Phagocytic response to fully controlled plural stimulation of antigens on macrophage using on-chip microcultivation system

To understand the control mechanism of innate immune response in macrophages, a series of phagocytic responses to plural stimulation of antigens on identical cells was observed. Two zymosan particles, which were used as antigens, were put on different surfaces of a macrophage using optical tweezers in an on-chip single-cell cultivation system, which maintains isolated conditions of each macrophage during their cultivation. When the two zymosan particles were attached to the macrophage simultaneously, the macrophage responded and phagocytosed both of the antigens simultaneously. In contrast, when the second antigen was attached to the surface after the first phagocytosis had started, the macrophage did not respond to the second stimulation during the first phagocytosis; the second phagocytosis started only after the first process had finished. These results indicate that (i) phagocytosis in a macrophage is not an independent process when there are plural stimulations; (ii) the response of the macrophage to the second stimulation is related to the time" delay from the first stimulation. Stimulations that occur at short time intervals resulted in simultaneous phagocytosis, while a second stimulation that is delayed long enough might be neglected until the completion of the first phagocytic process

Large Ulceration of the Oropharynx Induced by Methotrexate-Associated Lymphoproliferative Disorders

We present a case of a 67-year-old Japanese man with a serious oropharyngeal ulceration that at first seemed to be destructive malignant lymphoma or oropharyngeal carcinoma. We suspected methotrexate (MTX)-associated lymphoproliferative disorder (LPD) induced by MTX treatment for rheumatoid arthritis (RA). About 3 weeks after simple discontinuation of MTX, complete regression of the disease was observed, confirming our diagnosis

Tracheal Stenosis Caused by Unnoticed Foreign Bodies

We describe an extremely rare case of tracheal stenosis caused by unnoticed microscopic fiber-like foreign bodies. A 66-year-old woman complained of dyspnea with inspiratory stridor. Magnifying electroendoscopy and computed tomography revealed stenosis involving the entire circumference of the tracheal lumen. Tracheotomy and biopsy were performed. Histologically, the lesion showed chronic inflammation with a deposition of fiber-like foreign bodies. The patient had no history of trauma or inhalation injury, but had undergone intratracheal intubation on 4 occasions. The lesion was incised using semiconductor laser photoresection, and the postoperative course was good. To the best of our knowledge, this represents the first report in the English literature of tracheal stenosis caused by unnoticed foreign bodies. The origin of these fiber-like foreign bodies remains unclear but might be related to chronic inflammation resulting from intratracheal intubations

Clinical Significance of Cytoplasmic IgE-Positive Mast Cells in Eosinophilic Chronic Rhinosinusitis

Cross-linking of antigen-specific IgE bound to the high-affinity IgE receptor (Fc epsilon RI) on the surface of mast cells with multivalent antigens results in the release of mediators and development of type 2 inflammation. Fc epsilon RI expression and IgE synthesis are, therefore, critical for type 2 inflammatory disease development. In an attempt to clarify the relationship between eosinophilic chronic rhinosinusitis (ECRS) and mast cell infiltration, we analyzed mast cell infiltration at lesion sites and determined its clinical significance. Mast cells are positive for c-kit, and IgE in uncinated tissues (UT) and nasal polyps (NP) were examined by immunohistochemistry. The number of positive cells and clinicopathological factors were analyzed. Patients with ECRS exhibited high levels of total IgE serum levels and elevated peripheral blood eosinophil ratios. As a result, the number of mast cells with membranes positive for c-kit and IgE increased significantly in lesions forming NP. Therefore, we classified IgE-positive mast cells into two groups: membrane IgE-positive cells and cytoplasmic IgE-positive cells. The amount of membrane IgE-positive mast cells was significantly increased in moderate ECRS. A positive correlation was found between the membrane IgE-positive cells and the radiological severity score, the ratio of eosinophils, and the total serum IgE level. The number of cytoplasmic IgE-positive mast cells was significantly increased in moderate and severe ECRS. A positive correlation was observed between the cytoplasmic IgE-positive cells and the radiological severity score, the ratio of eosinophils in the blood, and the total IgE level. These results suggest that the process of mast cell internalization of antigens via the IgE receptor is involved in ECRS pathogenesis

A Spot Reminder System for the Visually Impaired Based on a Smartphone Camera

The present paper proposes a smartphone-camera-based system to assist visually impaired users in recalling their memories related to important locations, called spots, that they visited. The memories are recorded as voice memos, which can be played back when the users return to the spots. Spot-to-spot correspondence is determined by image matching based on the scale invariant feature transform. The main contribution of the proposed system is to allow visually impaired users to associate arbitrary voice memos with arbitrary spots. The users do not need any special devices or systems except smartphones and do not need to remember the spots where the voice memos were recorded. In addition, the proposed system can identify spots in environments that are inaccessible to the global positioning system. The proposed system has been evaluated by two experiments: image matching tests and a user study. The experimental results suggested the effectiveness of the system to help visually impaired individuals, including blind individuals, recall information about regularly-visited spots

Significance of IgG4-positive cells in severe eosinophilic chronic rhinosinusitis

Background: IgG4 production is regulated by type 2 (IL-4 and IL-13) and regulatory (IL-10) cytokines involved in the pathophysiology of chronic rhinosinusitis (CRS). We sought to determine the pathophysiological characteristics of IgG4-positive cells in sinonasal tissues in CRS, especially eosinophilic CRS (ECRS). Methods: IgG4-positive cells in uncinate tissues (UT) and nasal polyps (NP) were examined by immunohistochemistry. Associations between the number of IgG4-positive cells and clinicopathological factors were analyzed. Receiver operating characteristics (ROC) analysis was performed to determine the cut-off value of IgG4-positive cells in tissue that can predict the post-operative course. Results: IgG4 was mainly expressed in infiltrating plasma and plasmacytoid cells, and the number of IgG4-positive cells was significantly higher in NP, especially those from severe ECRS patients, than in UT. In CRS patients, the number of IgG4-positive cells significantly and positively correlated with blood and tissue eosinophilia, radiological severity, and serum level of total IgE. The number of infiltrating IgG4-positive cells was significantly higher in patients with a poor post-operative course (sustained sinus shadow 6 months after surgery) than in those with a good one. The number of IgG4-positive cells in NP could discriminate patients with a good or a poor post-operative course (area under the curve: 0.769). Also, 73.3% sensitivity and 82.5% specificity were achieved when the cut-off value was set at 17 cells/high-power field. Conclusions: Our results suggest that the local expression of IgG4 on cells may be used as a biomarker that reflects the pathophysiology of CRS, including the post-operative course

Computed Tomography Findings for Diagnosing Follicular Thyroid Neoplasms

Since no diagnostic method has been established to distinguish follicular thyroid carcinoma (FTC) from follicular thyroid adenoma (FTA), surgery has been the only way to reach a diagnosis of follicular neoplasm. Here we investigated the computed tomography (CT) features of follicular neoplasms, toward the goal of being able to identify specific CT features allowing the preoperative differentiation of FTC from FTA. We retrospectively analyzed the cases of 205 patients who underwent preoperative CT of the neck and were histopathologically diagnosed with FTC (n=31) or FTA (n=174) after surgery between January 2002 and June 2016 at several hospitals in Japan. In each of these 205 cases, non-enhanced and contrast-enhanced CT images were obtained, and we analyzed the CT features. On univariate analysis, inhomogeneous features of tumor lesions on contrast-enhanced CT were more frequently observed in FTC than in FTA (p=0.0032). A multivariate analysis identified inhomogeneous features of tumor lesions on contrast-enhanced CT images as an independent variable indicative of FTC (p=0.0023). CT thus offers diagnostic assistance in distinguishing FTC from FTA

The engraftment and differentiation of transplanted bone marrow-derived cells in the olfactory bulb after methimazole administration

Conclusion: Bone marrow-derived cells can be engrafted in the olfactory bulb and a few cells can differentiate into mitral/tufted cells in the olfactory bulb. Objectives: To investigate whether bone marrow-derived cells can be engrafted into the olfactory bulb and differentiate into neurons and glial cells after methimazole administration. Methods: Bone marrow of GFP (green fluorescence protein) mice was transplanted into lethally irradiated recipient mice. Immunostaining was performed to confirm the cell types of bone marrow-derived cells expressing GFP. Results: GFP-positive cells were observed in the olfactory bulb at 2 days after methimazole administration. The number of dendritic GFP-positive cells increased up to 30 days after methimazole administration and then decreased. Double immunostaining for GFP and Iba1 or TBX21 showed that a large population of the GFP-positive cells had characteristics of microglia/macrophages and a few cells had characteristics of mitral/tufted cells