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Biomedical subjects

C Godard

Publications and source records attributed to C Godard.

At least 19 recordsLinked to original sources

Differential effects of inactivated Axin1 and activated beta-catenin mutations in human hepatocellular carcinomas.

Perturbations to the Wnt signaling pathway have been implicated in a large proportion of human hepatocellular carcinomas (HCCs). Activating beta-catenin mutations and loss of function mutations in Axin1 are thought to be functionally equivalent. We examined the Wnt pathway in HCC by comparing the expression of beta-catenin target genes and the level of beta-catenin-dependent transcriptional activation, in 45 HCC tumors and four cell lines. Among these samples, beta-catenin and AXIN1 were mutated in 20 and seven cases, respectively. We found a significant correlation between activated beta-catenin mutations and overexpression of mRNA for the target genes glutamine synthetase (GS), G-protein-coupled receptor (GPR)49 and glutamate transporter (GLT)-1 (P=0.0001), but not for the genes ornithine aminotransferase, LECT2, c-myc and cyclin D1. We also showed that GS is a good immunohistochemical marker of beta-catenin activation in HCC. However, we observed no induction of GS, GPR49 or GLT-1 in the five inactivated Axin1 tumors. Beta-catenin-dependent transcriptional activation in two Axin1-mutated HCC cell lines was much weaker than in beta-catenin-mutated cell lines. Our results strongly suggest that in HCC, contrary to expectation, the loss of function of Axin1 is not equivalent to the gain of function of beta-catenin. Our results also suggest that the tumor suppressor function of Axin1 in HCC may be related to another, non-Wnt pathway.

Axin Protein↗

APRAND programme: an intervention to prevent relapses of anxiety and depressive disorders. First results of a medical health promotion intervention in a population of employees.

OBJECTIVE: The study sought to determine whether an organized health promotion intervention during medical consultations improves the outcome for patients who meet the ICD10 criteria for anxiety or depressive disorders. METHODS: In 2001, physicians used the MINI to screen 9743 employees on sick leave and consulting physicians in 21 medical centres of a large company. A health promotion intervention was implemented in eight "active" centres. It took place immediately after diagnosis and consisted of explaining the disorders, delivering the test results and leaflets based on WHO recommendations, and advising patients to consult their personal physician, psychiatrist or occupational physician, if necessary. Its effectiveness, evaluated by symptom severity and outcome over 1 year, was assessed by comparing the eight active centres to 13 control centres (without the intervention). RESULTS: Disorders were detected among 10.6% of the subjects, 29.4% of whom had no previous diagnosis of anxiety or depressive disorder. The intervention was associated with a positive effect on the 6-week and 6-month HAD scores. Total absence of disorders at 1 year was associated with age, sex, and intervention, among all identified cases (OR=1.53), among those with at least one anxiety disorder (OR=1.45), and among those with at least one depressive disorder (OR=1.40). CONCLUSION: Combining detection with organized provision of information including printed material improves patients' outcome and physicians' diagnostic abilities.

Adult↗

International dissemination of a high virulence rabbit Staphylococcus aureus clone.

High virulence rabbit Staphylococcus aureus strains cause chronic and spreading problems of mastitis, pododermatitis and subcutaneous abscesses on rabbit flock level, whereas infections with low virulence strains are limited to individual rabbits. In the present report, 13 high virulence rabbit S. aureus strains, selected out of a large collection of strains isolated in five European countries between 1983 and 2004, were genotyped using pulsed-field gel electrophoresis, spa typing, multilocus sequence typing (MLST) and accessory gene regulator (agr) group typing. Two low virulence rabbit S. aureus strains were also included in the study. The results indicate the clonal origin of high virulence rabbit S. aureus strains present in Europe. Furthermore, the results of MLST and spa typing form a basis for international epidemiology of rabbit S. aureus strains, as these DNA sequence-based typing techniques can easily be used for intercentre comparisons.

Animals↗

New phage type among methicillin-resistant Staphylococcus aureus associated with a local outbreak in Belgium during 2002.

In total, 150 methicillin-resistant Staphylococcus aureus (MRSA) isolates collected during 2002 from a general Belgian hospital were phage-typed at routine test dilution x 100. The majority (45%) belonged to phage group (J)*, while 10% were classified as a new phage type 29/(42E)/54/(D11)*. The isolates belonging to this new type carried the aac(6')-aph(2'') and the aph(3') aminoglycoside resistance genes and showed high-level resistance to oxacillin. Molecular typing revealed that they belonged to the multiresistant clonal pulsed-field gel electrophoresis (PFGE) type D8. PFGE group D, characterised as genotype ST228-MRSA-I, has been present in Belgian hospitals since 1999.

Bacteriophage Typing↗

A change in Belgian epidemic methicillin-resistant Staphylococcus aureus phage types in 2000: phenotypic and genotypic characterization of isolates from a general hospital.

During 2000, new methicillin-resistant Staphylococcus aureus (MRSA) epidemic phage types became preponderant in Belgium. In the present study, phenotypic and genotypic characteristics of 130 MRSA isolates from a general Belgian hospital were investigated. The MRSA nature of the isolates was confirmed by coagulase test, oxacillin screen plate test and detection of the mecA gene by polymerase chain reaction. Phage typing categorized the MRSA strains into two main groups: the [O]* types and the [J]* types. SmaI macrorestriction analysis by pulsed-field gel electrophoresis gave the same pulsotype in the majority of strains. All strains of the [O]* and [J]* groups, except one, belonged to this pulsotype. Aminoglycoside-modifying-enzyme genes could only be detected in a minority of strains. Although the epidemic phage types of the mid-1990s appear to have been supplanted by the [O]* and [J]* groups, the MRSA population examined showed a remarkably uniform profile corresponding to the previous major clone B.

Adult↗

Liver-targeted disruption of Apc in mice activates beta-catenin signaling and leads to hepatocellular carcinomas.

Although inappropriate activation of the Wnt/beta-catenin pathway has been implicated in the development of hepatocellular carcinoma (HCC), the role of this signaling in liver carcinogenesis remains unclear. To investigate this issue, we constructed a mutant mouse strain, Apc(lox/lox), in which exon 14 of the tumor-suppressor gene adenomatous polyposis coli (Apc) is flanked by loxP sequences. i.v. injection of adenovirus encoding Cre recombinase (AdCre) at high multiplicity [10(9) plaque-forming units (pfu) per mouse] inactivated the Apc gene in the liver and resulted in marked hepatomegaly, hepatocyte hyperplasia, and rapid mortality. beta-Catenin signaling activation was demonstrated by nuclear and cytoplasmic accumulation of beta-catenin in the hepatocytes and by the induction of beta-catenin target genes (glutamine synthetase, glutamate transporter 1, ornithine aminotransferase, and leukocyte cell-derived chemotaxin 2) in the liver. To test a long-term oncogenic effect, we inoculated mice with lower doses of AdCre (0.5 x 10(9) pfu per mouse), compatible with both survival and persistence of beta-catenin-activated cells. In these conditions, 67% of mice developed HCC. beta-Catenin signaling was strongly activated in these Apc-inactivated HCCs. The HCCs were well, moderately, or poorly differentiated. Indeed, their histological and molecular features mimicked human HCC. Thus, deletion of Apc in the liver provides a valuable model of human HCC, and, in this model, activation of the Wnt/beta-catenin pathway by invalidation of Apc is required for liver tumorigenesis.

Animals↗

Ten years phage-typing of Belgian clinical methicillin-resistant Staphylococcus aureus isolates (1992-2001).

Gradual changes have been observed in the phage-types of methicillin-resistant Staphylococcus aureus (MRSA) isolates from Belgian hospitals. A total of 6551 isolates, collected in 93 Belgian hospitals over 10 years (1992-2001), was examined. A decreasing incidence of the main early Belgian epidemic phage-types ([A], [B], [H]*, Jo*) was observed. Since 1997 and 2000, a new series of phage-types ([Hv]*, [J]*, [O]*), which were likely related to the previous group [H]*, have been noted. The general trends were confirmed in two particular hospitals. Local epidemic and/or endemic phage-types were also encountered.

Aged↗

Is pulsed-field gel electrophoresis a valuable tool to identify nosocomial cases of Legionella pneumophila disease?

Pulsed-field gel electrophoresis (PFGE) was used to type Legionella pneumophila isolates collected from the water systems of Besançon University Hospital and other hospitals in Franche-Comté region between January 2001 and December 2002 and compare them with patient isolates to identify hospital-acquired pneumonia. Genomic DNA was digested with SfiI and subjected to PFGE in a clamped, homogeneous electric field apparatus. Two of 11 Legionella infections were hospital-acquired. Both were with the same type, also present in the ward water. An environmental strain isolated from the water system of Vesoul Hospital, exhibited DNA pattern 6, also found in three patients with community-acquired pneumonia, who had never been in Vesoul hospital and lived in different towns located >60 km away. Patient 11, who lived in Besançon, was infected with a DNA pattern 12 strain. This patient had never been to the Besançon swimming pool, from which a similar strain was collected. Subtype matching of patient and environmental isolates should be interpreted with caution, and it is important to combine a molecular typing method with sound epidemiological data to ensure that the most stringent criteria are used to determine whether a hospital-reservoir is responsible for nosocomial pneumonia.

Cross Infection↗

[Domestic, leisure activity and sports-related accidents in an active population: perspectives for prevention by health education].

Resulting from the findings of epidemiological surveys on non-work-related accidents conducted in 1996 and 1997 among employees covered by a special health insurance programme for gas and electric company workers, this article identifies avoidable and recurrent accidents that may be targeted by health education interventions. It also emphasizes the importance of considering the needs expressed by the population at large when developing the themes for information campaigns. Finally, it proposes a sequel to the "survey-action plan" released in 1996. The proposed follow-up takes into account the occupational setting and its professionally-related barriers, and includes delivering prevention messages, conducting in-house experimental health promotion activities (and evaluating them), and disseminating intermediary external campaigns aimed at impeding avoidable accidents among adults. The preventable accidents identified in this study are not specific to the employed population group studied here; they may also be targeted by more general health promotion programmes and interventions.

Accident Prevention↗

Socioeconomic, demographic, occupational, and health factors associated with participation in a long-term epidemiologic survey: a prospective study of the French GAZEL cohort and its target population.

The purpose of this paper is to examine personal and health factors, both at the beginning of the study and thereafter, associated with participation in the GAZEL cohort, set up in 1989 in a large French company. The authors used logistic regression to analyze the associations between participation and data available for both participants (n = 20,093) and nonparticipants (n = 24,829). Higher participation was associated with male sex, marriage, children, managerial status, and residence in particular regions. Among men, lower participation was associated with sick leave in the year before recruitment and afterwards. During follow-up, participation was negatively associated with several groups of diseases, especially those associated with alcohol consumption. The risk of upper respiratory and digestive tract and lung cancer during follow-up was higher among nonparticipants. The same phenomenon occurred among women, but less markedly, for cancers of the breast and genital organs. During follow-up, mortality among men was higher among nonparticipants, especially for alcohol-related diseases. The association among women was less strong. Among men, but not among women, diseases caused by alcohol, smoking, or dangerous behavior were the primary reason for the health differences observed between participants and nonparticipants. Overall, the most important determinants of participation were cultural factors and lifestyle behaviors.

Absenteeism↗

On ring carbomers of cyclobutane, cyclopentane, and cyclodecane and cyclization reactions through bis(alkynyl-propargyl) coupling.

A copper-mediated procedure for terminal alkynyl-propargyl coupling has been applied to "skipped" bis-terminal undecatetrayne and 1,4-bis(pseudo)halobut-2-ynes with the aim of preparing ring carbomers of representative strained and loose cycloalkanes, namely [N]pericyclynes. Two unprecedented, cyclic. "skipped" polyynes with CH2 vertices have been isolated as mixtures of diastereoisomers: an isomer 1b and a dimer 2a of [5]pericyclyne 1a. The isomer 1b is a cyclotetrayne with an exocyclic allene function resulting from a unique formal SN process. Its structure has been established by 1H/13C HMQC and HMBC two-dimensional NMR analysis. According to density functional theory calculations, it is about 6 kcalmol(-1) more stable than [5]pericyclyne (1a). Compound 1b can also be regarded as a C13-relaxed [4]pericyclyne, a long sought "skipped" C12 tetrayne. The dimer 2a is a C30 ring that results from a formal SN process. It is a stable ring carbomer of cyclodecane, that is, a [10]pericyclyne, with four CH2 vertices.

Journal Article↗

Ultrastructural study of the FVB/N mouse thymus: presence of an immature epithelial cell in the medulla and premature involution.

FVB/N inbred mice have been widely used to generate a variety of transgenic lines, but their physiology and especially their immunological characteristics are poorly documented. We therefore studied the ultrastructure of the thymus and the distribution of thymocyte subpopulations in FVB/N mice at several ages. In young FVB/N mice the stromal microenvironment exhibits the three types of epithelial cells and the two types of bone-marrow derived cells (macrophages and interdigitated cells) previously described in other strains of mice. Moreover, in the thymic medulla of young FVB/N mice, a fourth cell type with the morphological characteristics of an immature epithelial cell was present in relatively high number. Furthermore, thymocyte subpopulations distribution shows an earlier thymocyte maturation than in other strains. Finally, changes associated with thymic involution were observed about 5 months earlier than in many other mouse strains. Our results demonstrated that the FVB/N strain has a specific immunological status.

Animals↗

[ A registry of ischaemic cardiopathies among active workers at Electricité de France-Gaz de France. Program development and first results].

BACKGROUND: The social security department of the French national electric and gas company has established an ischemic heart disease register among a population of about 140 000 employees based on sick leaves as well as deaths recorded with their medical cause. METHODS: History of the illness, medical tests and treatments were known retrospectively from the consulting physicians of the company. Acute coronary events recorded were: inaugural angina pectoris, myocardial infarction, sudden coronary death and fortuitous discovery of coronary disease. RESULTS: A first study conducted on employees during the 1993-1995 period showed infarction incidence age rates similar to those estimated from the French MONICA registers for France as a whole. Regional discrepancies were observed for myocardial infarction rates: Nord-Pas de Calais, Champagne-Ardennes, Lorraine, Franche-Comté and Limousin were at the most elevated risk (SIR=131, 155, 169, 125 and 178 resp). Large variations according to socio-economic status were observed. CONCLUSION: This register will permit studies on the links between socio-economic status at different professional career points and the occurrence of ischemic heart disease and the evaluation of the impact of psychosocial factors such as previous depressive disorders.

Absenteeism↗

Doc'CISMEF: a search tool based on "encapsulated" MeSH thesaurus.

In the year 2000, the Internet became a major source of health information for the health professional and the Netizen. The objective of Doc'CISMeF (D'C) was to create a powerful generic search tool based on an structured information model which â encapsulates' the MeSH thesaurus to index and retrieve quality health resources on the Internet. To index resources, D'C uses four sections in its information model: 'meta-term', keyword, subheading, and resource type. Two search options are available: simple and advanced. The simple search requires the end-user to input a single term or expression. If this term belongs to the D'C information structure model, it will be exploded. If not, a full-text search is performed. In the advanced search, complex searches are possible combining Boolean operators with meta-terms, keywords, subheadings and resource types. D'C uses two standard tools for organising information: the MeSH thesaurus and the Dublin Core metadata format. Resources included in D'C are described according to the following elements: title, author or creator, subject and keywords, description, publisher, date, resource type, format, identifier, and language.

Abstracting and Indexing↗

[Research in general practice. Plea for organized and high quality clinical research by general practice physicians in Switzerland].

The clinical research in the practitioner's office is indispensable for the teaching of the medicine of first recourse. On the basis of the analysis of 109 publications, the authors propose to structure this research under the shape of investigator's networks while guaranteeing an interface between the primary care physicians and the academic specialists. To realise this network, an institutional support is necessary.

Academic Medical Centers↗

Colonisation of rabbits with Staphylococcus aureus after experimental infection with high and low virulence strains.

Four groups of 12 rabbits each were inoculated in the nose with strains with suspected differences in virulence. In the two groups infected with strains from severe outbreaks, belonging to a rabbit-pathogenic biotype-phage type combination, 6-12 rabbits were found positive at the successive bacteriological samplings over a period of 28 days. In the two other groups, infected with strains obtained from rabbitries without a history of staphylococcosis, the number of Staphylococcus aureus positive animals quickly became negative but increased again after 1 week to 1-5 positive animals until the end of the experiment. Two rabbits in each group inoculated with a high virulence strain developed purulent skin lesions, while in the groups inoculated with low virulence strains, all animals remained clinically healthy. Results indicate that colonisation capacity is an important virulence determinant in rabbit staphylococcosis.

Administration, Intranasal↗