12 research outputs found
Correlation between systolic function and presence of myofibroblasts in doxorubicin-induced cardiomyopathy
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A novel interaction between FlnA and Syk regulates platelet ITAM-mediated receptor signaling and function
Filamin A (FlnA) cross-links actin filaments and connects the Von Willebrand factor receptor GPIb-IX-V to the underlying cytoskeleton in platelets. Because FlnA deficiency is embryonic lethal, mice lacking FlnA in platelets were generated by breeding FlnAloxP/loxP females with GATA1-Cre males. FlnAloxP/y GATA1-Cre males have a macrothrombocytopenia and increased tail bleeding times. FlnA-null platelets have decreased expression and altered surface distribution of GPIbα because they lack the normal cytoskeletal linkage of GPIbα to underlying actin filaments. This results in ∼70% less platelet coverage on collagen-coated surfaces at shear rates of 1,500/s, compared with wild-type platelets. Unexpectedly, however, immunoreceptor tyrosine-based activation motif (ITAM)- and ITAM-like–mediated signals are severely compromised in FlnA-null platelets. FlnA-null platelets fail to spread and have decreased α-granule secretion, integrin αIIbβ3 activation, and protein tyrosine phosphorylation, particularly that of the protein tyrosine kinase Syk and phospholipase C–γ2, in response to stimulation through the collagen receptor GPVI and the C-type lectin-like receptor 2. This signaling defect was traced to the loss of a novel FlnA–Syk interaction, as Syk binds to FlnA at immunoglobulin-like repeat 5. Our findings reveal that the interaction between FlnA and Syk regulates ITAM- and ITAM-like–containing receptor signaling and platelet function
Prognostic impact of reduced connexin43 expression and gap junction coupling of neoplastic stromal cells in giant cell tumor of bone
Missense mutations of the GJA1 gene encoding the gap junction channel protein connexin43 (Cx43) cause bone malformations resulting in oculodentodigital dysplasia (ODDD), while GJA1 null and ODDD mutant mice develop osteopenia. In this study we investigated Cx43 expression and channel functions in giant cell tumor of bone (GCTB), a locally aggressive osteolytic lesion with uncertain progression. Cx43 protein levels assessed by immunohistochemistry were correlated with GCTB cell types, clinico-radiological stages and progression free survival in tissue microarrays of 89 primary and 34 recurrent GCTB cases. Cx43 expression, phosphorylation, subcellular distribution and gap junction coupling was also investigated and compared between cultured neoplastic GCTB stromal cells and bone marow stromal cells or HDFa fibroblasts as a control. In GCTB tissues, most Cx43 was produced by CD163 negative neoplastic stromal cells and less by CD163 positive reactive monocytes/macrophages or by giant cells. Significantly less Cx43 was detected in alpha-smooth muscle actin positive than alpha-smooth muscle actin negative stromal cells and in osteoclast-rich tumor nests than in the adjacent reactive stroma. Progressively reduced Cx43 production in GCTB was significantly linked to advanced clinico-radiological stages and worse progression free survival. In neoplastic GCTB stromal cell cultures most Cx43 protein was localized in the paranuclear-Golgi region, while it was concentrated in the cell membranes both in bone marrow stromal cells and HDFa fibroblasts. In Western blots, alkaline phosphatase sensitive bands, linked to serine residues (Ser369, Ser372 or Ser373) detected in control cells, were missing in GCTB stromal cells. Defective cell membrane localization of Cx43 channels was in line with the significantly reduced transfer of the 622 Da fluorescing calcein dye between GCTB stromal cells. Our results show that significant downregulation of Cx43 expression and gap junction coupling in neoplastic stromal cells are associated with the clinical progression and worse prognosis in GCTB
The transverse placement laminoplasty using titanium miniplates for the reconstruction of the laminae in thoracic and lumbar lesion
Molecular Dynamics Study for the Base Sequence Recognition Probe of Nucleic Acids Modified with the Pyrenyl Group
Ventral Intradural Endodermal Cyst in the Cervical Spine Treated With Anterior Corpectomy -Case Report-
A 14-year-old girl who presented with an endodermal cyst manifesting as severe neck and shoulder pain along with vesicorectal disturbances. Cervical magnetic resonance imaging showed a slightly enhanced intradural cyst at the C6-7 level in the ventral side of the spinal canal, with significant dorsal shortening and thinning of the spinal cord. Anterior corpectomy was chosen because of the dorsal effacement of the spinal cord. The cyst wall was subtotally removed to avoid damage to the normal spinal cord. After cyst removal, the iliac bone and an anterior cervical plate were used for anterior fusion. Postoperatively, her pain subsided without neurological deficits. The histological diagnosis was endodermal cyst. The cyst did not recur during a follow-up period of 18 months. Endodermal cysts are rare congenital lesions of the spine lined by endodermal epithelium. The natural history of this lesion is unclear, and the surgical strategy for the approach route and the extent of removal of the cyst wall remain controversial. We suggest that the anterior approach may allow a safer and more effective surgical route for the treatment of ventrally located endodermal cyst compared to the posterior approach.ArticleNEUROLOGIA MEDICO-CHIRURGICA. 51(12):863-866 (2011)journal articl
α-L-Fucosidase from Bombyx mori has broad substrate specificity and hydrolyzes core fucosylated N-glycans
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