Invasive Fungal Rhinosinusitis with Orbital Apex Syndrome Leading to Brain Abscess in a Patient with Ulcerative Colitis

We report the case of a 65-year-old male who presented with a 1-week history of right periorbital pain and progressive visual loss. He had a history of ulcerative colitis and was taking oral corticosteroids and mesalazine. Neurological and radiological examination demonstrated a rare case of invasive fungal rhinosinusitis that began with orbital apex syndrome. Initial endoscopic sinus surgery was performed and fungal culture identified Aspergillus fumigatus. Although antifungal treatment was started empirically before the operation, the patient had improved orbital pain but continued to have decreased right vision. Five months after the first surgical procedure, his condition deteriorated, including loss of consciousness, and a right temporal lobe abscess was found and surgically drained. Since then, the patient received antifungal treatment for 4 years without recurrence. Invasive fungal rhinosinusitis with orbital apex syndrome should be treated with long-term postoperative antifungal medication. It should be noted that even in immunosuppressive individuals such as ulcerative colitis, fungal rhinosinusitis with orbital apex syndrome may become severe

Higher plant myosin XI moves processively on actin with 35 nm steps at high velocity

High velocity cytoplasmic streaming is found in various plant cells from algae to angiosperms. We characterized mechanical and enzymatic properties of a higher plant myosin purified from tobacco bright yellow-2 cells, responsible for cytoplasmic streaming, having a 175 kDa heavy chain and calmodulin light chains. Sequence analysis shows it to be a class XI myosin and a dimer with six IQ motifs in the light chain-binding domains of each heavy chain. Electron microscopy confirmed these predictions. We measured its ATPase characteristics, in vitro motility and, using optical trap nanometry, forces and movement developed by individual myosin XI molecules. Single myosin XI molecules move processively along actin with 35 nm steps at 7 μm/s, the fastest known processive motion. Processivity was confirmed by actin landing rate assays. Mean maximal force was ∼0.5 pN, smaller than for myosin IIs. Dwell time analysis of beads carrying single myosin XI molecules fitted the ATPase kinetics, with ADP release being rate limiting. These results indicate that myosin XI is highly specialized for generation of fast processive movement with concomitantly low forces

Inhibition of IL-17A in Tumor Microenvironment Augments Cytotoxicity of Tumor-Infiltrating Lymphocytes in Tumor-Bearing Mice

<div><p>It remains controversial whether IL-17A promotes or inhibits cancer progression. We hypothesized that IL-17A that is locally produced in the tumor microenvironment has an important role in angiogenesis and tumor immunity. We investigated the effect of inhibiting IL-17A at tumor sites on tumor growth and on local and systemic anti-tumor immunity. MC38 or B16 cells were inoculated subcutaneously into mice, and intratumoral injection of an adenovirus vector expressing siRNA against the mouse IL-17A gene (Ad-si-IL-17) significantly inhibited tumor growth in both tumor models compared with control mice. Inhibition of IL-17A at tumor sites significantly suppressed CD31, MMP9, and VEGF expression in tumor tissue. The cytotoxic activity of CD8⁺ T cells from tumor-infiltrating lymphocytes in mice treated with Ad-si-IL-17 was significantly higher than in control mice; however, CD8⁺ T cells from splenocytes had similar activity levels. Suppression of IL-17A at tumor sites led to a Th1-dominant environment, and moreover, eliminated myeloid-derived suppressor cells and regulatory T cells at tumor sites but not in splenocytes. In conclusion, blockade of IL-17A at tumor sites helped suppress tumor growth by inhibiting angiogenesis as well as cytotoxic T lymphocytes activation at tumor sites.</p> </div

Inhibition of IL-17A in tumor sites increases Th1 cells in tumor microenvironment.

<p>Splenocytes and TILs were collected from spleens or tumor tissues of MC38 subcutaneous tumor model. Th1/Th2 cells were detected by intracellular staining assay of anti-IFN-γ mAb and anti-IL-4 mAb. Representative flow cytometry analysis profiles gated on anti-CD4 mAb. Ad-si-IL-17 treatment increased Th1 phenotype of TILs compared to control, but that of splenocytes was similar level in both treatments. Th2 phenotype was similar ratio of TILs and splenocytes in both treatment. Data are representative of two independent experiments (<i>n</i> = 5).</p

Inhibition of IL-17A at tumor sites suppresses tumor growth.

<p>(A, left panel) 1×10⁶ B16 tumor cells were injected subcutaneously into C57BL/6 mice, and PBS, Ad-SNC, or Ad-si-IL-17 with 1×10⁹ PFU was injected intratumorally at 7, 10, and 13 d. Data represent means ± SE (<i>n</i> = 7 mice per group of two independent experiments). *<i>P</i><0.05, one-way ANOVA. (A, right panel) 5×10⁵ MC38 tumor cells were injected subcutaneously into mice, in the same way adenovirus vectors were injected at 5, 8, and 11 d. Data represent means ± SE (<i>n</i> = 7 mice of two independent experiments). *<i>P</i><0.05, one-way ANOVA. (B).Levels of IL-17A protein were measured by ELISA in tumor lysates from mice after having been treated with PBS, Ad-SNC, or Ad-si-IL-17. In B16 and MC38 tumor tissues, Ad-si-IL-17 treatment showed lower levels of IL-17A compared with PBS or Ad-SNC treatment. Data are representative of two independent experiments. Data are presented as means ± SE (<i>n</i> = 4). *<i>P</i><0.05, Student's <i>t</i> test.</p

Inhibition of IL-17A at tumor sites decreases the intratumoral microvessel density.

<p>(A) The endothelial maker CD31-stained sections of tumor tissue are shown in Ad-SNC and Ad-si-IL-17 treatment models, Ad-si-IL-17 treatment decreased the intratumoral microvessel density compared with Ad-SNC. Vessels in five high-power fields (×200 magnification) were counted. Positive cells were quantified by an image-processing application. Data are representative of two independent experiments. Data are presented as means ± SE (<i>n</i> = 5). *<i>P</i><0.05, Student's <i>t</i> test. (B) Intratumoral MMP-9 expression was decreased by the inhibition of IL-17. MMP-9 stained sections of tumor tissue were shown in Ad-SNC and Ad-si-IL-17 treatment models. Ad-si-IL-17 treatment decreased the intratumoral MMP-9 density compared with Ad-SNC. MMP-9 in five high-power fields (×200 magnification) was counted. Positive cells were quantified by an image-processing application. Data are representative of two independent experiments. Data are presented as means ± SE (<i>n</i> = 5). *<i>P</i><0.05, Student's <i>t</i> test. (C) VEGF and IL-17A levels produced by MC38 cells were measured by ELISA. MC38 cells did not secretion IL-17A protein and produce VEGF protein. Levels of VEGF in vivo were measured by ELISA in tumor lysates from mice at 14 d after having been treated with Ad-SNC, or Ad-si-IL-17. In tumor tissues, Ad-si-IL-17 treatment showed lower levels of VEGF compared with Ad-SNC treatment. Data are representative of two independent experiments. Data are presented as means ± SE (<i>n</i> = 4). *<i>P</i><0.05, Student's <i>t</i> test. ND: not detected.</p