T cell immunity in interstitial lung disease with non-small cell lung cancer patients.

OBJECTIVES: Limited treatment options are available for non-small cell lung cancer (NSCLC) patients with interstitial lung disease (ILD). The rationale for immunotherapy and its adverse events for NSCLC with ILD remains unclear. In this study, we examined T cell profiles and functions in the lung tissues of NSCLC patients with or without ILD to provide evidence for the potential mechanism of immune checkpoint inhibitor (ICI)-related pneumonitis in NSCLC patients with ILD. MATERIAL AND METHODS: We investigated T cell immunity in the lung tissues of NSCLC patients with ILD to support the application of immunotherapy for these patients. We analyzed T cell profiles and functions in surgically resected lung tissues from NSCLC patients with and without ILD. The T cell profiles of infiltrating cells in lung tissues were analyzed by flow cytometry. T cell functions were measured based on cytokine production by T cells stimulated with phorbol 12-myristate 13-acetate and ionomycin. RESULTS: The percentages of CD4+ T cells expressing immune checkpoint molecules (Tim-3, ICOS, and 4-1BB), CD103+CD8+ T cells, and regulatory T (Treg) cells were higher in NSCLC patients with than in those without ILD. A functional analysis of T cells in lung tissues indicated that CD103+CD8+ T cells positively correlated with IFNγ production, whereas Treg cells negatively correlated with IFNγ and TNFα production. Cytokine production by CD4+ and CD8+ T cells did not significantly differ between NSCLC patients with and without ILD, except for TNFα production by CD4+ T cells being lower in the former than in the latter. CONCLUSION: In NSCLC patients with ILD stable for surgery, T cells were active participants and balanced in part by Treg cells in lung tissues, suggesting the potential development of ICI-related pneumonitis in NSCLC patients with ILD.

Myelin basic protein expression in thymoma after methylprednisolone administration for multiple sclerosis.

The relationship between thymic epithelial tumour and demyelinating disease (DD) is unknown and surgical resection has not been optimized. A 39-year-old woman was administrated methylprednisolone for newly diagnosed multiple sclerosis. A thymic tumour was found in the antero-superior mediastinum via computed tomography of the chest. Video-assisted thoracoscopic thymectomy was performed. Histologically, the tumour was diagnosed as Type AB thymoma. Immunohistochemical staining showed positive myelin basic protein (MBP) in the cytosol of spindle cells in the tumour specimen. Germinal centres or lymphocytes infiltration were not noted. Ectopic MBP presentation in thymoma might be correlated with DD.

A Pilot Study to Develop a New Method of Assisting Children in Taking Their Medication by Using Immersive Virtual Reality.

Taking bitter-tasting drugs can be stressful for children who have underdeveloped swallowing skills and do not understand the meaning of medication. Furthermore, the senses of vision and smell are known to majorly influence taste. This pilot study was aimed at determining the effect of visual stimulation by immersive virtual reality (iVR) on taste and the safety of this approach for developing a new method to assist children with taking medication. Ten subjects participated in this study, and their mean (standard deviation (S.D.)) age was 21.8 (0.8) years. The subjects tasted the bitter aqueous solution (quinine 0.00375%) while viewing two different VR images (strawberry sponge cake and orange juice) alternately and received sensory tests immediately after the tasting and again 30 s later. In addition, nausea was assessed 30 s after tasting for each VR image. The primary endpoint was the difference in sensory test scores immediately after the tasting and 30 s later, between the two images. There were no significant differences in the sensory test scores between the placebo and either strawberry sponge cake or orange juice immediately after tasting. However, 30 s after tasting, the scores changed significantly to a tendency to perceive sweetness from the strawberry sponge cake and orange juice images compared with the placebo. No subject experienced nausea. Therefore, the findings of this study suggest that displaying images of sweet foods by using iVR to stimulate visual perception could safely reduce the sense of bitterness.

SS-A52 antigen expression in thymic carcinoma accompanied with Sjögren syndrome: A case report.

RATIONALE: The relationship between thymic tumors and Sjögren syndrome (SjS) is unknown, and surgical resection has not been optimized. Especially, thymic carcinoma with autoimmune disease is rare. Analysis of SS-A52, germinal centers, plasma cells, and Foxp3+ Treg in thymic carcinoma has never been reported, and their pathological roles in causing SjS have not been studied. PATIENT CONCERNS: A 78-year-old man presented with sputum production and xerostomia while asleep. Chest computed tomography showed a homogeneous and hypodense mass in the anterosuperior mediastinum. Serum levels of the antinuclear antibody, antibody to SS-A, and antibody to SS-B were positive. DIAGNOSES: Thymic carcinoma (squamous cell carcinoma) and SjS. INTERVENTIONS: Video-assisted thoracoscopic resection of the mediastinal tumor and postoperative radiation therapy was performed. OUTCOMES: The histological diagnosis was thymic squamous cell carcinoma. Histologically, the squamous carcinomatous cells were arranged in nests and cords in the fibrohyaline stroma with capsular invasion. In the stroma, dense lymphoid tissues containing large reactive germinal centers and many plasma cells were also noted. In the involuted thymus, CD20-positive mature lymphocytes infiltrated, and germinal centers were noted. Double immunohistochemical staining revealed that SS-A52 antigen was positive in both the carcinoma component and CD20-positive mature B cells. Postoperatively, the xerostomia persisted, and serum SS-A and SS-B remained positive. No evidence of carcinoma recurrence with chest computed tomography scan was observed at 18-months follow-up. LESSONS: In the surgical treatment of thymic tumors with SjS, extended thymectomy might be worth considering to stop the progressive destruction of the targets of SjS-specific autoantibodies. However, the postoperative symptoms may not dramatically improve because the target organs might have changed irreversibly, and memory B cells might persist. This is the first report that demonstrated the SS-A52 antigen presentation in a thymic tumor to the best of our knowledge.

Winged scapula following axillary thoracotomy with long thoracic nerve preservation.

Winged scapula is a rare condition caused by injuries to the long thoracic nerve (LTN) and accessory nerves. A 69-year-old man underwent surgery for right lung cancer. Video-assisted thoracic surgery was converted to axillary thoracotomy at the fourth intercostal space. The latissimus dorsi was protected, and the serratus anterior was divided on the side anterior to the LTN. Two months after discharge, he presented with difficulty in elevating his right arm and protrusion of the scapula from his back. Active forward flexion of the right shoulder was limited to 110° and abduction to 130°. He was diagnosed with winged scapula. After 6 months of occupational therapy, the symptoms improved. The LTN may have been overstretched or damaged by the electric scalpel. We recommend an increased awareness of the LTN, and to divide the serratus anterior at a site as far as possible from the LTN to avoid postoperative winged scapula.

Eosinophilic Pneumonia Putatively Induced by Vancomycin: A Case Report.

BACKGROUND Herein, we describe a case of eosinophilic pneumonia that was likely to have been induced by vancomycin. CASE REPORT A 65-year-old man on maintenance hemodialysis presented with chest pain and dyspnea. He subsequently developed methicillin-resistant Staphylococcus aureus-positive acute pleural empyema in an evacuated right-sided pneumothorax. Surgical thoracoscopic curettage was ultimately performed, but dyspnea recurred postoperatively. Computed tomography depicted widespread reticular shadowing of the left lung, and peripheral eosinophilia was detected. The proportion of eosinophils found in bronchoalveolar lavage fluid was also remarkable (43%). All symptoms and the results of laboratory tests immediately improved after the discontinuation of vancomycin and initiation of prednisolone therapy. CONCLUSIONS We attribute this case of eosinophilic pneumonia to vancomycin, because all other candidate causes were ruled out, and only vancomycin fulfilled the criteria of both drug-induced eosinophilic pneumonia and drug-induced lung injury. If confirmed, this constitutes the first reported case of vancomycin-induced eosinophilic pneumonia.

[Metastatic Atypical Meningioma of the Lung;Report of a Case].

A 56-years-old woman, who had undergone a complete resection for atypical meningioma (grade 2 of World Health Organization classification)8 years before was admitted to our hospital to treat a mass on the right middle lobe detected by chest X-ray. The mass was resected successfully by video-assisted thoracoscopic surgery and pathological diagnosis of the tumor was a metastatic atypical meningioma. We experienced a rare case of extracranial pulmonary metastasis of meningioma. Grade 2 meningioma is thought to have malignant potential of local recurrence and extracranial metastasis compared to grade 1 meningioma, so long-term observation may be necessary after resection of atypical meningioma.

[Pulmonary Metastasis of Sacral Chordoma Fifteen Years after Resection of Primary Site;Report of a Case].

A 71-years-old man, who had undergone resection for sacral chordoma 15 years before, was admitted to our hospital to treat a nodule in the right middle lobe detected by computed tomography. The nodule was resected and was histologically diagnosed as lung-metastasis of chordoma.

[Metastatic Ovarian Granulosa Cell Tumor of the Diaphragm Resected by Video-assisted Thoracoscopic Surgery;Report of a Case].

A 75-years-old woman, who had undergone a total abdominal hysterectomy and bilateral salpingo-oophorectomy for ovarian granulosa cell tumor( OGCT) 6 years ago, was admitted to our hospital to treat a mass on the right diaphragm detected by computed tomography. The mass was resected successfully by video-assisted thoracoscopic surgery and pathological diagnosis of the tumor was a metastatic OGCT of the diaphragm. To our knowledge, this is the 3rd case report of metastatic OGCT of the diaphragm.

Endothelial Cell-Selective Adhesion Molecule Expression in Hematopoietic Stem/Progenitor Cells Is Essential for Erythropoiesis Recovery after Bone Marrow Injury.

Numerous red blood cells are generated every second from proliferative progenitor cells under a homeostatic state. Increased erythropoietic activity is required after myelo-suppression as a result of chemo-radio therapies. Our previous study revealed that the endothelial cell-selective adhesion molecule (ESAM), an authentic hematopoietic stem cell marker, plays essential roles in stress-induced hematopoiesis. To determine the physiological importance of ESAM in erythroid recovery, ESAM-knockout (KO) mice were treated with the anti-cancer drug, 5-fluorouracil (5-FU). ESAM-KO mice experienced severe and prolonged anemia after 5-FU treatment compared to wild-type (WT) mice. Eight days after the 5-FU injection, compared to WT mice, ESAM-KO mice showed reduced numbers of erythroid progenitors in bone marrow (BM) and spleen, and reticulocytes in peripheral blood. Megakaryocyte-erythrocyte progenitors (MEPs) from the BM of 5-FU-treated ESAM-KO mice showed reduced burst forming unit-erythrocyte (BFU-E) capacities than those from WT mice. BM transplantation revealed that hematopoietic stem/progenitor cells from ESAM-KO donors were more sensitive to 5-FU treatment than that from WT donors in the WT host mice. However, hematopoietic cells from WT donors transplanted into ESAM-KO host mice could normally reconstitute the erythroid lineage after a BM injury. These results suggested that ESAM expression in hematopoietic cells, but not environmental cells, is critical for hematopoietic recovery. We also found that 5-FU treatment induces the up-regulation of ESAM in primitive erythroid progenitors and macrophages that do not express ESAM under homeostatic conditions. The phenotypic change seen in macrophages might be functionally involved in the interaction between erythroid progenitors and their niche components during stress-induced acute erythropoiesis. Microarray analyses of primitive erythroid progenitors from 5-FU-treated WT and ESAM-KO mice revealed that various signaling pathways, including the GATA1 system, were impaired in ESAM-KO mice. Thus, our data demonstrate that ESAM expression in hematopoietic progenitors is essential for erythroid recovery after a BM injury.

Benzene risk estimation using radiation equivalent coefficients.

We estimated benzene risk using a novel framework of risk assessment that employed the measurement of radiation dose equivalents to benzene metabolites and a PBPK model. The highest risks for 1 microg/m(3) and 3.2 mg/m(3) life time exposure of benzene estimated with a linear regression were 5.4 x 10(-7) and 1.3 x 10(-3), respectively. Even though these estimates were based on in vitro chromosome aberration test data, they were about one-sixth to one-fourteenth that from other studies and represent a fairly good estimate by using radiation equivalent coefficient as an "internal standard."

The herbal medicine inchin-ko-to (TJ-135) induces apoptosis in cultured rat hepatic stellate cells.

Use of herbal remedies in the treatment of various diseases has a long tradition in Eastern medicine and the liver diseases are not an exception. In their use, lack of elucidation of mechanism(s) as well as randomized, placebo-controlled clinical trials has been a problem. Recently, we and others reported that inchin-ko-to (TJ-135), one of herbal remedies, suppressed hepatic fibrosis in animal models. In the course of clarifying the mechanism, we directed our focus on hepatic stellate cells (HSCs), playing a pivotal role in hepatic fibrosis, and found that rat HSCs cultured with TJ-135 changed their morphology to star-like configuration with thin, slender and dendritic processes with fewer stress fibers, which might be the features in apoptosis. In fact, TJ-135 induced HSC apoptosis in a time- and concentration-dependent manner as judged by the nuclear morphology, quantitation of cytoplasmic histone-associated DNA oligonucleosome fragments and caspase 3 activity. In HSCs treated with TJ-135, increased expression of p53 and decreased expression of Bcl-2 and phosphorylated Akt and Bad were determined. HSC apoptosis is shown to be involved in the mechanisms of spontaneous resolution of rat hepatic fibrosis and the agent which induces HSC apoptosis has been shown to reduce experimental hepatic fibrosis in rats. Thus, the induction of HSC apoptosis could be the mechanism how TJ-135 works on the resolution of hepatic fibrosis. Our current data may shed light on the novel effect of the herbal remedy.

Arabidopsis CAMTA family proteins enhance V-PPase expression in pollen.

The pollen-specific cis-acting region of the AVP1 gene is involved in the expression of the Arabidopsis V-PPase gene during pollen development. We isolate AtCAMTA5, which binds to the 38-bp pollen-specific cis-acting region, by one-hybrid screening using the cis-acting region as a probe. The green fluorescent protein-fused AtCAMTA5 is specifically localized to the nucleus in Arabidopsis suspension cultured cells. The promoter-beta-glucuronidase reporter experiment shows the expression not only of AtCAMTA5 but also of AtCAMTA1 in pollen. In particular, AtCAMTA1 is specifically expressed in pollen. Both the one-hybrid analysis in the reporter yeast and in vivo transient effector-reporter analysis in Arabidopsis suspension cultured cells revealed that AtCAMTA1 could regulate gene expression depending on the CGCG-box within the 38-bp pollen-specific cis-acting region. These results indicate that AtCAMTA1 as well as AtCAMTA5 possibly enhance AVP1 expression in pollen.