H4 influenza viruses have been isolated from birds across the world. In recent years, an H4 influenza virus infection has been confirmed in pigs. Pigs play an important role in the transmission of influenza viruses to human hosts. Therefore, it is important to develop a new vaccine in the case of an H4 influenza virus infection in humans, considering that this virus has a different antigenicity from seasonal human influenza viruses. In this study, after selecting vaccine candidate strains based on their antigenic relation to one of the pig isolates, A/swine/Missouri/A01727926/2015 (H4N6) (MO/15), an inactivated whole-particle vaccine was prepared from A/swan/Hokkaido/481102/2017 (H4N6). This vaccine showed high immunogenicity in mice, and the antibody induced by the vaccine showed high cross-reactivity to the MO/15 virus. This vaccine induced sufficient neutralizing antibodies and mitigated the effects of an MO/15 infection in a mouse model. This study is the first to suggest that an inactivated whole-particle vaccine prepared from an influenza virus isolated from wild birds is an effective countermeasure in case of a future influenza pandemic caused by the H4 influenza virus.
A 62 year-old male was admitted to our hospital for detailed examinations of a low density mass in the spleen by abdominal CT scan at a physical checkup. Abdominal CT scan also demonstrated portal obstruction and collateral veins around pancreatic head. Furthermore, abdominal angiograhy showed a hypovascular lesion in the spleen. Upper gastroendoscopy demonstrated esophageal varices, which were eradicated after EVL. The above examinations, however, could not make the definitive diagnosis, therefore splenectomy was carried out on 5 July 2000. The tumor size of the cut surface was 4×5cm in diameter. Histopathological diagnosis was non-functioning pancreatic endocrine tumor. The patient remains well with no evidence of recurrence one year and seven months after the operation.
Abstract Although coagulation abnormalities, including microvascular thrombosis, are thought to contribute to tissue injury and single- or multiple-organ dysfunction in severe influenza, the detailed mechanisms have yet been clarified. This study evaluated influenza-associated abnormal blood coagulation utilizing a severe influenza mouse model. After infecting C57BL/6 male mice with intranasal applications of 500 plaque-forming units of influenza virus A/Puerto Rico/8/34 (H1N1; PR8), an elevated serum level of prothrombin fragment 1 + 2, an indicator for activated thrombin generation, was observed. Also, an increased gene expression of oxidized low-density lipoprotein (LDL) receptor-1 ( Olr1 ), a key molecule in endothelial dysfunction in the progression of atherosclerosis, was detected in the aorta of infected mice. Body weight decrease, serum levels of cytokines and chemokines, viral load, and inflammation in the lungs of infected animals were similar between wild-type and Olr1 knockout (KO) mice. In contrast, the elevation of prothrombin fragment 1 + 2 levels in the sera and intravascular thrombosis in the lungs by PR8 virus infection were not induced in KO mice. Collectively, the results indicated that OLR1 is a critical host factor in intravascular thrombosis as a pathogeny of severe influenza. Thus, OLR1 is a promising novel therapeutic target for thrombosis during severe influenza.
Abstract: No remarkable improvement has yet been achieved in the survival of patients with advanced intrathoracic esophageal cancer. In particular, patients with complications such as esophago‐bronchial fistula or invasion into the mediastinum have an especially miserable prognosis, even with surgical treatment. To improve the quality of life (QOL) of such patients, extensive palliative therapy should be provided. Thus, we have introduced an endoscopic esophageal intubation technique for the treatment of stenosis or perforation in patients with T4 esophageal cancer. Nine patients with unresectable intrathoracic esophageal cancer, complicated by stenosis or perforation, were treated with an endoscopic esophageal prosthesis. Four cases had an esophago‐bronchial fistula, and in three the tumor had perforated the mediastinum. The prosthesis was successfully placed under endoscopic guidance in all nine cases. Six patients (66.7%) subsequently resumed oral intake without discomfort, while two had reasonably good outcomes in this regard (efficacy rate; 88.9%). Complications were seen in three patients: mainly chest discomfort, reflux esophagitis and migration of the prosthesis in one patient each. Six patients required prolonged administration of chemotherapeutic agents following prosthesis placement. Mean survival was 123.4±77.0 days. Four of the nine patients died in the hospital. Palliative endoscopic esophageal prosthesis was considered to be useful for patients with advanced esophageal cancer. With this technique, an improvement in QOL was achieved, as sufficient oral intake was facilitated and pulmonary and mediastinal complications due to perforation were diminished.
Abstract Influenza viruses circulate globally, causing seasonal influenza outbreaks. Although antibody-inducing vaccines are the most effective way to combat seasonal infections, current vaccines can have poor efficacy, especially in children and immunocompromised individuals. We investigated the immunogenicity and efficacy of monovalent and quadrivalent formulations of the whole virus particle vaccine (WPV) in comparison to the commonly used split vaccines (SVs) in a non-human primate model. Naïve cynomolgus macaques vaccinated with either monovalent or quadrivalent WPV formulations consistently induced a stronger neutralizing antibody response against vaccine-matched virus strains, while reactogenicity was minimal. In contrast to the modest responses in SV-vaccinated animals, responses in WPV-primed animals were further increased by boosting with either formulation. Using a 28-parameter multiplex bead array to define key antibody features, we found that while both WPV and SV induced elevated IgG responses against A/H1N1 nucleoprotein, only WPV elevated IgG responses against A/H1N1 haemagglutinin (HA) and HA-Stem after each vaccine dose. Higher IgA responses to A/H1N1-HA were also induced after each WPV dose. Antibodies to A/H1N1-HA and HA-Stem that could engage FcγR2a and FcγR3a were present at higher levels after one dose of WPV compared to SV and remained elevated after the second dose. WPV-enhanced antibody responses were associated with higher frequencies of HA-reactive B-cells and IFN-γ-producing CD4 + T-cell responses. Our data suggest that robust antibody responses require WPV to be given as a priming dose but do not depend on the vaccine type used for the second dose. In contrast, antibody responses are not as prominent when SV is given first. Our findings support vaccination regimens using WPV, which may be particularly beneficial for priming immunologically-naïve individuals, such as the young and immunocompromised, and also advantageous in the event of a pandemic outbreak.
We performed transbronchoscopic microwave electrodes for two cases of respiratory tract tumors. One case had had a left complete atelectasis for bronchial tumor, after microwave electrodes had been carried out surgery. The otherhad had a right complete atelectasis for epidermoid carcinoma ; we performed transbronchial biopsy for diagnosis with using microwave electrodes for occasional bronchial bleeding.We experienced less bleeding and smoke, a larger area could be coagulated in single procedure than high power laser ablation therapy. This method was effective in treating airway obstruction, especially in patients for administrating oxygen for respiratory failure because of less its ignitable.
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