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Biomedical subjects

C Philippe

Publications and source records attributed to C Philippe.

At least 19 recordsLinked to original sources
PubMed2000

A locus for autosomal dominant colobomatous microphthalmia maps to chromosome 15q12-q15.

Congenital microphthalmia is a common developmental ocular disorder characterized by shortened axial length. Isolated microphthalmia is clinically and genetically heterogeneous and may be inherited in an autosomal dominant, autosomal recessive, or X-linked manner. Here, we studied a five-generation family of Sephardic Jewish origin that included 38 members, of whom 7 have either unilateral or bilateral microphthalmia of variable severity inherited as an autosomal dominant trait with incomplete penetrance. After exclusion of several candidate loci, we performed a genome-scan study and demonstrated linkage to chromosome 15q12-q15. Positive LOD scores were obtained with a maximum at the D15S1007 locus (maximum LOD score 3.77, at recombination fraction 0.00). Haplotype analyses supported the location of the disease-causing gene in a 13.8-cM interval between loci D15S1002 and D15S1040.

Adolescent↗
PubMed2000

Polymeric proanthocyanidins are catabolized by human colonic microflora into low-molecular-weight phenolic acids.

Polymeric proanthocyanidins are common constituents of many foods and beverages. Their fate in the human body remains largely unknown. Their metabolism by human colonic microflora incubated in vitro in anoxic conditions has been investigated using nonlabeled and (14)C-labeled purified proanthocyanidin polymers. Polymers were almost totally degraded after 48 h of incubation. Phenylacetic, phenylpropionic and phenylvaleric acids, monohydroxylated mainly in the meta or para position, were identified as metabolites by gas chromatography coupled to mass spectrometry (GC-MS). Yields were similar to those previously reported for flavonoid monomers. These results provide the first evidence of degradation of dietary phenolic polymers into low-molecular-weight aromatic compounds. To understand the nutritional properties of proanthocyanidins, it is therefore essential to consider the biological properties of these metabolites.

Anthocyanins↗
PubMed1999

Amniotic fluid alpha-fetoprotein is not a useful biological marker of pregnancy outcome.

The aim of our study was to determine if the amniotic fluid alpha-fetoprotein (AFP) level could be a useful predictive biochemical marker of pregnancy outcome. Amniotic fluid AFP measurement was prospectively carried out over a three-year period. After excluding factors susceptible to modifying AFP measurements, 587 subjects with gestational age between 14 and 20 weeks were selected to compare the amniotic fluid AFP mean levels depending on the occurrence of an adverse outcome. No significant associations between amniotic fluid AFP level and poor pregnancy outcome, i.e. pre-eclampsia, preterm delivery, premature rupture of fetal membranes, fetal growth retardation and placental abnormalities were observed. The routine measurement of amniotic fluid alpha-fetoprotein during an amniocentesis procedure was not considered useful in predicting pregnancy complications.

Adult↗
PubMed1999

Economic studies and 'technical' evaluation of telemedicine: the case of telemonitored polysomnography.

Information and communication technology (ICT) is not yet integrated into current medical practice and frequently, organizational patterns of health care production are held responsible for this situation. However, and quite paradoxically, measures recently taken in France indicate that a preferential role is granted to ICT in order to promote the development of healthcare networks. In this context, one should carefully examine which factors, other than organizational ones, can explain the very slow diffusion of telemedicine. Actually, medical assessment of telemedicine is very seldom and the medical community is unable to appreciate the extent that this technology would modify the quality of care provided. Furthermore, and as a consequence of the former, there is no economic evaluation of telemedicine applications and its effects, in terms of productivity, remain virtual. In this article, based on an early evaluation of telemonitored polysomnography to diagnose sleep apnea syndrome, we show that it is possible, even at an experimental stage, to produce appropriate and convincing clinical results stating the true technological effectiveness (choice of an adequate clinical trial, selection of appropriate endpoints). Specific attention is given to the technical conditions in which the technology is assessed, we also provide most of the data that should be taken into account to foresee the major organizational transformations of the production processes. Our results show that early clinical ad hoc evaluations of telemedicine applications can be conducted promptly, providing strong clinical results and useful data for any forthcoming economic evaluation.

Adult↗
PubMed1999

The signal transducer and activator of transcription STAT5b gene is a new partner of retinoic acid receptor alpha in acute promyelocytic-like leukaemia.

Acute promyelocytic leukaemia (APL) exhibits a characteristic t(15;17) translocation that fuses the promyelocytic leukaemia (PML) gene on 15q22 to the retinoic acid receptor alpha (RARA) gene on 17q12-q21.1. In a small subset of acute promyelocytic-like leukaemias (APL-L), RARA is fused to a different partner: the pro-myelocytic leukaemia zinc finger (PLZF) gene on 11q23, the nucleophosmin (NPM) gene on 5q35 or the nuclear mitotic apparatus (NuMA) gene on 11q13. We report on the molecular characterization of a RARA gene re-arrangement in a patient with APL-L and demonstrate that the signal transducer and activator of transcription STAT5b gene is fused with RARA. STAT5b belongs to the janus kinase (JAK)-STAT signalling pathway. Remarkably, the STAT5b component of the chimeric protein is delocalized from the cytoplasm to the nucleus, where it displays a microspeckled pattern. Therefore, unusual features of this APL-L might result from dysregulation of the JAK/STAT5 signal transducing pathways in the patient leukaemic cells. In this study, we identified STAT5b as a new gene fused to RARA in leukaemia; this is the first human tumour bearing a structurally abnormal STAT gene.

Aged↗
PubMed1999

Reactive oxygen and nitrogen intermediates increase transforming growth factor-beta1 release from human epithelial alveolar cells through two different mechanisms.

Transforming growth factor (TGF)-beta1 is a growth factor involved in the mechanisms of lung repair and fibrosis that follow inflammatory processes. We sought to examine the link between the generation of reactive oxygen intermediates (ROI) or reactive nitrogen intermediates (RNI) by inflammatory cells and the expression of TGF-beta1 by alveolar epithelial cells. Exposure of the A549 lung epithelial cell line to either an ROI generating system (xanthine and xanthine oxidase) or an RNI donor (S-nitroso-N-acetyl-penicillamine [SNAP]) promoted a time- and dose-dependent increase in TGF-beta1 release, as measured by a specific enzyme-linked immunosorbent assay. At the peak, the levels of TGF-beta1 were twice the control values. The induction of TGF-beta1 release by ROI was blunted by catalase and unaffected by superoxide dismutase, indicating the involvement of hydrogen peroxide. The response was also blunted by 5, 6-dichloro-1-beta-D-ribofuranosyl benzimidazole (DRB), a specific RNA polymerase II inhibitor, and accompanied by a corresponding increase in TGF-beta1 messenger RNA, as measured by quantitative/competitive reverse transcription polymerase chain reaction, suggesting the involvement of transcriptional mechanisms and possibly other downstream mechanisms. In contrast, RNI-induced TGF-beta1 release was unaffected by DRB and blunted by the protein synthesis inhibitor cycloheximide, suggesting the involvement of translational and post-translational mechanisms. This response required cyclic guanosine monophosphate (cGMP)- mediated processes because (1) immunoreactive cGMP accumulated in the culture medium of SNAP-treated cells; (2) SNAP-induced TGF-beta1 release was blunted by KT 5823, an inhibitor of cGMP-dependent protein kinase; and (3) similar increase in TGF-beta1 release was obtained by cell exposure to membrane-permeable dibutyryl-cGMP or to atrial natriuretic factor, a known agonist of particulate guanylate cyclase. These data suggest that in vitro exposure of human alveolar epithelial cells to ROI and RNI enhances TGF-beta1 release through different mechanisms. In vivo, this control may constitute a molecular link between inflammatory and fibrotic processes.

Arginine↗
PubMed1999

[Comparison of accreditation procedures, ISO 9000 certification procedures and total quality management. Personal experiences and application of quality assurance in a department of radiology and medical imaging].

Management of quality assurance protocols in a radiology department can be done by using several tools or models. Some are specific like accreditation manuals issued by some organizations, others like the ISO 9000 certification and the Total Quality management are more general and already well known by manufacturers. In order to implement a process of quality improvement, we have reviewed three models of quality assurance: evaluation in total quality based on the European model "EFQM", accreditation based on booklets from French cancer centers and Canadian radiology centers and, finally, accreditation based on the ISO 9002 certification model. Based on results of our comparative study, these three tools of quality management are not contradictory and may be complementary. However, they can be compared in terms of constraints they impose, of their historical background, of the criteria evaluated as well as the role of different teams. In conclusion, we suggest that directors of radiology department interested in implementing a quality assurance program first evaluate their department using the Canadian accreditation model issued in 1993 which is useful to become familiar with this new concept of quality. In a second step, a self assessment using the EFQM has to be done in collaboration with all members of the administration board in order to integrate all parameters and to share this protocol with all decision makers. The last step is to consolidate the organization of the quality assurance protocols by means of the ISO 9002 certification.

Accreditation↗
PubMed1999

[From accreditation to certification. Quality management in a radiology department].

The leaders of a radiology department started a quality process based on ISO 9001 certification and the total quality management program. The purpose of this work is to match the conformity of this quality system to ANAES recommendations. If the concordance is obvious, the advantages of using quality insurance to get an accreditation are important. In conclusion, a quality process is proposed, it includes a quality insurance manual of ISO 9001 norm, the total quality management in the first point of the norm and the ANAES recommendations spread over the 20 points of the norm.

Accreditation↗
PubMed1999

Double telomeric signals on single chromatids revealed by FISH and PRINS.

FISH probes for all human telomeres and specific telomeric probes that hybridize to unique sequences on individual chromosomes have been used to characterize the telomeric hybridization pattern of human peripheral blood lymphocytes and bone-marrow cells in interphase and metaphase chromosomes. We have identified the existence of double hybridization signals on chromatids both with the (TTAGGG)n telomere repeat arrays and on non chromosome-specific subtelomeric regions as well as on chromosome-specific sequences located several kilobases from the end of chromosomes. Preliminary results using cosmid or YAC probes that hybridize to regions rich in GC sequences also revealed double fluorescent spots on a single chromatid. Double spots were detected by PRINS on terminal and interstitial telomeric sequences in avian cells. The significance of this phenomenon is discussed based on some models of chromatid and DNA organization such as uninemy, looped chromatid organization and quartet DNA structures. The occurrence of double spots should be taken into consideration for the clinical cytogenetic diagnosis of duplications.

Base Sequence↗
PubMed1998

Low environmental pH is responsible for the induction of nitric-oxide synthase in macrophages. Evidence for involvement of nuclear factor-kappaB activation.

Stimulation of macrophages with endotoxin and/or cytokines is responsible for the expression of the inducible isoform of nitric oxide synthase (iNOS). Because macrophages are exposed to low pH within the microenvironment of inflammatory lesions, the potential role of acidic pH as an additional regulator of iNOS was investigated. Substitution of the culture medium of rat peritoneal macrophages at pH 7.4 with medium at pH 7.0 up-regulated iNOS activity, as reflected by a 2.5-fold increase in nitrite accumulation. The increase in iNOS activity was associated with a similar increase in iNOS mRNA expression that reflected an increase in iNOS mRNA synthesis rather than stability. Low environmental pH-induced iNOS gene transcription involved the activation of nuclear factor-kappaB (NF-kappaB) transcription factor since exposure of macrophages to low environmental pH both increased NF-kappaB binding activity in the nucleus and enhanced NF-kappaB-driven reporter gene expression. In addition, treatment of macrophages with pyrrolidine dithiocarbamate or n-acetyl-leucinyl-leucinyl-norleucinal, two drugs preventing NF-kappaB translocation to the nucleus, canceled low pH-induced nitrite accumulation. The overall mechanism required the synthesis of tumor necrosis factor alpha (TNFalpha). Indeed, 1) elevated TNFalpha bioactivity was observed in the medium of macrophages exposed to pH 7.0, and 2) incubation of macrophages with a neutralizing anti-TNFalpha antibody impaired both NF-kappaB activation and nitrite accumulation in response to acid challenge. In summary, exposure of macrophages to acidic microenvironment in inflammatory lesions leads to the up-regulation of iNOS activity through the activation of NF-kappaB.

Acids↗
PubMed1998

A human homologue of the Drosophila melanogaster diaphanous gene is disrupted in a patient with premature ovarian failure: evidence for conserved function in oogenesis and implications for human sterility.

Premature ovarian failure (POF) is a defect of ovarian development and is characterized by primary or secondary amenorrhea, with elevated levels of serum gonadotropins, or by early menopause. The disorder has been attributed to various causes, including rearrangements of a large "critical region" in the long arm of the X chromosome. Here we report identification, in a family with POF, of a gene that is disrupted by a breakpoint. The gene is the human homologue of the Drosophila melanogaster diaphanous gene; mutated alleles of this gene affect spermatogenesis or oogenesis and lead to sterility. The protein (DIA) encoded by the human gene (DIA) is the first human member of the growing FH1/FH2 protein family. Members of this protein family affect cytokinesis and other actin-mediated morphogenetic processes that are required in early steps of development. We propose that the human DIA gene is one of the genes responsible for POF and that it affects the cell divisions that lead to ovarian follicle formation.

Amino Acid Sequence↗
PubMed1998

The UTX gene escapes X inactivation in mice and humans.

We recently have identified a ubiquitously transcribed mouse Y chromosome gene, Uty , which encodes a tetratricopeptide repeat (TPR) protein. A peptide derived from the UTY protein confers H-Y antigenicity on male cells. Here we report the characterization of a widely transcribed X-linked homologue of Uty , called Utx , which maps to the proximal region of the mouse X chromosome and which detects a human X-linked homologue at Xp11.2. Given that Uty is ubiquitously transcribed, we assayed for Utx expression from the inactive X chromosome (Xi) in mice and found that Utx escapes X chromosome inactivation. Only Smcx and the pseudoautosomal Sts gene on the mouse X chromosome have been reported previously to escape inactivation. The human UTX gene was also found to be expressed from Xi. We discuss the significance of these data for our understanding of dosage compensation of X-Y homologous genes in humans and mice.

Amino Acid Sequence↗
PubMed1998

Characterisation of an inverted X chromosome (p11.2q21.3) associated with mental retardation using FISH.

We report on a patient with a pericentric inversion of the X chromosome, 46,Y,inv(X) (p11.2q21.3), who was referred for cytogenetic analysis because of mild mental retardation, short stature, prepubescent macro-orchidism, and submucous cleft palate. The same chromosomal abnormality was found in the proband's mother. The inverted X chromosome was late replicating in all the mother's lymphocytes studied, indicative of a likely unbalanced inversion. We show, by fluorescence in situ hybridisation (FISH) using a panel of ordered yeast artificial chromosome (YAC) clones, that the Xp breakpoint is localised in Xp11.23 between DXS146 and DXS255 and that the Xq breakpoint is assigned to the X-Y homologous region in Xq21.3. YACs crossing the Xp and Xq breakpoints have been identified. One of these two breakpoints could be linked to the mental retardation in this patient as many non-specific mental retardation (MRX) loci have previously been located in the pericentromeric region of the X chromosome. Morever, the elucidation at the molecular level of this rearrangement will also indicate if cleft palate or prepubescent macro-orchidism, or both, in this boy are related to one of the two X breakpoints.

Azure Stains↗
PubMed1998

Neutrophil alveolitis in bronchioloalveolar carcinoma: induction by tumor-derived interleukin-8 and relation to clinical outcome.

Tumor infiltrate, predominantly constituted by lymphocytes, may represent an important prognostic factor in bronchioloalveolar carcinoma (BAC), in addition to tumor extension and histological type. In the present study, we determined the presence, the origin, and the prognostic importance of neutrophils that also participate in leukocyte infiltrates of BAC. Neutrophil alveolitis was determined immunohistochemically in both lung biopsies and bronchoalveolar lavage (BAL) fluid samples from 29 patients with histologically proved BAC. The local expression of interleukin (IL)-8 was determined by immunohistochemical and immunoenzymatic techniques. Neutrophil counts were analyzed in relation to the clinical outcome of patients by the Kaplan-Meier method and Cox's univariate and stepwise multivariate models. Lymphocytes and neutrophils dominated the inflammatory cell population in the lower respiratory tract of patients with BAC. Neutrophils were located mainly in the alveolar lumen and seldom in alveolar wall whereas lymphocytes were exclusively present in alveolar wall. A relationship was observed between the number of neutrophils and the level of IL-8 in BAL fluid suggesting the involvement of that chemokine in neutrophil recruitment. The tumor cells were the predominant cells that appeared to express IL-8 by immunolocalization. The presence of increased numbers of neutrophils was significantly associated with a poorer outcome in patients with BAC (P = 0.02). In a multivariate analysis, the neutrophil percentage in BAL fluid was an independent predictor of clinical outcome. The risk of death was increased substantially (rate ratio, 5.2; 95% confidence interval, 1.1 to 24.7) among patients with BAL neutrophil percentage of > or = 39% (median of the distribution) as compared with the others. In BAC, neutrophils accumulate in the alveolar lumen. Elaboration of IL-8 by tumor cells may be responsible for this event, which is associated with a significantly higher risk of death.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1998

Characterization of cosmids and telomeres in cytogenetic preparations by 3D confocal fluorescence.

OBJECTIVE: To analyze, with fluorescent probes, by three-dimensional (3D) emission patterns, fluorescence in situ hybridization (FISH) preparations (cosmids, telomeres) and to perform factor analysis of medical image sequences (FAMIS); to use FISH to track relevant DNA sequences in cell nuclei during interphase and in mitotic chromosomes; and to use cytogenetic techniques, resulting in flat preparations of whole cells that are assumed to preserve probe access to their targets. STUDY DESIGN: The study design entailed labeling targets by probes (sequences labeled by fluorescein isothiocyanate) in nuclei and/or chromosomes stained by propidium iodide. Visualization of targets was improved when 3D sequences of images obtained on a single photomultiplier detector of the confocal microscope by z stepping were investigated by FAMIS. RESULTS: Factors and factor images showed that targets could be detected and differentiated in focal planes inside nuclei or chromosomes. CONCLUSION: It is possible to localize cosmids in cell nuclei at interphase and telomeres in mitotic chromosomes by means of 3D sequences of images.

Cosmids↗