[Childhood otorhinolaryngologic disease and swimming pools].
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to T Soussi.
Explore the source record for details and available documents.
The frequency of obstructive sleep apnea syndromes in children is not negligible. The diagnosis is based on the parents' answers and on sleep recordings. Radiographs sometimes help defining the site of obstruction. However, except when there is a considerable, clinically obvious tonsillar hypertrophy (which is fortunately the most frequent case), the exact location of the obstruction may be difficult to assess. In fact, it is far less obvious and more often multiple than in adults, especially in cases of craniofacial malformation. A pharyngolaryngeal exploration technique with a flexible endoscope under general anesthesia (GA) has been developed in our department. With natural ventilation, when a GA is induced with halothane through a mask, muscular relaxation similar to that of natural sleep is obtained. A thin flexible endoscope is then inserted through the mask to observe the obstructive structures at the nasal, rhino/oropharyngeal or pharyngolaryngeal levels. During the past two years, 17 children were examined with this technique, which allows an extremely accurate diagnosis of the site of the obstruction. Four children had a craniofacial malformation. The examination evidenced 9 cases of adenotonsillar hypertrophy, 4 cases of dynamic laryngeal obstruction, 3 cases of basilingual obstruction and one case of circular collapse of the oropharynx. The evolution under treatment confirm the merits of this endoscopic examination technique for the etiological diagnosis of respiratory obstruction.
Mutations of the tumor suppressor gene p53 are found in a wide variety of human tumors. In hematological malignancies, p53 alterations are involved in the evolution of chronic phase CML to myeloid blast crisis. p53 mutations were also found associated with Burkitt lymphoma (35%) and its leukemic counterpart, L3 type B-cell acute lymphoblastic leukemia (60%). These observations suggest that several common mechanisms are involved in the transformation process of these two hematological disorders.
Our laboratory is studying genes involved in the regulation of the balance between cell growth and differentiation during embryonic development in Xenopus. We have analyzed the developmental expression of the proto-oncogenes c-myc, and KiRas 2B, the proliferating cell nuclear antigen (PCNA), and the tumor suppressor gene p53. These genes, usually expressed during cell proliferation, are expressed in the oocyte in large quantities, but the majority of their maternal RNAs are degraded by the gastrula stage. The expression of c-myc and the localization of the protein indicate that c-myc has the characteristics expected for a gene involved in the regulation of the mid-blastula transition, when zygotic expression is turned on in the embryo. Its expression during late development or during regeneration indicates that it enables the cells to remain competent for cycling during organogenesis. In vitro systems that reproduce the principal cellular functions during early development are used as model systems to understand the mechanisms involved in early embryogenesis.
Explore the source record for details and available documents.
We have investigated the biochemical properties of Xenopus laevis p53. With an in vitro binding assay, we can detect a specific association between X. laevis p53 and simian virus 40 large T antigen. Furthermore, X. laevis p53 expressed in monkey COS cells is stably associated with this viral antigen. Like mammalian p53, X. laevis p53 in complex with simian virus 40 large T antigen exhibits a 20-fold increase of its half-life. On the other hand, X. laevis p53 is unable to associate either in vivo or in vitro with adenovirus type 5 E1B 55-kilodalton protein. We show by an immunological technique that X. laevis p53 forms specific complexes with mammalian hsp72 and hsp73 heat shock proteins only at a temperature well above the optimal growth temperature for X. laevis. Our results suggest that the protein-binding properties of p53 are closely related to the functional activity of the protein.
The c-myc proto-oncogene is expressed as a maternal protein during oogenesis in Xenopus laevis, namely, in nondividing cells. A delayed translation of c-myc mRNA accumulated in early oocytes results in the accumulation of the protein during late oogenesis. The oocyte c-myc protein is unusually stable and is located in the cytoplasm, contrasting with its features in somatic cells. A mature oocyte contains a maternal c-myc protein stockpile of 4 x 10(5) to 6 x 10(5) times the level in a somatic growing cell. This level of c-myc protein is preserved only during the cleavage stage of the embryo. Fertilization triggers its rapid migration into the nuclei of the cleaving embryo and a change in the phosphorylation state of the protein. The c-myc protein content per nucleus decreases exponentially during the cleavage stage until a stoichiometric titration by the embryonic nuclei is reached during a 0.5-h period at the midblastula stage. Most of the maternal c-myc store is degraded by the gastrula stage. These observations implicate the participation of c-myc in the events linked to early embryonic development and the midblastula transition.
A cDNA encoding the acidic eye-derived growth factor (EDGF II) similar to the acidic fibroblast growth factor (aFGF), a potent cell mitogen, has been isolated from a bovine retinal cDNA library. The cDNA, 4.1 kb in size, has a sequence coding for the 155 amino acids of bovine aFGF, and shows similarity with human aFGF (87% identity). The coding sequence is flanked by a 5'-untranslated region of 0.8 kb and a 3'-untranslated end of 3.0 kb. Northern blot analysis of bovine brain and retina poly(A+) RNAs showed the existence of four aFGF mRNA species. Two of these species are 9.9 and 6.0 kb in size, not abundant and could represent premessengers. The other two species, 4.2 and 2.5 kb, are abundant.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Surgical orbital decompression in 5 patients with basedowian optic neuropathy restored the visual acuity and visual field in all cases. The place of surgery among the different therapeutic options proposed for this serious complication of Basedow's disease is discussed, as well as the advantages over other decompression techniques of the procedure used : the cutaneous approach to a trans-ethmoidonasal decompression.
A Xenopus laevis oocyte cDNA library was screened with a murine p53 cDNA probe for the presence of p53-related clones. Several such clones were isolated and analysed. The nucleotide sequence of the largest cDNA clone (2.2 kb) showed a high degree of homology with the human (68%) and murine (70%) p53 coding sequences. This clone contains a single large open-reading frame, coding for a protein of 363 amino acids, which is 51% homologous to human p53 and 57% homologous to murine p53. Furthermore, five highly conserved internal regions were found in all three proteins. The three proteins have a highly similar amino acid composition (including, notably, the presence of a high proportion of proline residues), and they display a comparable distribution of charged amino acids and hydropathic index profile. The in vitro transcription-translation products of the X. laevis clone were successfully immunoprecipitated by human anti-p53 sera, demonstrating that there is at least one epitope in common between the X. laevis protein and human, and possibly murine, p53.
We investigated whether the VP1 protein of simian virus 40 binds to DNA. In vitro DNA-binding experiments clearly indicate that VP1 bound strongly to double-stranded and single-stranded DNA, with a higher affinity for the latter; additional experiments show that VP1 did not bind to a specific sequence of simian virus 40 DNA.
The epithelial HBL-100 cell line was established in vitro from milk of an apparently healthy woman. It exhibits characteristics of transformation from the very beginning and evolves during in vitro maintenance, until becoming tumorigenic in nude mice. This immortal cell line represents a useful model for studying the progression of human epithelial cells toward malignancy. In the course of our investigations we detected a 94K protein in HBL-100 cells obtained from four different sources. This protein is shown to be indistinguishable from the SV40 large T-antigen on the basis of: Recognition by polyclonal and different monoclonal antibodies. Partial peptide map analysis. Specific binding capacity to the SV40 DNA origin of replication. The presence of a tandemly integrated SV40 genome is demonstrated by Southern blotting. Successful rescue of SV40 DNA by fusion with permissive COS-7, but not CV-1 cells, indicates that the SV40 T-antigen from HBL-100 cells is defective in a function(s) essential to the replication of the viral DNA. The possible origin of the SV40 genetic information that we have detected in HBL-100 cells and the implications of this finding on studies involving this cell line are discussed.
Explore the source record for details and available documents.
Medullary breast carcinoma (MBC) is a rare pathological type of breast cancer. The rate of p53 protein accumulation is higher in MBC than in common invasive ductal carcinoma. Whether this particular feature of MBC influences the outcome after treatment is unknown. We retrospectively analyzed the characteristics, treatment and outcome of 71 patients with MBC treated between 1981 and 1996. The median age was 51 years (range 27-81) and the median clinical tumor size was 25 mm (range 0-70 mm). Breast-conserving treatment was offered when possible: 55 patients had undergone a tumorectomy and radiotherapy while 16 patients had undergone a mastectomy. p53 protein accumulation was determined by immunohistochemistry on paraffin-embedded tumor specimens from 58/71 samples available for this study. The median follow-up for the 56 survivors was 113 months (range 30-241). The 10-year survival and metastasis-free survival rates were 81% and 81.4%, respectively. The local recurrence rate was 16.4%. The two factors predicting outcome were pathological axillary node involvement in the 60 patients who underwent axillary dissection and adjuvant chemotherapy. p53 accumulation was found in 33/58 patients (57%). p53 status was not predictive of survival nor of distant or local recurrences. We confirm that medullary breast carcinoma has a favorable prognosis despite its aggressive pathological features. p53 protein accumulation, found in the majority of MBCs, was not related to outcome.
Explore the source record for details and available documents.
p53 alterations are the most common alteration found in human cancer. Protein p53 was studied in 102 patients with early lesions or advanced squamous cell carcinoma of the head and neck (SCCHN). Biopsies and sera samples were collected before the initiation of treatment. Protein p53 expression was evaluated by immunohistochemistry using Pab 1801, Pab 240, DO7 and CM1 antibodies on paraffin-embedded sections. Antibodies specific for p53 protein were analysed in the sera of these patients by an ELISA procedure. We demonstrated that p53 protein overexpression (> or = 20% positive cells) was an early event in the carcinogenesis of SSCHN and correlated to the progression of carcinogenesis. Overexpression of protein p53 was frequent (56.5%) in advanced tumors. No correlation was found with clinical stage or the differentiation status of the tumor, but we demonstrated differences in protein p53 expression according to the initial localisation of the tumor, with high expression in hypopharynx (67%) and oropharynx (65%) versus larynx (12%). The prevalence of p53 antibodies was high (44%) and was correlated with the rate of p53 overexpression (> or = 30% positive cells) in tumors (p < 0.0001 chi square test). These results suggest that the humoral response is an indicator of the presence of squamous cell carcinoma with immunogenic mutant p53 protein. Therefore the detection of anti-p53 antibodies could be used as a precocuous marker of p53 alteration and a prognostic marker, in order to screen for patients with a better prognosis.