Biomedical subjects

Anne-Lise Delezoide

Publications and source records attributed to Anne-Lise Delezoide.

29 records · Page 2Linked to original sources

PubMed2004

Expression of fibroblast growth factors 18 and 23 during human embryonic and fetal development.

Fibroblast Growth Factor (FGF) 18 and 23 are two recently identified members of the FGF family, a family of structurally related polypeptides with diverse roles in physiological and pathological processes. Studies mostly performed in rodents and chicken have demonstrated that FGF18 is a pleiotropic growth factor involved in the development of various organs, while there are no data supporting a direct role of FGF23 in cell proliferation or differentiation either in physiology or pathology in any species. However, it is now established that FGF23 can be a humoral messenger and an important regulator of phosphate homeostasis and vitamin D metabolism. As a first step towards elucidating the roles of these FGF in human development, we examined FGF18 and FGF23 mRNA expression by in situ hybridization in whole human embryos at 30 days and 8 weeks of gestation (GW) and in specific fetal tissues at different ages. We report a highly restricted expression pattern for both FGF genes in human embryonic development.

Cell Differentiation↗

PubMed2004

Molecular characterization of early human T/NK and B-lymphoid progenitor cells in umbilical cord blood.

The early stages of human lymphopoiesis are poorly characterized. Here, we compared the lymphoid potential of a novel umbilical cord blood CD34(+)CD45RA(hi)CD7(+) hematopoietic progenitor cell (HPC) population with that of CD34(+)CD45RA(hi)Lin(-)CD10(+) HPCs, previously proposed as candidate common lymphoid progenitors. Limiting-dilution and clonal analysis, fetal thymic organ cultures, and culture onto Notch ligand Delta-like-1-expressing OP9 cells, showed that although CD34(+)CD45RA(hi)CD7(+) HPCs could generate cells of the 3 lymphoid lineages, their potential was skewed toward the T/natural killer (T/NK) lineages. In contrast, CD34(+)CD45RA(hi)Lin(-)CD10(+) HPCs predominantly exhibited a B-cell potential. Gene expression profiling with DNA microarrays confirmed that CD34(+)CD45RA(hi)CD7(+) HPCs selectively expressed T-lymphoid and NK lineage-committed genes while retaining expression of genes affiliated to the granulomonocytic lineage, whereas CD34(+)CD45RA(hi)Lin(-)CD10(+) HPCs displayed a typical pro-B-cell transcription profile and essentially lacked genes unrelated to the B lineage. In addition, both populations could be generated in vitro from CD34(+)CD45RA(int)CD7(-) and CD34(+)CD45RA(hi)Lin(-) HPCs with mixed lymphomyeloid potential, from which they emerged independently with different growth/differentiation factor requirements. These findings indicate that CD34(+)CD45RA(hi)CD7(+) and CD34(+)CD45RA(hi)Lin(-)CD10(+) HPCs correspond to multipotent early lymphoid progenitors polarized toward either the T/NK or B lineage, respectively.

Antigens, CD↗

PubMed2004

Oto-onycho-peroneal syndrome: further delineation and first fetal report.

We report on the sixth case and first fetal description of oto-onycho-peroneal syndrome (MIM 259780). This entity consists in the association of ear anomalies (-oto), hypoplastic nails (-onycho), hypoplastic or absent fibulae (-peroneal), and shoulder anomalies. Described for the first time by Leiba et al. [1975: Birth Defects 11:67-73] in a male patient, coined by Pfeiffer [1982: Eur J Pediatr 138:317-320], and confirmed by Devriendt et al. [1998: J Med Genet 35:508-509] this condition is most likely autosomal recessive, given the occurrence in sibs of both sexes with normal parents.

Abnormalities, Multiple↗

PubMed2004

Recurrence of achondrogenesis type II within the same family: evidence for germline mosaicism.

Achondrogenesis type II is a lethal skeletal dysplasia caused by new dominant mutations within the type II collagen gene (COL2A1). Here we report on two pregnancies of a healthy, nonconsanguineous young couple. In the first pregnancy, severe micromelia and generalized edema were noted on ultrasound at 21 weeks' gestation. Clinical, radiological, and histological evaluation of the fetus after termination of the pregnancy showed typical findings of achondrogenesis type II. In the second pregnancy, fetal hygroma was noted at 11 weeks' gestation. Similar clinical, radiographic, and histologic findings were observed in the second fetus, suggesting the recurrence of achondrogenesis II within this family. Molecular analysis of genomic DNA extracted from amniotic cells of the second fetus revealed heterozygosity for a 1340G > A missense mutation (G316D) in the COL2A1 gene. This mutation was not found in the parents. Although, we could not evaluate the presence of this mutation in the first fetus, we strongly believe that our data are in favor of germline mosaicism as the most likely explanation for the recurrence of type II achondrogenesis in both sibs.

Achondroplasia↗

PubMed2004

Expression of the RSK2 gene during early human development.

The 90 kDa ribosomal S6 serine/threonine kinase 2 gene (RSK2, U08316) has been recently identified as a disease-causing gene in an X-linked disorder, the Coffin-Lowry Syndrome (MIM 303600) characterized by severe mental retardation, facial dysmorphisms and progressive skeletal malformations. To investigate its possible role in cerebral cortex development, we performed RNA in situ hybridization at three stages of human development: day 32 (Carnegie 15), 9 weeks (Carnegie 23) and 13 weeks. RSK2 expression is detected in the embryonic anterior and posterior telencephalon (hippocampus anlagen), mesencephalon, rhombencephalon and cerebellum. RSK2 gene expression is also observed in dorsal root ganglia, cranial nerve ganglia, and sensory epithelium of the inner ear, liver, lung and jaw anlagen. This pattern of expression may be involved in cognitive impairment and facial dysmorphisms found in Coffin-Lowry Syndrome.

Central Nervous System↗

PubMed2004

Contribution of fetal MR imaging in the evaluation of cerebral ischemic lesions.

BACKGROUND AND PURPOSE: Little is known about the different patterns of fetal cerebral ischemic lesions at MR imaging. Our purpose was to evaluate the contribution of MR imaging in the evaluation of such lesions by correlating the results with ultrasonography (US) and neurofetopathologic (NFP) findings. METHODS: We examined 28 fetuses (mean, 28 weeks' gestation) with cerebral ischemic lesions on NFP examination. MR findings were correlated with US and NFP results with regard to the depiction of gyration and parenchymal abnormalities. RESULTS: MR imaging added to US findings in 24 cases by revealing lesions (gyration abnormalities, parenchymal lesions). These results were either overlooked during US (n = 16) or more extensive than expected with US (n = 8). MR findings were always confirmed by NFP. NFP yielded additional findings for 14 lesions that were overlooked during MR imaging (n = 4) or that were more extensive than expected with MR imaging (n = 10). T1-, T2-, and T2*-weighted MR patterns of different lesions (cavitations, gliosis, softening of the white matter, laminar necrosis, calcified leukomalacia, old hemorrhage) were identified. CONCLUSION: MR imaging is a valuable tool in the evaluation of fetal brain ischemia. The results of this study emphasize the role of the different sequences (T1-, T2-, T2*-weighted) required to detect fetal cerebral ischemic lesions. MR imaging is more accurate in the detection of small focal lesions than in the evaluation of diffuse white matter abnormalities.

Brain↗

PubMed2003

Expression patterns of parathyroid hormone-related peptide (PTHrP) and parathyroid hormone receptor type 1 (PTHR1) during human development are suggestive of roles specific for each gene that are not mediated through the PTHrP/PTHR1 paracrine signaling pathway.

Close temporal and spatial relationships between Pthrp and Pthr1 gene expression are reported during fetal life in rats, suggestive of a developmental role via a paracrine signaling pathway. In agreement, disruption of this signaling pathway is associated with developmental defects, as documented in mice and humans. Surprisingly, however, only few organs are affected. We report here PTHrP and PTHR1 gene expression during human embryo-fetal development. We describe three patterns: in some organs, both genes are active ('hand-in-glove' fashion), while in others either PTHrP or PTHR1 transcripts are detected. In addition, in some tissues, expression of PTHrP or PTHR1 genes is transient. Abnormal development has been documented only for organs expressing both genes. The patterns that we observe are compatible with specific roles for each gene not mediated through the PTHrP/PTHR1 signaling pathway.

Gene Expression Profiling↗

PubMed2002

Organ weights in human fetuses after formalin fixation: standards by gestational age and body weight.

This study provides new standards of fetal organ weights (brain, heart, liver, pancreas, spleen, lungs, kidneys, adrenals, thymus, and thyroid) and body dimensions (crown-heel and crown-rump lengths, head circumference, and foot length). Subjects came from a large dataset including more than 4,000 fetuses autopsied in fetopathology units of pediatric hospitals in Paris between 1986 and 2001. From this dataset, 673 subjects were carefully selected by exclusion of multiple pregnancies, macerated and malformed fetuses, subjects with abnormal karyotypes, and those with severe infections. Fetal age ranged from 9 to 42 gestational weeks, with a very large sample of fetuses in the first half of gestation. Each organ was weighed after fixation in formalin. The standards were computed in relation to age and body weight. The mathematical models used to fit the percentile growth curves were carefully selected for each organ or dimension. This study, based on reliable methodology, affords a whole set of accurate growth standards useful for pathologists.

Biometry↗

PubMed2002

Parathyroid hormone receptor type 1/Indian hedgehog expression is preserved in the growth plate of human fetuses affected with fibroblast growth factor receptor type 3 activating mutations.

The fibroblast growth factor receptor type 3 (FGFR3) and Indian hedgehog (IHH)/parathyroid hormone (PTH)/PTH-related peptide receptor type 1 (PTHR1) systems are both essential regulators of endochondral ossification. Based on mouse models, activation of the FGFR3 system is suggested to regulate the IHH/PTHR1 pathway. To challenge this possible interaction in humans, we analyzed the femoral growth plates from fetuses carrying activating FGFR3 mutations (9 achondroplasia, 21 and 8 thanatophoric dysplasia types 1 and 2, respectively) and 14 age-matched controls by histological techniques and in situ hybridization using riboprobes for human IHH, PTHR1, type 10 and type 1 collagen transcripts. We show that bone-perichondrial ring enlargement and growth plate increased vascularization in FGFR3-mutated fetuses correlate with the phenotypic severity of the disease. PTHR1 and IHH expression in growth plates, bone-perichondrial rings and vascular canals is not affected by FGFR3 mutations, irrespective of the mutant genotype and age, and is in keeping with cell phenotypes. These results indicate that in humans, FGFR3 signaling does not down-regulate the main players of the IHH/PTHR1 pathway. Furthermore, we show that cells within the bone-perichondrial ring in controls and patients express IHH, PTHR1, and type 10 and type 1 collagen transcripts, suggesting that bone-perichondrial ring formation involves cells of both chondrocytic and osteoblastic phenotypes.

Achondroplasia↗

PubMed2002

Glial cell-derived neurotrophic factor expression in normal human lung and congenital cystic adenomatoid malformation.

CONTEXT: It has been recently suggested that dysregulation of developmental factors and disruption of cell turnover could play a role in the pathogenesis of congenital cystic adenomatoid malformation of the lung (CCAM). The glial cell-derived neurotrophic factor (GDNF) is a growth factor involved in organogenesis, and the temporal pattern of GDNF expression suggests that this factor may play a role in lung development. DESIGN: We studied GDNF expression by immunohistochemistry in postnatally resected CCAM of the lung (n = 10), normal fetal lung (n = 5), and normal postnatal lung (n = 5). We also studied the association between GDNF expression and both cell proliferation and apoptosis. RESULTS: GDNF was expressed in both epithelial and endothelial compartments of normal fetal lung, whereas no expression was found in normal postnatal lung. In contrast, in CCAM tissue, there was strong GDNF immunostaining that was restricted to epithelial cells. The percentage of proliferating epithelial cells was higher in CCAM tissue than in normal postnatal lung (6.3% vs 1.7%, P <.005). Apoptotic bodies were found in the mesenchyme of both normal fetal lung and CCAM tissue, whereas virtually no apoptotic bodies were detected in normal postnatal lung. CONCLUSIONS: Abnormal GDNF expression in CCAM suggests a dysregulation of the GDNF signaling pathway and argues in favor of a focal arrest in maturation during development. GDNF expression in lung tissue seems to be correlated with cell proliferation, suggesting that this factor could play a role in the growth of both fetal lung and CCAM.

Apoptosis↗

PubMedDate not supplied

Unusual variant of holoprosencephaly in monosomy 13q.

The clinical phenotype related to the terminal deletion of the long arm of the chromosome 13 (the so-called 13q- syndrome) includes a considerable number of malformations, especially of the brain. This report describes five cases of a cerebral midline anomaly that leads to a particular clover-shaped type of holoprosencephaly in 13q- fetuses at different stages of the second and third trimesters of gestation. Our cases are compared to those in literature reviews. This malformation has only been described by computer tomography and magnetic resonance imaging in eight children of various ages and has been called "middle interhemispheric fusion" or syntelencephaly. Recently, the human gene ZIC2, the mutation of which leads to holoprosencephaly, has been mapped to the long arm of chromosome 13. on band q32. These findings suggest that this particular type of holoprosencephaly may be related to ZIC2 gene loss of function.

Adult↗