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N Guérin

Publications and source records attributed to N Guérin.

At least 19 recordsLinked to original sources
PubMed2000

Evaluation of polyether-polyethyleneimine graft copolymers as gene transfer agents.

Cationic copolymers consisting of polycations linked to non-ionic polymers are evaluated as non-viral gene delivery systems. These copolymers are known to produce soluble complexes with DNA, but only a few studies have characterized the transfection activity of these complexes. This work reports the synthesis and characterization of a series of cationic copolymers obtained by grafting the polyethyleneimine (PEI) with non-ionic polyethers, poly (ethylene oxide) (PEO) or Pluronic 123 (P123). The PEO-PEI conjugates differ in the molecular mass of PEI (2 kDa and 25 kDa) and the degree of modification of PEI with PEO. All of these conjugates form complexes upon mixing with plasmids, which are stable in aqueous dispersion for several days. The sizes of the particles formed in these systems vary from 70 to 200 nm depending on the composition of the complex. However, transfection activity of these systems is much lower than that of PEI (25 kDa) or Superfect as assessed in in vitro transfection experiments utilizing a luciferase reporter expression in Cos-7 cells as a model system. In contrast, conjugate of P123 with PEI (2 kDa) mixed with free P123 (9:1(wt)) forms small and stable complexes with DNA (110 nm) that exhibit high transfection activity in vitro. Furthermore, gene expression is observed in spleen, heart, lungs and liver 24 h after i.v. injection of this complex in mice. Compared to 1,2-bis(oleoyloxy)-(trimethylammonio) propane:cholesterol (DOTAP:Chol) and PEI (25 kDa) transfection systems, the P123-PEI system reveals a more uniform distribution of gene expression between these organs, allowing a significant improvement of gene expression in liver.

Animals↗
PubMed2000

A combination of poloxamers increases gene expression of plasmid DNA in skeletal muscle.

Intramuscular administration of plasmid DNA is a promising strategy to express therapeutic genes, however, it is limited by a relatively low level of gene expression. We report here that a non-ionic carrier, SP1017, composed of two amphiphilic block copolymers, pluronics L61 and F127, also known as poloxamers, significantly increases intramuscular expression of plasmid DNA. Two reporter genes, luciferase and beta-galactosidase, and one therapeutic gene, erythropoietin, were injected intramuscularly with and without SP1017 into C57Bl/6 and Balb/C mice and Sprague-Dawley rats. SP1017 increased gene expression by about 10-fold and maintained higher gene expression compared with naked DNA. Comparison of SP1017 with polyvinyl pyrrolidone (PVP) showed that SP1017 exhibited a significantly higher efficacy and its optimal dose was 500-fold lower. Experiments with beta-galactosidase using X-gal staining suggested that SP1017 considerably increased plasmid DNA diffusion through the tissue. SP1017 also improved expression of the erythropoietin gene leading to an increase in its systemic level and hematocrits. Previous toxicity studies have suggested that SP1017 has over a 1000-fold safety margin. Poloxamers used in SP1017 are listed in the US Pharmacopeia as inactive excipients and are widely used in a variety of clinical applications. We believe that the described system constitutes a simple and efficient gene transfer method to achieve local or systemic production of therapeutic proteins.

Animals↗
PubMed2000

Block and graft copolymers and NanoGel copolymer networks for DNA delivery into cell.

Self-assembling complexes from nucleic acids and synthetic polymers are evaluated for plasmid and oligonucleotide (oligo) delivery. Polycations having linear, branched, dendritic. block- or graft copolymer architectures are used in these studies. All these molecules bind to nucleic acids due to formation of cooperative systems of salt bonds between the cationic groups of the polycation and phosphate groups of the DNA. To improve solubility of the DNA/polycation complexes, cationic block and graft copolymers containing segments from polycations and non-ionic soluble polymers, for example, poly(ethylene oxide) (PEO) were developed. Binding of these copolymers with short DNA chains, such as oligos, results in formation of species containing hydrophobic sites from neutralized DNA polycation complex and hydrophilic sites from PEO. These species spontaneously associate into polyion complex micelles with a hydrophobic core from neutralized polyions and a hydrophilic shell from PEO. Such complexes are very small (10-40 nm) and stable in solution despite complete neutralization of charge. They reveal significant activity with oligos in vitro and in vivo. Binding of cationic copolymers to plasmid DNA forms larger (70-200 nm) complexes. which are practically inactive in cell transfection studies. It is likely that PEO prevents binding of these complexes with the cell membranes ("stealth effect"). However attaching specific ligands to the PEO-corona can produce complexes, which are both stable in solution and bind to target cells. The most efficient complexes were obtained when PEO in the cationic copolymer was replaced with membrane-active PEO-b-poly(propylene oxide)-b-PEO molecules (Pluronic 123). Such complexes exhibited elevated levels of transgene expression in liver following systemic administration in mice. To increase stability of the complexes, NanoGel carriers were developed that represent small hydrogel particles synthesized by cross-linking of PEI with double end activated PEO using an emulsification/solvent evaporation technique. Oligos are immobilized by mixing with NanoGel suspension, which results in the formation of small particles (80 nm). Oligos incorporated in NanoGel are able to reach targets within the cell and suppress gene expression in a sequence-specific fashion. Further. loaded NanoGel particles cross-polarized monolayers of intestinal cells (Caco-2) suggesting potential usefulness of these systems for oral administration of oligos. In conclusion the approaches using polycations for gene delivery for the design of gene transfer complexes that exhibit a very broad range of physicochemical and biological properties, which is essential for design of a new generation of more effective non-viral gene delivery systems.

Cations↗
PubMed1999

Comparison of the safety and immunogenicity of the lyophilized Mérieux seed and the World Health Organization working reference BCG vaccines in school-aged children in Senegal.

In order to validate two new lots of Mérieux BCG vaccine (Mérieux seed derived from strain 1072), a calibration study was performed to compare their safety and immunogenicity to a full dose of the WHO-reference BCG vaccine (Tokyo strain 172) as well as the WHO-reference vaccine given at 1/10 of its normal concentration, in an open, randomized, four-arm, multicenter study in Senegal. A total of 1041 healthy Senegalese children aged 8-10 years were screened for participation in this study, of whom 548 had a negative Mantoux test and complied with inclusion and exclusion criteria. These children were randomly allocated a single dose of one of the following vaccines: full-dose Mérieux BCG vaccine (lot E0650); full-dose Mérieux BCG vaccine (lot E0624); full-dose WHO-reference vaccine (Tokyo strain 172); or 1/10 dose WHO-reference vaccine. A follow-up examination, including a tuberculin test, was performed 10-12 weeks after BCG vaccination for 465 (85%) children: 236 Mérieux BCG vaccine (117 lot E0650; 119 lot E0624); 115 full-dose WHO; 114 1/10 dose WHO. The percentage of subjects with a positive tuberculin test after vaccination was significantly lower (P < 0.001) in the 1/10 dose group (81.5%) compared to the other three groups (> 96%). The mean induration diameter was significantly smaller in subjects who received the low-dose of WHO vaccine compared to the others, according to analyses considering all subjects vaccinated, as well as only those subjects with a positive tuberculin test after vaccination. More children in the low-dose group did not have a vaccination scar, and the mean diameter of scars was smaller in this group. The rate of tuberculin reactions, the classification of reactions (Palmer and Edwards), and the characteristics of the vaccinal lesion were similar for the Mérieux BCG vaccines and the full-dose WHO-reference vaccine. All vaccines were safe, as evidenced by the absence of adenitis or suppurative adenitis during the course of the study. Results from this trial show that the two lots of Mérieux BCG vaccine behave equally as well as the full-dose WHO-reference BCG vaccine. The WHO-reference vaccine, given at 1/10 of its normal concentration was significantly less immunogenic, according to all parameters evaluated.

BCG Vaccine↗
PubMed1998

Assessing immunization coverage: how and why?

Assessment of immunization coverage is an important part of evaluating an immunization programme and it is a useful aid in programme management and decision making. Coverage assessment should be carried out at the national and district levels. Routine methods currently used in EU countries vary and are not always accurate, and should be validated regularly by specific surveys.

France↗
PubMed1998

Multiresolution texture based adaptive clustering algorithm for breast lesion segmentation.

OBJECTIVE: A specific algorithm is presented for the automatic extraction of breast tumors in ultrasonic imaging. METHOD: The algorithm involves two-dimensional adaptive K-means clustering of the gray scale and textural feature images. The segmentation problem is formulated as a maximum a posteriori (MAP) estimation problem. The MAP estimation is achieved using Besag's iterated conditional modes algorithm for the minimization of an energy function. This function has three components: the first constrains the region to be close to the data; the second imposes spatial continuity; and the third takes into consideration the texture of the various regions. A multiresolution implementation of the algorithm is performed using a waveless basis. RESULTS: Experiments were carried out on synthetic images and on in vivo breast ultrasound images. Various parameters involved in the algorithm are discussed to evaluate the robustness and accuracy of the segmentation method. CONCLUSION: Including textural features in the segmentation of ultrasonic data improves the robustness of the algorithm and makes the segmentation result less parameter dependent.

Adenocarcinoma↗
PubMed1998

[Expanded program of vaccination. Results and prospects].

The expanded program on immunization, jointly launched by WHO and UNICEF in 1974 aimed in the beginning at immunizing 80% of the children of the world against measles, tetanus, pertussis, poliomyelitis, diphtheria and tuberculosis. After reaching the objectives in 1990, countries have been urged towards eradication of poliomyelitis, elimination of neonatal tetanus, and measles control. Immunization against hepatitis B and yellow fever were also proposed according to local epidemiology. Tremendous results have been already delivered: the American continent has eliminated poliomyelitis since August 1991, it has reduced dramatically the incidence of measles. All the countries, including those from Africa, are organizing campaigns aiming at polio eradication. Active surveillance systems have been implemented. But financial and operational constraints persist, linked to vaccines prices, their heat sensitivity, injection techniques, and to the sterilisation and waste disposal. Major efforts are still needed.

Adolescent↗
PubMed1997

[Lingual thyroid and intra-lingual thyroglossal cyst. Apropos of 2 cases].

Lingual thyroid and intra lingual thyro-glossal cyst are two benign tumours of similar embryological pathogenesis respectively with the arrest in the ectopic position of the thyroid gland during its downward migration and from abnormal persistence of the thyro-glossal tract for the cyst. The occurrence of lingual thyroid is rare 1/100,000 patients and outnumbers the incidence of intra-lingual cyst which represents an estimated 2.1% of the thyro-glossal cysts or fistulas. Both lesions are a rare cause of dysphagia and dyspnoea due to oropharyngeal obstruction, and radionuclide scintigraphy combined with CT and/or MRI will establish the diagnosis. Surgical pharyngotomy with an infra-hyoid approach provides excellent access to the lesions and complete removal of the tumours.

Adolescent↗
PubMed1996

[Osteoma of the mastoid: apropos of 2 cases].

The authors report two cases of mastoid osteoma: it is a rare benign tumor attached to the cortex of the mastoid bone, approximatively fifty cases have been described in the english language literature and eight in the french literature. The clinical and radiological characteristics combined with histopathologic evidence demonstrate the diagnosis of mastoid osteoma, the most common type being the compact osteoma. Differential diagnosis should be considered with others benign bone-forming lesions (osteochondroma, chondroma, osteoblastoma, exostosis, fibrous dysplasia...) and with malignant lesions (osteosarcoma...). Surgical removal proposed for cosmetic deformity is a simple procedure for the vast majority of small osteomas. Early surgical intervention is recommended to avoid the evolution toward giant osteoma with potential risks of surgical complications.

Adult↗
PubMed1996

[Stereotaxic mammary microbiopsy. I. Technical aspects].

The authors present a review of the literature about the procedure of stereotactic core breast biopsy. Developed since the beginning of the 1990s, this histopathological sampling technique presents numerous advantages. Its low cost, its simplicity and its diagnostic efficacy are the main arguments for its development. The diagnostic efficacy confirmed on clinical trials (see 2nd part of article) must be preserved if core biopsy is performed routinely. This means avoiding wrong choices in indications and respecting evaluated procedures.

Biopsy, Needle↗
PubMed1995

Efficacy of BCG vaccination of the newborn: evaluation by a follow-up study of contacts in Bangui.

BACKGROUND: The efficacy of Bacillus of Calmette and Guérin (BCG) vaccination given at birth is still controversial. We therefore conducted a study in Bangui (Central African Republic) to estimate the protection afforded over the first seven years of life by BCG administered at birth. METHODS: One thousand children who had lived in contact with a recently diagnosed case of contagious tuberculosis were followed up for a period of 6 months in order to detect the occurrence of tuberculosis. Diagnosis of tuberculosis was made through a scoring system. Vaccine efficacy (VE) was calculated on the basis of the relative risk of contracting tuberculosis according to vaccination status. RESULTS: The efficacy of BCG was estimated to be 71% (95% confidence interval: 56-81%). This result remained practically the same after changing the definition used for tuberculosis cases (VE = 75% for a threshold with a score of 15 instead of 6, VE = 74% when only confirmed cases were considered). There was no difference between the two groups in the variables measuring intensity of contact with the source of contamination, but there was a difference in age distribution. Vaccine efficacy adjusted for this factor was the same as the crude VE. CONCLUSION: This study, based on a methodology that controls for most of the risks of bias inherent to field efficacy measurement, confirms the protective capacity of neonatal BCG against childhood tuberculosis. Therefore BCG vaccination at birth must remain a public health priority especially in countries with high incidence of the disease.

BCG Vaccine↗
PubMed1993

Weekly changes in psychophysiological variables of 8- to 10-year-old school girls.

Three groups of schoolgirls 8, 9, and 10 years of age, respectively, self assessed sleep onset/offset and duration, as well as oral temperature and a set of cognitive measures, at school at 09:00, 11:00, 14:00, and 16:00 h on Mondays, Tuesdays, Thursdays, and Fridays (and/or Saturday) for 2 consecutive weeks (spring 1987 and 1989). The scores of a letter cancellation test exhibited neither daily nor weekly temporal variation at the age of 8 years [analysis of variance (ANOVA), p > 0.05]. In contrast, in the 10-year-olds, changes as a function of both time of day (peak time 14:00-16:00 h) and day of week (peak day Tuesday-Friday) were substantiated. Moreover, the time of best performance on the letter cancellation test varied systematically according to the day of the week (ANOVA, p = 0.000). Day of the week changes in the observed duration of sleep, self-rated fatigue, drowsiness, and attention changes were not detected in any of the age groups. It is hypothesized that temporal performance variations in the girls during the 7-day period was age related.

Age Factors↗