Search

Competing Interests: The authors declare that they have no conflict of interest.

Case : A 66-year-old man started carboplatin + etoposide + atezolizumab therapy for advanced small cell lung cancer. Seventeen days after the start of treatment, the patient presented with hematemesis and underwent emergency endoscopy, which revealed multiple erosions and ulcers in the duodenum. Some ulcers showed pulsating bleeding, which was stopped by clipping and cauterization using hemostats. Biopsy of the mucosal peri-ulcer showed lymphocyte, eosinophil, and plasma cell infiltration. The patient was suggested to have acute hemorrhagic duodenitis, which was associated with immune checkpoint inhibitors (ICIs), and conservative treatment with blood transfusion and antacids was continued. However, 11 days after hemostasis, bleeding from a new ulcer was observed. Hemostasis was achieved by coagulation and clipping again, but the general condition of the patient deteriorated owing to the rapid progression of the primary disease, and he died 8 weeks after the start of treatment. Discussion : Although there have been several reports of colitis and other adverse events caused by ICIs, there have been very few reports of duodenitis. Endoscopic findings include diffuse erythema, erosions/ulcerations, and villous atrophy, and pathological findings include eosinophilic infiltration and increased levels of CD8-positive T cells. However, there have been no reports of duodenal mucosal damage caused after administration of atezolizumab nor of severe cases of massive bleeding requiring endoscopic hemostasis and blood transfusion, as in this case., Competing Interests: Authors declare no conflict of interests for this article., (© 2021 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Phosphatidylserine (PS) has skewed distributions in the plasma membrane and is preferentially located in the inner leaflet of normal cells. Tumour cells, however, expose PS at the outer leaflet of cell surfaces, thereby potentially modulating the bio-signalling of cells. Interestingly, exosomes - or, more properly, small extracellular vesicles (sEVs) - which are secreted from tumour cells, are enriched with externalized PS, have been proposed as being involved in the progression of cancers, and could be used as a marker for tumour diagnostics. However, the sEV fractions prepared from various methods are composed of different subtypes of vesicles, and knowledge about the subtypes enriched with exposed PS is still limited. Here, we differentiated sEVs from cancer cell lines by density gradient centrifugation and characterized the separated fractions by using gold-labelling of PS in atomic force microscopy, thrombin generation assay, size and zeta potential measurements, and western blot analysis. These analyses revealed a previously unreported PS + -enriched sEV subtype, which is characterized by a lower density than that of canonical exosomes (1.06 g/ml vs. 1.08 g/ml), larger size (122 nm vs. 105 nm), more negative zeta potential (-28 mV vs. -21 mV), and lower abundance of canonical exosomal markers. The identification of the PS-exposed subtype of sEVs will provide deeper insight into the role of EVs in tumour biology and enhance the development of EV-based tumour diagnosis and therapy.

Sulfatide is abundantly expressed in various mammalian organs, including the intestines and trachea, in which influenza A viruses (IAVs) replicate. However, the function of sulfatide in IAV infection remains unknown. Sulfatide is synthesized by two transferases, ceramide galactosyltransferase (CGT) and cerebroside sulfotransferase (CST), and is degraded by arylsulfatase A (ASA). In this study, we demonstrated that sulfatide enhanced IAV replication through efficient translocation of the newly synthesized IAV nucleoprotein (NP) from the nucleus to the cytoplasm, by using genetically produced cells in which sulfatide expression was down-regulated by RNA interference against CST mRNA or overexpression of the ASA gene and in which sulfatide expression was up-regulated by overexpression of both the CST and CGT genes. Treatment of IAV-infected cells with an antisulfatide monoclonal antibody (MAb) or an anti-hemagglutinin (HA) MAb, which blocks the binding of IAV and sulfatide, resulted in a significant reduction in IAV replication and accumulation of the viral NP in the nucleus. Furthermore, antisulfatide MAb protected mice against lethal challenge with pathogenic influenza A/WSN/33 (H1N1) virus. These results indicate that association of sulfatide with HA delivered to the cell surface induces translocation of the newly synthesized IAV ribonucleoprotein complexes from the nucleus to the cytoplasm. Our findings provide new insights into IAV replication and suggest new therapeutic strategies.

Background: Management after heart transplantation must deal with the twin risks of rejection and infection. Early infection with viral infection, particularly cytomegalovirus (CMV), is becoming more prevalent two to three months after transplantation. To our knowledge, there has been no previous report of human polyomavirus (HPOV) infection after heart transplantation., Case: A 20-year-old male with a history of Kawasaki disease and who had suffered from severe congestive heart failure after a coronary artery bypass graft, underwent heart transplantation. Urinary cytology demonstrated HPOV infection, the diagnosis of which was established by the immunoperoxidase technique, in situ hybridization and electron microscopy., Conclusion: The definitive diagnosis of HPOV infection after a heart transplant can be made on urinary cytology.

A 50-year-old man who had undergone successful aortic valve replacement for fungal endocarditis was presented. He had been doing well until October 1993, when he suddenly developed shock with high fever. In two weeks he recovered from septic shock with vigorous medical treatment including intravenous administration of antibiotics. The infecting organism was not detected on repeated blood cultures. Four months later he was admitted to our hospital because of left heart failure. Although he was afebrile on admission, a two dimensional echocardiogram revealed vegetation on the aortic valve and massive aortic regurgitation. Inflammatory signs persisted and the vegetation increased in size, and therefore an aortic valve replacement was performed. A surgical specimen of the aortic valve revealed perforation in each of three cusps and vegetation on the non-coronary cusp. Pathological exploration revealed typical colonies of fungi. Following the diagnosis of fungal endocarditis, administration of an anti-fungal drug was started. His post-operative course was uneventful, and there was no evidence of recurrence with the anti-fungal medication for one year postoperatively.