Publications by authors named "Yasuyo Okada"

Background: Healthcare workers (HCWs) caring for patients with coronavirus disease-2019 (COVID-19) can experience physical and mental health burdens. It is imperative that hospitals reduce such burdens on frontline HCWs, protect them, and support their healthcare. This study aimed to investigate the association between occupation and the manifestation of physical or psychological symptoms among HCWs during the current COVID-19 pandemic.

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Introduction: Genetic testing is gaining increasing importance as a part of antimicrobial stewardship (AS). Rapid identification and determination of methicillin susceptibility using the Xpert MRSA/SA BC assay can improve the management of Staphylococcus aureus bacteremia (SAB) and reduce inappropriate antibiotic use. However, few reports have described the effectiveness of this approach.

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Article Synopsis
  • * A new treatment option, mono-6-O-α-maltosyl-γ-CD (G2-γ-CD), shows promise for NPC by reducing disease symptoms in mouse models and having less ototoxicity compared to the current option, HP-β-CD.
  • * Research indicates that G2-γ-CD forms a more stable 1:1 cholesterol complex, unlike HP-β-CD, which forms a 2:1 complex at higher concentrations; this difference could explain its better safety profile and effectiveness for clinical use.
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Introduction: Coronavirus disease 2019 (COVID-19) has greatly impacted medical care practices. Although the effects on infectious disease treatment and infection control, such as antimicrobial resistance, have been specified, very few reports exist on the specific effects of COVID-19.

Methods: We investigated the effects of COVID-19 on daily medical practices at a tertiary hospital in Japan by comparing the use of hand sanitizers, the detection of bacteria from blood cultures, and the amount dose of antibacterial drugs used for one year before (April 2019 to March 2020, fiscal year 2019.

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Background: Healthcare workers (HCWs) who manage patients with the novel coronavirus disease 2019 (COVID-19) are at an increased risk and fear of contracting the infection themselves. Hospitals must reduce both the physical and mental burden of HCWs on the front lines and ensure their safety. No prospective study has focused on the physical health complaints among HCWs engaged in the care of critically ill COVID-19 patients.

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Introduction: Clostridioides difficile is an important causative pathogen in antibiotic-associated colitis and nosocomial infections. This study aimed to assess immunochromatographic test results for C. difficile infection and the utility of PCR-based open-reading frame typing (POT) for potentially controlling the intra-ward transmission of C.

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Objectives: Cases of positive blood cultures were previously reported by a microbiological technologist (MT) to an attending physician (AP), and the Antimicrobial Stewardship team provided medical assistance by grasping the situation at the morning meeting the next day. Since April 2018, MTs have reported positive blood cultures to an infectious disease physician (IDP), who proposes the management approach to the AP and provides weekend support. This study assessed the effectiveness of blood culture reports provided by IDPs to APs on outcomes of bacteremia, including weekend-onset cases.

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The effect of antimicrobial stewardship (AS) on anaerobic bacteremia is uncertain. This study aimed to assess the effect of interventions by the AS team (AST) on clinical and microbiological outcomes and antimicrobial use. An AS program was introduced at Osaka City University Hospital in January 2014; an interdisciplinary AST was established.

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Antibiotic stewardship (AS) improves patient outcomes and rates of antibiotic susceptibilities. However, the long-term effect of AS programs (ASPs) on mortality is unclear. This study aimed to assess the impact of bedside interventions by an AS team (AST) on clinical and microbiological outcomes.

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Niemann-Pick disease Type C (NPC) is a rare lysosomal storage disease characterized by the dysfunction of intracellular cholesterol trafficking with progressive neurodegeneration and hepatomegaly. We evaluated the potential of 6--α-maltosyl-β-cyclodextrin (G2-β-CD) as a drug candidate against NPC. The physicochemical properties of G2-β-CD as an injectable agent were assessed, and molecular interactions between G2-β-CD and free cholesterol were studied by solubility analysis and two-dimensional proton nuclear magnetic resonance spectroscopy.

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Patients with invasive fungal diseases (IFDs) generally have a high mortality rate, and resistance to antifungal drugs and the high costs associated with it have led to recent problems, necessitating the appropriate use of antifungals. To this end, we launched Antifungal Stewardship Programs (AFSPs) in our hospital. Patients who were systemically administered antifungals from January 2011 to December 2016 were enrolled this study and divided into pre-intervention and intervention groups.

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We aimed to investigate whether 6-O-α-maltosyl-β-cyclodextrin (Mal-βCD) is incorporated into cells and lysosomes during the release of unesterified cholesterol in Npc1-deficient Chinese hamster ovary (CHO) cells (Npc1 KO cells) and CHO-JP17 cells (JP17 cells). Internalization of Mal-βCD in cells and lysosomes and extracellular release of lysosomal unesterified cholesterol were demonstrated by LC/MS/MS and LC/MS, respectively. Internalization of Mal-βCD was greater in Npc1 KO cells than in JP17 cells.

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Objective Coagulase-negative staphylococci are among the most frequently isolated microorganisms in blood cultures. The aim of this study was to assess [1] the clinical characteristics of methicillin-resistant, coagulase-negative staphylococci bacteremia and [2] the susceptibility of the isolated bacteria to glycopeptides. Methods We retrospectively reviewed the medical records of 70 patients from whom methicillin-resistant coagulase-negative staphylococci had been isolated at Osaka City University Hospital between January 2010 and December 2013.

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Polymerase chain reaction (PCR)-based open reading frame typing (POT) helps differentiate between bacterial strains based on the open reading frames (ORFs) of the prophage-encoding genes; multiplex PCR screening is performed to identify strains based on keeping patterns. At our hospital, surveillance of nosocomial methicillin-resistant Staphylococcus aureus (MRSA) transmission is undertaken using POT to conduct molecular epidemiological analysis for all newly detected MRSA strains. In 2014, we performed POT only once a month; however, in 2015, we increased the frequency of POT to once a week, which helped us detect nosocomial transmission that would normally be difficult to detect, and thus achieve 40% reduction in nosocomial transmission, compared to that in 2014.

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We investigated the susceptibility of 400 Pseudomonas aeruginosa (P. aeruginosa) clinical isolates to 3 antipseudomonal carbapenems, namely, doripenem (DRPM), meropenem (MEPM), and imipenem (IPM). The test strains were isolated from the following specimens: respiratory (n = 194), urinary (n = 61), digestive (n = 38), pus (n = 36), skin (n = 21), blood (n = 9), upper respiratory tract and oral cavity (n = 8), and others (n = 33) at Osaka City University Hospital from July to October 2013.

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Integrins are heterodimeric adhesion receptors essential for adhesion of non-adherent cells to extracellular ligands such as extracellular matrix components. The affinity of integrins for ligands is regulated through a process termed integrin activation and de novo synthesis. Integrin activation is regulated by lipid raft components and the actin structure.

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We have previously described 6-O-α-maltosyl-β cyclodextrin (Mal-βCD), which forms soluble inclusion complex with cholesterol. Here we further investigated the effect of Mal-βCD and cholesterol/Mal-βCD inclusion complex (CLM) on cellular cholesterol levels in a mouse mast cell line, mastocytoma P-815 cells (P-815 cells). Mal-βCD removes cellular cholesterol forming inclusion complexes, while Mal-βCD-induced lack of cellular cholesterol was replenished by the addition of CLM without cytotoxicity.

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The physicochemical and biological properties of the new branched cyclomaltooligosaccharides (cyclodextrins; CDs), 2-O-α-D-galactosyl-cyclomaltohexaose (2-O-α-D-galactosyl-α-cyclodextrin, 2-Gal-αCD) and 2-O-α-D-galactosyl-cyclomaltoheptaose (2-O-α-D-galactosyl-β-cyclodextrin, 2-Gal-βCD), were investigated. The formation of inclusion complexes of 2-Gal-CDs with various kinds of guest compounds (clofibrate, cholesterol, cholecalciferol, digitoxin, digitoxigenin, and prostaglandin A(1)) was examined by a solubility method, and the results were compared with those of non-branched CDs and other 6-O-glycosyl-CDs such as 6-O-α-D-galactosyl-CDs, 6-O-α-D-glucosyl-CDs, and 6-O-α-maltosyl-CDs. The inclusion abilities of 2-Gal-αCD for clofibrate and prostaglandin A(1), and 2-Gal-βCD for clofibrate, cholecalciferol, cholesterol, and digitoxigenin were markedly weaker than those of non-branched CD and other 6-O-glycosyl-CDs in each series, probably because of a steric hindrance caused by the α-(1→2)-galactoside linkage.

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We previously demonstrated that prostaglandin (PG) E₂ stimulates adhesion of mastocytoma P-815 cells (P-815 cells) to the Arg-Gly-Asp (RGD)-enriched matrix via the PGE₂ receptor subtype EP4 [Hatae N, Kita A, Tanaka S, Sugimoto Y, Ichikawa A. Induction of adherent activity in mastocytoma P-815 cells by the cooperation of two prostaglandin E₂ receptor subtypes, EP3 and EP4. J Biol Chem 2003;278:17977-81].

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Sorbic acid (SA: CH(3)-CH=CH-CH=CH-COOH) is one of the widely used food preservatives, although there have been some reports of its toxic activity, for example, on DNA and skin cells. In order to examine the effects of SA on mammalian tissues, we have developed a highly sensitive analytical method using LC/MS/MS with positive and negative ion mode electrospray ionization (ESI). In a previous study, we found that a nonacidic eluent offers better ionization efficiency than acids or their ammoniun salts.

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A 62-year-old man presented with clinical signs of acute abdominal pain and adrenal insufficiency. Computerized tomographic scans revealed bilateral adrenal tumors and the left adrenal tumor was surgically resected. The patient was found to have retroperitoneal mesothelioma presenting as bilateral metastatic adrenal tumors, which were well controlled by systemic chemotherapy with CDDP and 5-FU.

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Mass spectral measurements by electrospray ionization mass spectrometry (ESI-MS) detected the ions of beta-cyclodextrin (betaCD) or branched betaCDs (glucosyl-, galactosyl-, mannosyl- and maltosyl-betaCD)-prostaglandins (PGs: PGA(2), PGD(2), PGE(1), PGE(2), PGF(2alpha) and PGJ(2)) complexes, i.e., betaCD-PG complexes, with a host:guest ratio of 1:1 in the negative ion mode.

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Sorbic acid (SA: CH(3)-CH=CH-CH=CH-COOH) and its salts are widely used as preservatives in foodstuff because of their growth inhibitory effects on mold, yeast and a wide range of bacteria. However, it is still unclear whether SA and its salts are actually incorporated in these organisms and a higher organisms like mammalian cells. Acidic compounds such as SA are usually analyzed by HPLC with eluents containing acetic acid, formic acid and their ammonium acetates, but such acidic buffers may suppress the ionization efficiency of the acidic compounds in negative-mode electrospray ionization (ESI).

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Di-O-alpha-maltosyl-beta-cyclodextrin ((G2)(2)-beta-CD) was synthesized from 6-O-alpha-maltosyl-beta-cyclodextrin (G2-beta-CD) via a transglycosylation reaction catalyzed by TreX, a debranching enzyme from Sulfolobus solfataricus P2. TreX showed no activity toward glucosyl-beta-CD, but a transfer product (1) was detected when the enzyme was incubated with maltosyl-beta-CD, indicating specificity for a branched glucosyl chain bigger than DP2. Analysis of the structure of the transfer product (1) using MALDI-TOF/MS and isoamylase or glucoamylase treatment revealed it to be dimaltosyl-beta-CD, suggesting that TreX transferred the maltosyl residue of a G2-beta-CD to another molecule of G2-beta-CD by forming an alpha-1,6-glucosidic linkage.

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A unique multibranched cyclomaltooligosaccharide (cyclodextrin, CD) of 6(1),6(3),6(5)-tri-O-alpha-maltosyl-cyclomaltoheptaose [6(1),6(3),6(5)-tri-O-alpha-maltosyl-beta-cyclodextrin, (G(2))(3)-betaCD] was prepared. The physicochemical and biological properties of (G(2))(3)-betaCD were determined together with those of monobranched CDs (6-O-alpha-D-glucopyranosyl-alpha-cyclodextrin (G(1)-alphaCD), 6-O-alpha-D-glucopyranosyl-beta-cyclodextrin (G(1)-betaCD), and 6-O-alpha-maltosyl-beta-cyclodextrin (G(2)-betaCD)). NMR spectra of (G(2))(3)-betaCD were measured using various 2D NMR techniques.

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