PubMed Health⌕ Search

Biomedical subjects

M Thellier

Publications and source records attributed to M Thellier.

At least 19 recordsLinked to original sources

Subacute clinical forms of Plasmodium falciparum malaria in travelers receiving chloroquine-proguanil prophylaxis.

We have observed 4 French travelers, returning from African countries, who were not immune to malaria and were receiving chloroquine-proguanil prophylaxis, in whom the diagnosis of malaria could easily have been missed because the clinical signs were uncommon. These cases suggest that chloroquine-proguanil prophylaxis is not always effective and that travelers with unexplained symptoms should be monitored closely for malaria.

Adult↗

[Disseminated strongyloidiasis].

ENDEMIC ZONES: Strongyloidiasis is an intestinal parasitosis which is frequently found in tropical and subtropical regions. RISK: The "autoinfection" cycle during this helminthiasis explains why the infection can be perpetuated without further exposure to exogenous, infective larvae. Hyperinfection may occur by dissemination of Strongyloides stercoralis in immuno-compromised patients, particularly those under corticotherapy. DISSEMINATATED STRONGYLOIDIASIS: Disseminated strongyloidiasis is characterized by severe gastrointestinal and respiratory tract involvement, meningitis, skin rash, or Gram-negative bacteremia. Since disseminated stronglyoidiasis is fatal in 80% of cases it is imperative to diagnose and treat this condition before long-term corticotherapy. Ivermectin is currently recommended because it is effective and well tolerated.

Adrenal Cortex Hormones↗

[Biology and pathogenicity of fungi].

Men live with a multitude of fungal species and few species can become parasites. Some species are obligatory pathogenic (dermatophytes, dimorphic fungi...) and the majority is opportunistic pathogen. Host-parasite complex is indissociable. For example, Candida albicans is a commensal of the gastrointestinal tract and can dramatically proliferate when host defences are alterated. Passage from the commensal status to pathogenicity is accompanied by modifications of the fungus, which then act as virulence factors (development of filamentous forms, changes in surface hydrophobicity...). Biologic, genetic and antigenic modifications are also observed. Colonisation and adhesion, penetration, multiplication and survival are necessary for infectiosity in a host. Host defence mechanisms are described with non-specific mechanisms by humoral and cellular factors and more specific immune mechanisms involving antibodies, T lymphocytes and the role of cytokines.

Adult↗

[Antifungal drugs in the treatment of systemic candidiasis: susceptibility to antifungal drugs, drug resistance, pharmacological data].

The available antifungal agents are amphotericin B (conventional or lipid formulation), flucytosin and azole derivatives (ketoconazole, fluconazole, itraconazole). The main target of these molecules are a specific compound of fungal membrane, ergosterol. Determination of the fungal sensitivity to antifungal drugs is difficult and no consensus has been achieved so far. Minimal inhibitory concentrations are poor predictors of clinical success or failure. A good correlation between in vitro and in vivo results has been observed only in patients with oropharyngeal candidiasis associated with HIV infection. Combinations of antifungal drugs are currently under study. The role of hemopoietic growth factors (G-CSF, GM-CSF) as an adjuvant has not been fully established. New antifungal drugs (triazole derivatives, echinocandins) should be available within months.

Antifungal Agents↗

One-step purification of Enterocytozoon bieneusi spores from human stools by immunoaffinity expanded-bed adsorption.

An original, reliable, and reproducible method for the purification of Enterocytozoon bieneusi spores from human stools is described. We recently reported the production of a species-specific monoclonal antibody (MAb) 6E52D9 immunoglobulin G2a (IgG2a) raised against the exospore of E. bieneusi spore walls. The MAb was used as a ligand to develop an immunoaffinity matrix. The mouse IgG2a MAb was bound directly to a Streamline rProtein A adsorbent, used for expanded-bed adsorption of immunoglobulins, for optimal spatial orientation of the antibody and maximum binding efficiency of the antigen. The complex was then cross-linked covalently using dimethyl pimelimidate dihydrochloride. After incubation of the immunoaffinity matrix with filtered stool samples containing numerous E. bieneusi spores and before elution with 6 M guanidine HCl, the expansion of the adsorbent bed eliminated all the fecal contaminants. The presence of spores in the elution fractions was determined by an indirect immunofluorescence antibody test (IFAT). E. bieneusi spores were found in the elution fraction in all four experiments and were still highly antigenic as indicated by IFAT. Smears examined by light microscopy contained very clean spores with no fecal debris or background bacterial and fungal contaminants. However, spore recovery rates were relatively low: an average of 10(7) spores were purified per run. This technique for isolating E. bieneusi spores directly from human stool samples with a high degree of purity opens up new approaches for studying this parasite.

AIDS-Related Opportunistic Infections↗

A mathematical model for storage and recall functions in plants.

In plantlets of Bidens pilosa L., under severely limiting environmental conditions the growth of the buds at the axil of the cotyledons (cotyledonary buds) is asymmetric (i.e. one of the buds starts growing before the other one), this asymmetry being oriented by the pricking of one of the cotyledons (i.e. pricking one cotyledon increases the probability that the bud at the axil of the other cotyledon be the first to start to grow). As long as the plant apex (i.e. the terminal bud) is present, the growth of the cotyledonary buds is inhibited (apical dominance), but the souvenir of the asymmetric message caused by sub-optimal environmental conditions and the orientation given by the cotyledon pricking is always present in the plant and can be revealed by removing the apex. Depending on the conditions for removing the plant apex and/or on the application of a variety of symmetrical treatments (e.g. thermal treatment, symmetrical pricking treatments, etc.) the stored asymmetry will either take effect (the bud at the axil of the non-pricked cotyledon will be the first to start to grow more often than the other one) or not (both buds will have equal chance to be the first to start to grow). This has been termed 'recalling' the stored asymmetry. By combining several successive symmetrical treatments, it is possible to reversibly switch on and off the recall function several times. This recall of the stored plant-asymmetry is analogous to the evocation function of a memory system. In this paper, we will present first a discrete logical version of the observed interaction structure between the main components of the bud growth system, then a continuous differential version, taking into account the main features of the observed experimental reality and trying to explain this phenomenology. The interaction structure of both the discrete and the continuous models presents similar positive and negative feedback circuits, necessary condition for observing multistationarity and stability.

Environment↗

Long-distance transport, storage and recall of morphogenetic information in plants. The existence of a sort of primitive plant 'memory'.

An asymmetrical treatment of Bidens seedlings (pricking one of the seedling cotyledons) causes the cotyledonary buds to grow asymmetrically after release of apical dominance by decapitation of the seedlings. The symmetry-breaking signal propagates within the seedlings at a rate of at least a fraction of a millimetre per second. This information may be 'stored' (STO function) within the seedlings, without taking effect, for at least 2 weeks; then the information may be 'recalled' (RCL function), thus permitting transduction of the signal into the final response (differential growth of the buds), as a consequence of subjecting the seedlings to various symmetrical or asymmetrical treatments. A similar behaviour was observed with stimuli other than pricking (including non-traumatic stimuli), with plants other than Bidens (flax, tomato), and with responses other than cotyledonary-bud growth (hypocotyl elongation, induction of meristems, thigmomorphogenesis). There are indications that storage may involve the activation of elements implicated in cell cycle control, and that the last steps of the final response involve genes such as tch1 and hsp70. The adaptive advantage for plants in possessing STO/RCL functions is discussed. Manipulating the STO/RCL functions may have interesting practical applications, e.g. in the resistance of plants to natural stresses. The existence of the STO/RCL functions in plants constitutes an elementary form of 'memory' which may provide an experimental system simpler than the animal brain to test the validity of the theoretical models of interpretation of important features such as memory storage and evocation.

Environment↗

Secondary ion mass spectrometry imaging of the fixation of 15N-labelled NO in pollen grains.

We used secondary ion mass spectrometry to image cellular targets of nitrogen oxides (widespread air pollutants) in pollen grains of birch (Betula verrucosa Ehrh.) and cockfoot (Dactylis glomerata L.). The pollen samples were exposed to air supplemented with high doses of 15NO. The pollen grains were then fixed, dehydrated using a newly developed 'vapour phase' preparation method and embedded in LRW resin. Semithin sections were then analysed. Imaging was performed in scanning mode. As usual, the two isotopes 14N and 15N were imaged as 12C14N- and 12C15N-, respectively. The isotopic percentages of 15N were quantitatively determined either by image processing or by direct analysis. We show that the preferential areas of NO fixation in the pollen cell are the sporoderm and discrete intracytoplasmic structures that we tentatively describe as globoid-like structures similar to those encountered in seeds.

Air Pollutants↗

The microculture tetrazolium assay (MTA): another colorimetric method of testing Plasmodium falciparum chemosensitivity.

Malarial lactate dehydrogenase (LDH), which uses 3-acetyl pyridine adenine dinucleotide as coenzyme in a reaction leading to the formation of pyruvate from L-lactate, may be used to study the susceptibility of Plasmodium falciparum to a drug in vitro. Several methods to determine the activity of this enzyme are available. One, the colorimetric method of Makler and colleagues, was modified slightly, by using sodium-2,3-bis-[2-methoxy-4-nitro-5-sulphophenyl]-2H-tetrazolium-5 - carboxanilide (XTT) and following the reaction by measuring the optical density at 450 nm. Using two, culture-adapted strains of P. falciparum, this LDH assay was compared with the unmodified Makler's assay and with the isotopic microtest based on the incorporation of tritium-labelled hypoxanthine. Fresh, clinical P. falciparum isolates were also tested in the presence of several drugs, including chloroquine, mefloquine, quinine, halofantrine, atovaquone and qinghaosu derivatives. The results of the three assays were correlated for all the drugs tested except atovaquone. The two enzymatic assays are non-radioactive, rapid, reliable, inexpensive to perform and semi-automatic. However, they do require an initial parasitaemia of 2% with a haematocrit of 1.8%.

Animals↗

Production of monoclonal antibodies directed against the microsporidium Enterocytozoon bieneusi.

Several hybridomas producing antibodies detected by indirect immunofluorescence antibody test (IFAT) were established by fusion of mouse myeloma SP2/O with spleen cells from BALB/c mice immunized against whole spores (protocol 1) or chitinase-treated spores (protocol 2) of Enterocytozoon bieneusi and were cloned twice by limiting dilutions. Two monoclonal antibodies (MAbs), 3B82H2 from protocol 1, isotyped as immunoglobulin M (IgM), and 6E52D9 from protocol 2, isotyped as IgG, were expanded in both ascites and culture. IFAT with the MAbs showed that both MAbs reacted exclusively with the walls of the spores of E. bieneusi, strongly staining the surface of mature spores, and produced titers of greater than 4,096. Immunogold electron microscopy confirmed the specific reactivities of both antibodies. No cross-reaction, either with the spores of the other intestinal microsporidium species Encephalitozoon intestinalis or with yeast cells, bacteria, or any other intestinal parasites, was observed. The MAbs were used to identify E. bieneusi spores in fecal specimens from patients suspected of having intestinal microsporidiosis. The IFAT was validated against standard staining methods (Chromotrope 2R and Uvitex 2B) and PCR. We report here the first description and characterization of two MAbs specific for the spore wall of E. bieneusi. These MAbs have great potential for the demonstration and species determination of E. bieneusi, and their application in immunofluorescence identification of E. bieneusi in stool samples could offer a new diagnostic tool for clinical laboratories.

AIDS-Related Opportunistic Infections↗

Cambium pre-activation in beech correlates with a strong temporary increase of calcium in cambium and phloem but not in xylem cells.

Using secondary ion mass spectrometry (SIMS), calcium was imaged in cambium cells and in the adjacent secondary phloem and xylem cells during the different phases of cambium functioning in beech (Fagus sylvatica L.). At the end of the period of quiescence, immediately before the resumption of cell divisions (i.e. at the cambium pre-activation phase), a strong temporary increase of calcium concentration was observed to take place in cambium and phloem but not in xylem cells.

Calcium↗

Imaging and microanalysis of 14N and 15N by SIMS microscopy in yeast and plant samples.

We have investigated the usefulness of Secondary Ion Mass Spectrometry (SIMS) for studying the tissue distribution of 15N labelling in yeast cells and soybean leaf tissues. The secondary ions best suited for this are 12C14N- and 12C15N-. Using a mass resolution of 6000, all problems of interference by other ions were avoided. The lateral resolution was of the order of 300 nm, i.e. well suited for subcellular studies. The sensitivity was good enough to allow the detection and the mapping of 15N, even when it was present at its natural value concentration of the isotopic ratio of only 0.37%. Using yeast cells at isotopic equilibrium with their nutrient medium, the nitrogen isotopic ratios in the cells were consistent with those in the medium. In the soybean leaf samples, the mapping of 14N and 15N was well correlated with the anatomical structures of the tissues. The mean isotopic ratios (100 15N/14N, at/at), measured in the leaf tissues by SIMS, were slightly below those in the nutrient medium as well as those measured in the leaf tissue by conventional mass spectrometry. This may be explained by differences in the methods of preparation of the leaf samples for SIMS and for mass spectrometry, and by the fact that the plants were probably still not perfectly at isotopic equilibrium with their external medium at the time the experiments were performed.

Cell Compartmentation↗

Polysaccharide distribution in the cellular junctions of immature fibre cells of flax seedlings.

The characteristic features of the pectins present in the walls of immature fibre cells of the hypocotyl of flax seedlings have been studied by a combination of three subtractive methods (treatment with boiling water, calcium chelator, and free endopolygalacturonase), three staining reactions (periodic acid-thiocarbohydrazide-silver, Ruthenium Red, and ferric hydroxylamine) and labelling with an endopolygalacturonase-gold probe. The primary wall and the periphery of the tricellular junctions were shown to contain pectic molecules made of blocks either with free acidic functions or methyl-esterified, these molecules being removed from the wall by splitting alpha (1-4) linkages. On the contrary, the pectic molecules in the core of the tricellular junctions were mainly with free acidic groups, but with an appreciable acetylesterification of their hydroxyl groups; and they were linked with one another chiefly by calcium bonds. This unexpected constitution of the core of the tricellular junctions may be considered to be an early marker of the cells destined to give rise to the fibre bundles of the mature plant.

Cell Wall↗

Kinetic study of the alpha-chymotrypsin-catalyzed hydrolysis and synthesis of a peptide bond in a monophasic aqueous/organic reaction medium.

We have studied the hydrolysis and synthesis reactions of the peptide bond involved in N-Cbz-L-tryptophanyl-glycineamide as catalyzed by alpha-chymotrypsin in various mixtures of water and 1,4-butanediol. Using a constant nonsaturating concentration of substrate, the initial reaction rates decreased exponentially with decreasing water content in the solvent mixture. When the water content was decreased from 100 to 20% (v/v), the maximum rate of reaction did not vary by more than a factor of 2 to 4, whereas the Michaelis constant increased exponentially. This exponential variation of the Michaelis constant was due to changes in the partitioning of the substrate between the active site of the enzyme and the solvent. In these processes, the actual rate constants did not vary when the relative contents of water and 1,4-butanediol were varied.

Animals↗

Determining the transient kinetic behavior of complex multi-enzyme systems by use of network thermodynamics.

As an example of the application of network thermodynamics to the treatment of complicated enzymatic systems, we have studied the transient kinetic behavior of a sequence of five enzymatic reactions, four with Michaelis-Menten kinetics and the final one with sigmoid kinetics. The object was to determine how the time-courses of the concentrations of all the intermediate substrates involved, depend on the effect of forward activation by the first substrate on the final enzymatic step. The case with forward activation exhibited an unexpected behavior with a reversal of the direction of the reaction before reaching equilibrium. The solution of the set of five non-linear differential equations was achieved using the student version of the simulation package PSPICE. The same approach can be utilized to study the behavior of any type of complex multienzymatic system (steady-states, transients, oscillations, chaos), or of combinations of enzymatic reactions with transmembrane transport in compartmental systems.

Multienzyme Complexes↗