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Biomedical subjects

G Soula

Publications and source records attributed to G Soula.

At least 19 recordsLinked to original sources

DI2ADEM: an adaptive hypermedia designed to improve access to relevant medical information.

The World Wide Web (web) provides the same type of information to widely different users and these users must then find the information suitable for their use in the package offered. The authors present the DI2ADEM project designed to take the user into account and intended to provide this user with appropriate medical information. To do that, DI2ADEM is suggesting an adaptive hypermedia based on the management of a meta-knowledge of the user and a knowledge of the information that can be circulated. An adaptive hypermedia prototype devoted to paediatric oncology was implemented on the intranet network of a university hospital.

Diffusion of Innovation↗

The French Virtual Medical University.

This paper is the description of a French Virtual Medical University based on the federation of existing or currently being developed resources in several Medical Schools in France. The objectives of the project is not only to share experiences across the country but also to integrate several resources using the New Information and Communication Technologies to support new pedagogical approaches for medical students and also for continuing medical education. The project includes: A virtual Medical Campus using secure access from several sites, The Integration of new interactive resources based on pedagogical methods, Implementation of new indexing and search engines based on medical vocabularies and ontologies, The definition of general and specific portals, the evaluation of the system for ergonomics and contents.

Computer-Assisted Instruction↗

Macromolecular Colloids of Diblock Poly(amino acids) That Bind Insulin.

The diblock polymer poly(l-leucine-block-l-glutamate), bLE, was synthesized by acid hydrolysis of the ester poly(l-leucine-block-l-methyl glutamate). During the hydrolysis reaction the leucine block precipitates from the reaction mixture, forming nanosized particulate structures. These particles can be purified and further suspended in water or in 0.15 M phosphate saline buffer (PBS) to give stable, colloidal dispersions. TEM analysis shows the predominant particle form to be that of platelets with a diameter of 200 nm. Smaller cylindrical or spherical particles form a relatively minor fraction of the sample. After fractionation, analysis shows the platelets to be compositionally rich in leucine, while the spheres are glutamate-rich. (1)H NMR, CD, and X-ray diffraction indicate that the core of the platelets is composed of crystalline, helical leucine segments. The poly(l-glutamate) polyelectrolyte brush extending out from the two faces of the disk stabilizes individual particles from flocculation. At pH 7.4, the nanoparticles (platelets and cylinders) spontaneously adsorb proteins, such as insulin, directly from solution. Partial desorption of the protein in its native configuration can be induced by simple dilution. The reversibility of the insulin-nanoparticle complex is the basis for a potential new delivery system. Copyright 1999 Academic Press.

Journal Article↗

[The focus of human trypanosomiasis in Campo (Cameroon). History and endemic situation in 1998].

For the first time in the last thirteen years, the human sleeping sickness focus at Campo, spanning the Cameroon-Equatorial Guinea border areas, has been prospected. The screening was carried out simultaneously on both sides of the border. This focus has been known since the beginning of the century but, contrary to what took place in other well-known foci in bordering countries south of Cameroon, either in the 1920s or the 1980s--there has never been an epidemic outbreak in that area. Such an epidemiological situation makes this focus particularly interesting. Though still active, trypanosomiasis is not very manifest. According to passive screening carried out in recent years, the estimated prevalence ranges between 0.2 and 0.5%. For this screening, 5,255 persons were examined on the Cameroonian side of the focus (90.6% of the census population). The serological screenings were carried out with the CATT 1.3, which is the CATT generally used in screening, and with the latex CATT which associates LiTat 1.3, 1.5 and 1.6. The search for trypanosomes was made by testing the lymph nod juice in presence of adenopathy and in the blood by Quantitative Buffy Coat (QBC), the mini anion exchange centrifugation (mAEC), as well as the in vitro culture using the kit for in vitro isolation of trypanosomes (KIVI) for individuals suspected to be serologically positive. 16 patients were identified in Cameroon but none in Equatorial Guinea. The results show that the Campo focus is active only on the Cameroonian side, centred on the village of Ipono with a limited prevalence (0.3%). The persisting epidemic is most likely to be associated with the presence of pigs carrying the Trypanosoma brucei gambiense which was identified during the study in Ipono. The strain that we isolated was studied by isoenzyme electrophoresis on cellulose acetate. Its zymodeme is the same as that of the human strain isolated in Campo. With the collected epidemiological data, a concerted medical and entomological action could be planned within the limits of the village of Ipono to eradicate the disease. This action may be organised by the existing local health structures. During this study, the latex CATT proved to be more cost-effective than the CATT 1.3 since a similar result was reached requiring eight times less work at a lower cost. This remains to be confirmed in a hyperendemic focus.

Animals↗

SupraMolecular BioVectors (SMBV) improve antisense inhibition of erbB-2 expression.

New therapeutic strategies are now being developed against adenocarcinoma associated with erbB-2 amplification, particularly by inhibiting p185erbB-2 expression. Antisense oligodeoxynucleotides seem promising for this purpose as long as they are efficiently protected against degradation and targeted into the cells. We present antisense oligonucleotide carriers, the supramolecular biovectors (SMBVs), for which we have already demonstrated the ability to improve both cellular uptake and protection of oligodeoxynucleotide. The present work demonstrates that SMBVs elicit a specific and non-toxic action of antisense compounds in a cell model, irrespective of their sensitivity to nucleases. This is a major point, considering the specificity problems associated with the use of nuclease-resistant phosphorothioate oligodeoxynucleotide. SMBVs improve antisense efficiency of oligodeoxynucleotide designed against p185erbB-2, with a complete growth arrest of SK-Br-3, human adenocarcinoma mammary cells that overexpress p185erbB-2 and no effect on MCF-7 cells that normally express p185erbB-2. The comparison of SMBVs with DOTAP reveals the statistically higher efficiency of SMBVs, which allows the antisense inhibition of p185erbB-2 expression in 65-75% of SK-Br-3 cells (P < 0.05). The efficiency and controlled synthesis of SMBVs underline their potentialities as oligodeoxynucleotide carriers for in vivo experiments.

Cell Division↗

Impact of the TOP-FORUM hypermedia system in a pediatric oncology care unit.

This paper describes our approach in analyzing the impact of the TOP-FORUM hypermedia in a pediatric oncology care unit. The impact of this technology is realized through the study of accommodation and assimilation adoption. Accommodation refers to the technological adoption and Assimilation refers to the professional adoption. Results show that accommodation depends on information and formation of the users. Assimilation is more difficult to evaluate because it depends on human, social and organizational problems.

Attitude of Health Personnel↗

Clinical immunogenicity and tolerance studies of liquid vaccines delivered by jet-injector and a new single-use cartridge (Imule): comparison with standard syringe injection. Imule Investigators Group.

A new needleless jet-injector, Mini-Imojet, was developed that administers liquid vaccines from a single-use, pre-filled cartridge named Imule, which avoids the risk of cross-contamination. We conducted clinical trials in several settings in France and West Africa to compare the immunogenicity and tolerance of five vaccines (influenza vaccine, Vi capsular polysaccharide typhoid vaccine, tetanus toxoid vaccine, diphtheria-tetanus-whole cell pertussis vaccine, and inactivated hepatitis A vaccine) administered with the Imule system vs standard syringe technique. In each vaccine study, all subjects of either group were tested for serum antibody titres to calculate the geometrical mean titres and seroconversion rates after complete vaccination. Immediate local-reactions were noted after each injection, and local and general reactions were evaluated during a predetermined period of follow-up. When delivered by the Imule technique, all the administered vaccines were of equivalent or superior immunogenicity, compared to the syringe technique. The tolerance to vaccines injected by the Imule system was acceptable in all studies. The most frequently observed reactions were mild (e.g. minor bleeding, superficial papules, erythema and induration) and could be considered to be inherent to the injection technique. The technical and safety advantages of the Mini-Imojet/Imule system, compared to sterilizable, standard disposable or autodestruct syringes and to classical multi-dose vial jet-injectors, reinforces the interest of this new injection technique for collective immunizations.

Adolescent↗

Designing medical hypermedia: the FORUM project.

Medical activity in learning stages or in usual tasks is a wide field for information technologies. But it would be a mistake to focus on technologies and minimize the organisational, social and cultural aspects of integrating such technologies. Medical hypermedia design based only on a technological approach is a case in point. This paper describes our experience in hypermedia development. It reports on the technical, methodological and organizational aspects destined to help the medical community get involved in the development of such applications.

Computer Communication Networks↗

Involvement of tyrosine kinase activity in the low-density lipoprotein receptor expression in human lung adenocarcinoma cell line A549.

In common with other tumour cell lines but in contrast to normal cells, the human adenocarcinoma cell line A549 showed a biphasic regulation of the LDL receptor activity during growth both LDL binding and metabolism (sum of internalised and degraded LDL) increased during the log exponential growth phase and decreased when the cells approached confluence. This period of increasing LDL receptor activity coincided with a high resistance to cholesterol down-regulation which suggested a sterol-independent pathway of stimulation. Since A549 cells have an autocrine loop of growth factors, two of which have tyrosine kinase activity, the LDL receptor activity was tested in the presence of the tyrosine kinase inhibitor, genistein. When cells were incubated in the absence of cholesterol (LPDS medium), the inhibition that occurred was two-fold higher during the exponential growth phase than during the confluent phase. Moreover, the residual LDL binding and metabolism after genistein inhibition were completely resistant to down-regulation by cholesterol only during the growth phase. When cholesterol was present (FCS medium). inhibition was observed only during the growth phase. The inhibition of LDL receptor activity by genistein was found to be the result of a loss in the number of LDL binding sites, while the dissociation constant was not affected. This loss was accompanied by a disappearance of mRNA as shown by RNase mapping. By comparison, LDL receptor activity of normal cells (fibroblasts) was also affected by genistein during the exponential growth phase but was much more cholesterol-dependent. Taken together, these results suggest that the tyrosine kinase pathway is essential to up-regulate LDL receptor expression in highly dividing cells and particularly in tumour cells in which the sterol regulation is deficient.

Adenocarcinoma↗

Potential prognostic value in human breast cancer of cytosolic Nme1 protein detection using an original hen specific antibody.

The metastasis-suppressor nme gene (also called nm23), first identified in murine melanoma cells, exists as two forms in human: nme1 and nme2. However, only the lack of expression of nme1 has been related to distant metastasis appearance in human breast cancer. The aim of this work was first to raise specific antibodies to allow the analysis of Nme1 and then, with this specific tool, to evaluate the predictive value of Nme1 detection in cytosolic extracts of human breast tumours. We obtained a hen antibody that specifically reacts with Nme1 without any cross-reaction with Nme2. We analysed the expression of the protein in 59 human breast tumours and found a significant relationship between this expression and oestrogen receptor status (P<0.001). Moreover, Nme1 expression is related to metastasis-free survival (P<0.001) and survival of patients (P<0.001). The determination of Nme1 expression in primary tumours using our antibody should be an interesting predictive test of the metastasis for clinical investigations.

Animals↗

[Top-Forum: an interactive multimedia knowledge database to improve quality of care in pediatric oncology].

The treatment of pediatric cancer patients is characterised by complex and aggressive chemotherapy, difficult decision making, the numerous protocols available and the necessity of highly skilled caregivers. Quality of care is a major issue in all pediatric oncology units. We created an interactive multi-media database available to each caregiver to permit him/her to have easy access to information and thus increase his/her knowledge and participate in increasing their group's know-how. The computer database is available to all on a free-access basis in each ward. This is a novel approach to quality care, as it accords great importance to personal formation, allowing each caregiver to broaden his/her knowledge via easily obtained data which he/she can help enrich by permanent feedback. This database may become the backbone of department know-how.

Adolescent↗

Involvement of the Ca(2+)-dependent phosphorylation of a 20 kDa protein in the proliferative effect of high-density lipoproteins (subclass 3) on the adenocarcinoma cell line A549.

Previous studies from our laboratory demonstrated that high-density lipoproteins (subclass 3; HDL3) bind to sites specific for apolipoprotein AI on the human adenocarcinoma cell line A549 and that HDL3 binding promotes a mitogenic effect [Favre, Tazi, Le Gaillard, Bennis, Hachem and Soula (1993) J. Lipid Res. 34, 1093-1106]. In the present study, we have examined the cell proteins that showed modified phosphorylation after binding of HDL3 to specific sites, and the roles of Ca2+ and protein kinase C. Native HDL3 (but not tetranitromethane-modified HDL3) and Ca2+ ionophore A23187 strongly enhanced the phosphorylation of a 20 kDa protein (x 3.6) and, to a lower extent, the phosphorylation of 24 and 28 kDa proteins (x 2.2 and 2.6 respectively). The two effectors were equally able to stimulate cell growth. Down-regulation of protein kinase C by a 24 h incubation of cells with phorbol myristate acetate prevented the effects of HDL3 on the phosphorylation of 24 and 28 kDa proteins. However, the extent of phosphorylation of the 20 kDa protein was not affected. In contrast, activation of protein kinase C by a short incubation with phorbol myristate acetate resulted in inhibition of proliferation and an increase in 24 and 28 kDa (but not 20 kDa) protein phosphorylation. These results suggest that HDL3 putative receptors exert their proliferative effect on A549 cells through activation of a Ca(2+)-dependent protein kinase. This kinase activity is not modulated by phorbol ester and thus may be a calmodulin kinase or an isoenzyme of protein kinase C that is independent of phorbol ester. It allows a subsequent 20 kDa protein to be phosphorylated.

Adenocarcinoma↗

[Risk factors in prematurity and intrauterine growth retardation in Burkina Faso].

A case-control study to investigate determinants of preterm delivery and intrauterine growth retardation (IUGR) in Bobo-Dioulasso, Burkina Faso, was conducted between December 1991 and November 1992. A total of 581 cases were recruited, 281 preterm infants with birthweight < 2500 g and 300 term infants with birthweight < 2500 g. 578 infants born at term with birthweights of 2500 g or more were recruited as controls. Logistic regression analyses identified three factors linked independently to both preterm delivery and IUGR: maternal illness during the pregnancy, nulliparity and failure to attend three antenatal consultations. In addition, primiparity and a maternal weight < 50 kg were associated with an increased risk of preterm delivery. Other factors associated with increased risk of IUGR were maternal height less than or equal to 155 cm, mid-upper arm circumference < 24 cm, and female sex of the infant. Improvements in the pre-pregnancy weight of women and in antenatal care focused on nulli- and primiparous women might in this population, reduce substantially the incidence of preterm delivery and IUGR.

Anthropometry↗

Reversion of transformed phenotype of human adenocarcinoma A549 cells by expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase complementary DNA.

3-Hydroxy-3-methylglutaryl CoA reductase (HMG-CoA reductase) plays a rate-limiting role in isoprenoid biosynthesis and is associated with cell proliferation and transformation. Although an elevated level of HMG-CoA reductase activity is consistently detected in cancer cell lines and tumors, the question remains whether HMG-CoA reductase activity may have a causative role in cell transformation. We have stably transfected the A549 human adenocarcinoma cells with both bicistronic and retroviral expression vectors, including the whole cDNA of human HMG-CoA reductase. Stably transfected cells showed strong morphological changes and disorganization in the filamentous actin architecture, became contact inhibited, and had a lower doubling time. Moreover, they exhibited anchorage-independent growth reduction and lost their capability to induce tumors in nude mice. Surprisingly, no quantitative modification of enzyme activity was observed following transfection, although expression of HMG-CoA reductase cDNA was shown by Northern blot analysis. When endogenous and transfected reductase activity was bypassed by the addition of mevalonate and compactin, a competitive inhibitor, the filamentous actin distribution in HMG-CoA reductase-transfected cells became very similar to that of control cells, demonstrating the role of exogenous HMG-CoA reductase activity in this process. All of our data together strongly suggest that phenotype reversion is dependent on exogenous HMG-CoA reductase expression and that enzymatic activity is implied in this mechanism. HMG-CoA reductase cDNA expression, by expression of a particular form of reductase, might be a negative regulator of cell growth and thus reverse the phenotype of tumor cells.

Acyl Coenzyme A↗

Handling information and knowledge in the FORUM hypermedia authoring system: application to uterine magnetic resonance imaging.

Hypertext and hypermedia are used to access loosely structured information. The lack of conceptual model for hypertext application makes it difficult to represent the mental model of the author. Users are often lost in the information and the objective of the author is not achieved. In this paper, we describe an approach to handle information and knowledge in the FORUM hypermedia authoring system. It allows the author to create and maintain the hypertext more easily and facilitates the navigation of the reader. An application for learning uterine magnetic resonance imaging is also presented.

Computer Systems↗

[Evaluation of computer-assisted instruction methods. Apropos of 26 comparative studies published between 1989 and 1992].

Information and knowledge processing technologies have contributed to the development of Computer assisted instruction (CAI) applications. Multimedia technologies will increase the possibilities of these programmes in the future. However the evaluation of the software as well as the other technologies is necessary. The authors have tried to quantify the contributions of CAI analysing the literature referenced in MEDLINE from 1989 to 1992. On the 470 papers indexed with the key-word "Computer Assisted Instruction", 56 studies take evaluation into account. Only 26, that is 5.5%, presented a clear and explicit methodology of evaluation. On the 26 studies, 16 were considered with positive result and among these, 6 presented a statistical significance. The conditions and the criteria of the evaluation studies do not permit a meta analysis. Is is necessary to develop standardized evaluation criteria to estimate the quantitative and qualitative impact of the CAI technics on the educational process and their own pedagogical contribution.

Computer-Assisted Instruction↗

Importance of mevalonate-derived products in the control of HMG-CoA reductase activity and growth of human lung adenocarcinoma cell line A549.

HMG-CoA reductase catalyzes the synthesis of mevalonate, a crucial intermediate in the biosynthesis of cholesterol and non-sterol isoprenoid compounds essential for cell growth. The HMG-CoA reductase activity of the A549 tumor cell line is higher than that of normal human fibroblasts. This deregulation in mevalonate needs was not due to an alteration in the activated state of the enzyme by short-term regulation. We show that the HMG-CoA reductase in A549 cell line was subject to a multivalent feedback control. A high fraction (40%) of the reductase activity was devoted to non-sterol products. In contrast, normal fibroblasts had only 15-20% of the reductase activity that generated non-sterol products. We also show that cholesterol and at least one of the non-sterol products are necessary for optimal cell growth of A549 cells. Our data strongly suggest that A549 cells produce more non-sterol substances which may be related to increased requirements of mevalonate for upregulated cell growth.

Adenocarcinoma↗

Biodistribution study of 99mTc-labeled LDL in B16-melanoma-bearing mice. Visualization of a preferential uptake by the tumor.

Since there is strong evidence of a preferential LDL accumulation in tumor cells, LDL might be of interest for tumor imaging. We have tested the ability of 99mTc-LDL in tumor imaging with B16-melanoma-bearing mice as a model for further applications in human studies. The LDL fixation rate was higher with 99mTc-labeled LDL than with 125I labeled LDL. Since technetium-99m remains trapped in the cells, 99mTc-LDL is a well-adapted radioligand because of information given by this radiotracer on the receptor metabolism. We observed that, at early growth stages, the tumor took up the LDL at a maximal rate, suggesting differences in cholesterol metabolism as a function of tumor growth. Accumulation of label in the tumor area was perfectly observable in tumor-bearing mice on scintigraphic images. Computerized quantification of the regions of interest (as well as biodistribution studies including killing of the animals) showed a 1.81-fold increase in uptake by the tumor as compared to the liver and a 28-fold increase as compared with corresponding normal tissue (muscle of the left leg) at day 8 of tumor growth. These data give strong support to the value of this non-invasive method in visualizing and quantifying the tissue LDL uptake in vivo, including the precise information provided by nuclear scintigraphy on the distribution of the radiolabeled LDL in the different tissues. 99mTc-LDL could be an efficient tool for further diagnostic or therapeutic exploration in cancer patients.

Animals↗