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Sophie Le Calvez

Publications and source records attributed to Sophie Le Calvez.

9 recordsLinked to original sources

Subcutaneous microchip-associated tumours in B6C3F1 mice: a retrospective study to attempt to determine their histogenesis.

Fifty-two subcutaneous tumours associated with microchip were collected from three carcinogenicity B6C3F1 mice studies. Two of these 52 tumours were adenocarcinoma of the mammary gland located on the dorsal region forming around the chip. All the other 50 were mesenchymal in origin and were difficult to classify on morphological grounds with haematoxylin-eosin. These sarcomas were investigated using a panel of immunohistochemistry and special stains consisting of desmin, smooth muscle actin (SMA), myogenin, S100, mouse macrophages, phosphotungstic acid haematoxylin (PTAH) and Masson's trichrome (MT). All the sarcomas displayed the same histochemical characteristics and a close immunophenotype, characterized by desmin +/-, SMA+, myogenin--, S100--, mouse macrophages + and PTAH-. These tumours thus appear to have similar histologic-type lineage and designation as sarcomas not otherwise specified (NOS) with a large myofibroblastic component appears today to be more appropriate and it is likely to clarify them in the future with the emergence of new markers.

Animal Identification Systems↗

Hepatitis C in 6,865 patients 65 yr or older: a severe and neglected curable disease?

BACKGROUND: Few data are available on chronic hepatitis C (CHC) in elderly patients. The aim of this study was to compare the features and severity of CHC and the efficacy/safety of antiviral therapy in patients<65, between 65 and 80, and >80 yr old, and to determine the usefulness of biochemical markers (Fibrotest-Fibrosure/ActiTest [FT-AT]) in aged patients. METHODS: This was a retrospective study with two groups of patients: Group 1: prospective cohort including all hepatitis C virus patients from our institution (N=4,182); Group 2: all consecutive patients who had FT-AT performed in France between 2002 and 2004 (N=33,738). RESULTS: A total of 6,865 patients>or=65 yr old was included (Group 1=881, Group 2=5,984). Group 1: patients>or=65 had a longer duration of and a higher age at infection, more genotype 1, and a history of transfusion (p<0.001). Among the 2,169 patients who underwent liver biopsy, bridging fibrosis (F2,F3,F4) was more frequent in patients>or=65 yr old, regardless of the duration of infection. In multivariate analysis, ages at biopsy and at infection were associated with F2,F3,F4. Discovery of CHC by a complication was more frequent in patients>or=65 yr (p<0.001). One hundred seventy patients>or=65 yr received antiviral therapy. A sustained virologic response was obtained in 45% of patients>or=65 yr treated with pegylated interferon/ribavirin. Group 2: At FT, 58% of patients>80 yr, 37% of patients between 65 and 80 yr, and 14% of patients<65 yr (p<0.001) had cirrhosis. Patients>80 yr (43%) with cirrhosis had nonelevated alanine amino transferase (ALT), compared with 31% of patients<65 yr (p<0.001). CONCLUSION: In patients>or=65 yr, CHC is more severe and presents with lower ALT than in younger patients. Treatment is effective. Biochemical markers seem particularly useful as a noninvasive alternative to liver biopsy in this population.

Aged↗

Prospective analysis of discordant results between biochemical markers and biopsy in patients with chronic hepatitis C.

BACKGROUND: The FibroTest and ActiTest are noninvasive biochemical markers of liver injury that are intended for use as alternatives to liver biopsy in patients with chronic hepatitis C. The aims of this study were to assess the quality of biopsy and the prevalence of discordances between biopsy and markers, to identify factors associated with discordances, and to attribute these discordances to either markers or biopsy failure. METHODS: Fibrosis stage and activity grade were prospectively assessed on the same day by a liver biopsy and by markers. On the basis of risk factors for failure and independent endpoints, discordance was classified as being attributable to biopsy or to markers. RESULTS: Only 74 of 537 patients (14%) had a biopsy size > or =25 mm. Discordance was observed in 154 of 537 patients (29%), including 16% for fibrosis staging and 17% for activity grading. Steatosis, an inflammatory profile, and biopsy size were associated with discordance. Discordance was attributable to failure of markers in 13 patients (2.4%) and to biopsy failure in 97 (18%; P <0.001 vs Fibrotest and Actitest), and was nonattributable in 44 patients (8.2%). The most frequent failures attributable to markers were false negatives (1.3%) attributable to inflammation. The most frequent failures attributable to biopsy were false negatives of activity grading (10.1%) and of fibrosis staging (4.5%), both associated with smaller biopsy size and steatosis. False positives of fibrosis staging (3.5%) were associated with fragmented biopsies. CONCLUSION: In this series, the size of liver biopsy is adequate in only a minor proportion (approximately 14%) of patients with chronic hepatitis C. When biopsy and marker results are discordant, a reason can be identified in more than two-thirds of cases and, in those cases, biopsy failure is >7 times more common than diagnostic failure of markers.

Adult↗

Long-term therapy with lamivudine in renal transplant recipients with chronic hepatitis B.

BACKGROUND: Lamivudine is a potent inhibitor of hepatitis B virus (HBV) replication. As other available HBV therapies, its efficacy is hampered by relapse after discontinuation and by the risk of viral breakthrough. A recent study suggests that pre-emptive lamivudine therapy improves survival in HBV renal transplants, but few data are available regarding its long-term use in this population. The clinical features, course and viral mutations associated with the emergence of viral resistance in this population have not been well studied. METHODS: We followed 14 consecutive renal transplant patients treated with lamivudine for chronic hepatitis B. Breakthrough was defined as the reappearance of HBV DNA by hybridization. In patients with breakthrough, lamivudine was always continued and patients were followed up monthly. Mutations associated with viral resistance were determined by sequencing the polymerase encoding gene at the beginning of treatment and at the time of breakthrough. RESULTS: The median duration of treatment was 64.5 months. Resistance to lamivudine appeared in eight patients (57%) after a median duration of treatment of 15 (9-24) months. During a 51 month follow-up after breakthrough, only three of eight patients had a flare-up with alanine aminotransferase levels more than 5 ULN, and no hepatic decompensation was observed. Analysis of HBV sequencing after breakthrough revealed specific resistance mutations in both the B and C domains of the polymerase (rtL180M/M204V, n = 5; rtM204I, n = 2). CONCLUSION: Lamivudine is a safe and effective treatment of active hepatitis B in renal transplant patients. Resistance to treatment is frequent but seems to have little clinical impact over the considered period. In our experience, the YMDD mutation accounts for most cases of virological escape in patients with good compliance.

Adult↗

A novel pathway for MuSK to induce key genes in neuromuscular synapse formation.

At the developing neuromuscular junction the Agrin receptor MuSK is the central organizer of subsynaptic differentiation induced by Agrin from the nerve. The expression of musk itself is also regulated by the nerve, but the mechanisms involved are not known. Here, we analyzed the activation of a musk promoter reporter construct in muscle fibers in vivo and in cultured myotubes, using transfection of multiple combinations of expression vectors for potential signaling components. We show that neuronal Agrin by activating MuSK regulates the expression of musk via two pathways: the Agrin-induced assembly of muscle-derived neuregulin (NRG)-1/ErbB, the pathway thought to regulate acetylcholine receptor (AChR) expression at the synapse, and via a direct shunt involving Agrin-induced activation of Rac. Both pathways converge onto the same regulatory element in the musk promoter that is also thought to confer synapse-specific expression to AChR subunit genes. In this way, a positive feedback signaling loop is established that maintains musk expression at the synapse when impulse transmission becomes functional. The same pathways are used to regulate synaptic expression of AChR epsilon. We propose that the novel pathway stabilizes the synapse early in development, whereas the NRG/ErbB pathway supports maintenance of the mature synapse.

Agrin↗

Image-adaptive deconvolution for three-dimensional deep biological imaging.

Deconvolution algorithms are widely used in conventional fluorescence microscopy, but they remain difficult to apply to deep imaging systems such as confocal and two-photon microscopy, due to the practical difficulty of measuring the system's point spread function (PSF), especially in biological experiments. Since a separate PSF measurement performed under the design optical conditions of the microscope cannot reproduce the true experimental conditions prevailing in situ, the most natural approach to solve the problem is to extract the PSF from the images themselves. We investigate here the approach of cropping an approximate PSF directly from the images, by exploiting the presence of small structures within the samples under study. This approach turns out to be practical in many cases, allowing significantly better restorations than with a design PSF obtained by imaging fluorescent beads in gel. We demonstrate the advantages of this approach with a number of deconvolution experiments performed both on artificially blurred and noisy test images, and on real confocal images taken within an in vitro preparation of the mouse hearing organ.

Algorithms↗

Exploring the living cochlea using confocal microscopy.

To obtain a more integrated view of the cellular behaviour of the cochlea it is essential to observe not only wider regions of the exposed turns but also to visualize structures below the reticular lamina. Using confocal microscopy and in vitro preparations of guinea pig and mouse inner ears, cellular structures within the intact organ of Corti can be visualized at high resolution. The approach thus offers a means to investigate detailed cellular events, e.g. structural reorganization following acoustic overstimulation. Confocal microscope images, although sharper than images acquired using regular light microscopy, are still subject to problems related to light scattering within the optical system and low signal-to-noise ratio. Significant image restoration can, however, be obtained by applying a combination of wavelet denoising techniques and deconvolution algorithms. Future work will focus both on more dynamical cellular events and on new in vivo models where the inner ear is visualized at a better functional state.

Animals↗