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Biomedical subjects

E Lucas

Publications and source records attributed to E Lucas.

At least 19 recordsLinked to original sources

FOXP3, a selective marker for a subset of adult T-cell leukaemia/lymphoma.

FOXP3 is a forkhead transcription factor family member, implicated in T-cell regulation, activation and differentiation. FOXP3 has been shown to be a master control gene for the development and function of CD4+/CD25+ regulatory T-cells (T(reg)). In this study, FOXP3 protein expression has been analysed using a new anti-FOXP3 monoclonal antibody in 172 paraffin-embedded lymphoma samples. FOXP3 expression in tumour cells was confined to adult T-cell leukaemia/lymphoma (ATLL) cases (17/25, 68%), with some variability in the intensity of the staining and the proportion of positive cells. No other lymphoma types studied exhibited FOXP3 expression in the malignant population. The selective expression of FOXP3 by tumour cells in ATLL makes this antibody a potentially useful diagnostic tool.

Antibodies, Monoclonal↗

Vesicular pityriasis rosea: response to erythromycin treatment.

Pityriasis rosea (PR) is a relatively common disease although its aetiology has not yet been identified. It occurs worldwide and there is no racial susceptibility factor. It usually affects teenagers and young adults between 10 and 35 years of age. Typical PR is much easier to diagnose than the rare atypical forms. We report a rare case of vesicular PR in a black woman who had vesicular lesions limited to her palms and soles in addition to regular typical lesions. We devised an efficient oral erythromycin treatment for this patient.

Administration, Oral↗

Nanocrystalline metal oxides as unique chemical reagents/sorbents.

A new family of porous inorganic solids based on nanocrystalline metal oxides is discussed. These materials, made up of 4-7 nm MgO, CaO, Al2O3, ZnO, and others, exhibit unparalleled destructive adsorption properties for acid gases, polar organics, and even chemical/biological warfare agents. These unique sorption properties are due to nanocrystal shape, polar surfaces, and high surface areas. Free-flowing powders or consolidated pellets are effective, and pore structure can be controlled by consolidation pressures. Chemical properties can be adjusted by choice of metal oxide as well as by incorporating other oxides as monolayer films.

Journal Article↗

Self-monitoring of water quality in sewer systems using absorbance of ultraviolet and visible light.

Continuous pollution measurement is interesting to optimize the operation of sanitary facilities as well as to minimize the stormwater discharges. An experimental study was carried out for the determination of Suspended Solids (SS) and Chemical Oxygen Demand (COD) concentrations in combined sewers using ultraviolet and visible absorbances. The maintenance of the measurement system requires six hours a month for the cleaning of the hydraulic feeding system and adjustment of the optical device. The feeding system developed increased the representativeness and reliability of the pollution measurement, but needs to be validated on other measurement sites. The determination of SS concentrations from visible absorbances requires 2 calibration curves for dry and rainy weather respectively. The corresponding accuracies appear satisfactory when compared with the results of standard sampling/laboratory analysis. The accuracy of COD determination from ultraviolet absorbance is less satisfactory, but could perhaps be improved taking into account another parameter. Then the optical measurement of SS and COD is interesting to determine average or long term pollution loads, for example the yearly impact of urban stormwater discharges. With this kind of continuous and on-line measurement, it is possible to react with short delay to unexpected phenomena which could damage the environment or water treatment efficiency.

Absorption↗

Optimisation of operational management practices for the detention basins.

The objective of this study is to develop new operational management practices for detention basins during rainfall events in order to limit flooding risk and, at the same time, to reduce pollutant discharges by optimising the settling process. For this work, a methodology was developed to study the integration of the stormwater treatment into existing detention structures. In this article, it was applied on two experimental sites. The current operation of the basins and "on/off" regulation studies were first carried out to quantify the freedom to act to change the control schemes. Relying on the support of these studies, new operational rules based on the current or "on/off" principle were then elaborated and tested on the experimental basins using a hydraulic model. Finally, their efficiency to protect against flooding and to reduce pollutant discharges was assessed.

Benchmarking↗

Lethal and sublethal effects of rice polishing process on Sitophilus oryzae (Coleoptera: Curculionidae).

The mechanical impact of rice polishingon the rice weevil, Sitophilus oryzae (L.), and the subsequent postpolishing effects associated with rice quality were studied. "Brown" rice (not polished), "White (infest then polish)" rice, and "White (polish then infest)" rice were used with different polishing process intensities and different initial weevil densities. Weevil progeny were more numerous in Brown than in White (infest then polish) or White (polish then infest) rice. Polishing corresponding to a weight loss of 11% in rice generated an immediate mortality of approximately 40%; the subsequent mortality caused by rice quality was also 40% (total >80%). A polishing process corresponding to 14 and 16% of rice weight loss generated a drastic mortality in the weevil population (>95%). The progeny per adult weevil was similar with high and low initial weevil densities. The development of weevil progeny was also delayed by about 1 wk in White (infest then polish) rice compared with Brown rice. Furthermore, weevil adults of the progeny were significantly heavier in Brown than in White (infest then polish) or White (polish then infest) rice.

Animals↗

Development of reactive topical skin protectants against sulfur mustard and nerve agents.

The potential for highly reactive nanoparticles (RNP) to absorb destructively, i.e. to neutralize highly toxic substances such as the warfare agents GA, GB, HD and VX, has been demonstrated in the laboratory. Reactive nanoparticles represent a new class of nanoscale particles of metals and metal oxides that differ from other nanoparticles in reactivity and crystalline morphology. The potential for incorporating RNP into a protective barrier skin cream also has been demonstrated. Preliminary studies indicate that RNP are physically and chemically compatible with a base cream provided by the Army Medical Research Office and, importantly, remain reactive with chemical agents while promising to be compatible with skin contact.

Administration, Topical↗

Knowledge, self-management, compliance and quality of life in asthma: a cross-sectional study of the French version of the Asthma Quality of Life Questionnaire.

The Asthma Quality of Life Questionnaire (AQLQ) is a well-validated instrument. Our objectives were to explore the cross-sectional validity of the French version, using usual outcomes of asthma, as well as assessment of knowledge of asthma, self-management and compliance. A self-administered version of the AQLQ was given to 124 consecutive patients recruited from two out-patient clinics and an emergency room in order to reflect a wide range of asthma severity. The other outcomes of asthma measured were the FEV1, patient-perceived asthma severity using a visual analogue scale, compliance, knowledge of asthma condition and self-management autonomy. Correlations were predicted before analysis ( r > 0.5, strong correlation, ++ r = 0.35-0.5, moderate correlation and + r = 0.20-0.35, fair correlation). The AQLQ scores correlated moderately to strongly with asthma severity and fairly with the pulmonary function results. Of the behavioural outcomes assessed, only knowledge of asthma correlated fairly with the AQLQ scores, as expected. This study of the French version of the AQLQ, while showing similar cross-sectional correlations with functional assessment and asthma severity to those observed with the original English version, suggested in addition a positive association between quality of life and knowledge of asthma.

Adult↗

The effect of surgery on the AC/A ratio.

The accommodative convergence/accommodation (AC/A) ratio is used clinically as a diagnostic tool in the assessment of convergence excess and near esotropia and the differentiation of true and simulated divergence excess. An abnormally high AC/A ratio has been implicated in the aetiology of some forms of strabismus but the evidence for alteration in the ratio following surgery is inconclusive. In a prospective study of 38 patients the effect of routine squint surgery was investigated in concomitant strabismus. The AC/A ratio was found to decrease significantly after surgery in both esotropes and exotropes. Furthermore a trend was demonstrated which suggested an increased risk of overcorrection in esotropes with a high (> or = 7:1) pre-operative AC/A ratio.

Accommodation, Ocular↗

Exploration of neutral endopeptidase active site by a series of new thiol-containing inhibitors.

With the aim of characterizing the active site of the neutral endopeptidase [EC 3.4.24.11 (NEP)] and especially its putative S1 subsite, two series of new thiol inhibitors designed to interact with the S1, S'1, and S'2 subsites of the enzyme have been synthesized. These molecules correspond to the general formula HSCH(R1)CH(R2)CONHCH(R3)COOH (series I) and HSCH(R1)CH(R2)CONHCH(R3)CONHCH(R4)COOH (series II). Due to the synthetic pathway used, these inhibitors were obtained as mixtures of four stereoisomers. HPLC separation of the stereoisomers of 17 HSCH[CH2CH(CH3)2]CH(CH2Ph)CONHCH(CH3)COOH allowed the stereochemical dependence of the inhibitory potency to be determined. The most active isomer 17b (IC50 = 3.6 nM) is assumed to have the S,S,S stereochemistry, as deduced from both NMR and HPLC data. Although none of the inhibitors obtained were significantly more active than thiorphan, HSCH2CH(CH2Ph)CONHCH2COOH (IC50 = 4 nM), which interacts only with the S'1 and S'2 subsites of NEP, their enhanced hydrophobicity is expected to improve their pharmacokinetic properties. All these compounds displayed low affinities for ACE (IC50s > 1 microM). The determination of the IC50s of two inhibitors of series II for NEP and for a mutated enzyme in which Arg102 was replaced by Glu102 allowed their mode of binding to the active site of NEP to be characterized. The R2 and R3 chains fit the S'1-S'2 subsites, while the R4 group is probably located outside the active site. Taken together these results indicate that the R1 chain of these inhibitors creates no additional stabilizing interactions with the active site of NEP. Two hypotheses may account for this: there is no hydrophobic S1 subsite in NEP or the inhibitors have structures which are too constrained for optimized interactions with the active site.

Angiotensin-Converting Enzyme Inhibitors↗

"Mixed inhibitor-prodrug" as a new approach toward systemically active inhibitors of enkephalin-degrading enzymes.

In order to evaluate the possible advantages of potentiating the effects of the endogenous enkephalins, to obtain analgesia without the serious drawbacks of morphine, it was essential to design systemically active compounds which inhibit the two metabolizing enzymes, aminopeptidase N (APN) and neutral endopeptidase 24.11 (NEP). A new concept combining the idea of "prodrug" and "mixed inhibitor" was therefore developed. Given the high efficiency of beta-mercaptoalkylamines as APN inhibitors and of N-(mercaptoacyl) amino acids as NEP inhibitors, compounds associating these molecules through disulfide or thioester bonds, which are known to increase lipophilicity and to favor passage across the blood-brain barrier, have been synthesized. An HPLC study indicated that the disulfide bridge was resistant to serum enzymes but was cleaved by brain membrane homogenates, suggesting that the active inhibitors were released in the central nervous system. The validity of the approach was verified by the efficient antinociceptive responses obtained in the hot plate test in mice after iv administration of disulfide-containing inhibitors (ED50s of from 4 to 26 mg/kg on the jump latency time). The analgesic potencies of the "mixed inhibitor-prodrug" RB 101 [H2NCH(CH2CH2SCH3)CH2SSCH2CH(CH2Ph)CONHCH( CH2Ph)COOCH2Ph] after iv administration were three times greater than those of a similar combined dose of its two constitutive moieties. The separation of the two diastereoisomers constituting RB 101 showed that the analgesia has a stereochemical dependence, the (S,S,S)-isomer being more active than the (S,R,S)-isomer. Furthermore, in the tail flick test in the rat, RB 101 gave 38% analgesia at a dose of 80 mg/kg. Due to its high efficiency and its longer pharmacological effect, RB 101 was selected for a complete study of its analgesic properties.

Aminopeptidases↗

Potent and systemically active aminopeptidase N inhibitors designed from active-site investigation.

Derivatives of amino acids bearing various zinc-coordinating moieties (SH, COOH, CONHOH, and PO3H2) were synthesized and tested for their ability to inhibit aminopeptidase N (APN). Among them, beta-amino thiols were found to be the most efficient with IC50's in the 11-50 nM range. These results suggest that the S1 subsite of APN is a deep but not very large hydrophobic pocket, optimally fitting side chains of moderate bulk endowed with some degree of freedom. The iv administration of the inhibitors, alone, did not induce antinociceptive responses on the hot plate test in mice. However, in presence of 10 mg/kg acetorphan, a prodrug of the neutral endopeptidase inhibitor thiorphan, these compounds gave a large increase in the jump latency time with ED50's of 2 and 2.4 mg/kg for the disulfides of methioninethiol H2NCH(CH2CH2SCH3)CH2S]2 and S-oxomethioninethiol [H2NCH(CH2CH2S(O)CH3)CH2S]2, respectively. These results show that the disulfide forms of beta-amino thiols are efficient prodrugs of aminopeptidase N inhibitors capable of crossing the blood-brain barrier.

Aminopeptidases↗

A 94-kDa protein, identified as neutral endopeptidase-24.11, can inactivate atrial natriuretic peptide in the vascular endothelium.

Neutral endopeptidase 24.11 (EC 3.4.24.11) inactivates atrial natriuretic peptide by cleaving the hormone between Cys7 and Phe8, and inhibitors of the enzyme have consequent natriuretic and diuretic properties. The in vivo sites of degradation of this peptide by the zinc-metallopeptidase, however, remain to be established. Because an endopeptidase-24.11-like activity has recently been reported in the rat mesenteric artery, we have further investigated the degradation of atrial natriuretic peptide in vascular tissue. Endopeptidase-24.11 activity was detected in solubilized membrane preparations from rat and rabbit vascular tissue, using [3H]D-Ala2-leucine enkephalin as substrate, and both rabbit and rat aorta preparations were also found to cleave atrial natriuretic peptide between Cys7 and Phe8. In both cases, hydrolysis was inhibited by neutral endopeptidase inhibitors, with Ki values close to their Ki values for the pure enzyme. In preparations of rabbit aorta denuded of endothelium by saponin treatment, the hydrolysis of the Gly3-Phe4 bond of [3H]D-Ala2-leucine enkephalin and the Cys7-Phe8 bond of atrial natriuretic peptide was reduced by greater than 90%. The high performance liquid chromatography method used to follow the degradation of atrial natriuretic peptide differed from previously published procedures, in that samples to be injected were first treated with excess dithiothreitol to reduce the Cys7-Cys23 disulfide bridge. This facilitated the separation of the intact peptide and its metabolites. The presence of the 94-kDa neutral endopeptidase in rabbit aortic tissue was definitively established using a new potent 125I-labeled inhibitor, [125I]RB104 [2-[(3-[125I]iodo-4-hydroxy)phenylmethyl]-4-N-[3- hydroxyamino-3-oxo-1-phenylmethyl propyl]amino-4-oxobutanoic acid] (Ki, 30 pM), which selectively labeled the enzyme after sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the membrane preparations. Therefore, despite its low concentrations in the vasculature, the presence of endopeptidase-24.11 almost exclusively in endothelial tissue suggests that the enzyme is ideally localized to inactivate circulating atrial natriuretic peptide.

Amino Acid Sequence↗

[Infections and systemic lupus erythematosus. Analysis of risk factors and prognosis. A prospective study (1979-1988)].

We have prospectively studied 48 patients previously diagnosed of systemic lupus erythematosus over a mean follow up period of 5.8 years of which 28 presented 36 episodes of infection and 20 did not develop infections. Urinary infections were the most frequent kind of infection followed by pneumonia and bacteriemia; the most frequently isolated microorganism responsible for those infections were E. colii, staphylococcus aureu and P. mirabillis. We have found a risk factors that and impared renal function an steroid treatment over 20 mg/day were significantly associated with a increasing number of infectious precesses. On the contrary, we have observed that only a bad and critical clinical situation had prognostic value and was significantly associated with an increased mortality.

Adult↗