Publications by authors named "Mitsuru Sada"

Oxidative stress plays an important role in the pathophysiology of bronchial asthma (BA), chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO), but its relevance has not been fully elucidated. The aim of this study was to measure the levels of oxidative stress and investigate its clinical significance in patients with BA, COPD, or ACO. We recruited 214 patients between June 2020 and May 2023 (109 patients with BA, 63 with COPD, and 42 with ACO).

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Acute exacerbation (AE) of interstitial lung disease (ILD) is a major challenge. This study aimed to retrospectively investigate occurrences of AEs in patients with ILDs, including idiopathic pulmonary fibrosis (IPF), non-IPF (iNSIP: idiopathic nonspecific interstitial pneumonia), and connective tissue disease (CTD)-associated ILDs (CTD-ILDs), at a single tertiary center before and after the coronavirus disease 2019 (COVID-19) pandemic. The study aimed to clarify the seasonal and regional trends of AEs of ILDs, assess the roles of viral and bacterial infections, and identify key prognostic factors for patient outcomes.

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Bronchoscopy is an invasive procedure, and patient coughing during examination has been reported to cause patient distress. This study aimed to clarify the relationship between cough severity and diagnostic yield of endobronchial ultrasonography with guide sheath transbronchial biopsy (EBUS-GS-TBB). Data of patients who underwent bronchoscopy at Kyorin University Hospital between April 2019 and March 2022 were retrospectively evaluated.

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To better understand the evolution of the SARS-CoV-2 Omicron subvariants, we performed molecular evolutionary analyses of the spike () protein gene/S protein using advanced bioinformatics technologies. First, time-scaled phylogenetic analysis estimated that a common ancestor of the Wuhan, Alpha, Beta, Delta variants, and Omicron variants/subvariants diverged in May 2020. After that, a common ancestor of the Omicron variant generated various Omicron subvariants over one year.

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We focused on Piper longum L., a herbal drug produced in Myanmar, which has a renoprotective effect. Thus, we attempted to isolate and identify compounds that enhance the expression of the ABCG2 gene from the aerial parts of the plant except for the fruit.

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Human respiratory syncytial viruses (HRSVs) are divided into subgroups A and B, which are further divided based on the nucleotide sequence of the second hypervariable region (HVR) of the attachment glycoprotein (G) gene. Understanding the molecular diversity of HRSV before and during the coronavirus disease 2019 (COVID-19) pandemic can provide insights into the effects of the pandemic on HRSV dissemination and guide vaccine development. Here, we analyzed HRSVs isolated in Fukushima Prefecture from September 2017 to December 2021.

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Few evolutionary studies of the human respiratory virus (HRV) have been conducted, but most of them have focused on HRV3. In this study, the full-length fusion (F) genes in HRV1 strains collected from various countries were subjected to time-scaled phylogenetic, genome population size, and selective pressure analyses. Antigenicity analysis was performed on the F protein.

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Despite the increasing evidence of the clinical impact of -derived cephalosporinase (PDC) sequence polymorphisms, the molecular evolution of its encoding gene, , remains elusive. To elucidate this, we performed a comprehensive evolutionary analysis of . A Bayesian Markov Chain Monte Carlo phylogenetic tree revealed that a common ancestor of diverged approximately 4660 years ago, leading to the formation of eight clonal variants (clusters A-H).

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Article Synopsis
  • The exact causes of asthma are not fully understood, but respiratory infections, particularly those caused by rhinovirus (RV), may trigger or worsen the condition.
  • Understanding the connection between viral infections and asthma can help address differences in immune responses between viral infections and allergies.
  • The complexity of RV-induced asthma involves both the immune response to the virus and allergic reactions triggered by various cytokines, highlighting the need to explore both RV infections and host defense mechanisms for a clearer understanding.
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Molecular interactions between respiratory syncytial virus (RSV) fusion protein (F protein) and the cellular receptor Toll-like receptor 4 (TLR4) and myeloid differentiation factor-2 (MD-2) protein complex are unknown. Thus, to reveal the detailed molecular interactions between them, in silico analyses were performed using various bioinformatics techniques. The present simulation data showed that the neutralizing antibody (NT-Ab) binding sites in both prefusion and postfusion proteins at sites II and IV were involved in the interactions between them and the TLR4 molecule.

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Article Synopsis
  • DNA gyrase, specifically the GyrA protein encoded by the
  • gene
  • , is vital for DNA replication in bacteria and mutations in GyrA lead to resistance against quinolone antibiotics like ciprofloxacin.
  • A study used advanced bioinformatics to analyze the evolution of the
  • gene
  • , revealing a common ancestor over 760 years ago and that certain mutations (T83I and D87N) related to drug resistance became prevalent after clinical use of quinolones.
  • The research showed that these mutations reduce the effectiveness of ciprofloxacin, suggesting that the
  • gene
  • evolved to help bacteria survive antibiotic treatment post-1962 when quinolone use began.
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There are currently no antiviral agents for human metapneumovirus (HMPV), respiratory syncytial virus (RSV), mumps virus (MuV), or measles virus (MeV). Favipiravir has been developed as an anti-influenza agent, and this agent may be effective against these viruses in vitro. However, the molecular mechanisms through which the agent affects virus replication remain to be fully elucidated.

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Article Synopsis
  • The study analyzed the evolution and genetic diversity of the RSV-A fusion (F) gene using 1465 global strains, revealing insights into its lineage and reinfection patterns.
  • It found that RSV-A and RSV-B diverged around 250 years ago and identified eight genotypes formed over the last 80 years.
  • The analysis showed that while the F gene is relatively conserved, mismatches between conformational epitopes and neutralizing antibody binding sites may lead to reinfection by RSV-A.
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The pandemic of COVID-19 caused by SARS-CoV-2 continues to spread despite the global efforts taken to control it. The 3C-like protease (3CLpro), the major protease of SARS-CoV-2, is one of the most interesting targets for antiviral drug development because it is highly conserved among SARS-CoVs and plays an important role in viral replication. Herein, we developed high throughput screening for SARS-CoV-2 3CLpro inhibitor based on AlphaScreen.

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To predict the clinical outcome of coronavirus disease-2019 (COVID-19), we examined relationships among epidemiological data, viral load, and disease severity. We examined viral loads of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) in fatal (15 cases), symptomatic/survived (133 cases), and asymptomatic cases (138 cases) using reverse transcription quantitative real-time PCR (RT-qPCR). We examined 5768 nasopharyngeal swabs (NPS) and attempted to detect the SARS-CoV-2 genome using RT-qPCR.

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Rationale: Severe eosinophilic asthma is characterized by airway eosinophilia and corticosteroid-resistance, commonly overlapping with type 2 inflammation. It has been reported that chemokine (C-C motif) ligand 5 (CCL5) is involved in the exacerbation of asthma by RNA virus infections. Indeed, treatment with a virus-associated ligand and a T helper type 2 cell (Th2) cytokine can synergistically stimulate CCL5 production in bronchial epithelial cells.

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Favipiravir was initially developed as an antiviral drug against influenza and is currently used in clinical trials against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (COVID-19). This agent is presumably involved in RNA chain termination during influenza virus replication, although the molecular interactions underlying its potential impact on the coronaviruses including SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV) remain unclear. We performed in silico studies to elucidate detailed molecular interactions between favipiravir and the SARS-CoV-2, SARS-CoV, MERS-CoV, and influenza virus RNA-dependent RNA polymerases (RdRp).

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commonly colonizes the airway of patients with chronic obstructive pulmonary disease (COPD) and exacerbates their symptoms. carries flagellin that stimulates toll-like receptor (TLR)-5; however, the role of flagellin in the pathogenesis of COPD remains unclear. The aim of the study was to evaluate the mechanisms of the flagellin-induced innate immune response in bronchial epithelial cells, and to assess the effects of anti-inflammatory agents for treatment.

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Rationale: Neutrophilic airway inflammation plays a central role in chronic obstructive pulmonary disease (COPD). CXC chemokine ligand (CXCL)1 is a neutrophil chemokine involved in the pathogenesis of COPD. However, its clinical significance in COPD patients is poorly understood.

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Background: Neutrophilic inflammation is associated with poorly controlled asthma. Serum levels of sST2, a soluble IL-33 receptor, increase in neutrophilic lung diseases. We hypothesized that high serum sST2 levels in stable asthmatics are a predictor for exacerbation within a short duration.

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Objective We investigated a novel diagnostic scoring system to differentiate Legionella pneumophila pneumonia from Streptococcus pneumoniae pneumonia. Methods We retrospectively reviewed the clinical data of 62 patients with L. pneumophila pneumonia (L-group) and 70 patients with S.

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