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result(s) for
"Takashi Shimizu"
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Infectious disease and labor management
2021
In the early 20th century, when Spanish flu and tuberculosis were prevalent, laborers in the Japanese textile industry worked long hours in poor conditions, and the risk of contracting an infectious disease was high. In such a situation, forward-thinking companies set up hospitals as a voluntary measure for dealing with infectious disease, provided free medical care and assistance payments in the event of illness, improved company dormitories, and introduced other measures for safeguarding workers’ welfare such as upgrading factories and offering educational programs. These programs influenced other companies and resulted in improvements in the working conditions at a number of firms, indicating that these countermeasures against infectious diseases were economically rational. This in turn implies that it is economically rational to upgrade sanitation and workers’ welfare in response to the current COVID-19 pandemic.
Journal Article
Infectious disease and labor management
2021
In the early 20th century, when Spanish flu and tuberculosis were prevalent, laborers in the Japanese textile industry worked long hours in poor conditions, and the risk of contracting an infectious disease was high. In such a situation, forward-thinking companies set up hospitals as a voluntary measure for dealing with infectious disease, provided free medical care and assistance payments in the event of illness, improved company dormitories, and introduced other measures for safeguarding workers’ welfare such as upgrading factories and offering educational programs. These programs influenced other companies and resulted in improvements in the working conditions at a number of firms, indicating that these countermeasures against infectious diseases were economically rational. This in turn implies that it is economically rational to upgrade sanitation and workers’ welfare in response to the current COVID-19 pandemic.
Journal Article
Role of the JAK2/STAT3 pathway on infection of Francisella novicida
2024
Francisella tularensis is a causative agent of the zoonotic disease tularemia, and is highly pathogenic to humans. The pathogenicity of this bacterium is largely attributed to intracellular growth in host cells. Although several bacterial factors important for the intracellular growth have been elucidated, including the type VI secretion system, the host factors involved in the intracellular growth of F . tularensis are largely unknown. To identify the host factors important for F . tularensis infection, 368 compounds were screened for the negative regulation of F . tularensis subsp. novicida ( F . novicida ) infection. Consequently, 56 inhibitors were isolated that decreased F . novicida infection. Among those inhibitors, we focused on cucurbitacin I, an inhibitor of the JAK2/ STAT3 pathway. Cucurbitacin I and another JAK2/STAT3 inhibitor, Stattic, decreased the intracellular bacterial number of F . novicida . However, these inhibitors failed to affect the cell attachment or the intrasaccular proliferation of F . novicida . In addition, treatment with these inhibitors destabilized actin filaments. These results suggest that the JAK2/STAT3 pathway plays an important role in internalization of F . novicida into host cells through mechanisms involving actin dynamics, such as phagocytosis.
Journal Article
Stages in the degeneration of flight ability and their interspecific comparisons in the genus Synuchus (Coleoptera: Carabidae) in Japan
2024
The degeneration in flight ability in beetles has rarely been studied in detail with regard to the polymorphism of flight traits within species. However, intraspecific diversity in flight traits means that the flight ability of species is in the process of degenerating, which could provide important insights into how flight ability in beetles degenerates. In this study, the flight muscle and hind wings of the genus Synuchus in Japan were studied, which revealed the morphological status of flight traits in 21 species of Synuchus. Several species in this genus were found to show intraspecific polymorphisms in the states of the flight muscle and hind wings, and in particular, the very high diversity of different types of hind wings. These results indicate that this genus contains a mixture of species at various stages in the degeneration of the ability to fly.
Journal Article
Identification of the Francisella novicida FTN_0096 as a factor involved in intracellular replication and host response
by
Watanabe, Kenta
,
Wardhana, Dhandy Koesoemo
,
Shimizu, Takashi
in
Animals
,
Antibodies
,
Bacteria
2025
Francisella tularensis is the causative agent of the zoonotic disease tularemia. We investigated a pathogenic factor of F . tularensis subsp. novicida (F. novicida). Accordingly, we established a novel infection model using HeLa cells. F. novicida usually infects macrophage lineage cells and less frequently epithelial cells. We successfully infected HeLa cells expressing the Fc receptor (HeLa–FcγRII cells) using F. novicida supplemented with mouse serum containing F. novicida antibodies. A total of 2,232 transposon mutants of F . novicida were screened to determine the relatively fewer cytotoxic strains of the HeLa–FcγRII cells, and 13 strains were thus isolated. Sequencing analysis of transposon insertion sites identified 13 genes, including FTN_0096 . We focused on FTN_0096 . Although the F. novicida wild-type strain proliferated in HeLa–FcγRII and THP-1 cells, the number of intracellular FTN_0096 mutant decreased. FTN_0096 mutant cannot escape from phagolysosomes in the initial phases of infection. Moreover, FTN_0096 mutant was detected in the mitochondria and Golgi complex. These findings indicate the importance of FTN_0096 of F. novicida for intracellular replication in the cells.
Journal Article
Soluble lytic transglycosylase SLT of Francisella novicida is involved in intracellular growth and immune suppression
2019
Francisella tularensis, a category-A bioterrorism agent causes tularemia. F. tularensis suppresses the immune response of host cells and intracellularly proliferates. However, the detailed mechanisms of immune suppression and intracellular growth are largely unknown. Here we developed a transposon mutant library to identify novel pathogenic factors of F. tularensis. Among 750 transposon mutants of F. tularensis subsp. novicida (F. novicida), 11 were isolated as less cytotoxic strains, and the genes responsible for cytotoxicity were identified. Among them, the function of slt, which encodes soluble lytic transglycosylase (SLT) was investigated in detail. An slt deletion mutant (Δslt) was less toxic to the human monocyte cell line THP-1 vs the wild-type strain. Although the wild-type strain proliferated in THP-1 cells, the number of intracellular Δslt mutant decreased in comparison. The Δslt mutant escaped from phagosomes during the early stages of infection, but the mutant was detected within the autophagosome, followed by degradation in lysosomes. Moreover, the Δslt mutant induced host cells to produce high levels of cytokines such as tumor necrosis factor-α, interleukin (IL)-6, and IL-1β, compared with the wild-type strain. These results suggest that the SLT of F. novicida is required for immune suppression and escape from autophagy to allow its survival in host cells.
Journal Article
Distinction of Paramecium strains by a combination method of RAPD analysis and multiplex PCR
2022
Paramecium is employed as a valuable model organism in various research fields since a large number of strains with different characteristics of size, morphology, degree of aging, and type of conjugation can be obtained. It is necessary to determine a method for the classification and simple identification of strains to increase their utility as a research tool. This study attempted to establish a polymerase chain reaction (PCR)-based method to differentiate strains of the same species. Genomic DNA was purified from several strains of P . caudatum , P . tetraurelia , and P . bursaria used for comparison by the random amplified polymorphic DNA (RAPD)-PCR method. In P . tetraurelia and P . bursaria , it was sufficiently possible to distinguish specific strains depending on the pattern of random primers and amplification characteristics. For the classification of P . caudatum , based on the sequence data obtained by RAPD-PCR analysis, 5 specific primer sets were designed and a multiplex PCR method was developed. The comparative analysis of 2 standard strains, 12 recommended strains, and 12 other strains of P . caudatum provided by the National BioResource Project was conducted, and specific strains were identified. This multiplex PCR method would be an effective tool for the simple identification of environmental isolates or the management of Paramecium strains.
Journal Article
Soluble PD-L1 changes in advanced non-small cell lung cancer patients treated with PD-1 inhibitors: an individual patient data meta-analysis
by
Ohkuma, Ryotaro
,
Wada, Satoshi
,
Shimizu, Takashi
in
advanced non-small cell lung cancer
,
Apoptosis
,
B7-H1 Antigen - metabolism
2023
Currently, first-line immune checkpoint inhibitors (ICIs), including programmed cell death protein-1 (PD-1) inhibitors, are utilized as monotherapy in advanced non-small cell lung cancer (NSCLC) patients with high programmed death ligand-1 (PD-L1) expression (≧50%). Pre-treatment or post-treatment serum soluble PD-L1 (sPD-L1) has been identified as a potential biomarker for assessing ICI efficacy through fixed-point observations. However, existing studies on sPD-L1 changes have produced inconsistent results or have had sample sizes too small to detect clinically meaningful effect sizes. To elucidate the role of sPD-L1, we conducted a collaborative individual patient data meta-analysis of PD-1 inhibitor treatments.
We conducted a thorough search of articles in PubMed via Medline, Embase, Scopus, and Cochrane databases from inception to October 20, 2023. Trials were deemed eligible if they contained individual datasets for advanced NSCLC patients, including data on overall survival (OS)/progression-free survival (PFS), as well as pre- and post-treatment sPD-L1 levels after 3-4 cycles of PD-1 inhibitor treatments. Our analysis focused on patients who completed 3-4 cycles of PD-1 inhibitor treatments. The primary outcome measure was OS/PFS, and we assessed changes in sPD-L1 concentration pre- and post-treatment through ELISA analyses.
From our search, we identified a potential seven trials, encompassing 256 patients. Among these, two trials with 26 patients met the criteria for inclusion in our primary analyses. Over a median follow-up period of 10 months, pooled univariate analysis revealed that increases in sPD-L1 levels during PD-1 inhibitor treatment were not associated with OS (HR = 1.25; CI: 0.52-3.02)/PFS (HR = 1.42; CI: 0.61-3.30) when compared to cases with sPD-L1 decreases. Subgroup analyses indicated that the impact of sPD-L1 changes on overall mortality/progression-related mortality remained consistent regardless of gender, age, or the type of treatment (nivolumab or pembrolizumab).
Our findings suggest that changes in sPD-L1 levels during PD-1 inhibitor treatment do not significantly influence the prognosis of advanced NSCLC patients, regardless of gender, age, or treatment type. Continuous monitoring of sPD-L1 may not offer significant advantages compared to fixed-point observations.
Journal Article
The association between gingivitis and oral spirochetes in young cats and dogs
2023
Although gingivitis frequently occurs in young cats, spirochetes are often found in the early stages of periodontal disease. This study was conducted to determine the association between gingivitis and oral spirochetes in young cats and dogs. The degree of gingivitis was evaluated in a total of 68 cats and 31 dogs under one year of age, and plaques were collected from each carnassial. To detect spirochetes or Porphyromonas gulae in plaque samples, 16S rRNA gene was amplified by polymerase chain reaction (PCR) using specific primers. All data were analyzed using Fisher’s exact probability test and odds ratio (OR) with a 95% confidence interval (95% CI). The prevalence of gingivitis was significantly higher in young cats (92.6%) than in young dogs (45.2%). The positive rate of spirochetes by PCR in gingivitis cases was 85.4% in young cats and 15.4% in young dogs, and the positive rate of P . gulae was 66.7% in young cats and 15.4% in young dogs. Both results were significantly higher in young cats than in young dogs. In young cats, spirochetes were significantly associated with gingivitis (OR = 7.95; 95% CI = 1.17, 53.83; P < 0.05), but P . gulae was not (OR = 2.44; 95% CI = 0.38, 15.66; P = 0.23). These results suggest that spirochetes may be associated with the early stages of periodontal disease in cats.
Journal Article