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Biomedical subjects

F Jaubert

Publications and source records attributed to F Jaubert.

At least 19 recordsLinked to original sources

XY sex reversal associated with a nonsense mutation in SRY.

Sex determination in humans is mediated through the expression of a testis-determining gene on the Y chromosome. In humans, a candidate gene for the testis-determining factor (TDF) that encodes a protein with a putative DNA-binding motif and has been isolated is termed SRY. Here we describe an XY sex-reversed female with pure gonadal dysgenesis who harbors a de novo nonsense mutation in the SRY open reading frame (SRY-orf). This single-basepair substitution results directly in the formation of a termination codon in the putative SRY DNA-binding motif, presumably leading to a nonfunctional gene product. This brings the number of reported XY sex-reversed females with de novo mutations in the known SRY-orf to three, each occurring in the putative DNA-binding domain. This provides further evidence to support SRY being TDF in humans and also indicates the functional importance of the putative DNA-binding domain of the SRY protein.

Base Sequence

Familial case with sequence variant in the testis-determining region associated with two sex phenotypes.

The human Y chromosome encodes a testis-determining factor (TDF) which is responsible for initiating male sex determination. Recently a region of the Y chromosome (SRY) was identified as part of the TDF gene. We have identified a three-generation family (N) in which all XY individuals have a single base-pair substitution resulting in a conservative amino acid change in the conserved domain of the SRY open reading frame. Three individuals are XY sex-reversed females, and two are XY males. Several models are proposed to explain association between a sequence variant in SRY and two sex phenotypes.

Adolescent

[Parotid carcinoma in children. Apropos of 3 cases].

Three pediatric cases of parotid carcinoma are reported two are acinic cell carcinoma of relatively good prognosis. The third case is a cystic variety of salivary duct carcinoma, more exceptional, which prognosis remains uncertain. A review of the parotid tumors of this age range is done.

Adenocarcinoma

Deduction from Wilms' tumour that glomerular podocytes produce the basement membrane material bearing Goodpasture determinants.

Using an indirect immunoperoxidase technique, we tested frozen specimens from one Wilms' tumour composed of numerous glomeruloid bodies devoid of blood vessels, with monoclonal antibodies directed against vimentin, cytokeratin, CALLA/CD10, CD24, CR1/CD35, endothelium factor VIII, class I and II MHC molecules, laminin, fibronectin, and non-collagenic domain NC1 of type IV collagen. Two reagents against Goodpasture determinants were used: P1 monoclonal antibody and serum IgG (GP antibodies) from a biopsy-proven Goodpasture patient. Glomeruloid bodies comprised two cell types: a peripheral layer of parietal epithelial cells (cytokeratin and CD24-positive) and central cell clumps of podocytes (vimentin and CALLA-positive). The basal lamina surrounding the glomeruloid bodies contained laminin and NC1 domain of type IV collagen, while that present between the podocytes reacted strongly with laminin, and P1 and GP antibodies. Endothelium factor VIII was not detected within the glomeruloid bodies and CR1 molecules bound to the basement membrane material within them. These data favour the hypothesis that podocytes produce the basement membrane material which bears Goodpasture determinants recently identified as a novel chain, named the alpha 3 chain, of type IV collagen.

Anti-Glomerular Basement Membrane Disease

Cell differentiation in Wilms' tumor (nephroblastoma): an immunohistochemical study.

Using an indirect immunoperoxidase technique, we tested frozen specimens from 12 Wilms' tumors with monoclonal antibodies (MoAbs) reacting against a large panel of molecules including laminin, fibronectin, cytokeratin, vimentin, villin, CD24, CALLA/CD10, CR1, CD26, class I and class II major histocompatibility complex (MHC) molecules, and endothelium factor VIII. These molecules were chosen because they are markers of specific segments of the mature kidney and because their loss or acquisition is indicative of different steps of human nephrogenesis. KI67 MoAb was used to evaluate the proliferating activity of the cells. The blastemal component (cell compact areas) of Wilms' tumors consisted of vimentin-positive cells with a fibronectin network. However, signs of epithelial maturation were present in compact areas where cytokeratin-positive cells producing laminin were observed. The cells exhibited a high degree of proliferating activity. The tubule formations consisted of cytokeratin-positive cells and had a defined laminin border. All the cells, whether in compact areas or in tubules, were strongly CD24-positive. Some tubular formations showed signs of proximal maturation with the presence of CALLA, CD26, and even villin. In four cases class I-MHC molecules were expressed by some tubular cells. Large cystic cavities present in five cases were edged by cytokeratin, CD24-positive cells, or by vimentin, CALLA, CR1-positive cells. Some glomeruloid bodies, present in two cases, were also composed of vimentin, CALLA, and CR1-positive cells which correspond to the mature podocyte phenotype. The interstitial tissue contained mainly laminin and fibronectin network with macrophages and few CD3 lymphocytes. The presence of large cells with muscular differentiation was noted; round vimentin and CD26-positive cells were also seen. The endothelial cells of the vessels exhibited vimentin, factor VIII, and class I and class II MHC molecules as do mature cells, but in some cases the endothelial cells lacked class II molecule expression and were CALLA-positive. These results which confirmed and extended those previously described show that cell differentiation in Wilms' tumor mimics that observed during metanephros development. Moreover, this study shows that tumoral cells in nephroblastoma share several antigens with cells from lymphoid lineage (CD24, CALLA, and CD26) as do developing and mature kidney cells. Such cell phenotype dissection provides a useful and reliable tool for testing the influence of various factors on the development of hetero-transplanted or cultured Wilms' tumors.

Antigens, CD

Effects of inflammation and fibrosis on pulmonary function in diffuse lung fibrosis.

To investigate the relation between lung function and inflammation and fibrosis in patients with diffuse lung fibrosis, a study was made of untreated patients without appreciable airway obstruction (14 patients with cryptogenic fibrosing alveolitis and seven with pneumoconiosis). Quantitative assessment of inflammatory infiltration and fibrosis was carried out on open lung biopsy specimens and compared with lung volumes, carbon monoxide transfer factor (TLCO), TLCO corrected for alveolar volume (TLCO/VA), and arterial blood gases at rest and during exercise. The degree of fibrosis and the degree of cellular infiltration were positively correlated. Lung volumes and TLCO were correlated with the grades of fibrosis and cellular infiltration of alveoli; arterial blood gases during exercise tended to correlate with both fibrosis and infiltration (p less than 0.06). In contrast, morphological data were not correlated with gas exchange at rest or with TLCO/VA. It is concluded that, in untreated patients with diffuse lung fibrosis, lung volumes, TLCO, and arterial blood gases during exercise reflect the lung lesions, and that the pulmonary function tests used cannot discriminate between fibrosis and infiltration of the lung by inflammatory cells.

Adult

[Solitary plasmacytoma of the trachea. Apropos of a case].

A case of solitary plasmacytoma of the trachea is reported. Immunohistochemical study is mandatory to prove a monoclonal immunophenotyping. Research for signs of systemic disease and follow up over a long period of time are indicated. Surgery alone, sometimes followed by irradiation, seem to be the treatment of choice. In most cases, complete resolution is observed.

Aged

[Carcinoid of the larynx. Well-differentiated neuroendocrine carcinoma. Apropos of 4 cases].

Four new cases of carcinoid (or well differentiated neuroendocrine carcinoma) of the larynx are reported. This tumor has been recognized since 1969 and may be misdiagnosed as a poorly differentiated carcinoma or adenocarcinoma if the Grimelius stain is not done. Chromogranin A, detected by immunocytochemical methods, is also a good marker of these tumors. The analysis of 41 previously published cases allows a better knowledge of this clinico-pathological entity. The main locations are supraglottic and the prognosis is poor which is very different from the bronchial carcinoid.

Female

[Pseudotumoral lambda chain pulmonary amyloidosis].

A case is described of primary multi-nodular pulmonary amyloidosis which was "pseudotumoral" and its progress had been under observation for eight years. Protein analysis revealed that it was a monoclonal light chain and there was no evidence of myeloma. It appears to be of a local pathology and is of the same type as amyloid tumors of the bronchi.

Amyloidosis

[Tumors of the nasal fossa. Retrospective study of a series of 67 cases].

This retrospective study reviews 67 tumors of the nasal fossa treated at hospital Laënnec (Paris). The clinical significance of histology and the therapeutic results for each pathological tumor (mainly, carcinoma, melanoma, lymphosarcoma, neuroma, malignant plasmocytoma, inverted papilloma, vascular tumors) are described. Treatment and surgical procedure will be analyzed.

Adult

Pulmonary gallium uptake in rats with granulomatosis induced by complete Freund adjuvant.

To investigate the mechanism of gallium-67 uptake in lung granulomatosis, we studied 13 rats in which lung granulomatosis was induced by injection of complete Freund adjuvant (CFA) and 14 controls. Gallium uptake was assessed in bronchoalveolar lavage fluid and lavaged lung. The cells responsible for gallium uptake were identified by latent image activation autoradiography. Gallium activity in both lavaged lungs and bronchoalveolar cells (BAC) was higher in CFA-treated animals than in controls [172,205 +/- 134,783 DPM versus 44,456 +/- 14,486 DPM +/- SD (p less than 0.05) and 40,083 +/- 16,350 DPM versus 9100 +/- 4114 DPM (p less than 0.05), respectively]. In control rats, about two-thirds of total lung gallium was located in the interstitium, whereas in CFA-treated rats it was found in the mononuclear cells of lung granulomas. Gallium tracks were more numerous in the alveolar macrophages (AM) of CFA-treated rats than in control AM (28.4 +/- 10.0/field versus 8.4 +/- 3.8/field, p less than 0.001) but the number of tracks was proportional to the number of AM (52.4 +/- 18.7 versus 12.2 +/- 4.3, respectively; p less than 0.001). It is concluded that in rats with CFA-induced lung granulomatosis 1) pulmonary gallium uptake increases, 2) mononuclear cells are responsible for this uptake in both granulomas and AM, and 3) the increased uptake is due to the increased number of mononuclear cells.

Animals

[Mobility of the vocal cord and the arytenoid in cancer of the larynx and the hypopharynx. Anatomo-clinical study].

Fourty one squamous cell carcinoma of the hypopharynx, laryngeal margin and larynx were studied in order to compare the vocal cord and arytenoid mobilities with the tumoral extension to the intrinsic laryngeal muscles. Several whole organ sections were performed on the surgical specimen for studying specifically the lateral and posterior cricoarytenoid muscles, thyroarytenoid muscles and crico-arytenoid joint. The weight of the tumor located at the top of the arytenoid cartilage without any tumoral extension of the crico-arytenoid muscles can fix the arytenoid, preserving the vocal cord mobility. On the other hand, the simultaneous immobility of vocal cord and arytenoid was associated respectively with 66% of tumoral extension to the crico-arytenoid muscles in hypopharynx and lateral margin carcinomas, and 33% in endolaryngeal tumors. The authors emphasize that a separate clinical evaluation of vocal cord and arytenoid mobilities would give more precise informations concerning surgical indications of laryngeal conservative surgery.

Arytenoid Cartilage

Histiocytes X and X body reactivity with concanavalin A, peanut agglutinin and BSPT.

The ultrastructural and histochemical exploration of histiocytes X done by the means of Concanavalin A (Con A), peanut agglutinin (PNA) and BSPT demonstrate that the plasma membrane of histiocytes X shared some properties with all the other cells and is also specialized. The rod part of the X body has the same properties as the plasma membrane while its vesicular part differs and is closer to the inner membrane system of the cell. In consequence it is suggested that the rod part of the X body is a specialized pathway or shuttle for receptor linked glycoprotein exchanges in highly specialized cells.

Benzothiazoles

Is true hermaphroditism a primary germ cell disorder?

Eleven cases of true hermaphroditism, 6 raised as female and 5 as male, were seen in the 20-year period from 1965 to 1985. External genitalia varied from Prader types II to IV. The ovotestis (11/22) was the most common gonad, and a marked variation in macroscopic and microscopic appearances with five patterns of distribution of gonadal tissue was noted. Ovulation was observed in ovarian tissue, and spermatogonia, but no spermatozoa, in testicular tubules. A hypothesis is developed suggesting abnormal testicular differentiation, and a model is presented to explain observed patterns of gonadal tissue distribution. A uterus was present in all cases, but a hemiuterus or lateralized uterus was noted in the 5 cases in which only testicular or predominantly testicular tissue was observed on the contralateral side. Karyotype analysis showed 46 XX in 5 cases (1 with an H-Y antigen) and a mosaic involving 46 XY in the remaining 5. Spontaneous puberty was achieved in 3 of the females, and of the 4 males with residual testicular tissue, all are prepubertal.

Disorders of Sex Development

[Demonstration of Langerhans cells in the human bronchial epithelium].

Ultrastructural and immunohistochemical analysis of six specimens revealed for the first time a small number of Langerhans cells in non-neoplastic bronchial epithelium. These cells were usually found either interspersed perpendicularly between columnar epithelial cells or just above the basal lamina with extending cytoplasmic processes. Usually few Birbeck granules, especially located in the Golgi region, were present throughout the cytoplasm. Immunohistochemical studies were performed on semi-thin sections with a polyclonal anti-S-100 protein. The population of S-100 positive cells represented about 1% of all the epithelial cells. Not all ultrastructurally identified Langerhans cells were shown to be positive for S-100 antigen. Our results suggest that Langerhans cells could be a constant cellular constituent for the normal bronchial epithelium. The exact function of Langerhans cells in the respiratory epithelium remains to be investigated, but they may have an immunologic function, such as antigen presentation to T lymphocytes.

Bronchi