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Biomedical subjects

P Moreau

Publications and source records attributed to P Moreau.

At least 19 recordsLinked to original sources
PubMed2006

Increase in HLA-G1 proteolytic shedding by tumor cells: a regulatory pathway controlled by NF-kappaB inducers.

HLA-G is expressed by tumors, in which it contributes to the evasion of immunosurveillance. NF-kappaB appears to be a candidate for regulating HLA-G expression, since it is considered to be a hallmark of cancer. We investigated the role of NF-kappaB in modulating HLA-G expression in HLA-G-positive tumor cells, JEG-3 (choriocarcinoma), FON (melanoma), and M8-HLA-G1 (HLAG1-transfected melanoma). The treatment of tumor cells with two NF-kappaB inducers, tumor necrosis factor-alpha and phorbol 12-myristate 13-acetate, decreased HLA-G1 cell surface expression but increased intracytoplasmic HLA-G proteins. Reduction in HLA-G1 cell surface expression is driven by NF-kappaB and involves a proteolytic shedding process dependent on metalloproteinase activity. In contrast, an increase in intracytoplasmic HLA-G proteins involves post-transcriptional mechanisms that are independent of NF-kappaB. These results, and the fact that soluble HLA-G1 reduces the cytotoxicity of the NKL cell line, lead us to propose a novel regulatory pathway for HLA-G expression by tumor cells that may have particular relevance in tumor escape.

Cell Line↗
PubMed2006

[The WSH percutaneous spine fixation device. Actual results and future expectations].

BACKGROUND AND PURPOSE: The purpose of this study was to report our initial experience with a new percutaneous spine fixation system, avoiding open exposure, excessive blood loss and extensive muscle dissection. With the specially designed plates, this system can be used whatever the conformation of the segment instrumented is kyphotic or lordotic. METHODS: Sixteen patients (9 men and 7 women ranging in age from 27 to 78 years, mean 54.9) underwent percutaneous pedicle fixation using this device. Twelve patients underwent single level fusions (discogenic lowback pain in 6 cases, spondylolisthesis in 1), and 4 underwent two-level fusions (2 for lumbar fracture and 2 for spondylolisthesis). TLIF by intersomatic cages were inserted at the same time in two patients with spondylolisthesis. The follow-up period ranged from 3 to 15 months (mean 5 months). RESULTS: Improvement in pain control was assessed using a specially designed scale, allowing qualitative self-evaluation of pain control. Pain control was excellent in 12 patients, good in 3 and poor in one case due to loss of independence related to multiple associated disabling conditions. CONCLUSIONS: Percutaneous pedicule screw insertion using this device is a safe and reliable technique. Further improvements in the system which allows a certain degree of spinal mobility after screw placement are in process. Early results shown in this study illustrate the perspectives.

Adult↗
PubMed2006

Impact of choice of treatment for bleeding episodes on inhibitor outcome in patients with mild/moderate hemophilia a and inhibitors.

Patients with mild/moderate hemophilia A (MHA) may develop inhibitors to factor VIII (FVIII). In this condition, FVIII clotting activity (FVIII:C) baseline levels may remain stable for some patients, but may be reduced to less than 0.01 U/mL for others. Several risk factors for the development of inhibitors in MHA have been proposed. Genetic factors, such as mutations in the FVIII gene, may play a central role; however, other influences, such as intensive treatment with FVIII products, may also be important. Optimal treatment regimens have yet to be determined, not only for the eradication of inhibitors, but also for the management or surgical prophylaxis of hemorrhages associated with this condition. Several treatment options for the control of bleeding in patients with MHA and inhibitors (MHAI) are currently available, and the choice of therapeutic strategy should be given careful consideration; some treatments may produce an anamnestic response, thus delaying the return to FVIII:C baseline levels and adversely affecting the duration of the severe bleeding phenotype. To increase our knowledge of MHAI, a retrospective collection of data is currently being performed among hemophilia centers in France and Belgium. Based on five examples of patients with MHAI collated from preliminary study data, we illustrate the impact on inhibitor outcome of the therapeutic choices used to treat bleeding episodes in these patients.

Blood Coagulation Factor Inhibitors↗
PubMed2006

Management of an insular thyroid carcinoma invading the larynx and trachea.

Management of an insular thyroid carcinoma invading the larynx and trachea. Carcinomas of the thyroid gland are usually classified into four types: papillary, follicular, medullary and anaplastic and into two main groups depending on their clinical behaviour: low and high grade malignancy. Insular carcinomas represent a rare subtype of follicular thyroid carcinoma, which are poorly differentiated. It is an aggressive and often lethal tumour. Thyroid cancers rarely invade the upper airways. We report the case of an insular carcinoma invading the larynx and trachea, which was treated by total laryngectomy, bilateral neck dissection and external beam irradiation. The patient presented no signs of tumour recurrence two years after treatment. Conservative treatment is usually recommended for thyroid carcinomas. Total laryngectomy is reserved for some extensive tumours invading the upper airways. A multidisciplinary approach is necessary to manage these cancers correctly.

Adenocarcinoma, Follicular↗
PubMed2005

Energy loss spectroscopic profiling across linear interfaces: the example of amorphous carbon superlattices.

Energy loss spectroscopic profiling is a way to acquire, in parallel, spectroscopic information across a linear feature of interest, using a Gatan imaging filter (GIF) fitted to a transmission electron microscope (TEM). This technique is capable of translating the high spatial resolution of a bright field image into a sampling of the spectral information with similar resolution. Here we evaluate the contributions of chromatic aberration and the various acquisition parameters to the spatial sampling resolution of the spectral information, and show that this can reach 0.5 nm, in a system not ordinarily capable of forming electron probes smaller than 2 nm. We use this high spatial sampling resolution to study the plasmon energy variation across amorphous carbon superlattices, in order to extract information about their structure and electronic properties. By modelling the interaction of the relativistic incident electrons with a dielectric layer sandwiched between outer layers, we show that, due to the screening of the interfaces and at increased collection angles, the plasmon energy in the sandwiched layer can still be identified for layer thicknesses down to 5 A. This allows us to measure the change in the well bandgap as a function of well width and to interpret it in terms of the changes in the sp2 -fractions due to the deposition method, as measured from the carbon K-edges, and in terms of quantum confinement of the well wavefunction by the adjacent barriers.

Journal Article↗
PubMed2005

Mcl-1 is overexpressed in multiple myeloma and associated with relapse and shorter survival.

We and others have shown that Mcl-1 was essential for the survival of human myeloma cells in vitro. Furthermore, this antiapoptotic protein is upregulated by interleukin-6, which plays a critical role in multiple myeloma (MM). For these reasons, we have evaluated the expression of Mcl-1 in vivo in normal, reactive and malignant plasma cells (PC), that is, myeloma cells from 51 patients with MM and 21 human myeloma cell lines (HMCL) using flow cytometry. We show that Mcl-1 is overexpressed in MM in comparison with normal bone marrow PC. In total, 52% of patients with MM at diagnosis (P=0.017) and 81% at relapse (P=0.014 for comparison with diagnosis) overexpress Mcl-1. Of note, only HMCL but not reactive plasmacytoses have abnormal Mcl-1 expression, although both PC expansions share similar high proliferation rates. Of interest, Bcl-2 as opposed to Mcl-1, does not discriminate malignant from normal PC. Finally, the level of Mcl-1 expression is related to disease severity, the highest values at diagnosis being associated with the shortest event-free survival (P=0.002). In conclusion, Mcl-1, which has been shown to be essential for the survival of human myeloma cells in vitro, is overexpressed in vivo in MM in relation with relapse and shorter survival. Mcl-1 represents a potential therapeutical target in MM.

Aged↗
PubMed2005

Synovial sarcoma of the larynx: case report and literature review.

Synovial sarcoma is a rare mesenchymal malignancy which represents 8.5% of all soft tissue sarcomas and usually occurs in the lower extremities of young adults. Because the incidence in the head and neck region is very low, only 13 patients with endolaryngeal localisation have been reported so far. We present here a case of aryepiglottic synovial sarcoma. The tumour was completely resected, under suspension micro-laryngoscopy, using a CO2 laser. No recurrence was observed three years after the surgery. Complete surgical excision is the treatment of choice. The role of chemotherapy and radiotherapy is still debated. However, this tumour has a poor prognosis because of the occurrence of distant metastasis.

Adult↗
PubMed2005

Subcutaneous emphysema and mediastinitis: unusual complications of tonsillectomy.

INTRODUCTION: Subcutaneous emphysema and mediastinitis are rarely reported complications of tonsillectomy. CASE REPORT: We describe two patients who developed subcutaneous emphysema, one of them with mediastinitis, within a few days after tonsillectomy. The diagnosis was based on the clinical presentation and confirmed by computed tomography (CT). For the patient without mediastinitis, the emphysema disappeared after a short period of reintubation and administration of antibiotics. For the patient with mediastinitis, surgical drainage of a cervico-mediastinal purulent collection was necessary to obtain healing. DISCUSSION: The events leading to subcutaneous emphysema and mediastinitis have not been entirely clarified. They probably include direct introduction of air into the neck via either the tonsillar bed or a laryngeal or pharyngeal wound caused by intubation. The clinical presentation, treatment and possible pathophysiology of subcutaneous emphysema and medisastinits are discussed. CONCLUSION: Emphysema and mediastinitis after tonsillectomy occur seldomly. If rapidly recognised and appropriately managed, mortality can be avoided.

Adult↗
PubMed2004

[HLA-G in organ transplantation].

The HLA-G molecule plays a crucial role in the protection of the fetus against aggression by the mother's immune system. Recently, it was shown that HLA-G was involved in the protection of the transplanted tissues, via the inhibition of all immune effectors that mediate graft rejection. The inhibitory functions of HLA-G were studied in vitro using allo- and xeno-geneic models, ex vivo on transplanted tissues biopsies, and in an in vivo animal model. In this review, we will summarize recent results which show that HLA-G acts as a regulator of immune function, seems to be directly involved in transplant acceptation, and should be taken into consideration when monitoring transplanted patients' status.

Animals↗
PubMed2004

Pharmacological inhibition of DNA repair enzymes differentially modulates telomerase activity and apoptosis in two human leukaemia cell lines.

PURPOSE: To investigate the effect of wortmannin and 3-aminobenzamide (3-AB) on telomerase activity and apoptosis in two human leukaemia cells. MATERIALS AND METHODS: MOLT-4 (p53-wild type) and KG1a (p53-null) cells were irradiated with gamma-rays (3 Gy at 1.57 Gy min(-1)) and the effects of wortmannin and 3-AB were evaluated. Telomerase activity was measured by polymerase chain reaction and the expression of human telomerase reverse transcriptase, human telomerase RNA and telomerase-associated protein 1 was assessed by reverse transcriptase-polymerase chain reaction. Apoptosis was evaluated by fluorescence microscopy and flow cytometry. RESULTS: A radiation-induced up-regulation of telomerase activity was observed from 4 h post-irradiation in both cell lines. This up-regulation was abrogated by wortmannin and 3-AB. Telomerase activity was maximal 24 h post-irradiation, coinciding with an accumulation of human telomerase reverse transcriptase mRNA. Apoptosis and G2/M arrest were evident from 4 h post-irradiation in MOLT-4 cells. KG1a cells exhibited a G2/M block at 24 h post-irradiation and apoptosis increased between 24 and 48 h post-irradiation. 3-AB abolished G2/M blockage and enhanced radiation-induced apoptosis in both cell lines, while wortmannin increased apoptosis only in MOLT-4 cells. CONCLUSIONS: 3-AB inhibits the radiation-associated telomerase activity increase and enhances apoptosis in MOLT-4 and KG1a cells. Wortmannin, which also inhibits the radiation-associated telomerase activity increase in both cell lines, does not modify radiation-induced apoptosis in KG1a cells. DNA repair enzymes might be selective targets for enhancing radiosensitivity in certain tumour cells.

Androstadienes↗
PubMed2003

Improved comparison of low energy loss spectra with band structure calculations: the example of BN filaments.

Electron energy loss spectra have been recorded from BN filaments for energy losses between 2 and 50eV. They compare well with other BN shapes (nanotubes, sheets, etc). The interpretation of all the peaks in the spectra has been made via an ab initio calculation using the FLAPW code WIEN97 (A full potential linearized augmened plane wave package for calculating crystal properties, Karlheinz Schwarz, Techn. Universität Wien, Austria, 1999. ISBN 3-9501031-0-4). In order to fully simulate the observed spectra, the geometry particular to the EELS experiment has been taken into account making use of Wessjohann's relativistic formula for thin anisotropic slabs (Phys. Stat. Sol. B 77 (1976) 535). Furthermore, the effect of the convergent beam has been introduced into the simulation and has been proven to be an important parameter in obtaining the corresponding peak intensities.

Actin Cytoskeleton↗
PubMed2003

Biology and functions of human leukocyte antigen-G in health and sickness.

In 1998, the first International Conference on human leukocyte antigen-G (HLA-G) was held in Paris. At that time, HLA-G was still a new HLA class I molecule, few aspects of its immunological functions were known, and its expression by tumors was just being described. In 1998, tools to properly study HLA-G were lacking, especially monoclonal antibodies, and three conclusions were drawn after the congress: (i) animal models were needed, (ii) the biology of HLA-G isoforms had to be confirmed, and (iii) HLA-G expression by tumors required clarification. Five years later, these three issues have been addressed. HLA-G is now gaining pace and is investigated for its immuno-inhibitory functions in the context of multiple pathologies. Eighty five oral presentations were given this year for more than 200 investigators working on HLA-G by speakers from over 20 countries. The success of the 3rd International Conference on HLA-G reflects the interest and tremendous work of the many research teams which, over the years, contributed to the publication of more than 500 peer-review articles. We summarize the key points that were presented and discussed during this meeting.

Autoimmune Diseases↗
PubMed2003

PCR detection of residual Bcl-2/IgH-positive cells after high-dose therapy with autologous stem cell transplantation is a prognostic factor for event-free survival in patients with low-grade follicular non-Hodgkin's lymphoma.

This study was designed to evaluate the results of high-dose therapy followed by purged autologous stem cell transplantation (ASCT) for patients with low-grade follicular non Hodgkin's lymphoma (LGFL), and the prognostic significance of PCR detection of residual Bcl-2/IgH-positive cells after ASCT. Between 1992 and 1998, 49 patients with LGFL received total body irradiation and high-dose cyclophosphamide followed by purged ASCT. PCR amplification of the Bcl-2/IgH rearrangement was performed at diagnosis, on stem cell collections before and after purging and on bone marrow and blood samples after ASCT. With a median follow-up of 76 months (37-103) 34 patients remain alive and event-free. A total of 20 patients had disease recurrence, three patients developed secondary myelodysplastic syndrome (MDS). In all, 11 patients died; 10 deaths were because of recurrent disease, one because of MDS. Kaplan-Meier estimates of event-free survival (EFS) and overall survival (OS) at 5 years were 65% (+/-7%) and 77% (+/-6%), respectively. Patients who achieved a sustained molecular complete response (CR) had a lower risk of disease recurrence and experienced significantly longer EFS (93% (+/-6%) vs 11% (+/-7%) P=0.0008) and OS (100 vs 55% (+/-12%) P=0.0057). In conclusion, myeloablative therapy followed by purged ASCT may induce long EFS in patients with LGFL. The achievement of sustained molecular CR after ASCT improves EFS and OS.

Adult↗
PubMed2003

t(11;14) and t(4;14) translocations correlated with mature lymphoplasmacytoid and immature morphology, respectively, in multiple myeloma.

Recent studies have shown that two recurrent translocations, t(4;14)(p16;q32) and t(11;14)(q13;q32), define distinct entities with different prognosis in multiple myeloma (MM). We addressed the issue of whether these illegitimate IGH rearrangements could contribute to the morphological heterogeneity of the malignant plasma cells (PC). Bone marrow aspirates of 178 untreated MM cases with successful molecular cytogenetics analysis using fluorescence in situ hybridization were reviewed. PC of 25/48 (52%) patients with t(11;14) exhibited a lymphoplasmacytoid morphology. Moreover, 25/27 (93%) of the cases with this morphological profile bore the t(11;14). In addition, both cytogenetics and morphological subtypes shared higher incidence of nonsecretory MM. In contrast, 17 out of 28 cases (61%) with t(4;14) exhibited PC with diffuse chromatin pattern. Interestingly, both t(4;14) translocation and immature morphology correlated with higher incidence of high tumor mass and chromosome 13 abnormality. In conclusion, our results suggest that a particular morphology can be the signature of chromosomal abnormalities in MM.

Chromosome Mapping↗
PubMed2002

HLA-G protein processing and transport to the cell surface.

Data are presented on the intracellular trafficking of HLA-G protein, taking the unique features of this non-classical molecule into consideration: the existence of seven isoforms resulting from alternative splicing (HLA-G1 to G7), and reduced tail length compared with HLA class I antigens. Biochemical studies and analysis of viral strategies for escaping the host immune system led to the demonstration that (i) both the membrane-bound (HLA-G1) and the soluble (HLA-G5) forms of the molecule require peptide association for cell surface expression, using TAP-dependent or TAP-independent pathways; (ii) peptide loading onto the HLA-G protein plays a critical role in controlling the quality of the molecule reaching the cell surface; (iii) surface expression of truncated HLA-G molecules is possible, and (iv) HLA-G expression may be restricted to soluble HLA-G5. These data reveal that HLA-G presents specific cell trafficking pathways and strongly support the contention that the primary function of HLA-G is as of an inhibitor ligand for immune-competent cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2002

[HLA-G: immune tolerance in normal and pathological physiology].

HLA-G is a low polymorphic non-classical major histocompatibility complex class I molecule which can be expressed upon seven isoforms, and whose expression is correlated to immune tolerance situations. Indeed, the expression of HLA-G may allow partially or non histocompatible cells to escape host's immune aimed to eliminate these "foreign" cells. Functions share by HLA-G molecules are the ability to inhibit lysis mediated by natural killer (NK) and by cytotoxic T cells, and to induce apoptosis of activated CD8+ T cells via the HLA-G soluble form. Such model which evades defenses of the immune system was described in the foeto-maternal symbiosis, in tumoral cells or histo-incompatible graft previously. The importance of the role of HLA-G molecules expressed by particular cells as a shield against immune defenses is actually largely studied. The control of HLA-G expression could be used as immunotherapeutic approach, either by up-modulating HLA-G expression in order to favour tolerance of incompatible cells such as foetal cell or graft, or by down-modulating HLA-G expression in order to support the destruction of tumoral cells by cytotoxic T cells. This article reports the recent data on polymorphism, HLA-G gene transcription and implication of HLA-G molecules in immune responses during pregnancy, transplantation or tumoral growth.

CD8-Positive T-Lymphocytes↗
PubMed2002

Front-line high-dose therapy with autologous stem cell transplantation for high risk Hodgkin's disease: comparison with combined-modality therapy.

This retrospective study compares high-dose therapy (HDT) with autologous stem cell transplantation and combined-modality treatment (CT) as a first-line therapy for Hodgkin's disease (HD) for patients with both a clinical stage (CS) IV and/or a mediastinal mass > or =0.45 of the thoracic diameter (MM > or =0.45) at diagnosis, and an incomplete response after the first-line chemotherapy. Data on 42 grafted patients (GP) in Nantes Hospital, France and on 108 combined-modality treated patients (CTP) from two protocols of the GOELAMS group, France (POF 81 and H90) was analyzed. Both groups were comparable except for pulmonary disease in excess in the grafted group (P = 0.01). Among GP, 95% were in complete response at the end of first-line treatment and 77% among CTP. Median follow-up was 53 months (range, 7 to 128 months) for GP and 88 months (range, 25 to 181 months) for CTP. The 5-year freedom from progression (FFP) and event-free survival (EFS) rates were better for GP (87% vs 55% for FFP: P = 0.0004 and 81% vs 51% for EFS: P = 0.0004) whereas the overall survival (OS) rates did not differ significantly (85% for GP vs 71% for CTP: P = 0.06). Similar results were obtained for the groups with a response > or =50% after initial chemotherapy: 91% vs 65% for FFP, P = 0.01; 87% vs 61% for EFS, P = 0.02; and 92% vs 77% for OS, P = 0.2; and for the groups with a response <50%: 80% vs 22% for FFP, P = 0.0003; 72% vs 13% for EFS, P = 0.0001; and 76% vs 46% for OS, P = 0.04. This study shows a better control of the disease with HDT.

Adolescent↗