32970 research outputs found
Sort by
Expression and localisation of Rab44 in immune-related cells change during cell differentiation and stimulation
Get PDFRab44 is a large Rab GTPase that contains a Rab-GTPase domain and some additional domains, such as EF-hand and coiled-coil domains at the N-terminus. Our previous study showed that Rab44 negatively regulates osteoclast differentiation by modulating intracellular calcium levels; however, aside from those findings, there is little information concerning Rab44 on other cells or tissues. In this study, we showed that Rab44 was highly expressed in bone marrow cells among various mouse tissues. Immunohistochemical studies indicated that Rab44 was detectable by only a small number of cells in the immune-related tissues and that Rab44 was partially detected in CD117-positive cells, but not in Stem cell antigen 1-positive cells in the bone marrow. Rab44 expression levels were decreased during differentiation of immune-related cells, such as neutrophils, macrophages, and dendritic cells compared with bone marrow cells. Although endogenous Rab44 in macrophages was localised in lysosomes, lipopolysaccharide (LPS) stimulation led to partial translocation to early endosomes and the plasma membrane. Moreover, Rab44 expression levels were altered by treatment with various immunomodulators, including LPS. These results indicate that Rab44 expression and localisation in bone marrow cells and macrophages alters with cell differentiation and stimulation
Cathepsin B Protease Facilitates Chikungunya Virus Envelope Protein-Mediated Infection Via Endocytosis or Macropinocytosis
Get PDFChikungunya virus (CHIKV) is an enveloped virus that enters host cells and transits
within the endosomes before starting its replication cycle, the precise mechanism of which is yet to be elucidated. Endocytosis and endosome acidification inhibitors inhibit infection by CHIKV,murine leukemia virus (MLV), or SARS-coronavirus, indicating that these viral entries into host cells
occur through endosomes and require endosome acidification. Although endosomal cathepsin B
protease is necessary for MLV, Ebola virus, and SARS-CoV infections, its role in CHIKV infection is unknown. Our results revealed that endocytosis inhibitors attenuated CHIKV-pseudotyped MLV vector infection in 293T cells but not in TE671 cells. In contrast, macropinocytosis inhibitors attenuated CHIKV-pseudotyped MLV vector infection in TE671 cells but not in 293T cells, suggesting
that CHIKV host cell entry occurs via endocytosis or macropinocytosis, depending on the cell lines used. Cathepsin B inhibitor and knockdown by an shRNA suppressed CHIKV-pseudotyped MLV vector infection both in 293T and TE671 cells. These results show that cathepsin B facilitates CHIKV infection regardless of the entry pathway
2013-2015年日本の地方都市長崎市における急性下気道感染症入院患児の原因ウイルスの解析
No full textBackground: Acute lower respiratory tract infections (ALRIs) are the most common disease for hospitalized children in Japan. The aim of this study was to identify viruses in children hospitalized for ALRIs and to demonstrate epidemiologic and clinical characteristics in Japan. Methods: During a 2-year period from February 2013 to January 2015, we collected nasopharyngeal swab specimens from almost all hospitalized children with ALRIs in Nagasaki, a regional city of Japan, and its environs. Viruses were detected by multiplex polymerase chain reaction from these samples. Results:
We detected one or more viruses from 259 (69%) of 374 patients, 227 of whom were infected with a single virus, 30 with 2, and 2 with 3 viruses. Detected viruses in this study were rhinovirus (46.4%), respiratory syncytial virus (29.7%), human metapneumovirus (6.8%), parainfluenza virus (5.5%), enterovirus D68 (3.4%), influenza virus (2.7%), adenovirus (2.4%), bocavirus (2.0%) and Coxsackie virus (1.0%). We detected a seasonal shift in respiratory syncytial virus outbreaks from the 2013–2014 to the 2014–2015 seasons. There was no significant difference in clinical course and severity among those viruses. Patients with a history of asthma or underlying diseases were older and more frequently required oxygen therapy than previously healthy patients. Conclusions: Viral etiology in hospitalized children with ALRIs in Nagasaki, Japan, was similar to that in many other countries. Enterovirus D68, which was recently recognized as a causative agent of severe ALRIs, was also identified in this study area. Severity of ALRIs may depend on underlying disease rather than type of etiologic virus.長崎大学学位論文 学位記番号:博(医歯薬)甲第1263号 学位授与年月日:令和2年6月3日Author: Hasuwa, Tomoyuki; Kinoshita, Fumiko; Harada, Sadatomo; Nakashima, Kazuhisa; Yoshihara, Keisuke; Toku, Yuichirou; Moriuchi, Hiroyuki; Yoshida, Lay MyintCitation: Pediatric Infectious Disease Journal, 39(8), pp.687-693; 202
Discontinuation of biosimilar infliximab in Japanese patients with rheumatoid arthritis achieving sustained clinical remission or low disease activity during the IFX-SIRIUS STUDY I (the IFX-SIRIUS STUDY II)
Get PDFBACKGROUND: The introduction of biological disease-modifying anti-rheumatic drugs into clinical practice has dramatically improved the clinical outcomes of individuals with rheumatoid arthritis (RA). We are conducting the IFX-SIRIUS STUDY I that evaluates whether switching from originator infliximab (IFX) to its biosimilar, CT-P13, is not inferior in maintaining nonclinical relapse to continue treatment with originator IFX in patients with RA achieving clinical remission. It is the next great issue whether disease activity can be maintained
in good condition after discontinuation of CT-P13 because no evidence is available regarding the clinical value of discontinuing biosimilars in patients with RA. Thus, we will evaluate whether a condition without clinical relapse will be maintained after discontinuation of CT-P13
in patients with RA, achieving clinical remission or low disease activity during the IFX-SIRIUS STUDY I. METHODS/DESIGN: This study is an interventional, multicenter, open-label, single-arm clinical trial with a 48-week follow-up. Patients with RA who are treated with CT-P13 and sustained nonclinical relapse during the IFX-SIRIUS STUDY I will be included. Patients will discontinue CT-P13 after the study period of the IFX-SIRIUS STUDY I. We will evaluate disease activity by clinical disease activity indices and musculoskeletal
ultrasound (MSUS). The primary endpoint is the proportion of patients who do not have clinical relapse during the study period.
Important secondary endpoints are the changes from the baseline of the MSUS scores. We will also comprehensively analyze the serum levels of multiple biomarkers, such as cytokines and chemokines. In addition, if a clinical relapse occurs in patients after the discontinuation of CT-P13, we will evaluate the effectiveness and safety of restarting CT-P13. DISCUSSION: The study results are expected to show the clinical benefit of the discontinuation of CT-P13 and effectiveness and safety of restarting CT-P13 after clinical relapse.
The strength of this study is to prospectively evaluate the therapeutic effectiveness by not only clinical disease activity indices but also standardized MSUS findings in multiple centers. We will explore whether parameters at baseline can predict a nonclinical relapse after the discontinuation of CT-P13 by integrating multilateral assessments, that is, patient's characteristics, clinical disease activity
indices, MSUS findings, and serum biomarkers. TRIAL REGISTRATION: This study was registered in the Japan Registry of Clinical Trials (https://jrct.niph.go.jp) on April 20, 2020 as jRCTs071200007
Anti-EJ Antibody-positive Anti-synthetase Syndrome Associated with Retroperitoneal Sarcoma
Get PDFA 74-year-old man with interstitial lung disease (ILD) underwent surgical excision of a growing retroperitoneal tumor and was diagnosed with spindle cell sarcoma. Just after the surgery, skin eruption and muscle weakness emerged. Based on his symptoms and examination findings, we diagnosed him with anti-synthetase syndrome (ASS) with positive anti-glycyl-transfer ribonucleic acid synthetase antibody (anti-EJ) as paraneoplastic syndrome. Immunosuppressive treatments kept his progressing ILD stable for 21 months, although an expanding lung metastatic lesion from primary sarcoma was detected. Measurements of myositis-specific antibodies may enable the prediction of the efficacy of immunosuppressive treatments for paraneoplastic syndrome, even if the primary disease becomes progressive
Development of an Intervention to Support the Reproductive Health of Cambodian Women Who Seek Medical Abortion: Research Protocol
Get PDFBackground: In Cambodia, abortion has been legally permitted on request during the first trimester of pregnancy since 1997.
However, although there has been an increase in the percentage of women having induced abortion and medical abortion, there has also been a decrease in the percentage of women who say they received help from a health worker with their abortion.
These data point toward the demedicalization of abortion, and although medical abortion has been shown to be safe,
there are concerns about safety, given the variety of available products and counseling provided. These concerns are particularly relevant for female factory workers, who typically come from rural areas where access to good health care and information about reproductive health care is limited. Objective: This study aims to understand the reproductive health needs of female Cambodian garment factory workers after medical abortion from a multidisciplinary and mixed-methods perspective, focusing on how they seek and share medical abortion- and health-related information; how they use their mobile phones for this and other purposes; what cultural challenges exist around reproductive health; and how they might be magnified or mitigated by mobile phones, linguistic challenges around health care, and mobile phone use. The main purpose of this study is to combine multidisciplinary methods, theories, and expertise to gain new, culturally grounded insights into family planning and medical abortion in Cambodia, but the findings could help inform the development of a relevant intervention to support comprehensive postabortion care. Methods: The methods proposed are interviews and participant observation among factory workers, health providers,
and mobile phone providers; a linguistic analysis of relevant data (interview transcripts, web-based sources,
and other fieldwork materials); and digital methods to understand what kind of information about medical abortion exists
on the web in Cambodia and how it is accessed by the targeted population. Results: The data collection part of the project
will end on December 31, 2020. The team conducted 67 semistructured interviews with female factory workers,
women who sought a medical abortion, health providers, and mobile phone providers; participant observation
with factory workers and health providers; and an analysis of YouTube and Facebook to understand what kind of information
is available, who creates it, and how it is used. The team is currently performing data analysis, and the findings are
clustered around (1) the use of mobile phones and digital resources for health-related and medical abortion-related
information, (2) the experience of medical abortion care, and (3) the development of an intervention through edutainment
videos. Conclusions: The project highlights both the widely untapped potential of using digital platforms
(especially YouTube and Facebook) to distribute accurate information on medical abortion and the challenges in providing
individual information via mobile phones while respecting individuals' privacy
Periodicity due to Coalescence of Atmospheric Pressure Discharge
No full textWe experimentally investigate the control of atmospheric pressure discharge exhibiting chaotic oscillation. Atmospheric pressure discharge systems, before and during coalescence, are investigated based on photographs, time series, power spectra, and the largest Lyapunov exponents. Through these experiments, it is discovered that the merged discharge system after coalescence shows a periodic oscillation with coherence, and that dynamic behaviors transform from chaotic to orderly