene polymorphism can influence drug toxicity and/or efficacy. In order to improve current applications of pharmacogenomics, some technical limitations regarding marker generation, genotyping and biostatistical analysis are being overcome.

Drug Design↗

Aseptic meningitis after posterior fossa surgery treated by pseudomeningocele closure.

Aseptic meningitis is a recognised complication after posterior fossa surgery. It is often self limiting but occasionally runs a protracted course requiring repeated CSF examination to exclude infection, and treatment with systemic steroids. A patient is described with aseptic meningitis after posterior fossa surgery who underwent posterior fossa re-exploration nearly 3 years after the initial operation. This disclosed a pseudomeningocele, which was closed. The patient remains symptom free almost 2 years after closure. In this case of chronic aseptic meningitis after posterior fossa surgery, closure of the pseudomeningocele found at exploratory surgery led to resolution of the symptoms.

Adolescent↗

Differential parasite (Trematoda) encapsulation in Gammarus aequicauda (Amphipoda).

Because resistance to parasites usually has a cost for host species, it is theoretically expected that, in case of multi-infection, host immune responses should vary according to the levels of parasite pathogenicity. The crustacean gammarid Gammarus aequicauda is the second intermediate host of 4 trematode species. Three of these parasites always encyst in the abdomen of gammarids and have no particular effect on the host. However, 1 of these species is sometimes able to encyst in the cerebroid ganglia of the gammarid and strongly alter its behavior in a way that increases its predation risk by aquatic birds, the definitive hosts. In accordance with the hypothesis that the level of parasite pathogenicity influences the likelihood and the degree of host reaction, cases of melanization in our gammarid collection almost exclusively concern the cerebral metacercariae. Our results also indicate that this melanization is able to cancel the behavioral alterations induced by the parasite, suggesting that the cause of the manipulation is not the physical presence of metacercariae in the brain.

Animals↗

Partition coefficients (free ligands and their iron(III) complexes) and lipophilic behavior of new abiotic chelators. Correlation to biological activity.

Partition coefficients between n-octanol and water have been measured for ten tripodal ligands with catecholate or hydroxyquinolinate or pyridinophenolate chelating subunits and for their iron(III) complexes. The abilities of the ligands to cross an octanol phase and to extract ferric ion from its EDTA complex in an aqueous phase are studied. Correlation with biological properties are discussed.

Ferric Compounds↗

Calcein as a fluorescent probe for ferric iron. Application to iron nutrition in plant cells.

The recent use of calcein (CA) as a fluorescent probe for cellular iron has been shown to reflect the nutritional status of iron in mammalian cells (Breuer, W., Epsztejn, S., and Cabantchik, Z. I. (1995) J. Biol. Chem. 270, 24209-24215). CA was claimed to be a chemosensor for iron(II), to measure the labile iron pool and the concentration of cellular free iron(II). We first study here the thermodynamic and kinetic properties of iron binding by CA. Chelation of a first iron(III) involves one aminodiacetic arm and a phenol. The overall stability constant log beta111 of FeIIICAH is 33. 9. The free metal ion concentration is pFeIII = 20.3. A (FeIII)2 CA complex can be formed. A reversible iron(III) exchange from FeIIICAH to citrate and nitrilotriacetic acid is evidenced when these ligands are present in large excess. The kinetics of iron(III) exchange by CA is compatible with metabolic studies. The low reduction potential of FeIIICAH shows that the ferric form is highly stabilized. CA fluorescence is quenched by 85% after FeIII chelation but by only 20% using FeII. Real time iron nutrition by Arabidopsis thaliana cells has been measured by fluorimetry, and the iron buffer FeIIICAH + CA was used as source of iron. As a siderophore, FeIIICAH promotes cell growth and regreening of iron-deficient cells more rapidly than FeIIIEDTA. We conclude that CA is a good chemosensor for iron(III) in cells and biological fluids, but not for Fe(II). We discuss the interest of quantifying iron buffers in biochemical studies of iron, in vitro as well as in cells.

Cells, Cultured↗

Interaction of a spin-labeled adenine-acridine conjugate with a DNA duplex containing an abasic site model.

The abasic site is a common lesion in DNA that is also formed as an intermediate in the base excision repair of damaged bases. We have previously reported the adenine-acridine conjugate 1 that was designed to bind to the abasic site and interfere with the repair process. High-field NMR had shown that 1 forms specific complexes with a DNA duplex containing an apurinic abasic site model. We report here the dynamics of the interaction of the nitroxide-labeled analogue 3 of the conjugate 1 with the same apurinic oligonucleotide and with the parent unmodified duplex. Identical study of the labeled acridine subunit 5 used as a reference is also reported. In the presence of the apurinic duplex and depending on the concentrations and drug ratios, three species are observed: the radical "free in solution", the "intercalation" complex characterized by its similarity to that observed in the presence of the parent unmodified duplex, and the "abasic-site-specific" complex which is the sole species visible at low drug ratios. The experimental data reinforced by molecular modeling of the complex and theoretical calculation of correlation times suggest (i) the most immobilized form corresponds to that observed by NMR and (ii) complexation of the drug is little or not modified by the spin-label. We also show that the abasic site constitutes a binding site for the propylaminoacridine intercalator 5.

Adenine↗

Differential expression of a polygalacturonase gene family in Arabidopsis thaliana.

By systematic sequencing of a flower bud cDNA library from Arabidopsis thaliana, we have identified four cDNAs encoding polygalacturonase. The corresponding genes, together with seven other A. thaliana genes present in the databases, form a small gene family. Sequence comparisons of the deduced polypeptides within the gene family or with other plant polygalacturonases allow classification of the genes into different clades. Five polygalacturonases, including all those isolated from the flower buds, are closely related to the enzyme in pollen. Of the six remaining polygalacturonases, three are more closely related to the abscission-specific type of enzyme and two others to the fruit polygalacturonase. The last one is more distantly related to the others and might correspond to a new type of polygalacturonase. Expression of the different genes was analysed on Northern blots and by a PCR-based strategy. Results indicate that if, as expected, the cDNAs isolated from the flower bud library are strongly expressed in pollen, other genes are expressed at a low level in young developing tissues, such as in seedlings and roots, suggesting that they could be implicated in the cell wall modifications observed during cell elongation and/or expansion which occur in these tissues.

Arabidopsis↗

Long-term maintenance of weight loss after a very-low-calorie diet: a randomized blinded trial of the efficacy and tolerability of sibutramine.

BACKGROUND: Very-low-calorie diets are a well established method to achieve substantial short-term weight loss in obese patients, but long-term maintenance of the weight loss is very disappointing. A combined very-low-calorie diet and pharmacologic approach could be an effective means of prolonging its benefits. PATIENTS AND METHODS: Eligible patients had a body-mass index greater than 30 kg/m2; those who lost 6 kg or more during a 4-week treatment with a very-low-calorie diet were randomly assigned to 1 year of treatment with sibutramine (10 mg) or identical placebo. RESULTS: In an intention-to-treat analysis, mean (+/-SD) absolute weight change at 1 year (or study endpoint) was -5.2 (+/-7.5) kg in the 81 patients in the sibutramine group and +0.5 (+/-5.7) kg in the 78 patients in the placebo group (P = 0.004). When compared with their weight at study entry (before the very-low-calorie diet), 86% of patients in the sibutramine group had lost at least 5% of their weight, compared with only 55% of those in the placebo group (P <0.001) at the study endpoint. Similarly, at month 12, 75% of subjects in the sibutramine group maintained at least 100% of the weight loss achieved with a very-low-calorie diet, compared with 42% in the placebo group (P <0.01). CONCLUSION: Following a very-low-calorie diet, sibutramine is effective in maintaining and improving weight loss for up to 1 year.

Adult↗

Phenotypic variability induced by parasites:.

The diversity of ways in which parasites can modify the host genotypic signal has been documented in recent years. For example, parasites can shift the mean value and increase the variance of phenotypic traits in host populations, or alter the phenotypic sex ratio of host populations, with several evolutionary implications. Here, Robert Poulin and Frederic Thomas review the types of host traits that are modified by parasites, then explore some of the evolutionary consequences of parasite-induced alterations in host phenotypes and suggest some avenues for future research.

Animals↗

Therapeutic efficacy of the thymidine kinase/ganciclovir system on large experimental gliomas: a nuclear magnetic resonance imaging study.

Contradictory experimental results and human trials have questioned the clinical relevance of the HSVtk/ganciclovir system. To bypass the problem of transfection efficiency, we used a glioma cell line stably expressing the HSVtk gene, which was also fully characterized from gene to protein. We also designed a more clinically relevant experimental protocol, consisting of late GCV delivery on large tumor formations. In short-term studies, histological examination revealed a significant decrease in tumor volume in GCV-treated animals from day 1 or from day 10 after cell inoculation. We observed that late GCV delivery is as efficient as early delivery, probably because GCV can reach tumor cells more easily when neoangiogenesis occurs. In long-term experiments, the survival of treated rats bearing 15-day tumors was improved by 60% compared with C6 control animals. Surprisingly, a 30% survival rate was observed in C6TK control animals. Nuclear magnetic resonance imaging demonstrated, in all surviving animals, a complete regression of tumors without mass effect. These results clearly demonstrate that the HSVtk/GCV system remains a potent therapeutic strategy, even when tested in large tumors, in contrast with the microscopic tumor formations previously reported.

Animals↗

Determinants of left ventricular mass in a French male population.

The aim of this analysis was to study the determinants of left ventricular mass evaluated by echocardiography. A total of 843 healthy men aged 47-61 years, who had a standard health check-up at the Centre d'Investigations Preventives et Cliniques (IPC Center), were included in the study. None of the subjects were being treated for cardiovascular disease at the time of their visit and each had a standard clinical and biological examination. The answers to a lifestyle questionnaire, weight at 20 years and family history were recorded. All subjects had an echocardiogram to evaluate left ventricular mass. Left ventricular mass values were adjusted for height using the ratio of left ventricular mass to height. Current body mass index, systolic and diastolic blood pressure, brachial circumference, triglycerides and a family history of sudden death were positively associated with this ratio (p < 0.01). Physical activity and tobacco consumption were associated with left ventricular mass. Body mass index at 20 years, variation of body mass index since that age, systolic blood pressure and family history of sudden death explain 21% of the ratio of left ventricular mass/height (body mass index at 20 years: 11.8%; variation of body mass index: 5.1%; systolic blood pressure: 2.3%; and family history of sudden death: 0.4%). The other factors explain only 1.4% of this variance and were not significantly associated with the ratio of left ventricular mass to height. Body mass index at 20 years was the strongest determinant of left ventricular mass, suggesting that left ventricular mass at middle age is in large measure determined much earlier in life. A family history of sudden death before the age of 60 years is also an important determinant of left ventricular mass, independent of obesity. These factors must be taken into account in order to prevent an increase in left ventricular mass.

Age Factors↗

Associations between heart rate and other risk factors in a large French population.

OBJECTIVES: In a large general French population of 100,000 subjects, the relationship of resting heart rate with age, gender, demographic parameters, physical activity and classical risk factors was evaluated. POPULATION AND METHODS: A population composed of all the subjects who had a free health check-up at the IPC Centre between 1992 and 1995 (62,353 men and 35,371 women) was analysed. Heart rate was considered either as a continuous parameter or as a qualitative parameter. The study population was divided into four heart rate classes: < 65, 65-74, 75-84 and > or = 85 beats/min. RESULTS: Women had significantly higher heart rate values than men, and this gender difference was constant in the different age groups. In both genders, heart rate was positively associated with blood pressure, triglycerides, glycaemia and physical inactivity, and negatively with body height Heart rate was also correlated with total cholesterol but only in men. The only factor having opposite effects on heart rate in men and women was tobacco smoking (positive in men and negative in women). Among untreated hypertensive men, 21.3% had a heart rate > or = 85 beats/min compared with only 4.0% among normotensive men. In women, these percentages were 23.6 and 7.6%, respectively. Subjects with untreated mild hypertension or uncontrolled treated hypertension also showed increased rates of tachycardia compared to normotensives. CONCLUSIONS: The present analysis, performed in a large French population, shows that high heart rate is associated with several other risk factors, especially hypertension, suggesting that tachycardic subjects have a high risk profile.

Adult↗

Calf-thigh sequential pneumatic compression compared with plantar venous pneumatic compression to prevent deep-vein thrombosis after non-lower extremity trauma.

OBJECTIVE: To compare the effectiveness of calf-thigh sequential pneumatic compression devices with the effectiveness of plantar venous intermittent pneumatic compression devices in prevention of venous thrombosis after major trauma. SUBJECTS AND METHODS: We evaluated 181 consecutive patients after major trauma without lower extremity injuries that precluded the use of pneumatic compression devices. We randomly assigned 149 patients to either calf-thigh sequential pneumatic compression or plantar venous pneumatic compression. After blinding the observers to the method of prophylaxis against deep-vein thrombosis, we performed bilateral compression ultrasonography on or before day 8 after randomization. RESULTS: Among 149 randomized patients, 62 who received calf-thigh sequential pneumatic compression and 62 who received plantar venous intermittent pneumatic compression devices completed the trial. Thirteen patients randomized to plantar venous intermittent pneumatic compression (21.0%) and 4 patients randomized to calf-thigh sequential pneumatic compression (6.5%) had deep-vein thrombosis (p = 0.009). Seven of 13 patients with deep-vein thrombosis after prophylaxis with plantar venous intermittent pneumatic compression had bilateral deep-vein thromboses, whereas all 4 patients with deep-vein thrombosis after prophylaxis with calf-thigh sequential pneumatic compression had unilateral deep-vein thrombosis. CONCLUSION: Calf-thigh sequential pneumatic compression prevents deep-vein thrombosis more effectively than plantar venous intermittent pneumatic compression after major trauma without lower extremity injuries.

Adult↗