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Background
The mitogen-activated protein kinases, MAPKs for short, constitute cascades of signalling pathways involved in the regulation of several cellular processes that include cell proliferation, differentiation and motility. They also intervene in neurological processes like fear conditioning and memory. Since little remains known about the MAPK-Activated Protein Kinase, MAPKAPK5, we constructed the first MAPKAPK knockin mouse model, using a constitutive active variant of MAPKAPK5 and analyzed the resulting mice for changes in anxiety-related behaviour. 相似文献4.
Céline Chipoy Martine Berreur Séverine Couillaud Gilbert Pradal Fran?ois Vallette Caroline Colombeix Fran?oise Rédini Dominique Heymann Frédéric Blanchard 《Journal of bone and mineral research》2004,19(11):1850-1861
The effects of OSM on proliferation and differentiation of osteosarcoma and nontransformed osteoblasts were analyzed. OSM downregulates osteoblast markers but induces the glial fibrillary acidic protein by the combined activation of PKCdelta and STAT3, offering new lines of therapeutic investigations. INTRODUCTION: Oncostatin M (OSM) is a multifunctional cytokine of the interleukin-6 family implicated in embryonic development, differentiation, inflammation, and regeneration of various tissues, mainly the liver, bone, and the central nervous and hematopoietic systems. One particularity of OSM relies on its growth inhibitory and pro-differentiating effects on a variety of tumor cell lines such as melanoma, providing arguments for a therapeutic application of OSM. The objective of this study was to analyze the effects of OSM on osteosarcoma cell lines proliferation and differentiation. MATERIALS AND METHODS: Proliferation was analyzed by 3H thymidine incorporation. Differentiation was analyzed by semiquantitative RT-PCR and immunocytochemistry for various markers. Alizarin red S staining was used to evaluate bone nodule formation. Morphological changes were studied by confocal and electron microscopy. Western blotting, kinases inhibitors, and dominant negative STAT3 were used to identified the signaling pathways implicated. RESULTS: OSM inhibits the growth of rat osteosarcoma cell lines as well as normal osteoblasts, in correlation with induction of the cyclin-dependent kinases inhibitor p21WAF1. However, OSM reduces osteoblast markers such as alkaline phosphatase, osteocalcin, and bone sialoprotein, leading to strong inhibition of mineralized nodule formation. This inhibitory effect is restricted to mature osteoblasts and differentiated osteosarcoma because OSM effectively stimulates osteoblast markers and bone nodule formation in early, but not late, bone marrow mesenchymal stem cell (BMSC) cultures. In osteosarcoma cells or BMSC, OSM induces expression of the glial fibrillary acidic protein (GFAP) as well as morphological and ultrastructural changes, for example, elongated shape and bundles of microfilaments in cell processes. Rottlerin (PKCdelta inhibitor), and to a lesser degree UO126 (MEK/ERK inhibitor), prevents the loss of osteoblastic markers by OSM, whereas dominant negative STAT3 prevents GFAP induction. CONCLUSIONS: These results highlight the particular gene expression profile of OSM-treated osteosarcoma cells and BMSCs, suggesting either a osteocytic or a glial-like phenotype. Together with the implication of PKCdelta, ERK1/2, and STAT3, these results offer new lines of investigations for neural cell transplantation and osteosarcoma therapy. 相似文献
5.
The process presented here was designed and developed for study of various cell parameters in electron microscopy photographs and analysis of the location of certain differentiated cell-constituents relative to plasma membrane. It can also be used for many other applications, for example, in metallurgy, petrography and geostrategy. A photograph is analyzed using a plotting table interfaced with a microcomputer. 相似文献
6.
Martin Zeier Jolanta Perz Reinhold P Linke Ugo Donini Rüdiger Waldherr Konrad Andrassy Anthony D Ho Hartmut Goldschmidt 《Nephrology, dialysis, transplantation》2003,18(12):2644-2647
BACKGROUND: High-dose chemotherapy followed by autologous blood stem cell transplantation induces remission of plasma cell dyscrasia in patients with AL amyloidosis. The impact of this treatment on the glomerular amyloid mass is still unknown. METHODS: In the present study, the quantity of the renal amyloid mass before and more than 3 years after high-dose melphalan treatment and autologous blood stem cell transplantation was assessed in two patients. At the time of the second renal biopsy, both patients were in complete remission without detectable serum and urinary monoclonal IgA-lambda and a normal percentage of plasma cells in the bone marrow. RESULTS: In both patients with biopsy-proven AL amyloidosis, urinary protein excretion decreased from 7 g/24 h to <2 g/24 h more than 3 years after autologous blood stem cell transplantation. In contrast, glomerular amyloid deposits persisted, as shown in the second biopsy. CONCLUSION: Despite complete remission of the plasma cell dyscrasia and improvement of glomerular permeability, the amount of glomerular amyloid mass did not regress. 相似文献
7.
Andrea Sagripanti Adamasco Cupisti Ugo Baicchi Marco Ferdeghini Giuliano Barsotti 《International Journal of Clinical & Laboratory Research》1994,24(2):113-116
Summary Intraglomerular fibrin deposition has been implicated as an important pathogenetic mechanism in patients with glomerular diseases
and the nephrotic syndrome. To investigate fibrin formation and degradation in nephrosis, we measured fibrinopeptide A by
radio-immunoassay and D-dimer by enzyme-linked immunosorbent assay in the plasma of 30 consecutive adult patients with the
nephrotic syndrome; in 10 the serum creatinine was more than 2 mg/dl. Both fibrinopeptide A and D-dimer were abnormally elevated
in the majority of nephrotics (P<0.001 vs. healthy controls), providing evidence of increased fibrin generation and lysis “in vivo.” A positive correlation
was found between fibrinopeptide A and D-dimer (correlation coefficient 0.64,P<0.001), suggesting a close relationship between fibrin formation and degradation. Calcium heparin, administered to 12 nephrotics,
caused a marked decrease in plasma fibrinopeptide A, due to a reduction of in vivo thrombin activity. As enhanced thrombin
activity can favor fibrin deposition within the renal parenchyma, as well as vascular complications, it is reasonable to assume
that an antithrombotic treatment aimed at controlling thrombin generation may ameliorate the natural history of nephrosis. 相似文献
8.
Carlo Piccinni Chiara Sacripanti Elisabetta Poluzzi Domenico Motola Lara Magro Ugo Moretti Anita Conforti Nicola Montanaro 《European journal of clinical pharmacology》2010,66(2):199-206
Aim
The aim of the present study was to collect and compare cases of drug-induced PML in order to contribute to the debate about the role of the underlying diseases and/or drug immunosuppression in PML occurrence. 相似文献9.
Onelio Geatti Brahm Shapiro Pier Giuseppe Orsolon Gianni Proto Ugo Paolo Guerra Francesco Antonucci Daniele Gasparini 《European journal of nuclear medicine and molecular imaging》1994,21(1):17-22
Technetium-99m methoxyisobutylisonitrile (MIBI), like thallium-201, has recently been introduced as a myocardial perfusion agent and is now also showing very promising results in parathyroid scintigrapy. The results of 201Tl/99mTc-pertechnetate and 99mTc-MIBI/99mTc-pertechnetate subtraction scintigraphy, ultrasonography and computed tomography are presented in a series of 43 patients operated on for hyperparathyroidism. All four imaging modalities were confirmed to be reliable, scintigraphy being the most accurate. Sensitivities ranged from 81% to 95%, that of 99mTc-MIBI being the highest. Moreover this tracer, which has more favourable physical and also biochemical properties, yielded images of superior quality. This allowed localization of the lesion by visual inspection only in as many as 86% of the patients with positive 99mTc-MIBI/99mTc-pertechnetate subtraction scintigraphy. We believe that the higher sensitivity, superior image quality and lower cost of 99mTc-MIBI imaging will make 99mTc-MIBI the new radiopharmaceutical of choice for parathyroid scintigraphy (when one takes into account the stability of labelling with large activities it is possible to perform three or four cardiac studies together with one parathyroid scintigraphic examination using one lyophililzed vial). 相似文献
10.
Giovanni Perego Gabriele Lugli Ugo Pedretti Giuseppe Allegra 《Macromolecular chemistry and physics.》1988,189(11):2687-2701
The crystal structure of iodine/trans-polyacetylene complexes (CHIy)x (y = 0,009, 0,035, 0,17 and 0,30) was investigated by X-ray diffraction analysis of highly oriented samples. An iodine-containing phase (PAI) was observed in all cases, accompanied by residual crystallinity due to pristine polyacetylene (PA) for y < 0,17. A structural model is proposed for PAI, consisting of blocks of iodine-saturated PA (PAIs) and blocks of PA, arranged in a mosaic-like lattice, paracrystalline in character. PAIs, corresponding to (CHI0,40)x, is formed by layers of (CH)x chains alternating with layers containing polyiodide chains, the latter being characterized by ordered stacking of sequentially disordered (I3?-I5?-I3?) groups. I… C non-bonded interactions are identified in the lattice, which may be responsible for the electron transfer from the polymer to the polyiodide anions. Short-range transverse correlation occurs within the polyiodide layers with a resulting quasi-regular two-dimensional lattice of iodines. The iodine and the polymer lattices are incommensurate along c. The model fits the experimental data from an X-ray fibre diagram. A mathematical expression is derived, which allows to evaluate the intensity scattered by the iodine lattice. An approximate expression of the non-equatorial intensity along the ξ reciprocal direction was obtained, which accounts for the modulation of the streaks observed in the fibre pattern. 相似文献