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Biomedical subjects

I Godin

Publications and source records attributed to I Godin.

At least 19 recordsLinked to original sources

Barriers to prenatal care in Europe.

BACKGROUND: In Europe, it is sometimes assumed that few barriers to prenatal care exist because extensive programs of health insurance and initiatives to promote participation in prenatal care have been established for many decades. METHODS: A case-control study was performed in ten European countries (Austria, Denmark, Germany, Greece, Hungary, Ireland, Italy, Portugal, Spain, and Sweden). Postpartum interviews were conducted between 1995 and 1996. A total of 1283 women with inadequate prenatal care (i.e., with 0, 1, or 2 prenatal care visits or a first prenatal care visit after 15 completed weeks of pregnancy) and 1280 controls with adequate prenatal care were included in the analysis combining data from the ten countries. RESULTS: Based on combined data of the ten countries, lack of health insurance was found to be an important risk factor for inadequate prenatal care (crude odds ratio [OR] at 95% confidence interval [CI]: 30.1 [20.1-47.1]). Women with inadequate prenatal care were more likely to be aged < 20 years (16.4% vs 4.8%) and with higher parity (number of children previously borne) than controls. They were more likely to be foreign nationals, unmarried, and with an unplanned pregnancy. Women with inadequate care were also more likely to have less education and no regular income. They had more difficulties dealing with health services organization and child care. Cultural and financial barriers were present, but after adjusting for confounders by logistic regression, perceived financial difficulty was not a significant factor for inadequate prenatal care (adjusted OR [95% CI]: 0.7 [0.4-1.3]). CONCLUSIONS: Personal, socioeconomic, organizational, and cultural barriers to prenatal care exist in Europe.

Adult↗

Pluripotent hematopoietic stem cell development during embryogenesis.

Significant progress has been made towards a better understanding of the establishment of hematopoiesis in the embryo. Hematopoietic precursors have been shown to arise independently in the yolk sac and in the intra-embryonic mesoderm. From the combined analysis of differentiation potentials, expression patterns and mutant phenotypes, a picture has emerged: definitive hematopoietic precursors are transiently generated in a specific environment close to the endothelium of the main arteries.

Animals↗

Intraembryonic, but not yolk sac hematopoietic precursors, isolated before circulation, provide long-term multilineage reconstitution.

The relative contribution of yolk sac and intraembryonic precursors to hematopoiesis has been a matter of long-standing controversy. As reconstitution activity has so far only been found in embryonic tissues after the onset of circulation, the origin of reconstituting cells could not be formally established. Here, we separated yolk sac and intraembryonic splanchnopleura prior to circulation and maintained the explants in organ culture before transfer. Precursors derived from the intraembryonic site generated multilineage hematopoietic progeny in adult mice for more than 6 months. Yolk sac cells only provided myeloid short-term reconstitution. The results reveal a differential hematopoietic capacity of precirculation embryonic tissues in vivo, and indicate that the only cells capable of adult long-term hematopoiesis are of intraembryonic origin.

Animals↗

Blood pressure measurement in epidemiological investigations in teenagers.

BACKGROUND: The use of sphygmomanometers may lead to problems in investigations on health of young people. The purpose of this paper is to present the validation of the blood pressure (BP) collected during the survey 'Youth Heart Health' in Hainaut by using second sample of young people in Hainaut for which BP was measured by a manual taking of tension and by an electronic device. METHODS: Validation was done with a control sample of 343 young with five successive BP measures: twice with the mercury sphygmomanometer and three with DXL. We compared the manual and the electronic measures in order to study the correlation between the two methods. The control sample was used in order to compare the BP measurements with the results of the survey on the health of young people in Hainaut. RESULTS: The differences between manual systolic BP and Dinamap measures are significant (differences in averages 3.6 mmHg; d.s. 7.8; 95% CI: 2.8-4.4 mmHg; p < 0.001) and the regression coefficient is -0.015. Diastolic BP is significantly higher with the manual method than with Dinamap (differences in means: 8.2 mmHg; d.s. 7.0; 95% CI: 7.4-8.9 mmHg; p < 0.001) and the coefficient of regression is 0.096. We observe a difference in BP between the general survey and the control group (10.3 mmHg for systolic manual control and of 10.9 mmHg for systolic electronic control; 3.3 mmHg for diastolic manual control and of 11.5 mmHg for diastolic electronic control). CONCLUSIONS: The values of BP of the 'Youth Heart Health' are significantly higher. These observations indicate the difficulties in the choice of the tool for measurements of BP in epidemiological investigations in the teenagers. In order to decrease skews of observations in the measurement of BP, it is recommended to use a valid electronic instrument. Dinamap XL is an instrument of choice in such studies of young people. Environmental and organisational factors may also explain the observed difference, which means that survey's protocols should address this issue carefully.

Adolescent↗

[Microglia: origin and development].

As suggested by Del Rio Ortega a long time ago, it is now widely accepted that microglia are the resident macrophages of the central nervous system. Microglia represent about 10% of the adult brain cell population. We have previously shown that the late embryonic and adult mouse brain contain potential microglial progenitors. We report here that microglial progenitors can be detected in neural folds from embryonic day 8. They originate from the yolk sac in which macrophage progenitors are found from embryonic day 7. We also report that the bulk of microglial cells (about 95%) appear during post-natal development. A major finding is that microglia arise by an intense in situ proliferation comparable to that of neural cells. Taken together, these results show that adult mouse microglia originate from cells migrating from the yolk sac and whose progeny actively proliferates in the brain during development.

Age Factors↗

The splanchnopleura/AGM region is the prime site for the generation of multipotent hemopoietic precursors, in the mouse embryo.

The first hemopoietic cells were found in the yolk sac of mammalian embryos. Based on this observation it was postulated that hemopoietic stem cells are generated in this location. In the last few years, however, increasing evidence indicates that there is an independent site of hemopoietic cell generation, in the embryo proper, designated the paraaortic splanchnopleura/aorta, gonad, mesonephros region. Precursors of hemopoietic cells are found in this region before circulation is established between the yolk sac and the embryo proper. In contrast to the hemopoietic cells found in the yolk sac, the ones found in the embryo proper are multipotent lympho-myeloid precursors that rapidly acquire the capacity to reconstitute the hemopoietic system of adult irradiated recipients. We propose that these are the founder cells of adult definitive hematopoiesis.

Animals↗

Lmo2 and GATA-3 associated expression in intraembryonic hemogenic sites.

It is now widely accepted that hemopoietic cells born intraembryonically are the best candidates for the seeding of definitive hemopoietic organs. To further understand the mechanisms involved in the generation of definitive hemopoietic stem cells, we analysed the expression of the hemopoietic-related transcription factors Lmo2 and GATA-3 during the early steps of mouse development (7-12 dpc), with a particular emphasis on intraembryonic hemogenic sites. We show here that both Lmo2 and GATA-3 are present in the intraembryonic regions known to give rise to hemopoietic precursors in vitro and in vivo, suggesting that they act together at key points of hemopoietic development. (1) Lmo2 and GATA-3 are expressed in the caudal mesoderm during the phase of intraembryonic precursors determination. (2) A highly transient concomitant expression is observed in the caudal intraembryonic definitive endoderm, suggesting that these factors are involved in the specification of intraembryonic hemopoietic precursors. (3) Lmo2 and GATA-3 are expressed within the hemopoietic clusters located in the aortic floor during fetal liver colonisation. Furthermore, a strong GATA-3 signal allowed us to uncover previously unreported mesodermal aggregates beneath the aorta. A combined in situ and immunocytological analysis strongly suggests that ventral mesodermal GATA-3 patches are involved in the process of intraembryonic stem cell generation.

Adaptor Proteins, Signal Transducing↗

Microglia derive from progenitors, originating from the yolk sac, and which proliferate in the brain.

Microglia, the resident CNS macrophages, represent about 10% of the adult brain cell population. Although described a long time ago, their origin and developmental lineage is still debated. While del Rio-Hortega suggested that microglia originate from meningeal macrophages penetrating the brain during embryonic development, many authors claim that brain parenchymal microglia derive from circulating blood monocytes originating from bone marrow. We have previously reported that the late embryonic and adult mouse brain parenchyma contains potential microglial progenitors [F. Alliot, E. Lecain, B. Grima, B. Pessac, Microglial progenitors with a high proliferative capacity in the embryonic and the adult mouse brain, Proc. Natl. Acad. Sci. U.S.A. 88 (1991) 1541-1545]. We now report that they can be detected in the brain rudiment from embryonic day 8, after their appearance in the yolk sac and that their number increases until late gestation. We also show that microglia appear during embryonic development and that their number increases steadily during the first two postnatal weeks, when about 95% of microglia are born. Finally, the main finding of this study is that microglia is the result of in situ proliferation, as shown by the high proportion of parenchymal microglial cells that express PCNA, a marker of cell multiplication, in embryonic and postnatal brain. Taken together, our data support the hypothesis that terminally differentiated brain parenchymal microglia are derived from cells originating from the yolk sac whose progeny actively proliferates in situ during development.

Animals↗

Stem cell emergence and hemopoietic activity are incompatible in mouse intraembryonic sites.

In the mouse embryo, the generation of candidate progenitors for long-lasting hemopoiesis has been reported in the paraaortic splanchnopleura (P-Sp)/ aorta-gonad-mesonephros (AGM) region. Here, we address the following question: can the P-Sp/AGM environment support hemopoietic differentiation as well as generate stem cells, and, conversely, are other sites where hemopoietic differentiation occurs capable of generating stem cells? Although P-Sp/AGM generates de novo hemopoietic stem cells between 9.5 and 12.5 days post coitus (dpc), we show here that it does not support hemopoietic differentiation. Among mesoderm-derived sites, spleen and omentum were shown to be colonized by exogenous cells in the same fashion as the fetal liver. Cells colonizing the spleen were multipotent and pursued their evolution to committed progenitors in this organ. In contrast, the omentum, which was colonized by lymphoid-committed progenitors that did not expand, cannot be considered as a hemopoietic organ. From these data, stem cell generation appears incompatible with hemopoietic activity. At the peak of hemopoietic progenitor production in the P-Sp/AGM, between 10.5 and 11.5 dpc, multipotent cells were found at the exceptional frequency of 1 out of 12 total cells and 1 out of 4 AA4.1+ cells. Thus, progenitors within this region constitute a pool of undifferentiated hemopoietic cells readily accessible for characterization.

Animals↗

Regulation of embryonic/fetal globin genes by nuclear hormone receptors: a novel perspective on hemoglobin switching.

The CCAAT box is one of the conserved motifs found in globin promoters. It binds the CP1 protein. We noticed that the CCAAT-box region of embryonic/fetal, but not adult, globin promoters also contains one or two direct repeats of a short motif analogous to DR-1 binding sites for non-steroid nuclear hormone receptors. We show that a complex previously named NF-E3 binds to these repeats. In transgenic mice, destruction of the CCAAT motif within the human epsilon-globin promoter leads to substantial reduction in epsilon expression in embryonic erythroid cells, indicating that CP1 activates epsilon expression; in contrast, destruction of the DR-1 elements yields striking epsilon expression in definitive erythropoiesis, indicating that the NF-E3 complex acts as a developmental repressor of the epsilon gene. We also show that NF-E3 is immunologically related to COUP-TF orphan nuclear receptors. One of these, COUP-TF II, is expressed in embryonic/fetal erythroid cell lines, murine yolk sac, intra-embryonic splanchnopleura and fetal liver. In addition, the structure and abundance of NF-E3/COUP-TF complexes vary during fetal liver development. These results elucidate the structure as well as the role of NF-E3 in globin gene expression and provide evidence that nuclear hormone receptors are involved in the control of globin gene switching.

Animals↗

The molecular characterization of the fetal stem cell marker AA4.

We have identified and characterized the stem cell antigen AA4. This molecule is a type I transmembrane protein whose overall structure suggests a role in cell adhesion. During fetal ontogeny (days 9-14 of development), AA4 is expressed in three major cell types: vascular endothelial cells, aorta-associated hematopoietic clusters, and primitive fetal liver hematopoietic progenitors. In the adult, AA4 is abundant in lung, heart, and whole bone marrow. In the adult hematopoietic compartment, aa4 transcripts are present in bone marrow CD34(-/lo) Lin- Sca-1+ c-Kit+ and CD34hi Lin- Sca-1+ c-Kit+ stem and progenitor cell subsets. Our observations suggest that AA4 plays a role in cell-cell interactions during hematopoietic and vascular development.

3T3 Cells↗

Where do hematopoietic stem cells come from?

The experimental model constituted by a quail embryo grafted on a chick yolk sac has produced undisputable evidence according to which hematopoietic stem cells (HSC) colonizing the blood-forming rudiments are of intraembryonic origin in birds. Appropriate cell culture systems now make it feasible to demonstrate that ontogeny of the mouse hematopoietic system also involves at least two generations of HSC, one formed in the yolk sac and the other in the embryo, only the latter having lymphoid potential. Furthermore the developmental relationships between endothelial and hematopoietic cells are being analyzed in the avian model. Two distinct endothelial lineages are detected by means of interspecific transplantations, a dorsal one, somitic in origin, which is purely endothelial and a ventral one, splanchnopleural in origin, which is associated with the production of hematopoietic cells.

Animals↗

Lymphoid potential, probed before circulation in mouse, is restricted to caudal intraembryonic splanchnopleura.

Emergence of hemopoietic stem cells in the mammalian embryo has yet to be definitively allocated. Previously, we detected multipotent hemopoietic precursors in the region surrounding the dorsal aorta (paraaortic splanchnopleura) beginning at 8.5 days postcoitum (dpc). However, as circulation is already established, it remained unclear whether hemopoietic precursors arise in situ or are blood-delivered. By adding an organotypic step to our former culture system, we now detect lymphocyte and multipotent myeloid precursors from the intraembryonic splanchnopleura as early as 7.5 dpc. Under identical conditions, yolk sacs from the same embryos are unable to generate lymphoid progeny and have a reduced potential for myeloid differentiation and maintenance. Thus, if isolated before circulation, the yolk sac does not produce multipotent precursors and therefore does not contribute to definitive hemopoiesis in the mouse.

Animals↗

Emergence of multipotent hemopoietic cells in the yolk sac and paraaortic splanchnopleura in mouse embryos, beginning at 8.5 days postcoitus.

We show by an in vitro approach that multipotent hemopoietic cells can be detected in the body of the mouse embryo between the stages of 10-25 somites (8.5-9.5 days of gestation)--i.e., prior to liver colonization (28-32 pairs of somites). Interestingly, hemopoietic cells appear in parallel in this location, the paraaortic splanchnopleura, and in the yolk sac, where they represent a new generation by reference to the primitive hemopoietic stem cells. Lymphoid cell clones, which could differentiate into mature B cells, were obtained from yolk sac and paraaortic splanchnopleura cell preparations but not from other tissues of the embryonic body. These B-cell precursors were first detected around the stage of 10 somites; thereafter, their initial minute numbers increased in parallel in the yolk sac and the paraaortic splanchnopleura, suggesting that their emergence in the two sites was simultaneous. By single cell manipulation, we show that these precursors can generate B and T lymphocytes and myeloid cells; these precursors can thus be defined as multipotent hemopoietic cells.

Animals↗

B-lymphoid potential in pre-liver mouse embryo.

Increasing interest in the initial steps of hemopoiesis in the embryo is prompted by the lack of information about the primordial origin and the nature of hemopoietic stem cells. It appears critical to understand the emergence, diversification and differentiation potential of hemopoietic cells in the preliver embryo. In-vitro studies of B-potential in the mouse embryo prior to liver colonization show that, contrary to interpretations prevalent 10 years ago, there are two sources of B-cell progenitors (and most probably stem cells) at these stages: the yolk sac and the paraaortic splanchnopleura within the embryo proper. The analysis of the phenotype and differentiation potential of precursors from both sources shows them to be very similar, while different from the fetal liver progenitors. Indications for an independent generation of precursors in both sites are reviewed.

Animals↗

[Intra-embryonic hematopoiesis in mice].

In vertebrate embryos, all hemopoietic tissues that are successively active during ontogeny (fetal liver, thymus, spleen and bone marrow) are colonized by extrinsic hemopoietic stem cells (HSC). The exception to this rule is the yolk sac (YS) whose progenitors arise in situ. Moreover, the YS is the first hemopoietic site to appear in the embryo. In consequence, it was considered as the primary source of the HSC that transfer from one site to the other until the demonstration that, in birds, the source of definitive HSC was located in the aortic region of the embryo. To assess a possible contribution of intraembryonic sites to mouse hemopoietic development, we developed an in vitro approach that permits the detection of multipotent hemopoietic progenitors in the region surrounding the dorsal aorta. This new site, the paraaortic splanchnopleura (P-Sp), is active from the 10 somite stage to the stage of fetal liver colonization by HSC. The in vitro analysis of the hemopoietic potential of the P-Sp revealed that: 1) progenitors present in this region are multipotent since a single micromanipulated P-Sp cell can give rise to mature B and T lymphocytes and various myeloid cells, when cultivated in appropriate conditions; 2) the P-Sp is the only intraembryonic site endowed with this potential; 3) numbering progenitors present in the YS and P-Sp indicated that precursors appear in both locations at the 10-12 somite stage reaching 15 in each site at 9.5 dpc (25 somites), shortly before the beginning of fetal liver colonisation. During a cytological study of the 9-11 dpc embryo aimed to disclose the cellular basis for our experimental results, two potential hemopoietic sites were uncovered. Cells clusters that resemble avian intraaortic hemopoietic clusters were found in the arteries located close to the coelomic cavity (dorsal aorta, umbilical and omphalomesenteric arteries). Moreover, groups of cells strikingly similar to YS blood islands were uncovered in the mesentery. All these sites are located in areas formed from the P-Sp and are fully developed at the onset of fetal liver colonization. These hemogenic sites most probably develop from the hemopoietic precursors present in the P-Sp.

Animals↗