Surrounding Gastric Mucosa Findings Facilitate Diagnosis of Gastric Neoplasm as Gastric Adenoma or Early Gastric Cancer.

Background and Aim. It is difficult to master the skill of discriminating gastric adenoma from early gastric cancer by conventional endoscopy or magnifying endoscopy combined with narrow-band imaging, because the colors and morphologies of these neoplasms are occasionally similar. We focused on the surrounding gastric mucosa findings in order to determine how to discriminate between early gastric cancer and gastric adenoma by analyzing the characteristics of the gastric background mucosa. Methods. We retrospectively examined 146 patients who underwent endoscopic submucosal dissection for gastric neoplasm between October 2009 and January 2015. The boundary of atrophic gastritis was classified endoscopically according to the Kimura-Takemoto classification system. Of 146 lesions, 63 early gastric cancers and 21 gastric adenomas were ultimately evaluated and assessed. Results. Almost all gastric adenomas were accompanied by open-type gastritis, whereas 47 and 16 early gastric cancers were accompanied by open-type and closed-type gastritis, respectively (p = 0.037). Conclusions. The evaluation of the boundary of atrophic gastritis associated with gastric neoplasms appears to be useful for discrimination between early gastric cancer and gastric adenoma. When gastric neoplasm is present in the context of surrounding localized gastric atrophy, gastric cancer is probable but not certain.

Roles played by toll-like receptor-9 in corneal endothelial cells after herpes simplex virus type 1 infection.

PURPOSE: To determine the roles played by toll-like receptor 9 (TLR9) in cultured human corneal endothelial (HCEn) cells after herpes simplex virus type 1 (HSV-1) infection and to characterize the TLR9-mediated antiviral responses. METHOD: Immortalized HCEn cells were examined for TLR expression. The upregulation of inflammatory cytokines after HSV-1 infection was determined by real-time RT-PCR or protein array analyses. The TLR9-mediated HSV-1 replication was determined by real-time PCR and plaque assay. To determine whether there was an activation of the signal transduction pathway, HCEn cells that were transfected with pathway-focused transcription factor reporters were examined for promoter activity. RESULTS: TLR9 was abundantly expressed intracellularly in HCEn cells. The CpG oligonucleotide, a TLR9 ligand, stimulated the NF-κB activity in HCEn cells. HSV-1 infection also stimulated NF-κB and induced NF-κB -related inflammatory cytokines, including RANTES, IP-10, MCP-2, MIF, MCP-4, MDC, MIP-3α, IL-5, TARC, MCP-1, and IL-6. The induction of these cytokines was significantly reduced by blocking the activity of TLR9. In addition, viral replication in HCEn cells was significantly reduced by the inhibition of TLR9, but was preserved by a concomitant activation of the NF-κB cascade. Of the different HSV-1-induced inflammatory cascade-related transcription factors, TLR9 was found to activate NF-κB, cyclic AMP response element (CRE), and the CCAAT-enhancer-binding proteins (C/EBP) the most. CONCLUSIONS: Corneal endothelial cells transcriptionally initiate inflammatory programs in response to HSV-1 infection related to NF-κB, CRE, and C/EBP and express arrays of inflammatory cytokine induction by TLR9. On the other hand, HSV-1 exploits TLR9-mediated NF-κB activation for its own replication.

Herpes simplex virus type 1-induced transcriptional networks of corneal endothelial cells indicate antigen presentation function.

PURPOSE: To determine the transcriptional response of cultured human corneal endothelial (HCEn) cells after herpes simplex virus type (HSV-1) infection and to characterize the primary functional elements and antiviral responses. METHODS: Immortalized HCEn cells were infected with HSV-1, and the global transcriptional profile was determined. The transcriptional networks of HCEn cells were constructed, and the inflammatory network nodes were evaluated for induction of candidate inflammatory mediators by protein array analyses. HSV-1-specific allogeneic T cells isolated from HSV-1-infected donors were co-cultured with HSV-1-pulsed HCEn cells, and T cell activation was assessed for antigen-specific proliferation. RESULTS: HSV-1 infection induced a global transcriptional activation with 331 genes significantly up- or downregulated compared with mock-infected HCEn cells (P < 0.01; 4< or 0.25> threshold). Network analysis showed that the HSV-1-induced transcriptome was specifically associated with antigen presentation, interferon-related responses, and cellular development, and was characterized by NF-κB and extracellular signal-regulated kinase signaling pathways. The primary associated function in the transcriptome was antigen presentation. Protein array analysis identified significant elevation of genes related to antigen presentation: IL-6, IP-10, HVEML, and interferon-γ. In addition, inflammatory cytokines including IL-8, MCP-1, TIMP-1, RANTES, I-309, MIF, MCP-2, IL-10, and SDF-1, in descending order, were significantly elevated. Mixed lymphocyte reaction assays showed that HSV-1-pulsed HCEn cells stimulated antigen-specific proliferation of allogeneic T lymphocytes. CONCLUSIONS: HCEn cells respond to HSV-1 infection by initiating antigen presentation-related inflammatory responses, and they may serve as antigen-presenting cells.

[Short-term effects of intravitreal injection of bevacizumab on macular edema due to central retinal vein occlusion].

PURPOSE: To examine the short-term effects of intravitreal injections of bevacizumab on macular edema due to central retinal vein occlusion (CRVO). METHODS: Twenty one eyes of 21 consecutive patients with macular edema due to CRVO were included. The patients received intravitreal injections of 1.25 mg bevacizumab at the initial examination. They were followed up with best-corrected visual acuity (BVCA), fluorescein angiography, and central macular thickness (CMT) by optical coherence tomography for more than 4 months. Whenever the macular edema recurred, another intravitreal bevacizumab was given. RESULTS: The mean age of the patients was 68.1 +/- 11.8 and the mean follow up was 6.5 +/- 2.6 months. The mean baseline BVCA (logMAR) and CMT were 0.79 +/- 0.45 and 699 +/- 194 microm, respectively. After treatment, the mean BVCA improved significantly at 1 week (0.52 +/- 0.46, p<0.001), 1 month (0.48 +/- 0.46, p<0.001), 2 months(0.56 +/- 0.43, p<0.02), and 4 months (0.51 +/- 0.47, p<0.001). The mean CMT also decreased significantly at 1 week (296 +/- 86 microm, p<0.001), 1 month (286 +/-132 microm, p<0.001), 2 months (464 +/- 249 microm, p<0.05) and 4 months (362 +/- 198 microm, p<0.001). Similar effects on reducing CMT were obtained both after the initial injection and the second injection of bevacizumab. CONCLUSION: Intravitreal injection of bevacizumab improved visual acuity and macular edema due to CRVO.