Objective
The aim of this study was to investigate whether the stimulation of monocytic cells with procalcitonin (PCT) results in the release of proinflammatory cytokines. The effects of intravenous ...immunoglobulin (IVIG) on the production of cytokines from the cells stimulated with PCT were also studied.
Materials and methods
Cultured monocytic cells THP-1 cells treated with phorbol myristate acetate or peripheral blood mononuclear cells (PBMCs) were stimulated with PCT. The protein levels of proinflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and high mobility group box-1 in the culture supernatants were determined by ELISA kits. The concentration of PCT-specific IgG antibody in IVIG was measured using a specific ELISA.
Results
PCT induced the release of cytokines from THP-1 cells in a time- and dose-dependent manner. IVIG inhibited the release of cytokines from the cells stimulated with PCT. It was confirmed that IVIG also inhibited TNF-α release in the same dose range for PBMCs stimulated with PCT. The presence of PCT-specific IgG antibody was detected in the tested IVIG, which might be one of the mechanisms.
Conclusions
PCT induced the release of proinflammatory cytokines from THP-1 cells and PBMCs. The function of PCT was prevented by the presence of IVIG.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The present study aimed to evaluate the clinical benefits of leucovorin, 5-fluorouracil, irinotecan and oxaliplatin (FOLFIRINOX) vs. gemcitabine plus Nab-paclitaxel (GnP) as a first-line therapy for ...patients with inoperable pancreatic cancer. For this purpose, in-house data available for 45 patients who received FOLFIRINOX or GnP as first-line treatment between 2014 and 2019 were retrospectively analyzed. In total, 21 and 24 patients received FOLFIRINOX and GnP, respectively. Although there were no significant differences in the median progression-free survival, the median overall survival was longer in the FOLFIRINOX group than in the GnP group (16.7 vs. 7.2 months). A total of 14 patients received FOLFIRINOX followed by GnP, whereas 3 patients received GnP followed by FOLFIRINOX. All patients who did not switch to second-line therapy owing to poor feasibility were included in the GnP group. The data indicated that patients receiving GnP as first-line therapy were less likely to switch to FOLFIRINOX and, consequently, had a worse prognosis.The present study aimed to evaluate the clinical benefits of leucovorin, 5-fluorouracil, irinotecan and oxaliplatin (FOLFIRINOX) vs. gemcitabine plus Nab-paclitaxel (GnP) as a first-line therapy for patients with inoperable pancreatic cancer. For this purpose, in-house data available for 45 patients who received FOLFIRINOX or GnP as first-line treatment between 2014 and 2019 were retrospectively analyzed. In total, 21 and 24 patients received FOLFIRINOX and GnP, respectively. Although there were no significant differences in the median progression-free survival, the median overall survival was longer in the FOLFIRINOX group than in the GnP group (16.7 vs. 7.2 months). A total of 14 patients received FOLFIRINOX followed by GnP, whereas 3 patients received GnP followed by FOLFIRINOX. All patients who did not switch to second-line therapy owing to poor feasibility were included in the GnP group. The data indicated that patients receiving GnP as first-line therapy were less likely to switch to FOLFIRINOX and, consequently, had a worse prognosis.
Acute otitis media (AOM) occurs commonly in pediatric populations. We examined resistance genotype, antibiotic susceptibility, quinolone (QL) resistance, and multilocus sequence type (MLST) among ...Haemophilus influenzae isolates causing AOM following introduction of pneumococcal conjugate vaccines in Japan.
The AOM surveillance group included 69 participating otolaryngologists. Causative pathogens isolated from middle ear fluid (MEF) samples collected from 582 children with AOM were identified using both bacterial culture and real-time PCR. H. influenzae isolates among these pathogens were characterized by capsular type, resistance genotype, antibiotic susceptibility, QL resistance, and MLST.
In 2016, H. influenzae was identified in 319 samples (54.8%), among which 72.4% (n = 231) tested positive by both culture and PCR; remaining H. influenzae cases were only PCR-positive. This proportion of H. influenzae positivity has increased significantly from 41.2% in 2006 (p < 0.001). Among culture-positive strains, genotypic β-lactamase-nonproducing ampicillin (AMP)-resistant (gBLNAR) strains were frequent (63.2%), with β-lactamase-nonproducing AMP-susceptible (gBLNAS) strains accounting for only 24.2%. Susceptibilities of gBLNAR to oral antimicrobials were best for tosufloxacin, followed by cefditoren and tebipenem; MIC90s were 0.031 μg/mL, 0.5 μg/mL, and 1 μg/mL, respectively. In 7 gBLNAR isolates (3.0%), QL susceptibility was low, owing to amino acid substitutions in GyrA and/or ParC. Sequence types identified numbered 107, including 28 that were new.
Prevention of further increases in resistance to antimicrobial agents will require antibiotic selection based on characterization of causative pathogens in clinical practice.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
ABSTRACT
Immune checkpoint inhibitors (ICIs) are widely used in both monotherapy and combination chemotherapy for various types of cancers. Nivolumab is the most popular among ICIs, and the number of ...adapted malignant diseases for nivolumab is increasing. Bronchoesophageal fistula formation is a serious complication of the treatment for esophageal or lung cancer. However, the development of bronchoesophageal fistula as a complication of ICIs is obscure. A 59-year-old man who was diagnosed with carcinoma of unknown primary with a subgroup of lung squamous cell carcinoma had bronchoesophageal fistula formation after three cycles of nivolumab as the fourth line treatment. Before the initiation of nivolumab, he had received two esophageal stents and an angiogenesis inhibitor. These are known risk factors for fistula formation. This is a rare case showing that nivolumab monotherapy might induce bronchoesophageal fistulae. Therefore, clinicians should be aware of the factors related to fistula formation when using ICIs.
Recently, as the material of turbine discs for the civil airplane, P/M superalloys such as Rene95 and RR1000 have been in practical use. This is because the advantages of P/M superalloys are more ...pronounced in homogeneous structure, mechanical properties and yield rate than the disadvantage in the cost of the process such as HIP by the advance in technology to produce alloy powders. However, PPB (Prior Particle Boundary) is known to decrease the toughness and ductility of PM alloys. In this study, for getting the superfine grain and high strength, the gas-atomized powder was HIPed at a δ-subsolvus temperature. The relationship between the microstructure including PPB and mechanical properties was investigated using Inconel 718, which is used widely as a heat-resistant alloy for the aerospace and energy industries. It was found that HIP treatment at a δ-subsolvus temperature brought about the superfine grain and the high proof strength, and that the increase of the solution treatment temperature reduced the PPB influence.
Recently, as the material of turbine discs for the civil airplane, P/M superalloys such as Rene95 and RR1000 have been in practical use. This is because the advantages of P/M superalloys are more ...pronounced in homogeneous structure, mechanical properties and yield rate than the disadvantage in the cost of the process such as HIP by the advance in technology to produce alloy powders. However, PPB (Prior Particle Boundary) is known to decrease the toughness and ductility of PM alloys. In this study, for getting the superfine grain and high strength, the gas-atomized powder was HIPed at a delta-subsolvus temperature. The relationship between the microstructure including PPB and mechanical properties was investigated using Inconel 718, which is used widely as a heat-resistant alloy for the aerospace and energy industries. It was found that HIP treatment at a 5-subsolvus temperature brought about the superfine grain and the high proof strength, and that the increase of the solution treatment temperature reduced the PPB influence.
In the previous investigations, we showed that intravenous immunoglobulin (IVIG) prevented cytokine release in procalcitonin (PCT)-stimulated monocytic cells. The aim of the present study was to ...investigate the underlying mechanisms of inhibition of IVIG on cytokine production in PCT-stimulated THP-1 cells. THP-1 cells treated with phorbol myristate acetate were stimulated with PCT. The protein levels of pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and high-mobility group box 1 (HMGB1) in the culture supernatants were determined using enzyme-linked immunosorbent assay kits. The mRNA level of TNF-alpha was determined by reverse transcription-polymerase chain reaction. The phosphorylations of nuclear factor kappa B (NFkappaB) and the mitogen-activated protein kinases (MAPKs) were determined by Western blotting. IVIG reduced mRNA expression and protein production of TNF-alpha in PCT-stimulated THP-1 cells. Not only IVIG but also both the Fc fragment and the F(ab')^sub 2^ fragment inhibited PCT-induced TNF-alpha, IL-6, and HMGB1 production. Furthermore, IVIG and its fragments suppressed PCT-induced phosphorylations of NFkappaB, p38 MAPK, and c-Jun N-terminal kinase. Our results indicate that IVIG prevents PCT-induced cytokine production mediated by not only the Fab region but also the Fc region. The activity of IVIG and its fragments might be regulated by inhibiting NFkappaB and MAPKs pathways in THP-1 cells.PUBLICATION ABSTRACT
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The postnatal development of the Eustachian tube (ET) and its surrounding structures was investigated by means of computer-aided three-dimensional (3-D) reconstruction methods in 13 normal human ...temporal bones, obtained from individuals 3 months to 71 years old. The cross-sectional area, width and height of the lumen in most of the cartilaginous portion of the ET were significantly smaller in children than in adults. In particular, there was a marked, age-associated difference in the shape of the lumen in the cartilaginous portion of the ET. In adults, the cross-sectional area of the lumen declined monotonically between a large opening at the pharyngeal orifice and the narrowest portion of the ET (near the border of the cartilaginous and junctional regions). In children, by contrast, the ET lumen was uniformly smaller over the first 80% of its length from the pharyngeal orifice. It is suggested that this immature morphology of the ET lumen may confer increased risk of developing otitis media during childhood.
A survey was conducted about nursing information in volunteer activities of nursing faculty members and students after the Great East Japan Earthquake. Results indicated that it was important to ...attempt collecting information in every possible way and to always be prepared. During activities, it is important to record information, to share information with individuals other than nursing professionals and to make good use of it.
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