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Biomedical subjects

Philippe Simon

Publications and source records attributed to Philippe Simon.

17 recordsLinked to original sources
PubMed2006

Formation of isodialuric acid lesion within DNA oligomers via one-electron oxidation of 5-hydroxyuracil: characterization, stability and excision repair.

5-Hydroxyuracil is a major oxidized nucleobase that can be generated by the action of (*)OH radical and one-electron oxidants. The latter modified base that exhibits a low ionization potential is highly susceptible to further degradation upon exposure to various oxidants. Emphasis was placed in this work on the formation and characterization of one-electron oxidation products of 5-hydroxyuracil within DNA fragments of defined sequence. For this purpose, 5-hydroxyuracil containing single- and double-stranded oligonucleotides of various lengths were synthesized and then exposed to the oxidizing action of iridium salts. Isodialuric acid was found to be formed almost quantitatively by a one-electron oxidation mechanism for which relevant information was inferred from a freeze-quenched ESR study. Information on the stability of isodialuric acid thus formed and its conversion products in aqueous solutions was also gained from experiments performed at acidic, neutral and alkali pH's. Moreover, biochemical features dealing with the substrate specificity of several bacterial and yeast base excision repair enzymes to remove isodialuric acid from site-specifically modified DNA fragments were determined.

DNA Damage↗
PubMed2006

Ovarian function and spontaneous pregnancy after combined heterotopic and orthotopic cryopreserved ovarian tissue transplantation in a patient previously treated with bone marrow transplantation: case report.

Cryopreservation of ovarian tissue has been proposed for storing gametes of young patients at high risk of premature ovarian failure. Autotransplantation has recently provided some promising results and is still the unique option to restore ovarian function from cryopreserved ovarian tissue in humans. In this article, we analyse data from the combined orthotopic and heterotopic transplantation of cryopreserved ovarian tissue that restored the ovarian function and fertility. Orthotopic transplantation of cryopreserved ovarian tissue at ovarian and peritoneal sites, together with a heterotopic transplantation at the abdominal subcutaneous site, was performed to restore the ovarian function of a 29-year-old woman previously treated with bone marrow transplantation (BMT) for Hodgkin's disease. Ovarian reserve markers progressively suppress within values 5 months after the transplantation (basal FSH 5 mUI/ml and inhibin B 119 ng/ml). Follicular development was observed at all transplantation sites but was predominant at the ovarian site. Six natural cycles were fully documented and analysed. The patient became spontaneously pregnant following the sixth cycle, but unfortunately she later miscarried. Combined orthotopic and heterotopic transplantations succeeded in the restoration of normal spontaneous cycles. Furthermore, this spontaneous pregnancy confirmed the efficiency of this procedure for restoring human fertility.

Abortion, Spontaneous↗
PubMed2005

Tubular carcinoma of the breast and associated intra-epithelial lesions: a comparative study with invasive low-grade ductal carcinomas.

Ductal intra-epithelial lesions of the breast are associated with invasive neoplasms and comprise a large spectrum of histological patterns. We have examined 23 cases of pure tubular carcinomas (TCs) of the breast and 53 cases of invasive ductal low-grade carcinomas to determine the relationship and distribution of intra-epithelial lesions, mainly of ductal in situ carcinoma type, but including also lobular intra-epithelial neoplasia (LIN) in both entities. Eleven cases of TC showed flat epithelial atypia (FEA) (47.8%), and, in 14 and 6 cases, micropapillary and cribriform low-grade ductal carcinoma in situ (DCIS) were present (60.7 and 26.1%, respectively). On the opposite, in ductal grade I invasive carcinomas, the most frequent architectural pattern was low-grade DCIS growing in arcades in 26 cases (49%). While absent in TCs, low-grade DCIS of solid type was found in five (9.4%) cases of ductal invasive carcinomas, where FEA were present in seven (13.2%) cases. LIN lesions were present in four (17.4%) cases of TC, whereas they represented 7.5%, as reported by Carstens et al. (Am J Clin Pathol 58:231-238, 1972), of cases of low-grade carcinomas. These results suggest that invasive pure TC and low-grade ductal carcinomas of the breast are different lesions, and support the fact that TC, of low histopathological grade, is a particular distinct tumoural entity.

Adenocarcinoma↗
PubMed2005

NK-KIR transcript kinetics correlate with acute graft-versus-host disease occurrence after allogeneic bone marrow transplantation.

Natural killer (NK) cell alloreactivity observed during stem cell transplantation (SCT) can be either beneficial (graft-versus-leukemia effect) or detrimental to the host (graft-versus-host disease). Killer immunoglobulin-like receptors (KIRs), expressed on NK and CD8 memory T cells, are regulated at a posttranscriptional level and, because there are currently no KIR-specific antibodies available, the analysis of these receptors remains elusive. To better define the role of cells expressing KIR after SCT, we studied KIR transcript repertoires in 29 grafted patients who received myeloablative or nonmyeloablative regimens. We restricted our analysis to 3DL1, 3DL2, 2DL4, 2DS3, and 2DS4 KIR transcripts 6 months after SCT. Absolute counts of NK and CD8 T cells were determined by flow cytometry, and KIR transcripts were quantified by real-time reverse transcription polymerase chain reaction at days 14, 28, 60, 100, and 180 after transplantation. Three groups of patients were identified. Groups I and III were characterized by the absence or a delayed appearance of KIR transcripts, which correlated with the highest risk of acute graft-versus-host disease (aGvHD). In contrast, in group II, a significant transcript peak was observed early, and only one patient suffered from aGvHD (p = 0.025). Thus determining the kinetics of KIR transcription should make it possible to identify transplanted patients at a high risk of developing aGvHD.

Adolescent↗
PubMed2005

Is complete axillary lymph node dissection neccessary in T1 stage invasive pure tubular carcinomas of the breast?

The purpose of this study was to evaluate the frequency of axillary lymph node metastasis in invasive pure (not mixed) tubular carcinomas of the breast and to compare our results to other series published in the literature. We analyzed 16 cases of pure tubular carcinoma measuring 2 cm or less in diameter from our database from 1988 to 2004 diagnosed in lumpectomy and mastectomy specimens with associated axillary lymph node dissection. Histopathologic features were reviewed in all patients. In all cases, no axillary lymph node metastasis was observed (0%). These data slightly differ from the results of some studies recently published in the literature, in which the overall nodal involvement in pure tubular carcinomas ranges from 0% to 20%. We conclude that in invasive pure tubular carcinomas of the breast measuring less than 2 cm in diameter, complete axillary lymph node dissection should be avoided, and we propose a sentinel lymph node analysis instead.

Adenocarcinoma↗
PubMed2005

Progress towards a vaccine for cervical cancer.

PURPOSE OF REVIEW: The aim of this review is to present for gynaecologists new information on human papillomavirus infections, their spontaneous evolution, and their consequences on the transformation of target tissues. It emphasizes the need for vaccination, both as a preventive tool and therapeutic agent, and reports the progress made so far. RECENT FINDINGS: Human papillomavirus infection is often transient and spontaneously reversible. High-risk human papillomavirus persistence is the major cause of cancerous transformation in several tissues. Preventive vaccination has already demonstrated remarkable efficacy against the development of some human papillomavirus type related anogenital lesions. Therapeutic vaccination has now also been developed to cure pre-existing lesions. Some new screening protocols can be derived from these experiments. SUMMARY: Both preventive and therapeutic human papillomavirus vaccinations will probably change our approach to the screening and therapy of human papillomavirus-related diseases in the next few years. The mass vaccination of adolescent patients should lower the frequency of these very frequently lethal infections.

Cell Transformation, Viral↗
PubMed2004

Phase I/II trial of immunogenicity of a human papillomavirus (HPV) type 16 E7 protein-based vaccine in women with oncogenic HPV-positive cervical intraepithelial neoplasia.

PURPOSE: Infection with oncogenic human papillomavirus (HPV) and HPV-16 in particular is a leading cause of anogenital neoplasia. High-grade intraepithelial lesions require treatment because of their potential to progress to invasive cancer. Numerous preclinical studies have demonstrated the therapeutic potential of E7-directed vaccination strategies in mice tumour models. In the present study, we tested the immunogenicity of a fusion protein (PD-E7) comprising a mutated HPV-16 E7 linked to the first 108 amino acids of Haemophilus influenzae protein D, formulated in the GlaxoSmithKline Biologicals adjuvant AS02B, in patients bearing oncogenic HPV-positive cervical intraepithelial neoplasia (CIN). METHODS: Seven patients, five with a CIN3 and two with a CIN1, received three intramuscular injections of adjuvanted PD-E7 at 2-week intervals. Three additional CIN1 patients received a placebo. CIN3 patients underwent conization 8 weeks postvaccination. Cytokine flow cytometry and ELISA were used to monitor antigen-specific cellular and antibody responses from blood taken before and after vaccine or placebo injection. RESULTS: Some patients had preexisting systemic IFN-gamma CD4+ (1/10) and CD8+ (5/10) responses to PD-E7. Vaccination, not placebo injection, elicited systemic specific immune responses in the majority of the patients. Five vaccinated patients (71%) showed significantly increased IFN-gamma CD8+ cell responses upon PD-E7 stimulation. Two responding patients generated long-term T-cell immunity toward the vaccine antigen and E7 as well as a weak H. influenzae protein D (PD)-directed CD4+ response. All the vaccinated patients, but not the placebo, made significant E7- and PD-specific IgG. CONCLUSIONS: The encouraging results obtained from this study performed on a limited number of subjects justify further analysis of the efficacy of the PD-E7/AS02B vaccine in CIN patients.

Adult↗
PubMed2003

Preliminary experience of ovarian tissue cryopreservation procedure: alternatives, perspectives and feasibility.

Chemotherapy and radiotherapy induce premature ovarian failure in many patients treated for oncological or benign diseases. The present paper reviews the risk of developing premature ovarian failure according to the type of treatment and the different options to preserve fertility, focusing on the cryopreservation of ovarian tissue. This technique constitutes a promising approach to preserve the fertility of young patients and offers the advantage of storing a large number of follicles that could be subsequently transplanted or cultured in vitro to obtain mature oocytes. Based on 34 requests, from which 19 were performed, the feasibility of the ovarian cryopreservation procedure is evaluated. The medical and ethical approaches of this protocol are also discussed. Cryopreservation of ovarian tissue constitutes new hope for many patients, but must still be kept for selected cases, with a significant risk of premature ovarian failure after treatments such as bone marrow transplantation.

Adolescent↗
PubMed2003

Laparoscopical insertion of intraperitoneal catheters for intraperitoneal chemotherapy.

BACKGROUND AND METHODS: Eight patients (seven clinically negative stage Ill ovarian cancer and one peritoneal mesothelioma) respectively underwent second-look laparoscopy for staging, adhesiolysis and insertion of an intraperitoneal catheter and fixation of a portal. All patients had received six courses of cisplatin-paclitaxel-based chemotherapy intravenously. At the end of the laparoscopic staging, a 5-mm catheter was inserted under direct vision through a 5-mm trocar in the abdomen. A preaponevrotic forceps was used to grasp the catheter and bring it to the portal, which is located on the intercostal aponevrosis 2 or 3 cm above the laparoscope entry. RESULTS: Although previously operated, laparoscopy was possible in all patients and the catheters were easily inserted. All patients received intraperitoneal chemotherapy on the second postoperative day. We did not observe any complication after a mean follow-up of 12 months. CONCLUSIONS: Laparoscopic insertion of intraperitoneal catheters is a feasible and safe procedure but requires experience in laparoscopic surgery. In many cases it might preclude from performing non-useful laparotomies. It might help to reduce the hospital stay and the morbidity in relation to second-look laparotomies. Compared with the blind surgical technique of insertion of intraperitoneal catheters, this technique also allows intraabdominal staging. Nevertheless, further studies are necessary to confirm our results.

Aged↗
PubMed2002

Development of a flow controller for long-term sampling of gases and vapors using evacuated canisters.

Anthropogenic activities contribute to the release of a wide variety of volatile organic compounds (VOC) into microenvironments. Developing and implementing new air sampling technologies that allow for the characterization of exposures to VOC can be useful for evaluating environmental and health concerns arising from such occurrences. A novel air sampler based on the use of a capillary flow controller connected to evacuated canisters (300 mL, 1 and 6 L) was designed and tested. The capillary tube, used to control the flow of air, is a variation on a sharp-edge orifice flow controller. It essentially controls the velocity of the fluid (air) as a function of the properties of the fluid, tube diameter and length. A model to predict flow rate in this dynamic system was developed. The mathematical model presented here was developed using the Hagen-Poiseuille equation and the ideal gas law to predict flow into the canisters used to sample for long periods of time. The Hagen-Poiseuille equation shows the relationship between flow rate, pressure gradient, capillary resistance, fluid viscosity, capillary length and diameter. The flow rates evaluated were extremely low, ranging from 0.05 to 1 mL min(-1). The model was compared with experimental results and was shown to overestimate the flow rate. Empirical equations were developed to more accurately predict flow for the 300 mL, 1 and 6 L canisters used for sampling periods ranging from several hours to one month. The theoretical and observed flow rates for different capillary geometries were evaluated. Each capillary flow controller geometry that was tested was found to generate very reproducible results, RSD < 2%. Also, the empirical formulas developed to predict flow rate given a specified diameter and capillary length were found to predict flow rate within 6% of the experimental data. The samplers were exposed to a variety of airborne vapors that allowed for comparison of the effectiveness of capillary flow controllers to sorbent samplers and to an online gas chromatograph. The capillary flow controller was found to exceed the performance of the sorbent samplers in this comparison.

Air Movements↗
PubMed2002

Rare RHCE phenotypes in black individuals of Afro-Caribbean origin: identification and transfusion safety.

The molecular backgrounds of variants encountered in Afro-Caribbean black individuals and associated with the production of clinically significant antibodies against high-incidence antigens (anti-RH18, anti-RH34) and against Rhe epitopes were determined. We showed that RH:-18 phenotypes are produced by 3 distinct RHCE alleles: ceEK carrying 48G>C (exon 1), 712A>G, 787A>G, 800T>A (exon 5); ceBI carrying 48G>C (exon 1), 712A>G (exon 5), 818C>T (exon 6), 1132C>G (exon 8); and the already known ceAR allele carrying 48G>C (exon 1), 712A>G, 733C>G, 787A>G, 800T>A (exon 5), and 916A>G (exon 6). The RH:-34 phenotype is produced by the (C)ce(s) haplotype described previously and composed of a hybrid D-CE(3-8)-D gene with 4 extra mutations next to a ce(s) allele (733C>G; exon 5) with an extra mutation in exon 7 (1006G>T). Partial Rhe with risk of immunization against lacking epitopes can be produced by the new ce(s) allele carrying an extra mutation in exon 3 (340C>T) and by the ceMO allele described previously. A population of sickle cell disease patients was screened to estimate the incidence of these rare alleles, with the conclusion that a procedure is required to detect the associated phenotypes in black donors to ensure transfusion safety for patients. We also described a new variant [ce(s)(748)] and variants carrying different altered alleles in nonimmunized patients and for whom the risk of immunization is discussed.

Alleles↗