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Biomedical subjects

C Fournier

Publications and source records attributed to C Fournier.

At least 73 records · Page 4Linked to original sources
PubMed1999

Transmission of calicivirus by a foodhandler in the pre-symptomatic phase of illness.

After a Christmas party in a restaurant, 48 (68%) of the 82 guests contracted calicivirus gastroenteritis. The epidemiological investigation showed that salad was strongly associated with the disease episode (RR = 2.43, P = 0.0005). Similar symptoms occurred among other customers who had had a meal at the same restaurant on the same evening. A foodhandler who had only prepared salad and appetizers became sick about 30 min after the end of his shift. He had been free of symptoms while preparing food. Few outbreak investigations have shown calicivirus transmission by foodhandlers some hours before becoming symptomatic.

Adult↗
PubMed1999

Encapsulation in hollow fibres of xenogeneic cells engineered to secrete IL-4 or IL-13 ameliorates murine collagen-induced arthritis (CIA).

A strategy of gene therapy using IL-4 or IL-13 xenogeneic transfected cells encapsulated into permeable hollow fibres (HF) was used to treat CIA. Hydrogel-based hollow fibres were obtained from AN-69 copolymer, already known for its biocompatibility and tolerance in rodents. Permeability to IL-4 and lack of cell leakage from the fibres were ascertained in vitro and in vivo. Chinese hamster ovary (CHO) fibroblasts transfected with mouse IL-4 gene were encapsulated in HF (6.25 x 105 cells/HF). IL-4 was detected in vitro in the culture supernatant of filled fibres for at least 19 days. IL-4 or IL-13 transfected CHO cells encapsulated in HF were implanted in the peritoneum of mice on days 11-13 after immunization with type II collagen. Control mice were treated with fibre containing CHO cells transfected with beta-galactosidase (betagal) gene; a positive control group consisted of mice treated by subcutaneous injection of 106 cells on days 10 and 25. Mice were monitored for signs of arthritis by observers unaware of the status of animals. Results of these experiments indicate that severity of the articular disease was significantly reduced in the groups of mice treated with CHO/IL-4 or CHO/IL-13 cells encapsulated in HF, compared with control groups receiving CHO/betagal cells encapsulated in HF. Histological analysis confirmed these data and extended them to a better inhibitory effect of encapsulated cells compared with free cells on inflammatory and destructive joint disease. Moreover, such long-term treatment with HF was well tolerated; macroscopic and histological aspects of peritoneal cavity were moderately inflammatory. Thus, our results may have important implications for clinical use of gene transfected cells as therapeutic agents in the treatment of autoimmune diseases.

Acrylic Resins↗
PubMed1999

Concordance between dobutamine Doppler tissue imaging echocardiography and rest reinjection thallium-201 tomography in dysfunctional hypoperfused myocardium.

OBJECTIVE: To evaluate the efficiency of the new technique colour Doppler tissue imaging (DTI) by studying the concordance between dobutamine DTI, standard grey scale echocardiography (SE), and rest-reinjection TI-201 tomography (TI) in dysfunctional myocardium. PATIENTS: 23 patients with chronic wall motion abnormalities and proven coronary artery disease (> 70% diameter stenosis of at least one major coronary artery at angiogram). METHODS: The contractile reserve and the resting perfusion characteristics of dysfunctional myocardial segments were assessed with low dose dobutamine SE and/or DTI (2.5 up to 20 gamma/kg/min) and TI on a semiquantitative basis. The DTI or SE data were separately compared with TI, on the basis of a 13 segment ventricular model. The resulting score of combined DTI and SE was also compared with TI. Finally the results obtained from DTI were compared with SE. RESULTS: A total of 142 severely hypokinetic or akinetic segments were visualised. The viability study was feasible in 127 (89%) and 121 (85%) segments with DTI and SE, respectively. TI detected viability more frequently than DTI (84 v 61, p < 0.001) and SE (80 v 50, p < 0.001). However, as many viable segments were detected with combined DTI and SE as with TI (78 v 84, NS). The kappa values between TI and SE, DTI or combined SE and DTI were 0.38, 0.45, and 0.57, respectively, and increased to 0.52 and 0.76, respectively, for SE and DTI versus TI when mid-anterior and mid-inferior segments only were considered. The kappa value between SE and DTI was 0.34. CONCLUSIONS: DTI is a helpful adjunct to SE, when using low dose dobutamine. This combination revealed as many viable segments as TI and showed a better agreement than DTI or SE alone for the assessment of myocardial viable segments evidenced by TI.

Adrenergic beta-Agonists↗
PubMed1999

Prognostic value of circulating soluble E-selectin concentrations in node-negative breast cancer patients.

Several studies have suggested that endothelial cells participate in tumor development. Soluble E-selectin (sE-selectin) is specifically released by activated endothelial cells, and its serum concentration can be considered a marker of endothelial activation. In this study, we assessed the prognostic value of sE-selectin concentrations in node-negative breast cancer patients. Serum sE-selectin concentrations were measured by an ELISA method prior to surgery in 456 node-negative breast cancer patients. We analyzed also tumor size (TS), histoprognostic grading, and steroid hormone receptor status. The mean sE-selectin concentration was 24.9 +/- 15.0 ng/ml. The sE-selectin concentrations were mildly correlated with the TS but not with the other factors. For prognostic analyses, the median follow-up duration was 7.5 years. The cutoff sE-selectin concentration used was 40 ng/ml. In overall survival studies, univariate analyses demonstrated a prognostic value of sE-selectin, TS, and histoprognostic grading, and multivariate analyses demonstrated a prognostic value of sE-selectin and TS. For disease-free survival, univariate and multivariate analyses demonstrated a prognostic value of sE-selectin and TS. sE-selectin concentration is an easily measurable and strong prognostic factor in node-negative breast cancer patients. These results provide further evidence for the role of adhesion molecules expression by endothelial cells in tumor progression.

Adult↗
PubMed1999

[Therapeutic failure of melarsoprol among patients treated for late stage T.b. gambiense human African trypanosomiasis in Uganda].

The failure rate of melarsoprol after treatment of late stage cases of Human African Trypanosomiasis (HAT) is usually under 7%, even though the drug has been used for such treatment over the past 50 years. We report a melarsoprol treatment failure rate of 26.9% among 428 patients treated in Northern Uganda. Whatever its origin, this observation, the first documented in a HAT focus, is alarming, particularly since no second line trypanocidal drug is actually available for the treatment of late stage HAT. We believe that the current worrisome situation of HAT in several African countries and the risk of emergence of other foci of resistance, argue in favour of a greater attention on the part of the scientific community and the pharmaceutical companies being paid to this problem.

Drug Resistance↗
PubMed1998

Spectrin self-association site: characterization and study of beta-spectrin mutations associated with hereditary elliptocytosis.

Most of hereditary elliptocytosis (HE) cases are related to a spectrin dimer (SpD) self-association defect. The severity of haemolysis is correlated with the extent of the SpD self-association defect, which itself depends on the location of the mutation regarding the tetramerization site. This site is presumed to involve the first C helix of the alpha chain and the last two helices, A and B, of the beta chain to reconstitute a triple helical structure (A, B and C), as observed along spectrin. Using recombinant peptides, we demonstrated that the first C helix of the alpha chain and the last two helices of the beta chain alone are not sufficient to establish interactions, which only occurred when a complete triple-helical repeat was added to each partner. One adjacent repeat is necessary to stabilize the conformation of both N- and C-terminal structures directly involved in the interaction site and is sufficient to generate a binding affinity similar to that observed in the native molecule. Producing peptides carrying a betaHE mutation, we reproduced the tetramerization defect as observed in patients. Therefore, the betaW2024R and betaW2061R mutations, which replace the invariant tryptophan and a residue located in the hydrophobic core, respectively, affect alpha-beta interactions considerably. In contrast, the betaA2013V mutation, which modifies a residue located outside any presumed interacting regions, has a minor effect on the interaction.

Binding Sites↗
PubMed1998

The house dust mite allergen, Dermatophagoides pteronyssinus, promotes type 2 responses by modulating the balance between IL-4 and IFN-gamma.

A common property of allergens is their potential to generate type 2 cytokine responses. To understand the mechanisms involved in this phenomenon, we have evaluated the polarizing potential of a major allergen, Dermatophagoides pteronyssinus 1 (Der p 1), in an heterologous immunization system using the glutathione S-transferase of the parasite Schistosoma mansoni (Sm28-GST) as immunogen. In previous studies, we showed that immunization with the Sm28-GST emulsified in CFA induced a nonpolarized immune response. In contrast, when alum was used as adjuvant, a type 2 immune response was induced against Sm28-GST. Using this experimental model, we examined whether the administration of Der p 1 together with Sm28-GST influenced the nonpolarized and/or the Th2 profiles induced by the CFA or the alum immunization, respectively. Our results showed that the introduction of Der p 1 in the CFA immunization protocol was associated with diminished anti-Sm28-GST IgG2a Ab titers, reduced IFN-gamma mRNA expression, and frequency of IFN-gamma-producing cells. In contrast, the introduction of Der p 1 in the alum protocol did not affect IL-4 or Ig isotype responses. The effect of Der p 1 was specific, since coimmunization with tetanus toxin fragment C did not affect the profile of the response against Sm28-GST. Furthermore, inactivation of Der p 1 reduced its ability to modify the immune response profile, suggesting that its protease activity played an important role in deviating the immune response. Our results suggest that the Der p 1 has the ability to modify the profile of an immune response by modulating the balance between the polarizing cytokines IL-4 and IFN-gamma.

Adjuvants, Immunologic↗
PubMed1998

Modulation of proinflammatory cytokine production in tumour necrosis factor-alpha (TNF-alpha)-transgenic mice by treatment with cells engineered to secrete IL-4, IL-10 or IL-13.

TNF-alpha is one of the major proinflammatory cytokines involved in the pathogenesis of chronic inflammatory joint disease, in human rheumatoid arthritis as well as in murine models of this disease. It was previously described that a highly destructive chronic spontaneous inflammatory arthritis develops in mice expressing a human TNF-alpha transgene modified with the 3' untranslated region of beta-globin. The present study investigates in this mouse model the effects of the anti-inflammatory cytokines IL-4, IL-10 and IL-13 administered in vivo on proinflammatory cytokine expression. Groups of TNF-alpha-transgenic mice were engrafted with xenogeneic transfected Chinese hamster ovary (CHO) fibroblasts secreting murine IL-4, IL-10 or IL-13. In vivo treatments consisted of 3 or 4 weekly engraftments, starting when the mice were 4weeks old. Control groups of transgenic mice were engrafted with beta-galactosidase gene-transfected CHO cells or injected with medium. A significant decreased expression of TNF-alpha transgene, endogenous mouse TNF-alpha and IL-1 mRNA was observed in splenocytes of mice treated for 3 or 4 weeks with CHO/IL-4 and CHO/IL-13, and, to a lesser extent, with CHO/IL-10, compared with controls. Finally, attenuation of histological scores of arthritides was statistically significant only in the group of CHO/IL-4-treated mice after 3weeks of treatment (P<0.05), and was not significant in any other group. These results show that IL-4, IL-10 or IL-13, administered by gene therapy, can decrease the mRNA steady state levels of both endogenous and transgenic cytokines in human TNF-alpha transgenic mice. In addition, IL-4 can slightly attenuate the development of arthritides in this model.

Animals↗
PubMed1998

Intramural injection of biodegradable microspheres as a local drug-delivery system to inhibit neointimal thickening in a rabbit model of balloon angioplasty.

Restenosis remains the major limitation of coronary angioplasty. The objective of this study was to develop microspheres able to be delivered at the angioplasty site for long-term drug release and to test their effects in a model of balloon angioplasty. Polylactic-co-glycolide acid microspheres (5-10 microm in diameter) were prepared by using an oil-in-water emulsion-solvent evaporation method. In vitro experiments with hydrocortisone-loaded microspheres revealed a hydrocortisone release for 4 weeks. We studied the in vivo effect of injection of microspheres into the arterial wall of New Zealand White rabbits by using a perforated balloon. Deep penetration of microspheres in the arterial wall was documented immediately after angioplasty. Intimal hyperplasia was assessed in iliac arteries 4 weeks after angioplasty. The morphometric analysis was performed in four groups of animals; the first group was subjected only to conventional angioplasty (control, n = 10), whereas the other three groups after conventional angioplasty were received perforated balloon angioplasty with saline (n = 10), microspheres (n = 10), or hydrocortisone-loaded microspheres (n = 7). Intramural injection of saline did not induce greater intimal hyperplasia compared with control (0.17 +/- 0.03 vs. 0.18 +/- 0.03 mm2, respectively). Microspheres injection was associated with a trend toward a greater degree of intimal hyperplasia that did not reach statistical significance. Hydrocortisone-loaded microspheres were associated with a significant reduction in intimal hyperplasia compared with unloaded microspheres (0.16 +/- 0.02 vs. 0.26 +/- 0.03 mm2, respectively). The polylactic-co-glycolide acid microspheres are well tolerated, easily injected into the arterial wall, and the increase of intimal hyperplasia is easily inhibited by release of hydrocortisone for 4 weeks after initial injury.

Angioplasty, Balloon↗
PubMed1998

In vitro infection of adult normal human hepatocytes in primary culture by hepatitis C virus.

In vitro infection of adult normal human hepatocytes in primary culture has been performed for investigating the replication cycle of hepatitis C virus (HCV) in differentiated cells. Hepatocytes were prepared from liver tissue resected from donors who tested negative for HCV, and inoculation was performed 3 days after plating with 33 HCV serum samples of different virus load and genotype. The presence of intracellular HCV RNA, detected by a strand-specific rTth RT-PCR assay, was used as evidence of infection. A kinetics analysis of HCV replication revealed that intracellular negative-strand RNA appeared at day 1 post-infection with a maximum level at days 3 and 5, followed by a decrease until day 14. At day 5, we estimated that the copy level of viral RNA was amplified at least 15-fold in infected cells. The level of intracellular HCV RNA in response to different serum samples was reproducible from one hepatocyte culture to another, suggesting that there is no inter-individual variability in the susceptibility of hepatocytes to HCV infection. These findings indicate that adult human hepatocytes in primary culture retain their susceptibility to in vitro HCV infection and support HCV RNA replication. This model should represent a valuable tool for the study of initial steps of the HCV replication cycle and for the evaluation of antiviral molecules.

Adult↗
PubMed1998

Interaction and co-encapsidation of human immunodeficiency virus type 1 Gag and Vif recombinant proteins.

Human immunodeficiency virus type 1 (HIV-1) wild-type (WT) virion infectivity factor (Vif) protein (Vifwt) and full-length Gag precursor (Pr55Gag) were found to be co-encapsidated into extracellular, membrane-enveloped virus-like particles released by budding from Sf9 cells co-expressing the two recombinant proteins in trans, with an average copy number of 3.5+/-0.6 Vifwt per 100 Pr55Gag molecules. No preferential localization at the plasma membrane was observed for recombinant Vif in the absence of Gag expression, and a significant proportion of Vif accumulated within the nucleus. Two conserved motifs, W89RKRRY94 and P156KKIKP161, seemed to act as nuclear addressing signals. The Pr55Gag and Vifwt interacting domains were analysed by biopanning of a phage-displayed hexapeptide library. The Vif-binding domain, which spanned residues H421-T470 in Pr55Gag, corresponded to the C-terminal region of nucleocapsid (NC), including the second zinc finger, the intermediate spacer peptide sp2 and the N-terminal half of the p6 domain. Deletions in these Gag domains significantly decreased the Vif encapsidation efficiency, and complete deletion of NC abolished Vif encapsidation. In Vif, four discrete Gag-binding sites were identified, within residues T68-L81 (site I) and W89-P100 (site II) in the central domain, and within residues P162-R173 (III) and P177-M189 (IV) at the C terminus. Substitutions in site I and deletion of site IV were detrimental to Vif encapsidation, whereas substitution of basic residues for alanine in sites III and IV had a positive effect. The data suggest a direct intracellular Gag-Vif interaction and the occurrence of a Pr55Gag-mediated membrane-targeting pathway for Vif in Sf9 cells.

Amino Acid Sequence↗
PubMed1998

Survival, differentiation and collagen secretion of human fibroblasts after irradiation with carbon ions and X-rays.

Human fibroblasts are a suitable model to investigate early and late radiation-induced damages because they are involved in most medical irradiation. Early damages of healthy tissue in the entrance channel of the beam and around the tumor are estimated on the basis of cell inactivation measurements (X-ray 250kV, 3.2 Gy/min.; carbon ions at 199 MeV/u, LET 16.2 keV/micrometer; carbon ions at 11MeV/u, LET 153.5 keV/micrometer). Late effects have been assessed by measuring premature differentiation and increased collagen secretion of fibroblasts. In the organism premature differentiation and increased collagen secretion are part of a fibrotic reaction due to a response of tissue cells (among fibroblasts) to primary parenchymal damage. 10 days after irradiation fibroblasts show a dose--and LET--dependent increased collagen secretion correlating with premature terminal differentiation.

Carbon↗
PubMed1998

The relationship between concentrations of circulating soluble E-selectin and clinical, pathological, and biological features in patients with breast cancer.

Increasing evidence suggests that E-selectin contributes to tumor growth and metastasis. E-selectin may increase tumoral angiogenesis and the adhesion of tumoral cells to endothelial cells at distant sites. The aim of this study was to assess the relationship between concentrations of circulating soluble E-selectin (sE-selectin) and clinical, pathological, and biological features in patients with breast cancer (BC). Concentrations of sE-selectin were analyzed by an ELISA method in sera from 113 patients with metastatic BC, 30 patients with primary inflammatory BC, 105 patients with primary noninflammatory BC, and 42 healthy controls. These concentrations were analyzed in terms of the clinical and pathological features of the tumors as well as in terms of the concentrations of serum inflammatory parameters (erythrocyte sedimentation rate, C reactive protein, interleukin 1 beta, and tumor necrosis factor alpha), the response to chemotherapy or hormone therapy, and the survival duration. Tumoral angiogenesis was also assessed in 68 patients with primary noninflammatory BC who had had primary surgery. The mean concentration of sE-selectin in the metastatic BC group was significantly higher than the mean concentration found in the healthy control group (33.5 versus 21.8 ng/ml; P < 0.01). In metastatic BC, the mean concentration of sE-selectin was significantly higher in patients with liver metastasis than in patients without liver metastasis (55.3 versus 26.0 ng/ml; P < 10(-5). The univariate analysis showed that high concentrations of sE-selectin were associated with reduced overall survival (P < 0.05), but this probably reflected the association between high concentrations of sE-selectin and liver metastasis. In patients with primary noninflammatory BC, a negative correlation was found between sE-selectin concentrations and the tumoral microvessel count (r = -0.47; P = 10(-4). In patients with primary inflammatory or noninflammatory BC, no correlation was found between concentrations of sE-selectin and tumor size, lymph node involvement, response to chemotherapy or hormone therapy, and survival. No correlation was found between the concentrations of sE-selectin and serum inflammatory parameters in any of the patient groups. This study suggests that in patients with metastatic BC, levels of sE-selectin are higher in the presence of liver metastasis. In patients with primary BC, high concentrations seem to be associated with reduced tumoral angiogenesis. Although several studies have previously demonstrated that the expression of cell surface E-selectin enhances the metastatic process, the shedding of sE-selectin in circulation may be considered a mechanism of inhibition of tumor progression.

Adult↗
PubMed1998

[Doppler tissue imaging of pre-ejection left ventricular wall dynamics in normal subjects].

Pre-ejectional left ventricular wall motion has been demonstrated clinically by angiography. Intramyocardial wall velocities generated by cardiac contraction may be measured by Doppler tissue imaging. The aim of this study was to detect pre-ejectional wall motion and to analyse its sequencer. A long axis M Mode with simultaneous septal and posterior wall imaging was performed in 11 normal subjects (age 37 +/- 15 years) with velocity analysis between the electrocardiographic Q wave and the onset of ejection by digitised analysis between the electrocardiographic Q wave and the onset of ejection by digitised images with automatic velocity extraction (3.8 ms) along a horizontal subendocardial line. The total duration of the pre-ejectional periods in conventional and Doppler tissue imaging are compared. Oscillatory velocimetric appearances with alternate colours of adjacent bands in each wall and a mirror image between walls was observed. The mean and peak velocities of the first four bands were significantly different between the walls (p < 0.001) as were the absolute values between bands 2 (p < 0.02) and 3 (p < 0.006). The duration of band 2, related to motion mainly towards the center of the ventricular chamber exceeded that of the adjacent bands (septum p < 0.02, posterior wall p < 0.001). The correlation coefficient for total duration of the pre-ejectional period between Doppler tissue imaging and conventional Doppler was 0.83, p < 0.05 for the interventricular septum and 0.76, p < 0.04 for the posterior was. The authors conclude that regional pre-ejectional wall motion can be recorded. During isovolumic contraction, there is motion predominantly towards the center of the left ventricular chamber of the two walls, confirming previous angiographic findings. Its timing suggests that wall motion proceeds the increase in ventricular pressure.

Adult↗
PubMed1998

[Granisetron (per os) compared with ondansetron (per os) in the prevention of nausea and vomiting induced by mildly emetogenic chemotherapies. Groupe de Recherches en Cancerologie du Nord].

It is a randomised cross-over multicenter study comparing the efficacy and the tolerance of granisetron (Gra) 1 mg and ondansetron (Ond) 8 mg, oral, given during two consecutive cycles to 188 naive patients scheduled to receive a moderately emetogenic chemotherapy. The antiemetic treatment is given one day per course, 1 hour before chemotherapy and the second administration from 8 to 12 hours after the beginning, during each of the two cycles; alternatively according to the randomisation. Five criteria are assessed; nausea (ordinal and visual analogic scales), emeric episodes (vomiting orland retching), complete response (minor or no nausea, no emetic episode and no rescue treatment), patient preference and tolerance. The intent to treat analysis showed no significant difference at cycle 1 between Gra and Ond; at cycle 2, there is no significant difference in the number of emetic episodes; for the prevention of nausea, the ordinal scale shows a significant difference (p = 0.028 in favour of Gra at day 1 (D1) but not from D2 to D5. Gra induced more complete response than Ond at D1 (p = 0.028), but not from D2 to D5. The cross-over study did not show any period or order effect, whereas a treatment effect on Ond was significant in favour of Gra (p = 0.01). There is no significant patients preference in favour of Gra or Ond. In conclusion, Gra was more efficient in preventing nausea and obtaining complete response on the first day of treatment, significantly at the second cycle. Both Gra and Ond had a good antiemetic activity for moderately emetogenic chemotherapy with complete response rates always over 50% on day 1; delayed emesis remain less weli controlled.

Adult↗
PubMed1998

[Comparative study of tumor evaluation with computerized tomography and surgery in ovarian cancer].

PURPOSE: To evaluate the results of an abdomino-pelvic scan in cancers of the ovary in comparison with surgery. MATERIAL AND METHODS: We reviewed the observations concerning patients operated on for malignant tumors of the ovary between January 1992 and April 1995 in our anti-cancer center. We selected 32 patients who had had both a complete surgical abdominal exploration (laparotomy or laparoscopy) and an abdominal pelvic scan in the preceding months. We divided the abdomen into 33 areas and compared the scan of each with the surgical findings. Two cancer radiologists, including one gynecology specialist, studied the imaging separately. Neither knew the results of the surgical observations. RESULTS: Imaging findings varied with localization tumor size and presence or not of ascites radiologists. For certain localization, detection of lesions was difficult for both readers (pancreas, spleen, stomach), for others, recognition improved with experience (bowel, diaphragm, colon). CONCLUSION: The clinician must be aware of the variability of ovarian cancer assessment by CT scan, particularly if imaging alone is being used to guide treatment.

Abdominal Neoplasms↗
PubMed1997

Apamin, a blocker of the calcium-activated potassium channel, induces neurodegeneration of Purkinje cells exclusively.

Following acute intracerebroventricular injections of 1 ng of apamin and chronic apamin infusion (0.4 ng/microl, 0.5 microl/h, 14 days), the rat brains exhibited bilateral damage only in the cerebellum. The argyrophilic cells were Purkinje cells in copula pyramis, flocculus, paraflocculus, and paramedian lobules. These data demonstrate that the inactivation of small conductance Ca2+-activated K+ channels by apamin induces a non-limbic neurodegeneration.

Animals↗