Reduced Expression of TCR Zeta Is Involved in the Abnormal Production of Cytokines by Peripheral T Cells of Patients with Systemic Lupus Erythematosus

Accumulating evidence suggests that dysfunction of T cells underlies the pathogenesis of systemic lupus erythematosus (SLE). We revealed that SLE T cells produced an abnormally excessive amount of IFN-γin vitro upon stimulation through TCR, and the expression level of TCR zeta was significantly reduced. The production of IFN-γ by SLE T cells was negatively correlated with the expression level of TCR zeta. This correlation was abolished when the cells were stimulated with TPA and ionomycin, which bypass TCR and introduce signals directly into the cells, but the production of IFN-γ by SLE T cells remained abnormally elevated. Taken together, these data suggest that regulatory mechanisms not only for the expression of TCR zeta but also for the production of IFN-γ were impaired in SLE T cells. These impairments may be responsible for the aberrant responses of SLE T cells and partly involved in the development of SLE

Immunohistochemical Analysis of Oral Dysplasia: Diagnostic Assessment by Fascin and Podoplanin Expression

The aim of this study was to investigate fascin and podoplanin expression in oral dysplasia and carcinoma in situ (CIS) immunohistochemically, and to evaluate their relationship to histopathological diagnosis based on architectural and cytological features. Fascin and podoplanin expression patterns were analyzed immunohistologically in 26 specimens of oral lesions, including benign disease (hyperplasia, papilloma, and others), intraepithelial neoplasia/borderline disease (dysplasia), and malignant disease (CIS, invasive squamous cell carcinoma). Fascin expression was scored into four original categories, and podoplanin expression was scored into five previously established categories. The relationship between the immunohistochemically determined scores of fascin and podoplanin expression and the architectural and cytological features in the hematoxylin-eosin-stained slides was analyzed statistically. The immunostaining scores for fascin and podoplanin were significantly higher in dysplasia and CIS than in benign disease (p=0.0011, p=0.00036), and they were significantly higher in dysplasia than in benign disease (p=0.0087, p=0.0032). In all cases of invasive SCC, fascin was expressed mainly in the cytoplasm of the tumor cells and fascin expression extended from the destruction of the basal layer of the epithelium to the upper layer of the epithelium and podoplanin was expressed in the cytoplasm and membrane of the tumor cells. This was the first report of up-regulation of fascin in oral dysplasia. Our results suggest that it would be helpful for improving the diagnostic accuracy of oral dysplasia and CIS to assess the expression of fascin and podoplanin immunohistochemically

Identification of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible genes in human amniotic epithelial cells

BACKGROUND: Exposure to dioxins results in a broad range of pathophysiological disorders in human fetuses. In order to evaluate the effects of dioxins on the feto-placental tissues, we analyzed the gene expression in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) treated primary cultures of human amniotic epithelial cells. METHODS: Human amniotic epithelial cells were dispersed by trypsin from amniotic membranes and cultured in DME/Ham's F12 medium supplemented with 10% FBS. Two weeks after plating, cells were treated with 50 nM TCDD or DMSO (control), further incubated for 48 hrs, and the gene expression was analyzed by DNA microarray technology and quantitative real-time PCR. RESULTS: Thirty eight TCDD-inducible genes, including cytochromeP4501A1 and cytochromeP4501B1, were identified. One of the remarkable profiles of the gene expression was the prominent up-regulation of interferon-inducible genes. The genes involved in the interferon gene expression and interferon signaling pathways were also up-regulated. Furthermore, the expression of genes related to collagen synthesis or degradation was enhanced by TCDD. CONCLUSION: Using DNA microarray and quantitative real-time PCR analyses, we identified TCDD-inducible genes, including interferon-inducible genes and genes related to collagen synthesis or degradation, in human amniotic epithelial cells

Reduced Expression of TCR Zeta Is Involved in the Abnormal Production of Cytokines by Peripheral T Cells of Patients with Systemic Lupus Erythematosus

Accumulating evidence suggests that dysfunction of T cells underlies the pathogenesis of systemic lupus erythematosus (SLE). We revealed that SLE T cells produced an abnormally excessive amount of IFN-γ in vitro upon stimulation through TCR, and the expression level of TCR zeta was significantly reduced. The production of IFN-γ by SLE T cells was negatively correlated with the expression level of TCR zeta. This correlation was abolished when the cells were stimulated with TPA and ionomycin, which bypass TCR and introduce signals directly into the cells, but the production of IFN-γ by SLE T cells remained abnormally elevated. Taken together, these data suggest that regulatory mechanisms not only for the expression of TCR zeta but also for the production of IFN-γ were impaired in SLE T cells. These impairments may be responsible for the aberrant responses of SLE T cells and partly involved in the development of SLE

In vivo direct reprogramming of glial linage to mature neurons after cerebral ischemia

The therapeutic effect of in vivo direct reprogramming on ischemic stroke has not been evaluated. In the present study, a retroviral solution (1.5-2.0 × 107 /ul) of mock pMX-GFP (n = 13) or pMX-Ascl1/Sox2/NeuroD1 (ASN) (n = 14) was directly injected into the ipsilateral striatum and cortex 3 days after 30 min of transient cerebral ischemia. The reprogrammed cells first expressed neuronal progenitor marker Dcx 7 and 21 days after viral injection, then expressed mature neuronal marker NeuN. This was accompanied by morphological changes, including long processes and synapse-like structures, 49 days after viral injection. Meanwhile, therapeutic improvement was not detected both in clinical scores or infarct volume. The present study provides a future novel self-repair strategy for ischemic stroke with beneficial modifications of the inducer-suppressor balance

A Case of Miller-Fisher Syndrome with Syndrome of Inappropriate Secretion of Antidiuretic Hormone

We report a 72-year-old woman with Miller-Fisher syndrome (MFS) with syndrome of inappropriate secretion of antidiuretic hormone (SIADH). She developed diplopia and unsteady gait a week after an upper respiratory infection. Neurologic examination revealed ophthalmoplegia, ataxia, symmetrical weakness, numbness, and areflexia. She underwent intravenous immunoglobulin therapy. Her serum sodium concentration decreased to 119 mEq/L on day 12. She had low plasma osmolarity (254 mosm/kg), high urine osmolarity (457 mosm/kg), and high urine sodium level (73 mEq/L), while the blood level of antidiuretic hormone was normal. Anti-GD1b immunoglobulin G (IgG), -GQ1b IgG, -GT1a IgG, and -Gal-C IgM antibodies were positive. We diagnosed her with MFS overlapping with SIADH. Four weeks after onset, her symptoms recovered. The elevation of anti-GD1b, -GQ1b, and -GT1a antibodies that recognize disialosyl residue may be pathologically related to SIADH

Late presented congenital myasthenic syndrome with novel compound heterozygous CHRNE mutations mimicking seronegative myasthenia gravis

We found a late presented congenital myasthenic syndrome (CMS) patient with novel CHRNE gene mutations. Although our patient has shown blepharoptosis since youth, fatigable muscle weakness began at age 71. Genetic analysis revealed novel compound heterozygous CHRNE mutations (c.1032+2T>G, c.1306_1307 delGA). His myasthenic symptoms were well managed by oral anti‐cholinesterase drug until he died at 82‐year‐old. The present case showed mild myasthenic symptoms with very late presentation and slow progression. Late presented CMS is often underdiagnosed; therefore, genetic testing is important to distinguish it from other myasthenic disease