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Francis Jaubert

Publications and source records attributed to Francis Jaubert.

35 records · Page 2Linked to original sources
PubMed2004

Fetal intestinal obstruction induces alteration of enteric nervous system development in human intestinal atresia.

Intestinal motility disorders are a major cause of morbidity after surgical repair of intestinal atresia of unknown mechanism. We hypothesized that interruption of antenatal peristalsis may disturb the normal development of the enteric nervous system. Using a series of neuronal (synaptophysin, neuronal nitric oxide synthase, neurofilaments) and nonneuronal markers (glial acidic fibrillary protein and c-Kit) and immunohistochemistry, we have defined developmental steps of the enteric nervous system in normal intestine (12 fetuses, 15 children, and 4 adults) and their alterations above and below the obstacle in 22 human intestinal atresia compared with age-matched controls. Antisynaptophysin antibody revealed the progressive conversion of the myenteric plexus from a continuous belt into regularly spaced ganglions during normal fetal gut development and, by contrast, the significantly delayed appearance of individual neuronal ganglions in the distal segments of atresia (p < 0.05). Staging using three other markers for neuronal (neurofilaments and neuronal nitric oxide synthase) and nonneuronal cells (glial acidic fibrillary protein) confirmed that maturation of the myenteric plexus was significantly delayed below atresia (p < 0.01). These results indicate that intestinal atresia impairs the development of the enteric nervous system and provide an anatomical substrate for the motility disorders observed after surgical repair. They point to the role of peristalsis in normal gut development and suggest that stimulation of peristalsis might be used to accelerate recovery.

Biomarkers↗
PubMed2004

Difficult asthma in children: an analysis of airway inflammation.

BACKGROUND: Difficult asthma in children displays distinct clinical patterns, and its physiopathology remains poorly understood. OBJECTIVE: To determine the characteristics of the bronchial inflammatory profile in children with difficult asthma. METHODS: We performed endobronchial biopsy and bronchoalveolar lavage in 28 children with persistent bronchial obstruction despite high doses of inhaled corticosteroids and regular treatment with long-acting beta(2)-agonists: 13 had persistent symptoms and 15 had few or no symptoms. RESULTS: The number of eosinophils (P =.03) and neutrophils (P =.04) in the epithelium was significantly higher in symptomatic children than in children with few symptoms. Reticular basement membrane thicknening was similar in both groups. IFNgamma levels (P =.03) and IFNgamma/IL-4 ratio (P =.01) were significantly higher in children with few symptoms. CONCLUSIONS: In symptomatic children, T(H)2-type inflammation was associated with the presence of activated eosinophils in the epithelium, whereas asthma in children with few symptoms was associated with an increase in T(H)1 cytokine levels. The high levels of IFNgamma suggest that this T(H)1 cytokine may modulate the local inflammatory response.

Asthma↗
PubMed2004

[Hermaphroditism pathology].

Hermaphroditism is a general term referring to all discrepancies between phenotype and genotype of sex development. It must be preferred to sexual ambiguity which refers mainly to external genitalia anomalies. Hermaphroditism is studied on an historical and pathogenetical perspective. Short embryological summaries are integrated. The defects of sexual differentiation due to hormone deficiency are first studied: androgen insensitivity, steroid 5 alpha-reductase 2 deficiency, defects of testosterone synthesis, persistant mullerian ducts syndrome. Sexual determinism deficiencies are then presented: Turner syndrome, XX males, pure gonadal dysgenesis, true hermaphroditism, mixed gonadal dysgenesis, Drash and Frasier syndrome. Tumors of dysgenetic gonads followed. Mixed tumors developed in dysgenetic gonads are gonadoblastoma and dysgerminoma. Sex cord tumors are androgen insensitivity associated tumors, Leydig cells tumors and adrenal cell inclusion tumors. Sex reversion genes open new perspectives.

Disorders of Sex Development↗
PubMed2004

[Lynch syndrome pediatric: about a case].

A duodenal carcinoma centered on the vater ampulla is reported in a child of 15 years with Lynch syndrome. This case illustrates the problem of early diagnosis and treatment of Lynch syndrome associated tumors.

Adenocarcinoma↗
PubMed2004

Acute insulin responses to calcium and tolbutamide do not differentiate focal from diffuse congenital hyperinsulinism.

Congenital hyperinsulinism (CHI) is related to two main histological pancreas anomalies: focal adenomatous hyperplasia and diffuse beta-cell hypersecretion. Pharmacological tests to measure acute insulin responses (AIR) to peripheral i.v. injections of glucose, calcium, and tolbutamide have been reported as potential means to distinguish between these histological forms. In patients with defects in ATP-sensitive potassium channels, tolbutamide will fail to induce insulin release in affected portions of the pancreas, whereas calcium gluconate will enhance insulin release through spontaneously active voltage-gated Ca(2+) channels. Consequently, in focal CHI patients, calcium should promote AIRs from the lesion, whereas tolbutamide should act to promote insulin secretion from the healthy region of the pancreas (outside the focal hyperplasia). We therefore studied AIRs to calcium and tolbutamide stimulation tests in 16 children with focal (n = 9) or diffuse (n = 7) CHI before pancreatic surgery. We found hypervariable AIRs to glucose and calcium stimulation in both focal and diffuse CHI patients. AIRs to tolbutamide stimulation were found modest in focal CHI patients, which might account for beta-cell quiescence in the healthy portion of the pancreas of these patients. We conclude that AIRs to calcium and tolbutamide stimulation tests are not sufficient to differentiate the focal from the diffuse CHI patients.

Calcium Gluconate↗
PubMed2004

Focal and diffuse forms of congenital hyperinsulinism: the keys for differential diagnosis.

Congenital hyperinsulinism is clinically characterized by an inappropriate insulin secretion resulting in recurrent severe hypoglycemia. Nesidioblastosis, the proliferation of islets cells budding off from pancreatic ducts, has been considered for years as the histological lesion responsible for the syndrome. In our morphological studies, we demonstrated that nesidioblastosis is not specific for the disease, which is actually not a single entity. Indeed, we recognized the existence of two different forms--a diffuse form and a focal form--and demonstrated that they can be differentiated on the basis of morphological criteria, even on frozen sections during surgery. This histological distinction directs the therapeutic approach because the patients suffering from the focal form of the syndrome can be completely cured by a very limited pancreatectomy. Molecular findings confirmed the reliability of this histological distinction, showing a specific genetic background for each form.

Cell Nucleus↗
PubMed2003

Use of bovine jugular vein to reconstruct the right ventricular outflow tract: early results.

OBJECTIVE: We evaluate early results of bovine jugular vein conduits in the pulmonary outflow. METHODS: Between April 2000 and September 2001, 31 conduits were placed in the outflow of the right ventricle. Patients who received a conduit as a staged surgical procedure were excluded (n = 3). Implantation age ranged from 0 to 21 years (median, 3.4 years). Conduit diameter ranged from 12 to 20 mm (median, 14 mm). Transthoracic echocardiography was performed at discharge and 3 months after surgery. Patients with significant pulmonary regurgitation and/or stenosis underwent cardiac catheterization. RESULTS: Four patients died during the follow-up period. Three deaths were unrelated to the conduit. One death was related to the complete thrombosis of the conduit. At 3 months evaluation, pulmonary valve regurgitation was absent or trivial in 19, mild in 2 and severe in 3 of 24 survivors. Four patients had nonfatal conduit-related complications. A transient thrombus formation within 1 leaflet was noted postoperatively in a patient with a moderate pulmonary regurgitation. Three patients required reoperation 3 to 5.8 months after the implantation for conduit failure (mean, 4.3 months). Cardiac catheterization before replacement revealed an aneurysmal dilation of the conduit below a severe stenosis of the pulmonary bifurcation due to important neointimal proliferation. CONCLUSIONS: Early failure of bovine jugular vein valved conduits can occur because of exaggerated intimal proliferation or thrombotic process within the conduit. Because of these complications, close echocardiographic follow-up is mandatory during the first weeks after implantation.

Adolescent↗
PubMed2003

Attenuated virulence of Streptococcus agalactiae deficient in D-alanyl-lipoteichoic acid is due to an increased susceptibility to defensins and phagocytic cells.

D-alanylation of lipoteichoic acid (LTA), allows Gram-positive bacteria to modulate their surface charge, regulate ligand binding and control the electromechanical properties of the cell wall. In this study, the role of D-alanyl LTA in the virulence of the extracellular pathogen Streptococcus agalactiae was investigated. We demonstrate that a DltA- isogenic mutant displays an increased susceptibility to host defence peptides such as human defensins and animal-derived cationic peptides. Accordingly, the mutant strain is more susceptible to killing by mice bone marrow-derived macrophages and human neutrophils than the wild-type strain. In addition, the virulence of the DltA- mutant is severely impaired in mouse and neonatal rat models. This mutant was eliminated more rapidly than the wild-type strain from the lung of three-week-old mice inoculated intranasally and, consequently, is unable to induce a pneumonia. Finally, after intravenous injection of three-week-old mice, the survival of the DltA- mutant is markedly reduced in the blood in comparison to that of the wild-type strain. We hypothesize that the decreased virulence of the DltA- mutant is a consequence of its increased susceptibility to cationic antimicrobial peptides and to killing by phagocytes. These results demonstrate that the D-alanylation of LTA contributes to the virulence of S. agalactiae.

Animals↗
PubMed2003

The focal form of persistent hyperinsulinemic hypoglycemia of infancy: morphological and molecular studies show structural and functional differences with insulinoma.

Paternal mutation of ATP-sensitive K(+) (K(ATP)) channel genes and loss of heterozygosity (LOH) of the 11p15 region including the maternal alleles of ABCC8, IGF2, and CDKN1C characterize the focal form of persistent hyperinsulinemic hypoglycemia of infancy (FoPHHI). We aimed to understand the actual nature of FoPHHI in comparison with insulinoma. In FoPHHI, the lesion consists in clusters of beta-cells surrounded by non-beta-cells. Compared with adjacent islets, proinsulin mRNA is similar and proinsulin production higher (P < or = 0.02), indicating regulation at a translational level, with slightly lower insulin stock and lower ABCC8 peptide labeling (P<0.05). Insulinomas, composed of beta-cell nests or cords, have similar proinsulin mRNA compared with adjacent islets, highly variable proinsulin production, lower insulin stock (P < or = 0.02), and higher ABCC8 peptide labeling (P<0.05). Proinsulin mRNA is lower than in FoPHHI (P<0.001). Islets adjacent to FoPHHI appear to be resting, in contrast to those adjacent to insulinomas, evidencing intrapancreatic regulation of islet beta-cell activity. IGF2 peptide is present inside and outside both lesions, but IGF2 mRNA is restricted to the lesions. The 11p15 LOH and absence of CDKN1C peptide staining are demonstrated in all FoPHHI but also in three of eight insulinomas. Despite some molecular similarities, FoPHHI is thus fundamentally different from insulinoma.

ATP-Binding Cassette Transporters↗
PubMed2002

Aetiological diagnosis of male sex ambiguity: a collaborative study.

UNLABELLED: A collaborative study, supported by the Biomed2 Programme of the European Community, was initiated to optimise the aetiological diagnosis in genetic or gonadal males with intersex disorders, a total of 67 patients with external sexual ambiguity, testicular tissue and/or a XY karyotype. In patients with gonadal dysgenesis or true hermaphroditism, the incidence of vaginal development was 100%, a uterus was present in 60%; uni or bilateral cryptorchidism was seen in nearly all cases of testicular dysgenesis (99%) but in only 57% of true hermaphrodites. Mean serum levels of anti-mullerian hormone and of serum testosterone response to chorionic gonadotropin stimulation were significantly decreased in both conditions, by comparison with patients with unexplained male pseudohermaphroditism or partial androgen insensitivity (PAIS). Mutations in the androgen receptor, 90% within exons 2-8, were detected in patients with PAIS. Clinically, a vaginal pouch was present in 90%, cryptorchidism in 36%. In 52% of cases, no diagnosis could be reached, despite an exhaustive clinical and laboratory work-up, including routine sequencing of exons 2-8 of the androgen receptor. By comparison with PAIS, unexplained male pseudohermaphroditism was characterised by a lower incidence of vaginal pouch (55%) and cryptorchidism (22%) but a high incidence of prematurity/intrauterine growth retardation (30%) or mild malformations (14%). CONCLUSION: reaching an aetiological diagnosis in cases of male intersex is difficult because of the variability of individual cases. Hormonal tests may help to discriminate between partial androgen insensitivity and gonadal dysgenesis/true hermaphroditism but are of less use for differentiating from unexplained male pseudohermaphroditism. Sequencing of exons 2-8 of the androgen receptor after study of testosterone precursors following human chorionic gonadotrophin stimulation is recommended when gonadal dysgenesis and true hermaphroditism can be excluded.

Anti-Mullerian Hormone↗
PubMed2002

Detection of molecular cytogenetic aberrations in langerhans cell histiocytosis of bone.

Langerhans cell histiocytosis (LCH) is a disorder of unknown etiology that gives rise to clonal expansion of Langerhans-like cells or their precursors. The molecular basis include aberrant expression of several adhesion molecules and elevated expression of p53, c-myc, and H-ras. To identify new locations of LCH-related oncogenes or tumor-suppressor genes, we performed comparative genomic hybridization (CGH) and loss of heterozygosity (LOH) analysis on a series of 7 bone LCH lesions. Recurrent abnormalities were found by the CGH in all cases representing losses of DNA sequences on chromosomes 1p, 5, 6, 7, 9, 16, 17, and 22q. Gain of DNA copy number was seen on chromosomes 2q, 4q, and 12. The CGH data were supplemented by LOH analysis by means of 85 polymorphic microsatellite markers distributed along chromosomes 1, 7, 9, and 22. The highest frequency of LOH was found on 1p region in 3 of 7 informative cases and on chromosome 7 in 4 cases. Allelic loss was also detected on chromosomes 9 in 2 of 7 informative cases and on 22q in 1 of 7 cases. These results indicate that the deleted chromosomal segments may contain genes important in LCH initiation and progression.

Adolescent↗
PubMed2002

Molecular genetics of sex determination.

In humans, the choice between male or female development is genetically determined. Sex determination take place when the bipotential embryonic gonad becomes either testis or ovary. This process is directed by genes that have been discovered by genetic analysis of sex-reversed patients and confirmed by knockout experiments in mice. The testis-determining pathway is better known than the ovary pathway. SRY, a gene located on the Y chromosome, triggers a complex genetic cascade leading to testicular differentiation. In this cascade, two genes play a crucial role in male differentiation, SOX9 and FGF9, which contribute to testicular cord formation. However, only a minority of 46,XY sex-reversed patients can be explained by mutations in known genes such as SRY, SOX9, WTI, and SF1, suggesting that other genes influencing sex determination are yet to be discovered. In females, some rare genes that induce ovarian failure or female-to-male sex reversal have been found through gene-targeted inactivation in mice or positional cloning of mutations in humans and goats. In both sexes, genetic analysis of sex-reversed individuals (XX males, XX and XY hermaphrodites, and XY with complete or partial dysgenesis) remains an approach of choice to isolate new genes involved in sex determination.

Animals↗
PubMed2002

[Persistent hyperinsulinemic hypoglycemia of infancy: the pathologist's experience].

Persistent hyperinsulinemic hypoglycemia of Infancy (PHHI) is characterized by episodes of severe hypoglycemia exposing the child to serious neurological sequelae. The morphologic pancreatic anomalies observed consist in either a focal lesion which can be totally cured by a selective surgical resection, or a diffuse and poorly understood lesion of pancreatic tissue, which may appear at first glance to be both macroscopically and microscopically normal, the treatment of which, requires a near-total pancreatectomy. The studies presented concentrate on several pathogenic hypotheses of this latter form of PHHI. We first demonstrate that nesidioblastosis, long considered as the original lesion for the diffuse form of hyperinsulinism, does indeed exist although it is not specific to this disease and does not correspond to a permanent proliferation of endocrine cells. We then dismiss the hypothesis of an enhanced B cell mass, as the volume density of B cells is not systematically increased in hyperinsulinemic children compared to controls. The third hypothesis looking to a decreased D cell mass has to be approached with circumspection as the difference in volume density of somatostatin cells, which tends to be slightly lower in hypoglycemic children, is small and inconsistent. The fourth hypothesis concerns an intrinsic functional lesion of the B cells, and is supported by an increased quantity of proinsulin detected in the Golgi area as well as by the observation of voluminous nuclei and a particularly abundant cytoplasm in certain B cells. These histological anomalies are detected on per-operative frozen sections and guide the surgical treatment.

Humans↗
PubMedDate not supplied

Gonad development in Drash and Frasier syndromes depends on WT1 mutations.

The study of the gonads of 8 cases of Drash syndrome (6 ambiguous males, 2 females) and of 2 Frasier syndrome shows that WT1 mutations gives a dysgenetic testis which is the cause of the genital ambiguity observed at birth. By contrast the same mutations have no effect on ovary development giving normal females. However intron mutations in KTS with isoforms imbalance of WT1 proteins cause streak gonads with a female phenotype in XY patients. In consequence WT1 mutations are the cause of a spectrum of male genital malformations associated with glomerulonephritis and tumors. The absence of WT1 protein detection in sertoli cells shown by immunohistochemistry for 3 cases suggests an imprinting effect of the normal WT1 allele promotor rather than a low level of protein production. A caryotype is mandatory for a correct diagnosis.

Adolescent↗