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Biomedical subjects

F Thomas

Publications and source records attributed to F Thomas.

At least 73 records · Page 4Linked to original sources

Parasites and host life-history traits: implications for community ecology and species co-existence.

Most of the evidence for a key role of parasites in structuring communities is based on the idea of a differential susceptibility of host species to infection and its consequences. Recent advances in community ecology suggest that life-history traits of free-living species can be an important determinant of their co-existence within communities. On the other hand, parasites have the potential to indirectly alter the life-history traits of their hosts, such as developmental time or dispersal. We discuss the idea that these indirect effects could influence the structure of free-living and parasite communities. We explore this idea in relation to related concepts including 'parasitic arbitration' and engineering processes.

Animals↗

A decrease in diastolic blood pressure combined with an increase in systolic blood pressure is associated with a higher cardiovascular mortality in men.

OBJECTIVES: The study evaluated the risk of cardiovascular mortality according to combined spontaneous (non-treatment-related) changes in both systolic and diastolic blood pressure (BP). BACKGROUND: Long-term longitudinal changes in blood pressure may be a more accurate determinant of cardiovascular risk since changes in systolic or diastolic blood pressure over a period of time reflect the evolution of arterial and arteriolar alterations. METHODS: Two independent French male cohorts were studied: the IPC cohort (Investigations Préventives et Cliniques) composed of 15,561 men aged 20 to 82 years who had had two visits spaced four to 10 years apart, and the Paris Prospective Study composed of 6,246 men aged 42 to 53 years, examined annually for a period of four years. None of the subjects were taking antihypertensive medication. Annual changes in BP were estimated, and subjects were divided into groups according to the increase, lack of change, or decrease of systolic or diastolic BP. Nine groups were formed by combining the changes of systolic and diastolic BP. Cardiovascular mortality was assessed for a mean period of 13.5 years for the IPC Study and 17 years for the Paris Prospective Study. RESULTS: In both cohorts, after adjustment for age and major risk factors, the group with an increase in systolic and a decrease in diastolic BP presented the highest relative risk of cardiovascular mortality compared to the group with no changes in either systolic or diastolic BP (relative risk: 2.07 [1.05 to 4.06] in the IPC Study and 2.16 [1.16 to 4.01] in the Paris Prospective Study). CONCLUSIONS: Assessment of spontaneous changes of BP over a long period of time can contribute to the evaluation of cardiovascular risk. Subjects whose systolic BP increased while their diastolic BP decreased had the highest cardiovascular risk independently of absolute values of BP or other risk factors.

Adult↗

Immunological tolerance as an adjunct to allogeneic tissue grafting.

Since its clinical inception, our group has worked in clinical and experimental transplantation. The exciting early results of composite tissue allografts (CTA) attracted our attention during the 1980s, when some of the first experimental CTA literature appeared. The recent extraordinary results of clinical CTA grafts, primarily the Louisville and Lyon results, have been highlighted at this meeting. Interestingly, this success followed not long after the first International meeting in Louisville in 1997. This is clearly an exciting new application of transplant techniques to one of the newest and most unique types of transplants. Previous studies used immunosuppression for skin allografting. Early results seem quite exciting and we expect to see a rapid growth of interest and activity in this area. We believe that the entire field would benefit from the novel, highly effective and minimally toxic immune tolerance induction using CD3-immunotoxin (CD3-IT) and deoxyspergualin (DSG).

Animals↗

Recombinant Nup153 incorporates in vivo into Xenopus oocyte nuclear pore complexes.

Nup153 is a molecular constituent of the nuclear basket of the nuclear pore complex (NPC) that plays a critical role in nuclear export of RNAs and proteins. In an effort to map this nucleoporin more precisely within the nuclear basket we have developed an experimental approach for localizing Nup153 expressed and incorporated in vivo into Xenopus oocyte NPCs. This approach involves the microinjection into the cytoplasm of Xenopus oocytes of in vitro synthesized mRNA from a vector encoding an epitope-tagged cDNA. Here we present results obtained by Western blots, fluorescence microscopy, and immuno-electron microscopy, which clearly document that the heterologous protein is properly expressed, targeted, and incorporated into preexisting Xenopus NPCs. This new approach for localizing nucleoporins within the structure of the NPC overcomes limitations of previous techniques and allows for greater specificity and resolution than have been possible with previous methods.

Animals↗

Modalities of the food intake-reducing effect of sibutramine in humans.

Sibutramine is a serotonin and noradrenaline reuptake inhibitor exerting a weight reducing effect partly via its anorectic properties. We investigated the effects of 15 mg sibutramine on objective (intake) and subjective (sensations) parameters of eating behavior in 24 young male subjects. At 0830 h subjects took either placebo or sibutramine in a counterbalanced order, followed by a fixed amount of breakfast. Intake was covertly recorded in the laboratory until the dinner meal, and then until the next morning using diary reports. Sibutramine induced a highly significant reduction in energy (1304 kJ, p < 0.001), protein (294 kJ, p < 0.001), fat (414 kJ, p < 0.01), and carbohydrate (CHO, 594 kJ, p < 0.001) intakes compared to placebo. This reduction was further enhanced when 24-h intake was analyzed (1601 kJ, p < 0.001). The effect of sibutramine occurred mainly at lunch (637 kJ, p = 0.005). Throughout the test day the number of items consumed and the weight of food were reduced by sibutramine (1.6, p < 0.01 and 222 g, p < 0.001, respectively), whereas energy density was not changed. Meals minus dessert items were the most altered by sibutramine. A specific CHO reduction was found in the dinner meal, although the proportions of macronutrients in total daily energy intake were not changed by sibutramine. Hunger ratings began to be lower than placebo 240 min after sibutramine. These results show that a single dose of sibutramine in lean humans induces a potent reduction in intake, and that its action is modulated according to the time of occurrence and the structure of the meal.

Adolescent↗

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↗