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Biomedical subjects

L Dubois

Publications and source records attributed to L Dubois.

At least 19 recordsLinked to original sources

Preschool children's eating behaviours are related to dietary adequacy and body weight.

OBJECTIVE: The aim of this paper is to analyse the relationships between eating behaviours (picky eating, irregular eating and overeating), and dietary adequacy in accordance with nutrition recommendations and body weight during the preschool years. DESIGN AND SETTING: Our analyses were performed using data from the Longitudinal Study of Child Development in Québec (1998-2002), a population-based birth cohort. SUBJECTS: The study followed a representative sample (n=2103) of children born in 1998 in the Canadian province of Québec. METHODS: Eating behaviours were derived from self-administered questionnaires when children were 2.5, 3.5 and 4.5 years. Nutrition data were collected from one 24-hour recall interview conducted at home by trained nutritionists at 4.5 years. Children's weight and height were measured at 4.5 years. Statistical analyses were carried out with SAS (version 8.2). Weighted data adjusted for within-variability were used in the analysis, and the significance level was set at 5%. RESULTS: Picky eaters consume fewer total fats, less energy and less protein than children never reporting picky eating behaviours. Picky eaters were more likely to consume less than dietary recommendations for fruit and vegetables, and meat and alternatives. Overeaters consumed more total energy and more of each macronutrient than children who were never reported as overeaters during the preschool years. These children consumed more servings of grain products and meats and alternatives per day than children not classified as overeaters. Even when the number of servings of grain products consumed was similar for overeaters and children who were never overeaters, overeaters had higher body mass index. CONCLUSION: Given that children as young as 4.5 years are displaying some form of problematic eating behaviour which is shown to be related to dietary adequacy and body weight, public health professionals should be targeting parents of young children to provide messages about strategies for coping with problematic eating behaviours in early childhood.

Body Mass Index↗

Repeated cycles of Clostridium-directed enzyme prodrug therapy result in sustained antitumour effects in vivo.

The unique properties of the tumour microenvironment can be exploited by using recombinant anaerobic clostridial spores as highly selective gene delivery vectors. Although several recombinant Clostridium species have been generated during the past decade, their efficacy has been limited. Our goal was to substantially improve the prospects of clostridia as a gene delivery vector. Therefore, we have assessed a series of nitroreductase (NTR) enzymes for their capacity to convert the innocuous CB1954 prodrug to its toxic derivative. Among the enzymes tested, one showed superior prodrug turnover characteristics. In addition, we established an efficient gene transfer procedure, based on conjugation, which allows for the first time genetic engineering of Clostridium strains with superior tumour colonisation properties with high success rates. This conjugation procedure was subsequently used to create a recombinant C. sporogenes overexpressing the isolated NTR enzyme. Finally, analogous to a clinical setting situation, we have tested the effect of multiple consecutive treatment cycles, with antibiotic bacterial clearance between cycles. Importantly, this regimen demonstrated that intravenously administered spores of NTR-recombinant C. sporogenes produced significant antitumour efficacy when combined with prodrug administration.

Animals↗

Prevalence of reticular pseudodrusen in age-related macular degeneration with newly diagnosed choroidal neovascularisation.

AIM: To investigate the prevalence of reticular pseudodrusen (RPD) in eyes of patients presenting with newly diagnosed choroidal neovascularisation (CNV) in age-related macular degeneration (AMD), and to analyse the association between RPD, age-related maculopathy (ARM) and AMD. METHOD: Two observational consecutive prospective series. In series 1, patients with AMD with newly diagnosed CNV were sampled to determine the incidence of RPD. Eyes with and without RPD were compared by the Mann-Whitney non-parametric test and Fisher's exact test for age, sex of patients, the eye involved and type of CNV. Series 2 comprised 100 patients referred for fundus photography, fluorescein and/or indocyanine green angiography, for whom pictures showed RPD. This second cohort was then selected from a larger group of patients. RESULTS: Patients with newly diagnosed CNV in series 1 comprised 67 women and 33 men, aged 57-96 years (mean 79.5). CNV was "classic" (32 eyes), "occult" (41) or exhibited vascularised pigment epithelial detachment (PED, 11), retinal angiomatous proliferation (RAP) with or without PED (13), or haemorrhagic or fibrovascular scarring (3). In all, 24 (24%) eyes had RPD. The prevalence of RAP was significantly higher in eyes with RPD than in those without (p = 0.0128), despite the small number of patients with RAP. In series 2, 100 patients with RPD were enrolled in 3 months, and corresponded to 8% of the overall cases referred to our centre (Centre Ophtalmologique d'Imagerie et de Laser, Paris, France). There were 77 women and 23 men, aged 54-93 years (mean 79.2). Eyes with RPD (n = 155) usually exhibited signs of ARM or AMD, including soft drusen (101 eyes) and/or retinal pigment epithelium abnormalities (70), geographical atrophy (27) and/or CNV (61). In both studies, examination of blue-light fundus pictures was extremely helpful in diagnosing RPD. CONCLUSION: RPD have a high prevalence among patients with AMD with newly diagnosed CNV (24% of cases). RPD were commonly associated with ARM or AMD. This study suggests that eyes with RPD could be classified as a phenotype of ARM.

Aged↗

Early determinants of overweight at 4.5 years in a population-based longitudinal study.

OBJECTIVES: The roots of the obesity epidemic need to be traced back as early in life as possible in order to develop effective means for preventing obesity and its health consequences in the future. The aim of this paper is to examine a broad range of factors that may simultaneously contribute to childhood overweight in a population-based cohort of children followed from birth to 4.5 years, to determine which factors exert the most influence in early life. DESIGN: The analyses were performed using data from the Quebec Longitudinal Study of Child Development 1998-2002 (QLSCD). SUBJECTS: The study follows a representative sample (n=2103) of children born in 1998 in the Canadian province of Quebec. MEASURE: Measured height and weight were available for 1550 children aged 4.5 years. At 4.5 years, BMI was analyzed using the US CDC sex- and age-specific growth charts. In order to study children at their highest weights at various ages, odds ratios were presented for high birth weight, weight-for-stature at or above the 95th percentile at 5 months, and BMI at or above the 95th percentile at 4.5 years. Monthly weight gain between birth and five months has been analyzed. Children were also evaluated by the Z-score obtained from the standardized weight divided by height. Factors potentially related to children's weight include sex, gestational age and birth rank, breastfeeding, mothers' smoking status during pregnancy, family type at child's birth, and family income before pregnancy and when the children were 5 months and 4.5 years old. Other parental factors such as height and overweight/obesity (based on BMI) and other maternal factors (age, education, immigrant status) were also part of the analysis. RESULTS: Being in the highest quintiles of weight gain between birth and 5 months, as well as maternal smoking during pregnancy, almost double the odds of being overweight at 4.5 years. Parental overweight or obesity also increased the odds of being overweight at this age, as well as being raised in middle-income or in poor families. A greater proportion of children born to nonsmoking mothers with higher weights (more than 4000 g) were overweight at 4.5 years, the percentage being greatest for those in the highest weight-gain categories from birth to 5 months. The pattern was different for children born to smoking mothers. The greatest proportion of 4.5-year-old overweight children was seen for children born in the normal weight-range category (3000-4000 g) who were in the highest quintiles of weight gain from birth to 5 months, and for children with high birth weights (more than 4000 g) who were in the lowest quintiles of birth-to-5-months weight gain. Children who were overweight at 4.5 years and who had been born to smoking mothers started life with a birth weight around that for the population means, but they gained more weight in the first 5 months of life than did the children of nonsmoking mothers. CONCLUSION: This study indicates that behavioral and social factors exert critical influences on the onset of childhood overweight in preschool years. From a population-health perspective, interventions aimed at preventing childhood obesity would do well to target smoking pregnant women, as well as nonsmoking pregnant women at risk for giving birth to high-birth-weight children, paying particular attention to rapid weight gain in the first months of life.

Adult↗

Evaluation of hypoxia in an experimental rat tumour model by [(18)F]fluoromisonidazole PET and immunohistochemistry.

This study aimed to evaluate tumour hypoxia by comparing [(18)F]Fluoromisonidazole uptake measured using positron emission tomography ([(18)F]FMISO-PET) with immunohistochemical (IHC) staining techniques. Syngeneic rhabdomyosarcoma (R1) tumour pieces were transplanted subcutaneously in the flanks of WAG/Rij rats. Tumours were analysed at volumes between 0.9 and 7.3 cm(3). Hypoxic volumes were defined using a 3D region of interest on 2 h postinjection [(18)F]FMISO-PET images, applying different thresholds (1.2-3.0). Monoclonal antibodies to pimonidazole (PIMO) and carbonic anhydrase IX (CA IX), exogenous and endogenous markers of hypoxia, respectively, were used for IHC staining. Marker-positive fractions were microscopically measured for each tumour, and hypoxic volumes were calculated. A heterogeneous distribution of hypoxia was observed both with histology and [(18)F]FMISO autoradiography. A statistically significant correlation (P<0.05) was obtained between the hypoxic volumes defined with [(18)F]FMISO-PET and the volumes derived from the PIMO-stained tumour sections (r=0.9066; P=0.0001), regardless of the selected threshold between 1.4 and 2.2. A similar observation was made with the CA IX staining (r=0.8636; P=0.0006). The relationship found between [(18)F]FMISO-PET and PIMO- and additionally CA IX-derived hypoxic volumes in rat rhabdomyosarcomas indicates the value of the noninvasive imaging method to measure hypoxia in whole tumours.

Animals↗

[Single ventricle and obstetric anaesthesia: two cases report].

Single ventricle is a relatively rare abnormality found only in 0.5-1.5% of patients with congenital heart disease. Pregnancy results in an increased maternal morbidity and mortality in patients with right to left shunting, especially in cases associated with pulmonary hypertension and polycythemia and decreased arterial oxygen saturation. Most complications arise from decreases in systemic vascular resistance, causing an increase in right to left shunting and further hypoxemia and acidosis. For this reason, the major regional anaesthetic techniques are often avoided in these patients. The authors reported two successful management of regional anaesthesia for both caesarean and vaginal delivery.

Adult↗

[Von Hippel-Lindau disease and obstetric anaesthesia: 3 cases report].

Von Hippel-Lindau (VHL) disease is a rare autosomal dominant genetic disorder with retinal and nervous system haemangioblastomas, phaeochromocytomia, kidney, pancreas and endolymphatic tumors. The management of childbirth, including epidural anaesthesia is controversial. The possible presence of vascular malformations (retinal and central nervous system and spinal haemangioblastomas) increases the risk of disrupting central nervous system haemangioblastoma during delivery and when epidural anaesthesia is initiated. We report 3 cases of patient with VHL disease with successful epidural anaesthesia 2 for delivery and 1 for Caesarean section.

Adult↗

Wingless capture by Frizzled and Frizzled2 in Drosophila embryos.

A variety of factors could influence how far developmental signals spread. For example, the Patched receptor limits the range of its ligand Hedgehog. Somehow, the Frizzled2 receptor has the opposite effect on its ligand. Increasing the level of Frizzled2 stabilizes Wingless and thus extends the Wingless gradient in Drosophila wing imaginal disks. Here we ask whether Frizzled or Frizzled2 affects the spread of Wingless in Drosophila embryos. We show that in the embryonic epidermis, the combined expression of both receptors is lowest in the engrailed domain. This is because expression of Frizzled is repressed by the Engrailed transcription factor, whereas that of Frizzled2 is repressed by Wingless signaling. Receptor downregulation correlates with an early asymmetry in Wingless distribution, characterized by the loss of Wingless staining in the engrailed domain. Raising the expression of either Frizzled or Frizzled2 in this domain prevents the early disappearance of Wingless-containing vesicles. Apparently, Wingless is captured, stabilized, and quickly internalized by either receptor. As far as we can tell, captured Wingless is not passed on to further cells and does not contribute to the spread of Wingless. Receptor downregulation in the posterior compartment may contribute to dampening the signal at the time when cuticular fates are specified.

Animals↗

Regulated endocytic routing modulates wingless signaling in Drosophila embryos.

Embryos have evolved various strategies to confine the action of secreted signals. Using an HRP-Wingless fusion protein to track the fate of endocytosed Wingless, we show that degradation by targeting to lysosomes is one such strategy. Wingless protein is specifically degraded at the posterior of each stripe of wingless transcription, even under conditions of overexpression. If lysosomal degradation is compromised genetically or chemically, excess Wingless accumulates and ectopic signaling ensues. In the wild-type, Wingless degradation is slower at the anterior than at the posterior. This follows in part from the segmental activation of signaling by the epidermal growth factor receptor, which accelerates Wingless degradation at the posterior, thus leading to asymmetrical Wingless signaling along the anterior-posterior axis.

Animals↗

The COE--Collier/Olf1/EBF--transcription factors: structural conservation and diversity of developmental functions.

One major conclusion of studies in Developmental Biology during the last two decades is that, despite profound anatomical differences, the building of vertebrate and arthropod bodies relies on the same fundamental molecular networks, including conserved cell signalling and transcription-regulatory cascades. Rodent Early B-Cell Factor/Olfactory-1 and Drosophila Collier belong to a recently defined, novel family of transcription factors, the Collier/Olf1/EBF (COE) proteins which have a unique DNA-binding domain. Early investigations revealed that, despite their high degree of sequence identity, the different vertebrate and invertebrate COE proteins play a variety of developmental roles. We review here the current evidence for this diversity of COE functions, including in the specification and differentiation of various neuronal populations. We also discuss the existence of an evolutionarily conserved pathway linking Notch signalling and COE regulatory functions in various developmental decisions.

Amino Acid Sequence↗

Social position and nutrition: a gradient relationship in Canada and the USA.

OBJECTIVE: [corrected] To study the existence of a graded relationship between the nutrient content of the diet and some measures of social position. DESIGN AND SETTING: The graded relationship hypothesis was verified by secondary analysis performed on two different nutrition surveys: the Quebec Nutrition Survey (QNS) and the NHANES III, both based on a single 24 h recall. The data of these surveys were collected on a representative sample of two different populations, the first (n=2103) in the province of Quebec (Canada) in 1990 (QNS) and the second in the US population (n=14 877) between 1988 and 1994 (NHANES III). MAIN OUTCOMES MEASURES: The social gradient hypothesis was tested with four different social position indicators. The analyses were performed separately for men and women aged from 18 to 74 y, for all the nutrients available in the databanks. For the USA, the graded relationship for the total population, for the non-Hispanic white population and for respondents sometimes or often experiencing a lack of food was also measured. RESULTS: A graded relationship between almost all nutrients and the studied social position measurements is observed for the consumption of total calorie-adjusted nutrients, for the proportion of people eating in accordance with dietary guidelines and for the proportion of individual not meeting 75% of the respective Recommended Dietary Allowances for their country. The direction of these relationships (positive or negative) is mainly in accordance with the clinical known impacts of nutrients on chronic diseases. CONCLUSIONS: It is possible that nutrition plays a role in the graded distribution of social health inequalities in North America even in the magnitude of this contribution remains to be evaluated.

Adolescent↗

The choice of a diet quality indicator to evaluate the nutritional health of populations.

BACKGROUND: The USA and Canada both want to reduce social health inequalities in their population. These two countries have recently begun a process of harmonization of their nutrient recommendations. OBJECTIVE: To develop a standardized indicator to measure the impact of these recommendations on the health of different social groups in North America. The authors have compared three of the methods currently used for measuring overall diet quality for a population. DESIGN AND SETTING: The three methods, adjusted to the 1990 Canadian nutrition recommendations, were used to analyse the Québec Nutrition Survey data collected by Santé Québec in 1990. RESULTS: The authors found that the indicator developed by Kennedy and collaborators works best for analysing the Québec data. Moreover, it allows comparisons with the USA. Some questions, such as whether or not to add calories from alcohol consumption to the model and whether the indicators should be adjusted to the different cultures and specific population groups remain unanswered. CONCLUSIONS: In order to determine the role of nutrition in social health inequalities, it is important to develop standard indicators that are suitable for monitoring the relationship between dietary recommendations and eating habits.

Canada↗

A novel polyomavirus (goose hemorrhagic polyomavirus) is the agent of hemorrhagic nephritis enteritis of geese.

We have identified the etiological agent of hemorrhagic nephritis enteritis of geese (HNEG), a fatal disease of European geese. HNEG has been recognized in almost all goose breeding areas, with an epizootic pattern, and up to now, the infectious agent has remained unknown. In order to identify the causative agent, infected tissues from HNEG-affected geese were inoculated to 1-day-old goslings, which then developed clinical signs typical of HNEG. Tissue homogenates from these birds were subjected to Freon extraction followed by sucrose density gradient ultracentrifugation. The resulting main band was examined by electron microscopy and consisted of spherical, naked, papovavirus-like particles approximately 45 nm in diameter. The virus was isolated and propagated in goose kidney cell primary culture. Tissue- or culture-purified virus allowed the experimental reproduction of the disease in goslings. Random PCR amplification of viral nucleic acid produced a 1,175-bp fragment which was shown to be associated with field samples collected from geese affected by HNEG on commercial farms in France. Sequence analysis of the PCR product revealed a unique open reading frame, showing 63 to 72% amino acid similarity with the major capsid protein (VP1) of several polyomaviruses. Finally, based on phylogenetic analysis, we conclude that the causative agent of HNEG is closely related to but clearly distinct from other polyomaviruses; we thus have named this newly identified virus Goose hemorrhagic polyomavirus.

Amino Acid Sequence↗

Head versus trunk patterning in the Drosophila embryo; collier requirement for formation of the intercalary segment.

Whereas the segmental nature of the insect head is well established, relatively little is known about the genetic and molecular mechanisms governing this process. In this paper, we report the phenotypic analysis of mutations in collier (col), which encodes the Drosophila member of the COE family of HLH transcription factors and is activated at the blastoderm stage in a region overlapping a parasegment (PS0: posterior intercalary and anterior mandibular segments) and a mitotic domain, MD2. col mutant embryos specifically lack intercalary ectodermal structures. col activity is required for intercalary-segment expression both of the segment polarity genes hedgehog, engrailed, and wingless, and of the segment identity gene cap and collar. The parasegmental register of col activation is controlled by the combined activities of the head-gap genes buttonhead and empty spiracles and the pair-rule gene even skipped; it therefore integrates inputs from both the head and trunk segmentation systems, which were previously considered as being essentially independent. After gastrulation, positive autoregulation of col is limited to cells of anterior PS0. Conversely, heat-pulse induced ubiquitous expression of Col leads to disruption of the head skeleton. Together, these results indicate that col is required for establishment of the PS(-1)/PS0 parasegmental border and formation of the intercalary segment. Our data support neither a simple combinatorial model for segmental patterning of the head nor a direct activation of segment polarity gene expression by head-gap genes, but rather argue for the existence of parasegment-specific second order regulators acting in the head, at a level similar to that of pair-rule genes in the trunk.

Amino Acid Sequence↗

[Demystifying the desire for control].

Demystifying the desire for control. Humans are constantly striving for various forms of control: to master a role or new responsibility, or to control their weight. The desire for control, therefore, is fundamental to the nursing profession because nurses are responsible for helping individuals maintain, regain or attain optimal health. Analysis of much of the literature reveals the lack of consensus on the terminology and definition of the desire for control. To remedy this shortcoming and clarify this key concept in nursing, the authors analysed this concept with the method described by Wilson, often used in nursing. The authors describe the background, characteristics and consequences of this concept. Identifying these factors should give nurses an opportunity to observe this concept in practice and to understand certain behaviors. Our view of reality shapes how we deliver care. Demystifying this concept will also open the field to research.

Humans↗

XCoe2, a transcription factor of the Col/Olf-1/EBF family involved in the specification of primary neurons in Xenopus.

BACKGROUND: Primary neurogenesis in Xenopus is a model for studying the control of neural cell fate decisions. The specification of primary neurons appears to be driven by transcription factors containing a basic region and a helix-loop-helix (HLH) motif: expression of Xenopus neurogenin-related-1 (X-ngnr-1) defines the three prospective domains of primary neurogenesis, and expression of XNeuroD coincides with neuronal differentiation. The transition between neuronal competence and stable commitment to a neuronal fate remains poorly characterised, however. RESULTS: Drosophila Collier and rodent early B-cell factor/olfactory-1 define a family of HLH transcription factors containing a previously unknown type of DNA-binding domain. We isolated an orthologous gene from Xenopus, Xcoe2, which is expressed in precursors of primary neurons. Xcoe2 is transcribed after X-ngnr-1 and before XNeuroD. Overexpression of a dominant-negative mutant of XCoe2 prevented neuronal differentiation. Conversely, overexpressed wild-type Xcoe2 could promote ectopic differentiation of neurons, in both the neural plate and the epidermis. In contrast to studies with X-ngnr-1 or XNeuroD, the supernumerary neurons induced by Xcoe2 appeared in a 'salt-and-pepper' pattern, resulting from the activation of X-Delta1 expression and feedback regulation by lateral inhibition. CONCLUSIONS: XCoe2 may play a pivotal role in the transcriptional cascade that specifies primary neurons in Xenopus embryos: by maintaining Delta-Notch signalling, XCoe2 stabilises the higher neural potential of selected progenitor cells that express X-ngnr-1, ensuring the transition between neural competence and irreversible commitment to a neural fate; and it promotes neuronal differentiation by activating XNeuroD expression, directly or indirectly.

Amino Acid Sequence↗

Molecular cloning of Zcoe2, the zebrafish homolog of Xenopus Xcoe2 and mouse EBF-2, and its expression during primary neurogenesis.

Xcoe2 is a recently identified HLH transcription factor of the Xenopus primary neurogenesis pathway, which is necessary downstream of Neurogenin to stabilize neuroblast determination (Dubois, L. et al., 1998. Curr. Biol. 8, 199-209). We report here the embryonic expression pattern of Zcoe2, its zebrafish homolog. As observed for Xcoe2, Zcoe2 is strongly expressed in a subset of the neurogenin1- (ngn1-) positive primary neuroblasts of the spinal cord. In the anterior neural plate, in contrast, Zcoe2 is expressed earlier and more widely than ngn1. This pattern is strongly maintained in the presumptive mesencephalon and rhombomeres 1-4 until the 2-3-somite stage. This expression of Zcoe2 in the brain anlage calls for a re-analysis in zebrafish of the functional relationship demonstrated in Xenopus between Coe2 and Neurogenin factors. At later stages, Zcoe2 is expressed in early forming neurons of the anterior brain and is a marker of the olfactory placodes.

Animals↗

Collier, a novel regulator of Drosophila head development, is expressed in a single mitotic domain.

BACKGROUND: Segmentation of the Drosophila embryo is based on a cascade of hierarchical gene interactions that is initiated by maternal morphogens; these interactions define spatially restricted domains of zygotic gene expression within the blastoderm. Although the hierarchy of the segmentation genes that subdivide the trunk is well established, the patterning of the head is less well understood. Seven head segments can be assigned on the basis of metameric patterns of segment-polarity gene expression and internal sensory organs. The domains of expression of head gap-like genes broadly overlap, with their posterior margins out of phase by one segment. Taken together with the lack of pair-rule gene expression in the head, these observations led to the suggestion that head gap genes act in a combinatorial manner, determining head segmental borders and segmental identity at the same time. RESULTS: We have identified a new Drosophila gene, collier (col), whose expression at the blastoderm stage is restricted to a single stripe of cells corresponding to part of the intercalary and mandibular segment primordia, possibly parasegment O. Reduction of col activity in early gastrula embryos by antisense RNA expression results in a specific lack of head structures derived from these segments. The expression of col coincides with a mitotic domain, which supports the proposal that cells in this domain undergo a concerted mitotic and differentiation program that is orchestrated at the transcriptional level. Col is an ortholog of mammalian early B-cell factor/Olfactory-1. These proteins define a new family of transcription factors that contain a helix-loop-helix dimerization motif and a new type of DNA-binding domain that is highly conserved during evolution. CONCLUSIONS: Here we describe Col, the first Drosophila member of a new family of transcription factors. Col may act as a "second-level regulator' of head patterning. The structural conservation of Col during evolution raises the questions of its conservation of function in head specification and its interactions with other factors conserved between insects and vertebrates.

Amino Acid Sequence↗