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Biomedical subjects

F Lefèvre

Publications and source records attributed to F Lefèvre.

At least 19 recordsLinked to original sources

Modulation of collagen metabolism by the nucleolar protein fibrillarin.

Metabolic functions of fibroblasts are tightly regulated by the extracellular environment. When cultivated in tridimensional collagen lattices, fibroblasts exhibit a lowered activity of protein synthesis, especially concerning extracellular matrix proteins. We have previously shown that extracellular collagen impaired the processing of ribosomal RNA (rRNA) in nucleoli by generating changes in the expression of nucleolar proteins and a premature degradation of neosynthesized rRNA. In this study, we have investigated whether inhibiting the synthesis of fibrillarin, a major nucleolar protein with decreased expression in collagen lattices, could mimic the effects of extracellular matrix. Monolayer-cultured fibroblasts were transfected with anti-fibrillarin antisense oligodeoxynucleotides, which significantly decreased fibrillarin content. Downregulation of fibrillarin expression inhibited procollagen secretion into the extracellular medium, without altering total collagen production. No changes of pro1(I)collagen mRNA expression or proline hydroxylation were found. A concomitant intracellular retention of collagen and its chaperone protein HSP47 was found, but no effect on the production of other extracellular matrix macromolecules or remodelling enzymes was observed. These data show that collagen processing depends on unknown mechanisms, involving proteins primarily located in the nucleolar compartment with other demonstrated functions, and suggest specific links between nucleolar machinery and extracellular matrix.

Cells, Cultured↗

Type I IFN modulates the immune response induced by DNA vaccination to pseudorabies virus glycoprotein C.

DNA vaccines have the capacity to induce strong Th1-biased immune responses that are of major importance to providing protection against intracellular pathogens. In the present study we have focused on the role played by type I IFN in immune responses induced after DNA vaccination. Mice lacking the IFNAR1 chain of the type I IFN receptor (IFNAR K/O mice) were immunized with a plasmid encoding glycoprotein C of pseudorabies virus (PRV-gC). After DNA vaccination, wild-type (WT) mice showed features characteristic of Th1 immune responses, such as high IgG2a:IgG1 anti-PRV Ab ratio and antigen-specific IFN-gamma production by spleen cells. In contrast, IFNAR K/O mice showed a significantly lower IgG2a:IgG1 Ab ratio and IFN-gamma production. In addition, the percentage of CD8(+) and B lymph-node cells expressing CD69 after PRV-gC DNA vaccination was lower in IFNAR K/O than in WT mice. These results support a major role played by type I IFN in shaping Th1 immune responses after DNA vaccination. Codelivery of plasmids encoding IL-12 and IL-18 along with the plasmid encoding PRV-gC restored Th1 responses in IFNAR K/O mice.

Animals↗

SWITCH1 (SWI1): a novel protein required for the establishment of sister chromatid cohesion and for bivalent formation at meiosis.

We have characterized a new gene, SWI1, involved in sister chromatid cohesion during both male and female meiosis in Arabidopsis thaliana. A first allele, swi1.1, was obtained as a T-DNA tagged mutant and was described previously as abnormal exclusively in female meiosis. We have isolated a new allele, swi1.2, which is defective for both male and female meiosis. In swi1.2 male meiosis, the classical steps of prophase were not observed, especially because homologs do not synapse. Chromatid arms and centromeres lost their cohesion in a stepwise manner before metaphase I, and 20 chromatids instead of five bivalents were seen at the metaphase plate, which was followed by an aberrant segregation. In contrast, swi1.2 female meiocytes performed a mitotic-like division instead of meiosis, indicating a distinct role for SWI1 or a different effect of the loss of SWI1 function in both processes. The SWI1 gene was cloned; the putative SWI1 protein did not show strong similarity to any known protein. Plants transformed with a SWI1-GFP fusion indicated that SWI1 protein is present in meiocyte nuclei, before meiosis and at a very early stage of prophase. Thus, SWI1 appears to be a novel protein involved in chromatid cohesion establishment and in chromosome structure during meiosis, but with clear differences between male and female meiosis.

Alleles↗

[Drug prescription from the perspective of elderly patients].

INTRODUCTION: Although modern drugs really benefit aged patients, they also entail an increased risk to this population. Elderly people have a particular risk because of using multiple drugs with implies having more adverse reactions. This study aimed to assess elderly patients' relationship with drug prescriptions. METHODS: A descriptive study of a qualitative methods was carried out using semi-structured interviews conducted in an intentional sample of 30 elderly patients living in the urban region of Maringá, Brazil, between February 25 and March 22, 1998. Participants were selected from the Co-Participative Pharmacy Database of the Department of Pharmacy and Pharmacology of the State University of Maringá. The thematic discourse analysis technique was employed for data analysis, using three methodological entities: central idea; key-expressions; and the collective subject's discourse. RESULTS: The average consumption of drugs by this elderly population was 3.6, within a 1-8 interval. The central ideas found in the collective subjects were as follows: I'm able to take them by myself; somebody helps me; I'll take them later; I never forget; there's a need to see the physician; they have never done any harm to me; I'm used to them; sometimes I read it, sometimes I don't; I always manage to buy them; I have already stopped taking them. CONCLUSIONS: More efficient ways of assessing the willingness of elderly patients of complying with the recommended drug therapy and instituting a better drug therapy follow-up must be investigated Further studies of qualitative cut-off should be carried out to understand better the problem and analyze it in depth.

Aged↗

[Contrast-enhanced MRA of the carotid arteries using 0.5 Tesla: comparison with selective digital angiography].

PURPOSE: To assess the feasability, the imaging quality and the effectiveness of contrast-enhanced MRA (CE MRA) using a 0.5 Tesla MR unit in the evaluation of internal carotid artery (ICA) stenosis. Materials and Methods. 29 patients underwent CE MRA and selective digital substraction angiography (DSA). All data were reviewed in a blinded fashion by 2 independant observers. Imaging quality was graded as good, moderate but interpretable, and insufficient. Stenosis was graded according to the NASCET classification from grade 1 to 4, with the following thresholds:<30%,<70%,<99% and occlusion. Inter and intra- observer agreement was evaluated using the kappa index. RESULTS: Imaging quality was good for 79 arteries, moderate for 24 and insufficient for 13 (k MRA=0.72 and 0.64 respectively for the right and left ICAs). Interobserver agreement was good with values for right/left ICA of 0.84/0.94, 0.72/0.74 respectively for CE-MRA and DSA. For the comparison between CE MRA and DSA, agreement was also good, with values of 0.74 and 0.64 for both readers. Sensitivity of CE MRA in the detection of hemodynamically significant stenosis (>70%) was of 0.95 and 0.94 and specifity of 0.91 and 0.89 respectively for reader n degrees 1 and reader n degrees 2. CONCLUSION: CE MRA using a 0.5T MR unit is a valuable technique in the evaluation of ICA stenosis.

Adult↗

[Imaging of the intrahepatic biliary tree with thick slice MR cholangiography].

PURPOSE: To assess the value of single shot fast spin echo MR sequence (SS-FSE) in the evaluation of the normal and pathologic intrahepatic biliary tree. MATERIAL AND METHODS: 418 consecutive patients (457 examinations) referred for clinical and/or biological suspicion of biliary obstruction underwent MR cholangiopancreatography (MRCP). All patients were imaged with a Signa 1.5 T GE MR unit, with High Gradient Field Strength and Torso Phased Array Coil. Biliary ducts were imaged with SS-FSE sequence, coronal and oblique coronal 20 mm thick slices on a 256 x 256 matrix. Total acquisition time was 1 second. Source images were reviewed by two radiologists blinded to clinical information. In case of disagreement, a third radiologist's opinion was requested. In all cases, MRCP results were compared with direct biliary tract evaluation, other imaging studies and clinical and biological follow-up. RESULTS: In all cases, MRCP produced high quality images. Numerous branch of division were observed although the peripheral intrahepatic ducts were well seen in more than 90% in an area 2 cm below the capsule. The number of division was statistically higher when mechanical obstruction was present. Intrahepatic calculi or peripheral cholangiocarcinoma were well detect by MRCP. For the detection of cholangitis, MRCP sensitivity was 87.5% but the positive predictive value was only 57.7% because of a high number of false positive. The diagnosis of primary sclerosing cholangitis must be made only on strict criteria and slightly dilated peripheral bile ducts unconnected to the central ducts in several hepatic segments were a characteristic MR sign of primary sclerosing cholangitis. CONCLUSION: MRCP can be proposed as a first intention imaging technique for the evaluation of intrahepatic ducts.

Adolescent↗

[Ultrasound contrast agents].

Ultrasound contrast agents are introducing a new vision to ultrasonography. The increase in the Doppler signal intensity improves difficult examinations. Technical failures in the study of transcranial, liver and renal vessel might be rescued with the injection of these new compounds. The introduction of specific image sequences such as harmonic imaging and pulse inversion imaging allows detection of parenchymal enhancement in liver and renal examinations. The injection of ultrasound contrast agents also provides dynamic quantitative information to develop functional imaging. However, it is mandatory to understand the interaction with the ultrasound beam in order to optimise their use and define the adequate ultrasound sequence.

Artifacts↗

[Bladder candidosis after renal transplantation: contribution of ultrasonography].

Candidosis of the ureter and the bladder is an infrequent complication after renal transplantation. A case occurring early after kidney transplantation is reported in a patient presenting with candiduria. Ultrasound examination detected several fungal bezoars, presenting as a proliferating, avascular lesions, located within the ureter and the bladder. It allowed to demonstrate the rapid extension of lesions, in spite of a medical treatment, leading to a successful endoscopic removal of fungus balls.

Aged↗

[Quid?].

Explore the source record for details and available documents.

Adult↗

[Upper urinary tract MRI].

New MRI modalities today available allow exploration of many kidney diseases. Main developments have been made in the diagnosis of small tumors and tumoral extension of huge masses. The other important way of application is MR urography which perfectly show the dilated urinary tract in few seconds. Their potential application are for renal insufficiency, allergic reaction to iodine contrast media and in cases of contra indication to ionised radiations. It is a complementary sequence to assess the urinary tract in pelvic exploration. The evaluation of kidney function will be possible in the near future.

Contraindications↗

Enhanced protective response and immuno-adjuvant effects of porcine GM-CSF on DNA vaccination of pigs against Aujeszky's disease virus.

This study was conducted to investigate whether the co-delivery of DNA encoding porcine cytokines would enhance a protective immune response in pigs to a Pseudorabies virus (PRV; or Aujeszky's disease virus) DNA vaccine. Aujeszky's disease in pigs results in respiratory and nervous symptoms with important economic losses. To evaluate cytokine effects, eukaryotic expression vectors were constructed for porcine GM-CSF, IL-2 and IFN-gamma. cDNA for each of these cytokines was inserted under the control of a CMV promoter in the pcDNA3 plasmid and cytokine expression was confirmed after DNA transfection in various mammalian cell cultures by bioassays (GM-CSF and IL2) and ELISA (IFN-gamma). Pigs were vaccinated by single intramuscular injection with plasmid DNA encoding PRV gB and gD along with various combinations of cytokine plasmid constructs. Pig serum was tested for the production of antibody by isotype specific anti-PRV ELISA. Pigs were then challenged with the highly virulent PRV strain NIA3 on day 21 after vaccination. The survival and growth rate of pigs were monitored for seven days after the viral challenge. The co-administration of GM-CSF plasmid increased the immune response induced by gB and gD PRV DNA vaccine. This immune response was characterized by an earlier appearance of anti-PRV IgG2, a significantly enhanced anti-PRV IgG1 and IgG2 antibody response, a significantly decreased and shortened viral excretion in nasal swabs and an improved protection to the viral challenge. In contrast, the co-administration of porcine IL-2 or IFN-gamma had no adjuvant effects. Our results thus demonstrate for the first time that the application of porcine GM-CSF gene in a DNA vaccine formulation can exert immuno-adjuvant and protective effects with single vaccination in the natural host pig against Aujeszky's disease.

Adjuvants, Immunologic↗

[Computed tomography study of the sigmoid colon: discriminating diagnostic criteria and interobserver correlations].

PURPOSE: To assess the value of pericolonic findings at CT in the evaluation of the sigmoid colon. MATERIALS AND METHODS: A total of 210 CT examinations were retrospectively reviewed by 3 blinded radiologists. Data was analyzed to determine the interobserver correlation and the value of pericolonic and colonic wall findings in diagnosis of sigmoid colon pathology. RESULTS: The interobserver correlation for pericolonic findings was equal to or superior to that for colonic wall findings. The presence of abnormal pericolonic fat was the most sensitive (88%) and specific (93%) sign to differentiate a diseased sigmoid colon from a normal one or from sigmoid diverticulosis. Wall-thickening was less sensitive (82%) and specific (76%). Findings suggesting malignancy over diverticulitis included acute zone of transition, focal fatty infiltration, and lymph nodes. Symmetrical and circumferential wall thickening, target-like enhancement, and local fatty proliferation were findings suggesting colitis over diverticulitis. Wall thickening more than 15 mm, involvement of 15 cm or less, asymmetrical involvement, acute zone of transition, and homogeneous or heterogeneous enhancement were findings suggesting malignancy over colitis. CONCLUSION: To render a diagnosis, the evaluation of the fat infiltration must prevail on the parietal thickening appreciation.

Adipose Tissue↗

[Marijuana, health, disease, and freedom: analysis of an Internet forum].

This paper takes a Health Education perspective to analyze a debate forum on the Brazilian Internet site entitled "Universo On-Line", in which the following questions were addressed: "Do you believe that marijuana is harmful to one's health?" "In your opinion, should marijuana use be decriminalized?" By applying qualitative discourse analysis techniques to responses from the forum, we were able to identify six main types of discourse, reflecting the opinions of six "collective subjects" concerning drugs, health, disease, and freedom and existing as social representations in the current Brazilian collective imagination. Research on these social representations allows one to establish criteria for intervention in the field of Health Education.

Alcoholism↗

Decreased number of nucleolar organizing regions in collagen lattice cultured fibroblasts.

Dermal fibroblasts cultivated in tridimensional matrices (lattices) of collagen exhibit a very low metabolic activity, and a low protein synthesis in particular. We have previously shown that ribosomal RNA content and half-life were decreased in collagen lattice cultured fibroblasts when compared to monolayer cultured fibroblasts. In this study, we seeded fibroblasts in collagen lattices and investigated the influence of matrix on the number of nucleolar organizing regions. We found that fibroblasts in fully retracted lattices exhibited a significant decrease of 45% (P < 0.001) in the number of nucleolar organizing regions when compared to monolayer cultured fibroblasts. This decrease was correlated to the decrease in ribosomal RNA content. These data suggest that extracellular matrix induces early alterations of synthesis and/or processing of ribosomal RNAs, explaining, at least partly, the resulting low metabolic activity.

Adult↗