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A 5-year-old female cross-breed dog was presented with a 1-month history of progressive changes in the posture of the head and in the gait. At neurological examination the dog showed a central vestibular syndrome lateralized to th...
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A 5-year-old female cross-breed dog was presented with a 1-month history of progressive changes in the posture of the head and in the gait. At neurological examination the dog showed a central vestibular syndrome lateralized to the left. MRI showed a space occupying lesion within the fourth ventricle, characterized by iso- to hypointensity in T1 and hyperintensity in T2 with a heterogeneous contrast uptake. Histologically, a neoplasia composed of meningothelial cells forming compact whorls with slight atypia, and stellate cells delimitating microcysts containing eosinophilic fluid was observed. Neoplastic cells were positive for vimentin and negative for GFAP and FVIII. A diagnosis of intraventricular microcystic meningioma was achieved. Intraventricular meningiomas in dogs are rarely encountered and reports of meningiomas within the fourth ventricle have not yet been described. Although choroid plexus tumor is the most frequent neoplasia localized in the fourth ventricle, intraventricular meningioma should be included in the differential diagnoses.
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The intermediate filament protein vimentin plays a key role in cell signaling and stress sensing, as well as an integrator of cytoskeletal dynamics. The vimentin monomer consists of a central rod-like domain and intrinsically diso...
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The intermediate filament protein vimentin plays a key role in cell signaling and stress sensing, as well as an integrator of cytoskeletal dynamics. The vimentin monomer consists of a central rod-like domain and intrinsically disordered head and tail domains. Although the organization of vimentin oligomers in filaments is beginning to be understood, the precise disposition of the tail region remains to be elucidated. Here we observed that electrophilic stress-induced condensation shielded vimentin from recognition by antibodies against specific segments of the tail domain. A detailed characterization revealed that vimentin tail segments are differentially exposed at distinct subcellular locations, both in basal and stress conditions. The 411–423 segment appeared accessible in all cell areas, correlating with vimentin abundance. In contrast, the 419–438 segment was more scantily recognized in perinuclear vimentin and lipoxidative stress-induced bundles, and better detected in peripheral filaments, where it appeared to protrude further from the filament core. These differences persisted in mitotic cells. Interestingly, both tail segments showed closer accessibility in calyculin A-treated cells and phosphomimetic mutants of the C-terminal region. Our results lead us to hypothesize the presence of at least two distinct arrangements of vimentin tail in cells: an “extended” conformation (accessible 419–438 segment), preferentially detected in peripheral areas with looser filaments, and a “packed” conformation (shielded 419–438 segment), preferentially detected at the cell center in robust filaments and lipoxidative stress-induced bundles. These different arrangements could be putatively interconverted by posttranslational modifications, contributing to the versatility of vimentin functions and/or interactions.
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Abstract Background Immune responses to tissue-restricted self-antigens are thought to play a role in chronic rejection after solid organ transplantation. De novo development of antibodies (Abs) to vimentin have been reported to b...
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Abstract Background Immune responses to tissue-restricted self-antigens are thought to play a role in chronic rejection after solid organ transplantation. De novo development of antibodies (Abs) to vimentin have been reported to be associated with interstitial fibrosis/tubular atrophy after kidney transplant, and it has been suggested that immunoglobulin isotype switching of Abs to vimentin may occur during this process. We aimed to determine the correlation between immunoglobulin isotype switching of Abs to vimentin and development of transplant glomerulopathy (TG) after kidney transplant, and to determine whether citrullinated modification of vimentin is required for de novo anti-vimentin development. Methods Sera were collected from 24 patients with TG (diagnosed on biopsy), 24 matched stable kidney transplant recipients (KTxRs) and 22 normal healthy subjects who did not undergo transplant. Serum vimentin Abs concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Immunoglobulin isotypes of anti-vimentin were determined using isotype-specific Abs conjugated with horseradish peroxidase. Samples were considered positive to vimentin Abs if the values were above mean+2× standard deviations of the levels in the healthy control subjects. Specificities of anti-vimentin for mutated citrullinated vimentin and anti-mutated citrullinated vimentin were measured by ELISA. Results In this retrospective analysis of 24 KTxRs with TG, 16/24 (67%) patients with biopsy-proven TG developed Abs to vimentin (645±427ng/ml). In contrast, only 4/24 (17%) stable KTxRs had detectable Abs to vimentin (275±293ng/ml; p=0.001). Of the patients with TG, 15/24 (63%) developed Abs to vimentin of IgG isotype (572±276ng/ml), whereas only 6/24 (25%) stable KTxRs (310±288ng/ml) had anti-vimentin of IgG isotype (p=0.002). However, no significant difference was noted in the concentration of IgM isotype anti-vimentin between KTxRs with TG (9/24 [38%], 407±401ng/ml) and stable KTxRs (5/24 [21%], 348±439ng/ml; p=0.631). The serum concentration of Abs specific for the mutated form of citrullinated vimentin was not significantly different between KTxRs with TG and stable KTxRs. Conclusions Patients with biopsy-proven TG demonstrated significantly increased levels of anti-vimentin Abs of the IgG isotype compared with stable KTxRs. Anti-vimentin in stable KTxRs was primarily of IgM isotype. Therefore, the observed isotype switching of anti-vimentin from IgM to IgG isotype strongly suggests ongoing immune responses to vimentin in KTxRs diagnosed with TG. Furthermore, as opposed to patients with rheumatoid arthritis (who develop immune responses primarily to citrullinated vimentin), KTxRs diagnosed with TG developed immune responses to non-citrullinated vimentin, suggesting that modification of vimentin protein via citrullination is not required for the de novo anti-vimentin response seen in patients with TG. Highlights ? De Novo developed anti-vimentin Abs was increased in KTxRs diagnosed with TG. ? Isotype switching of anti-vimentin Abs from IgM to IgG are associated with development of TG. ? IgG subclasses IgG1 and IgG2 are significantly increased in KTxRs with TG. ? MCV and Abs to mutated vimentin levels in KTxRs with TG and in stable KTxRs were similar.
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The distribution patterns of desmin and vimentin were determined in Zavot cattle skin using standard immunohistochemical techniques Skin samples were collected from the different regions of the bodies Vimentin-immunoreactivity was...
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The distribution patterns of desmin and vimentin were determined in Zavot cattle skin using standard immunohistochemical techniques Skin samples were collected from the different regions of the bodies Vimentin-immunoreactivity was observed in the cells of subepidermal region, in the myoepithelial cells surrounding sebaceous and sweat glands, in the fibroblast, smooth muscle, endothelial cells of vessels and some hair follicles. Desmin-immunoreactivity was dense in the smooth muscle of arrectores pilorum muscles and bulbus pilorum of the some hair follicles. Desmin and vimentin immunoreactivities were not different among the various regions of Zavot cattle skin.
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A tumour located in the pectoral region and the left front flipper was observed in a 29-year-old female California sea lion (Zalophus californianus) that died following signs of respiratory disease and inappetence. Metastases were...
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A tumour located in the pectoral region and the left front flipper was observed in a 29-year-old female California sea lion (Zalophus californianus) that died following signs of respiratory disease and inappetence. Metastases were present in the lung and adrenal gland. The histological pattern of the tumour was variable. In some areas the tumour consisted of pleomorphic fibroblast-like cells arranged in a storiform pattern, while in other areas it comprised oval or polygonal cells with round to oval nuclei and some bizarre cells arranged in an alveolar pattern. Occasionally, multinucleated giant cells were observed. Immunohistochemically, the neoplastic cells only expressed vimentin. On the basis of the microscopical and immunohistochemical features the tumour was diagnosed as an undifferentiated high-grade pleomorphic sarcoma. This type of neoplasm with disseminated involvement of other organs is rare in all species and has never been reported in California sea lions
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Macrophages have a vital role in the immune system through elimination of cell debris and microorganisms by phagocytosis. The activation of macrophages by tumour necrosis factor-α induces expression of extracellular cell-surface ...
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Macrophages have a vital role in the immune system through elimination of cell debris and microorganisms by phagocytosis. The activation of macrophages by tumour necrosis factor-α induces expression of extracellular cell-surface vimentin and promotes release of this vimentin into the extracellular environment. Vimentin is a cytoskeletal protein that is primarily located in the cytoplasm of cells. However, under circumstances like injury, stress, senescence and activation, vimentin can be expressed on the extracellular cell surface, or it can be released into the extracellular space. The characteristics of this extracellular vimentin, and its implications for the functional role of macrophages and the mechanism of secretion remain unclear. Here, we demonstrate that vimentin is released mainly from the back of macrophage-like cells. This polarisation is strongly enhanced upon macrophage activation. One-dimensional patterned lines showed that extracellular cell-surface vimentin is localised primarily at the back of activated macrophage-like cells. Through two-dimensional migration and phagocytosis assays, we show that this extracellular vimentin enhances migration and phagocytosis of macrophage-like cells. We further show that this extracellular vimentin forms agglomerates on the cell surface, in contrast to its intracellular filamentous form, and that it is released into the extracellular space in the form of small fragments. Taken together, we provide new insights into the release of extracellular cell-surface vimentin and its implications for macrophage functionality.
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Smoking produces substances that activate proinflammatory, prothrombotic and vasoconstrictive mediators via posttranslational carbamylation of proteins. As a new consequence of carbamylation, induction of anti-carbamylated autoant...
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Smoking produces substances that activate proinflammatory, prothrombotic and vasoconstrictive mediators via posttranslational carbamylation of proteins. As a new consequence of carbamylation, induction of anti-carbamylated autoantibodies were observed in rheumatoid arthritis (RA) patients, sometimes prior to onset of the disease. The overall aim of this study was to characterize the reactivity of different isotypes of autoantibodies against carbamylated antigens of vimentin in relation to established rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA) and markers of disease activity in a so far largely uncharacterized population of Latin American (Cuban) patients with RA. Antigenic properties of carbamylated vimentin as well as vimentin peptides were analyzed in 101 patients with RA, 50 disease controls and 51 healthy controls. The diagnostic performance was compared with established commercial ELISA rheumatoid factor, anti-cyclic citrullinated peptide antibodies of second generation (anti-CCP2) and anti-mutated citrullinated vimentin (anti-MCV) antibodies. Prevalence of anti-MCV IgG (86 %), anti-carbamylated vimentin (carbVIM) IgG (77 %) and anti-carbamylated MCV (carbMCV) IgG antibodies (65 %) was higher than the classical RF IgM (60 %) and anti-CCP2 IgG (52 %) in this RA cohort. Of note, smoking status was associated with positive IgG antibody reactivity against CCP2 in 75.0 % and against MCV in 90 % of patients. Furthermore, IgM antibody response against carbMCV and carbVIM was observed in 80 and 90.0 % of smokers, respectively. Due to a high sensitivity of the IgM antibody isotype of anti-carbVIM of 85.2 %, the combination of ACPA with anti-carbVIM IgM provided the best diagnostic performance so far achieved in a RA cohort of this ethnic origin. We demonstrate a high prevalence of anti-carbVIM antibodies and correlation with smoking in Latin American (Cuban) RA patients. Anti-carbVIM IgM represents an useful marker in ACPA-negative patients and, in combination with ACPA IgG assays, optimizes the strategy for autoantibody testing.
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Mock cataract surgery provides a unique ex vivo model for studying wound repair in a clinically relevant setting. Here wound healing involves a classical collective migration of the lens epithelium, directed at the leading edge by...
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Mock cataract surgery provides a unique ex vivo model for studying wound repair in a clinically relevant setting. Here wound healing involves a classical collective migration of the lens epithelium, directed at the leading edge by an innate mesenchymal subpopulation of vimentin-rich repair cells. We report that vimentin is essential to the function of repair cells as the directors of the wound-healing process. Vimentin and not actin filaments are the predominant cytoskeletal elements in the lamellipodial extensions of the repair cells at the wound edge. These vimentin filaments link to paxillin-containing focal adhesions at the lamellipodial tips. Microtubules are involved in the extension of vimentin filaments in repair cells, the elaboration of vimentin-rich protrusions, and wound closure. The requirement for vimentin in repair cell function is revealed by both small interfering RNA vimentin knockdown and exposure to the vimentin-targeted drug withaferin A. Perturbation of vimentin impairs repair cell function and wound closure. Coimmunoprecipitation analysis reveals for the first time that myosin IIB is associated with vimentin, linking vimentin function in cell migration to myosin II motor proteins. These studies reveal a critical role for vimentin in repair cell function in regulating the collective movement of the epithelium in response to wounding.
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Japanese encephalitis virus (JEV), a mosquitoborne flavivirus, causes acute encephalitis with high mortality in humans. We used a pair of virulent (RP-9) and attenuated (RP-2ms) variants of JEV to pull down the cell surface molecu...
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Japanese encephalitis virus (JEV), a mosquitoborne flavivirus, causes acute encephalitis with high mortality in humans. We used a pair of virulent (RP-9) and attenuated (RP-2ms) variants of JEV to pull down the cell surface molecules bound with JEV particle; their identities were revealed by LC-MS/MS analysis. One major protein bound with RP-9 and weakly with RP-2ms was identified as the intermediate filament protein vimentin. Infection of RP-9 but not that of RP-2ms was blocked by anti-vimentin antibodies and by recombinant-expressed vimentin proteins. Knockdown of vimentin expression reduced the levels of viral binding and viral production of RP-9, but not that of RP-2ms. The different vimentin dependency for JEV infection could be attributed to the major structural envelope protein, as the recombinant RP-9 with an E-E138K mutation became resistant to anti-vimentin blockage. Furthermore, RP-2ms mainly depended on cell surface glycosaminoglycans for viral binding and it became vimentin-dependent only when binding to glycosaminoglycans was blocked. Thus, we suggest that vimentin contributes to virulent JEV infection and might be a new target to intervene in this deadly infection.
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Hyperkinetic Jak2 tyrosine kinase signaling has been implicated in several human diseases including leukemia, lymphoma, myeloma, and the myeloproliferative neoplasms. Using structure-based virtual screening, we previously identifi...
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Hyperkinetic Jak2 tyrosine kinase signaling has been implicated in several human diseases including leukemia, lymphoma, myeloma, and the myeloproliferative neoplasms. Using structure-based virtual screening, we previously identified a novel Jak2 inhibitor named G6. We showed that G6 specifically inhibits Jak2 kinase activity and suppresses Jak2-mediated cellular proliferation. To elucidate the molecular and biochemical mechanisms by which G6 inhibits Jak2-mediated cellular proliferation, we treated Jak2-V617F expressing human erythroleukemia (HEL) cells for 12 h with either vehicle control or 25 mu M of the drug and compared protein expression profiles using two-dimensional gel electrophoresis. One differentially expressed protein identified by electrospray mass spectroscopy was the intermediate filament protein, vimentin. It was present in DMSO treated cells but absent in G6 treated cells. HEL cells treated with G6 showed both time and dose dependent cleavage of vimentin as well as a marked reorganization of vimentin intermediate filaments within intact cells. In a mouse model of Jak2-V617F mediated human erythroleukemia, G6 also decreased the levels of vimentin protein, in vivo. The G6-induced cleavage of vimentin was found to be Jak2-dependent and calpain-mediated. Furthermore, we found that intracellular calcium mobilization is essential and sufficient for the cleavage of vimentin. Finally, we show that the cleavage of vimentin intermediate filaments, per se, is sufficient to reduce HEL cell viability Collectively, these results suggest that G6-induced inhibition of Jak2-mediated pathogenic cell growth is concomitant with the disruption of intracellular vimentin filaments. As such, this work describes a novel pathway for the targeting of Jak2-mediated pathological cell growth.
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