Biomedical subjects

C Leblanc

Publications and source records attributed to C Leblanc.

At least 19 recordsLinked to original sources

PubMed2003

["Sunshine at school": a network for training on sun exposure. Assessment of knowledge among 683 children].

INTRODUCTION: The protection of children from sun exposure appears inadequate. We assessed the knowledge of pre-teenagers, before and after they attended a training session on sun exposure. This investigation was carried out in Orléans and in 5 surrounding cities, from September 2000 to April 2002. MATERIAL AND METHODS: A didactic slide show on sun exposure and photoprotection was presented to 683 children in grade 4 and 5 by a nurse and a dermatologist during 30 informative sessions. The children filled in questionnaires at each training session and then one month later. The questionnaires contained 10 closed questions involving 32 cognitive and behavioral items. RESULTS: Forty-five percent of the children claimed that they were exposed to the sun more than one hour a day during holidays, 14 p. 100 more than 3 hours a day; 26 p. 100 declared they had never been sunburnt; 46 p. 100 said they had been less than 5 times, 15 p. 100 from 5 to 10 times and 12 p. 100 more than 10 times; 74 p. 100 of the children claimed they enjoyed getting sun-tanned; 80 p. 100 knew that sun exposure could lead to serious diseases, while 73 p. 100 realized that contracting sunburns during childhood increases the risk of subsequent skin cancers; 89 p. 100 knew of the necessity of sun-screen use prior to exposure, 94 p. 100 knew that they help to protect the skin whereas 78 p. 100 knew it must be applied on a regular basis; 77 p. 100 of the children had been informed of the importance of sun protection factor; 92 p. 100 of them were aware of the relevance of a cap and sunglasses for protection from the sun, whereas only 45 p. 100 knew of the need for a tee-shirt. DISCUSSION: Our study showed that children are generally aware of the dangers of sun exposure. This might be the result of previously initiated information and prevention campaigns on skin cancers. This study suggests the efficiency of such projects, and the lasting effects of the information received within one month. However, large numbers of children are still overexposed and subsequently suffer from traumas. The appeal of sun embellishment appears to go back to childhood, and should be taken into account from the early stages of childhood in future preventive actions. An efficient policy of education on sun exposure - including teaching tools relevant to each age--still has to be developed.

Child↗

PubMed2000

Metallic salt promoted radical cyclization of beta-keto carboxamides and their corresponding beta-enamino carboxamides

Substituted lactams and spirolactams were obtained by Mn(III)-induced radical cyclization of unsaturated beta-keto carboxamides. Treatment of the corresponding tertiary enamines under similar reaction conditions and in the presence of K(2)CO(3) afforded the same cyclized products but with inversion of diastereoselectivity. The oxidation of optically pure secondary enamines leads to diastereomeric spirolactams in an approximately 3:1 ratio.

Journal Article↗

PubMed1999

Transformation of Nonselectable Reporter Genes in Marine Diatoms.

: We report the genetic transformation of two marine diatoms by microparticle bombardment. The pennate diatom Phaeodactylum tricornutum was transformed with the bacterial gene Sh ble from Streptoalloteichus hindustanus, which confers resistance to the antibiotics phleomycin and zeocin. Transformants contained between 1 and 10 copies of the exogenous DNA integrated into the genome by illegitimate recombination at apparently random locations. Transformation efficiencies were around 10(-6), and individual cell lines could be maintained at -80 degrees C following cryopreservation. Also, P. tricornutum could be transformed simultaneously with two different plasmids, one containing the Sh ble gene and another containing the firefly luciferase gene (LUC) under control of a promoter derived from a fucoxanthin, chlorophyll a/c-binding protein gene (FCP). In these cotransformants, LUC activity was light inducible. The transient transformation of the centric diatom Thalassiosira weissflogii with the bacterial beta-glucuronidase (GUS) gene has also been achieved using similar transformation technology. The availability of gene transfer protocols for marine diatoms, together with a range of functional reporter genes and regulated expression systems, will permit molecular dissection of their biology and allow an assessment of the biotechnological potential of these organisms.

Journal Article↗

PubMed1999

Combinatorial chemistry as a tool for drug discovery.

The question 'will combinatorial chemistry deliver real medicines' has been posed [96]. First it is important to realise that the chemical part of the drug discovery process cannot stand alone; the integration of synthesis and biological assays is fundamental to the combinatorial approach. The results presented in Tables 3.1 to 3.8 suggest that so far smaller directed combinatorial libraries have obtained equivalent results to those obtained previously from traditional medicinal chemistry analogue programs. Unfortunately, because of the long time it takes to develop pharmaceutical drugs there are no examples yet of marketed drugs discovered by combinatorial methods. There are interesting examples where active leads have been discovered from the screening of the same library against multiple targets (e.g. libraries 13, 39, 43, 66, 71 and 76). It is now possible to handle much larger libraries of non-oligomeric structures and the chemistry required for such applications is becoming available. Whether combinatorial approaches can also be adapted to deal with all the other requirements of a successful pharmaceutical (lack of toxicity, bioavailability etc.) is open to question but there are already examples such as cassette dosing [235-237]. However we can still be optimistic about the possibility of larger libraries producing avenues of investigation for the medicinal chemist to develop into real drugs. Combinatorial chemistry is an important tool for the medicinal chemist.

Combinatorial Chemistry Techniques↗

PubMed1999

Semi-quantitative RT-PCR analysis of photoregulated gene expression in marine diatoms.

The low cell densities of diatoms and other phytoplankton in culture has precluded the use of classical RNA analysis techniques for routine studies of gene expression in large numbers of samples. This has seriously hampered studies of the basic biology of such organisms. To circumvent this problem, we have developed a high-throughput semi-quantitative RT-PCR-based protocol and used it to monitor expression of a gene encoding a fucoxanthin, chlorophyll a/c-binding protein (FCP) in the centric planktonic diatom Thalassiosira weissflogii. Analysis of FCP gene expression in dark-adapted diatom cultures revealed that mRNA levels increase 5- to 6-fold in response to white light irradiation and peak around 6 to 8 h. To determine the photoreceptors involved in this response action spectra of FCP gene expression were determined using the Okazaki large spectrograph. Responses consistent with the presence of cryptochrome-, rhodopsin- and phytochrome-type receptors could be detected. The apparent presence of phytochrome-mediated responses is of particular interest given the low fluences of red and far-red light wavelengths in the marine environment.

Actins↗

PubMed1998

Sonographic evaluation of intervillous flow in early pregnancy: use of echo-enhancement agents.

The uteroplacental circulation of the cynomolgus monkey was examined in early pregnancy using a high-resolution ultrasound scanner. Intravenous injection of an echo-contrast agent, Albunex (sonicated albumin), was used to enhance the color Doppler images obtained. The flow of blood into and out of the intervillous compartment was readily assessed and quantified using pulsed and color Doppler. Flow within the intracotyledonary space was pulsatile and indicative of a low-resistance system. Flow within the decidual veins was non-pulsatile. The use of echo-contrast agents may assist in the determination of intervillous flow in human pregnancy at a correspondingly early stage.

Albumins↗

PubMed1998

Nasal response in subjects undergoing challenges by inhaling occupational agents causing asthma through the nose and mouth.

BACKGROUND: Subjects with occupational asthma (OA) often report nasal symptoms, but nasal reactions to inhalation challenges with occupational agents have not been well characterized. METHODS: Fifteen subjects with OA (eight due to high-molecular-weight agents--flour and guar gum--and seven due to isocyanates) underwent inhalational challenges using closed-circuit devices (dry particles for high-molecular-weight agents and gas generator for isocyanates) on two occasions, 2-4 weeks apart in a random fashion. On one occasion, they inhaled through the nose and, on another, through the mouth. The FEV1 was monitored for up to 8 h afterward, and symptoms were documented with a standardized questionnaire on nasal symptomatology, assessment of nasal resistance by rhinomanometry, and nasal lavage for the examination of cells and mediators. RESULTS: Inhaling through the mouth and through the nose: 1) yielded similar asthmatic responses (25+/-8% and 22+/-10% maximum changes in FEV1) 2) more than doubled the peak nasal symptoms and nasal resistance when the maximum daily response was compared with prechallenge results. This increase occurred on the days of inhalational challenges through the mouth and through the nose. There were some significant responses assessed by nasal lavage in terms of cells and mediators, again with no differences between the days of challenges through the mouth and through the nose. CONCLUSIONS: Inhaling occupational agents of high or low molecular weight, including isocyanates, whether through the mouth or nose: 1) results in a similar asthmatic response 2) causes a significant nasal response in terms of symptoms and an increase in nasal resistance 3) causes some significant changes in inflammatory cells and mediators.

Administration, Inhalation↗

PubMed1997

Calcium-mediated neurofilament protein degradation in rat optic nerve in vitro: activity and autolysis of calpain proenzyme.

In this study, we examined calcium-mediated degradation of a neurofilament protein (NFP), and autolytic activation of calpain in Lewis rat optic nerve in vitro. After incubation with calcium, homogenized optic nerve samples were analysed by SDS-PAGE in association with ECL immunoblot techniques. 68 kD NFP, calpain, and calpastatin antibodies were used for identification of the respective proteins. The extent of calcium-mediated 68 kD NFP degradation compared to EGTA controls, served to quantify calpain activity, while the extent of calpain autolysis measured the activation of the enzyme. A progressive loss of 68 kD NFP was observed at 15 min (42.1%), 1 hr (52.7%) and 6 hr (73.4%) incubation periods compared to EGTA controls. The immunoreactive calpain bands showed progressive autolysis after 15 min (26.6%), 1 hr (31.4%) and 6 hr (43.4%) incubations. We also found degradation of low molecular weight isoforms of calpastatin (43 kD and 27 kD) in the presence of calcium compared to controls. These results indicate that calpain is present in optic nerve in its inactive form but when calcium is added, it undergoes autolysis and becomes active. Thus, active calpain is capable of degrading endogenous substrates (e.g. cytoskeletal and myelin proteins) and may promote the degeneration of optic nerve in optic neuritis.

Animals↗

PubMed1997

Synthetic methods for polyamine linkers and their application to combinatorial chemistry.

Polyamines and polyamine conjugates display a diverse range of important biological functions, ranging from antibiotics to immunosuppressants and glutamate receptor antagonists. For these reasons, polyamines provide an excellent template/scaffold for combinatorial chemistry. In this paper we present methods for the solid-phase immobilisation of polyamines for use in synthetic and combinatorial chemistry and describe how they have been employed in the preparation of a number of important polyamine conjugates and polyamine libraries. Thus, we have designed, synthesised and utilised a number of polyamine linkers for both solution and resin screening combinatorial application.

Chemistry, Organic↗

PubMed1997

Origin and evolution of mitochondria: what have we learnt from red algae?

The purpose of this review is to present an account of our current understanding of the structure, organization and evolution of mitochondrial genomes, and to discuss the origin and evolution of mitochondria from the perspective recently provided by the extensive sequencing of various mitochondrial genomes. Mitochondrial-en-coded protein phylogenies are congruent with nuclear phylogenies and strongly support a monophyletic origin of mitochondria. The newly available data from red-algal mitochondrial genomes, in particular, show that the structural and functional diversity of mitochondrial genomes can be accounted for by paralogous evolution. We also discuss the influence of other constraints, such as uniparental inheritance, on the evolution of genome organization in mitochondria.

DNA, Circular↗

PubMed1996

Influence of inhaled steroids on recovery from occupational asthma after cessation of exposure: an 18-month double-blind crossover study.

Occupational asthma (OA) is a useful model for the study of asthma in humans. The possibility that inhaled corticosteroids, in addition to withdrawal from the workplace, could improve clinical and functional recovery from OA can be hypothesized. We assessed clinical, functional, and behavioral characteristics of 32 subjects (22 male, 10 female), in all but one of whom OA was confirmed by specific inhalation challenges induced by either high- (n=13) or low-molecular-weight (n=19) agents within 3 mo after cessation of exposure. In this randomized, crossover, double-blind study, subjects (paired for baseline PC20 and duration of symptoms after exposure) received either placebo or 1,000 micrograms of inhaled beclomethasone daily for 1 yr, followed by the alternate medication for 6 mo. Various clinical, functional, and behavioral parameters were examined at each 3-mo visit. Significant improvement in clinical (nocturnal symptoms, cough), functional (morning and evening peak expiratory flow rates), and behavioral (quality of life) parameters were detected in the active-treatment period, although the magnitude of the improvement was relatively small. Side effects (oropharyngeal, reduced cortisol) were similar in the placebo and treatment groups. Distinguishing subjects who started with the active preparation from those who were given placebo first showed that most clinical and behavioral parameters improved in the former instance, whereas there was no significant difference in the latter. We conclude that inhaled corticosteroids induce a small but significant overall improvement of the asthmatic condition in subjects with occupational asthma caused by high- and low-molecular-weight agents after withdrawal from exposure. The beneficial effect is, however, more pronounced if inhaled steroids are given early after diagnosis.

Administration, Inhalation↗

PubMed1996

Skin bruising in asthmatic subjects treated with high doses of inhaled steroids: frequency and association with adrenal function.

High doses of inhaled corticosteroids (ICS) (budesonide and beclo-methasone > or = 800 micrograms.day-1) are commonly used in the treatment of asthma. Some investigators have presented evidence for cutaneous effects (bruising), which suggests systemic absorption. This study aimed to assess the prevalence of skin bruising, relate the occurrence of skin bruising to adrenocortical function, and determine the risk factors for skin bruising. One hundred adult asthmatic subjects taking high doses (800-2,000 micrograms.day-1) of ICS for 3 months or more were recruited in an asthma clinic, and 100 control subjects paired for sex and age were recruited from an ophthalmology out-patient clinic. A detailed questionnaire on asthma, general habits and cutaneous lesions was administered. A cutaneous examination was performed. Urine cortisol levels were assessed on two consecutive days. Blood cortisol level and the response to Cortrosyn injection (60 min test) were evaluated. One hundred adult asthmatics (66 females and 34 males), 73 on beclomethasone and 27 on budesonide, were included. The prevalence of skin bruising was 71% based on the questionnaire (32% in controls) and 48% (39 out of 81 subjects) based on direct examination of the skin. We found a satisfactory association between the response to questionnaire and examination of the skin. Adrenocortical function testing showed that a minority of subjects (14 with at least one abnormal test) had lower urinary or blood cortisol levels. These low cortisol levels occurred in subjects who reported skin bruising. By multiple logistic regression, being a female (odds ratio (OR) = 20; 95% confidence interval (95% CI) = 13-33) and taking ICS for asthma (OR = 12; 95% CI = 8-18) were significantly (t = 5.4) related to the likelihood of developing skin bruising. In addition, among the asthmatic subjects, being older (OR = 1.6; 95% CI = 1.1-2.4/10 yrs interval) (t = 2.3) and being a female (OR = 22; 95% CI = 7-75) (t = 5.0) influenced the occurrence of skin bruising as documented by questionnaire. In asthmatic subjects, taking high doses of ICS is associated with: 1) increased occurrence of skin bruising by comparison with controls, particularly in older subjects; and 2) a generally normal adrenocortical function, although this function is significantly lower in subjects reporting skin bruising.

Administration, Inhalation↗

PubMed1995

Cellular distribution of protein kinase C isozymes in CD3-mediated stimulation of human T lymphocytes with aging.

Protein kinase C (PKC) is involved in a variety of cellular responses, such as the expression and secretion of IL-2, the regulation of cytotoxic killing and cell proliferation. It is known that these immune functions are altered with aging. Here, we show that anti-CD3-triggered T cell proliferation is significantly decreased with aging and that H7, an inhibitor of PKC, impairs the anti-CD3-induced T cell proliferation in a differential manner, lymphocytes of healthy young subjects being more sensitive to the PKC inhibitor than those of elderly subjects. We examined (Western blot) the presence and the cellular distribution of PKC isozymes in T lymphocytes of healthy young and elderly subjects in the resting state and after anti-CD3 mAb stimulation using antibodies directed against PKC alpha, beta, delta, epsilon and zeta isoforms in the cytosol and the plasma membrane fractions. These five PKC isotypes were present in human T cells of young and elderly subjects. However, their distribution between the cytosolic and membrane fractions varied according to the isozymes and the age of the subjects. In resting lymphocytes of young subjects, all the PKC isozymes were found in the cytosolic fraction, except PKC-zeta. In resting lymphocytes of elderly subjects PKC-zeta and -epsilon were almost equally distributed between the cytosolic and the membrane fractions, whereas PKC-alpha and -zeta were mainly found in the membrane fraction and PKC-beta was almost exclusively located in the cytosolic fraction. The translocation of PKC-alpha, -beta, -delta and -epsilon could be observed under anti-CD3 mAb stimulation in lymphocytes of young subjects, while in the case of elderly subjects only the PKC beta isoform was translocated. Our results suggest tha the decreased availability of cytosolic PKC may contribute to the diminished PKC-dependent responses to CD3-triggered stimulation of human T lymphocytes with aging.

Adult↗

PubMed1995

The mitochondrial LSU rDNA of the brown alga Pylaiella littoralis reveals alpha-proteobacterial features and is split by four group IIB introns with an atypical phylogeny.

The mitochondrial DNA region coding for the large ribosomal RNA subunit from the brown alga Pylaiella littoralis (L.) Kjellm was sequenced. The LSU rRNA was folded into a secondary structure and aligned with homologous, mitochondrial and eubacterial sequences. Taking into account the primary and secondary structure levels, the mitochondrial LSU rRNA of P. littoralis shares more structural features with alpha-proteobacterial genes than do those of the green alga Prototheca wickerhamii and land plants. In phylogenetic trees, branches leading to brown algae, red algae, the protozoan Acanthamoeba castellanii and land plants, respectively, emerge approximately at the same time, as they do in nuclear-gene based phylogenies. This suggests that there is only one origin for the mitochondrial rRNA genes found in these lineages. The LSU rDNA is split by four group IIB introns. The first two introns each contain one open reading frame which encodes a reverse transcriptase-like protein. Comparison of their amino acid sequences with those of other reverse transcriptase-like genes contained in group II introns shows that these genes are more closely related to plastid and cyanobacterial homologous genes than to any known mitochondrial intronic reverse transcriptase.

Amino Acid Sequence↗

PubMed1995

Complete sequence of the mitochondrial DNA of the rhodophyte Chondrus crispus (Gigartinales). Gene content and genome organization.

The complete nucleotide sequence of the circular mitochondrial (mt) DNA from the red alga Chondrus crispus was determined (25,836 nucleotides, A+T content 72.1%). Fifty one genes were identified. They include genes encoding three subunits of the cytochrome oxidase (cox1 to 3), apocytochrome b (cob), seven subunits of the NADH dehydrogenase complex (nad1 to 6, nad4L), two ATPase subunits (atp6 and atp9), three ribosomal RNAs (rrn5, srn and lrn), 23 tRNAs and four ribosomal proteins (rps3, rps11, rps12 and rpl16). Two subunits of the succinate dehydrogenase complex (sdhB and sdhC), usually found on nuclear genomes, are also located on the mtDNA of C. crispus. One group IIb intron is inserted in the tRNAIle gene. Six potentially functional open reading frames were identified, four of them having counterparts among green plant mtDNAs. The use of a modified genetic code and the absence of RNA editing, previously reported for the cox3 gene, appears as a general characteristic of this molecule. Mitochondrial genes are encoded on both DNA strands, in two opposite major transcriptional directions, suggesting the existence of two main transcriptional units. Two long and stable stem-loops were identified in intergenic regions, which are believed to be involved with transcription and replication. The main structural features of this genome are compared with the overall organization of mtDNAs and are discussed in view of the evolution of mitochondria.

Amino Acid Sequence↗

PubMed1995

DNA sequence, structure, and phylogenetic relationship of the mitochondrial small-subunit rRNA from the red alga Chondrus crispus (Gigartinales rhodophytes).

The entire nucleotide sequence containing the small-subunit ribosomal RNA gene (SSU rRNA) from the mitochondrial genome of Chondrus crispus was determined. To our knowledge, this is the first sequence of a mitochondrial 16S-like rRNA from a red alga. The length of this gene is 1,376 nucleotides. Its secondary structure was constructed and compared with other known secondary structures from eubacteria and from mitochondria of land plants, green and brown algae, and fungi. Phylogenetic trees were built upon SSU rRNA sequence alignment from mitochondria and eubacteria. The results show that rhodophytes and chromophytes provide additional links in the evolution of mitochondria between the green plant lineage and the "nonplant" lineages.

Base Sequence↗

PubMed1994

Nucleotide sequence of the cox3 gene from Chondrus crispus: evidence that UGA encodes tryptophan and evolutionary implications.

We present the nucleotide sequence of the gene encoding subunit 3 of cytochrome c oxidase in Chondrus crispus, the first report on a mitochondrial gene from a red alga. Amino acid alignment with homologous proteins shows that tryptophan is specified by UGA, as in the mitochondrial code of most organisms other than green plants. However, phylogenetic analyses of cox3 amino acid and nucleotide sequences indicate that C. crispus COX3 is related to the green-plant mitochondrial lineage. No RNA editing was detected on the corresponding transcript. As the only known photosynthetic eukaryotes that both share an immediate mitochondrial ancestor with green plants and exhibit features characteristic of non-plant mitochondria, ie, a small-sized mitochondrial genome and a modified genetic code, rhodophytes may be thought of as an intermediate evolutionary link at the root of the green-plant mitochondrial lineage.

Amino Acid Sequence↗

PubMed1994

Physical map and gene organization of the mitochondrial genome of Chondrus crispus (Rhodophyta, Gigartinales).

Organellar DNA, i.e. a mixture of plastid and mitochondrial DNAs, was purified from the rhodophyte Chondrus crispus and analysed with restriction endonucleases. Mitochondrial DNA fragments were identified by heterologous hybridization, cloned, mapped and partially sequenced. The mitochondrial genome of C. crispus consists of a 25.9 kb circular molecule on which twenty genes were localized. Compared with other plant mitochondrial genomes, C. crispus mitochondrial DNA appears as a relatively small molecule with a high coding capacity and a specific gene organization. The use of a modified genetic code and the absence of RNA editing, previously reported for the cox3 gene, is a general characteristic of the sequenced genes of this molecule. This is the first detailed description of a red algal mitochondrial genome.

Base Sequence↗