40 results on '"Nishimura, B."'
Search Results
2. Difficulty in writing Japanese semantic characters in a 9-year-old boy with Williams syndrome
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Nakamura, M., Hara, K., Watamaki, T., Nishimura, B., Kumagai, T., Matsumoto, A., Miura, K., Yamanaka, T., Hayakawa, C., and Miyazaki, S.
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- 1999
3. 2833 Clinical utility of predictive factor before treatment in patients with advanced head and neck cancer
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Nakayama, M., primary, Tabuchi, K., additional, Nishimura, B., additional, Wada, T., additional, and Hara, A., additional
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- 2015
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4. Ototoxicity: Mechanisms of Cochlear Impairment and its Prevention
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Tabuchi, K., primary, Nishimura, B., additional, Nakamagoe, M., additional, Hayashi, K., additional, Nakayama, M., additional, and Hara, A., additional
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- 2011
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5. Cochlear protection from acoustic injury by inhibitors of p38 mitogen-activated protein kinase and sequestosome 1 stress protein
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Tabuchi, K., primary, Oikawa, K., additional, Hoshino, T., additional, Nishimura, B., additional, Hayashi, K., additional, Yanagawa, T., additional, Warabi, E., additional, Ishii, T., additional, Tanaka, S., additional, and Hara, A., additional
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- 2010
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6. Clinical evaluation of a collagen-based dermal substitute (terudermis) in oral mucosal defects after the operation of jaw bone cysts and benign tumors
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Takahashi, N., Teranobu, O., Nakajima, K., Nishimura, B., Ri, S., Oko, T., and Shimada, K.
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- 1997
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7. Carbapenem-resistant Acinetobacter baumannii (CRAB): metabolic adaptation and transcriptional response to human urine (HU).
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Escalante J, Hamza M, Nishimura B, Melecio M, Davies-Sala C, Tuttobene MR, Subils T, Traglia GM, Pham C, Sieira R, Actis LA, Bonomo RA, Tolmasky ME, and Ramirez MS
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- Humans, Gene Expression Regulation, Bacterial drug effects, Anti-Bacterial Agents pharmacology, Acinetobacter Infections microbiology, Acinetobacter Infections urine, Adaptation, Physiological genetics, Urinary Tract Infections microbiology, Biofilms growth & development, Biofilms drug effects, Drug Resistance, Bacterial genetics, Acinetobacter baumannii genetics, Acinetobacter baumannii drug effects, Acinetobacter baumannii metabolism, Carbapenems pharmacology, Urine microbiology
- Abstract
Carbapenem-resistant Acinetobacter baumannii (CRAB) is a major human pathogen and a research priority for developing new antimicrobial agents. CRAB is a causative agent of a variety of infections in different body sites. One of the manifestations is catheter-associated urinary tract infection, which exposes the bacteria to the host's urine, creating a particular environment. Exposure of two CRAB clinical isolates, AB5075 and AMA40, to human urine (HU) resulted in the differential expression levels of 264 and 455 genes, respectively, of which 112 were common to both strains. Genes within this group play roles in metabolic pathways such as phenylacetic acid (PAA) catabolism, the Hut system, the tricarboxylic acid (TCA) cycle, and other processes like quorum sensing and biofilm formation. These results indicate that the presence of HU induces numerous adaptive changes in gene expression of the infecting bacteria. These changes presumably help bacteria establish and thrive in the hostile conditions in the urinary tract. These analyses advance our understanding of CRAB's metabolic adaptations to human fluids, as well as expand knowledge on bacterial responses to distinct human fluids containing different concentrations of human serum albumin (HSA)., (© 2024. The Author(s).)
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- 2024
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8. Human serum albumin-induced modification of Ton-B-dependent receptor expression in cefiderocol-exposed carbapenem-resistant Acinetobacter baumannii.
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Nishimura B, Escalante J, Mezcord V, Tuttobene MR, Subils T, Actis LA, Pasteran F, Tolmasky ME, Bonomo RA, and Ramirez MS
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- Humans, Cephalosporins pharmacology, Anti-Bacterial Agents pharmacology, Carbapenems pharmacology, Microbial Sensitivity Tests, Cefiderocol, Acinetobacter baumannii
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- 2023
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9. Fever-like temperature impacts on Staphylococcus aureus and Pseudomonas aeruginosa interaction, physiology, and virulence both in vitro and in vivo .
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Solar Venero EC, Galeano MB, Luqman A, Ricardi MM, Serral F, Fernandez Do Porto D, Robaldi SA, Ashari B, Munif TH, Egoburo DE, Nemirovsky S, Escalante J, Nishimura B, Ramirez MS, Götz F, and Tribelli PM
- Abstract
Background: Staphylococcus aureus and Pseudomonas aeruginosa cause a wide variety of bacterial infections and coinfections, showing a complex interaction that involves the production of different metabolites and metabolic changes. Temperature is a key factor for bacterial survival and virulence and within the host, bacteria could be exposed to an increment in temperature during fever development. We analyzed the previously unexplored effect of fever-like temperatures (39°C) on S. aureus USA300 and P. aeruginosa PAO1 microaerobic mono- and co-cultures compared with 37°C, by using RNAseq and physiological assays including in-vivo experiments., Results: In general terms both temperature and co-culturing had a strong impact on both PA and SA with the exception of the temperature response of monocultured PA. We studied metabolic and virulence changes on both species. Altered metabolic features at 39°C included arginine biosynthesis and the periplasmic glucose oxidation in S. aureus and P. aeruginosa monocultures respectively. When PA co-cultures were exposed at 39°C they upregulated ethanol oxidation related genes along with an increment in organic acid accumulation. Regarding virulence factors, monocultured SA showed an increase in the mRNA expression of the agr operon and hld, pmsα and pmsβ genes at 39°C. Supported by mRNA data, we performed physiological experiments and detected and increment in hemolysis, staphylxantin production and a decrease in biofilm formation at 39°C. On the side of PA monocultures, we observed increase in extracellular lipase and protease and biofilm formation at 39°C along with a decrease in motility in correlation with changes observed at mRNA abundance. Additionally, we assessed host-pathogen interaction both in-vitro and in-vivo . S. aureus monocultured at 39°C showed a decrease in cellular invasion and an increase in IL-8 -but not in IL-6- production by A549 cell line. PA also decreased its cellular invasion when monocultured at 39°C and did not induce any change in IL-8 or IL-6 production. PA strongly increased cellular invasion when co-cultured at 37°C and 39°C. Finally, we observed increased lethality in mice intranasally inoculated with S. aureus monocultures pre-incubated at 39°C and even higher levels when inoculated with co-cultures. The bacterial burden for P. aeruginosa was higher in liver when the mice were infected with co-cultures previously incubated at 39°C comparing with 37°C., Conclusion: Our results highlight a relevant change in the virulence of bacterial opportunistic pathogens exposed to fever-like temperatures in presence of competitors, opening new questions related to bacteria-bacteria and host-pathogen interactions and coevolution.
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- 2023
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10. Induced Heteroresistance in Carbapenem-Resistant Acinetobacter baumannii (CRAB) via Exposure to Human Pleural Fluid (HPF) and Its Impact on Cefiderocol Susceptibility.
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Mezcord V, Escalante J, Nishimura B, Traglia GM, Sharma R, Vallé Q, Tuttobene MR, Subils T, Marin I, Pasteran F, Actis LA, Tolmasky ME, Bonomo RA, Rao G, and Ramirez MS
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- Humans, Carbapenems pharmacology, Carbapenems therapeutic use, Microbial Sensitivity Tests, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, beta-Lactamases genetics, Iron pharmacology, Cefiderocol, Acinetobacter baumannii, Acinetobacter Infections drug therapy, Acinetobacter Infections microbiology
- Abstract
Infections caused by Carbapenem-resistant Acinetobacter baumannii (CRAB) isolates, such as hospital-acquired pneumonia (HAP), bacteremia, and skin and soft tissue infections, among others, are particularly challenging to treat. Cefiderocol, a chlorocatechol-substituted siderophore antibiotic, was approved by the U.S. Food and Drug Administration (FDA) in 2019 and prescribed for the treatment of CRAB infections. Despite the initial positive treatment outcomes with this antimicrobial, recent studies reported a higher-than-average all-cause mortality rate in patients treated with cefiderocol compared to the best available therapy. The cause(s) behind these outcomes remains unconfirmed. A plausible hypothesis is heteroresistance, a phenotype characterized by the survival of a small proportion of cells in a population that is seemingly isogenic. Recent results have demonstrated that the addition of human fluids to CRAB cultures leads to cefiderocol heteroresistance. Here, we describe the molecular and phenotypic analyses of CRAB heteroresistant bacterial subpopulations to better understand the nature of the less-than-expected successful outcomes after cefiderocol treatment. Isolation of heteroresistant variants of the CRAB strain AMA40 was carried out in cultures supplemented with cefiderocol and human pleural fluid (HPF). Two AMA40 variants, AMA40 IHC1 and IHC2, were resistant to cefiderocol. To identify mutations and gene expression changes associated with cefiderocol heteroresistance, we subjected these variants to whole genome sequencing and global transcriptional analysis. We then assessed the impact of these mutations on the pharmacodynamic activity of cefiderocol via susceptibility testing, EDTA and boronic acid inhibition analysis, biofilm formation, and static time-kill assays. Heteroresistant variants AMA40 IHC1 and AMA40 IHC2 have 53 chromosomal mutations, of which 40 are common to both strains. None of the mutations occurred in genes associated with high affinity iron-uptake systems or β-lactam resistance. However, transcriptional analyses demonstrated significant modifications in levels of expression of genes associated with iron-uptake systems or β-lactam resistance. The bla
NDM-1 and blaADC-2, as well as various iron-uptake system genes, were expressed at higher levels than the parental strain. On the other hand, the carO and ompA genes' expression was reduced. One of the mutations common to both heteroresistant strains was mapped within ppiA , a gene associated with iron homeostasis in other species. Static time-kill assays demonstrated that supplementing cation-adjusted Mueller-Hinton broth with human serum albumin (HAS), the main protein component of HPF, considerably reduced cefiderocol killing activity for all three strains tested. Notably, collateral resistance to amikacin was observed in both variants. We conclude that exposing CRAB to fluids with high HSA concentrations facilitates the rise of heteroresistance associated with point mutations and transcriptional upregulation of genes coding for β-lactamases and biofilm formation. The findings from this study hold significant implications for understanding the emergence of CRAB resistance mechanisms against cefiderocol treatment. This understanding is vital for the development of treatment guidelines that can effectively address the challenges posed by CRAB infections.- Published
- 2023
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11. Imaging of diffuse fibroepithelial polyps on surgical free flap in oral cancer patients: two case reports.
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Sakai M, Nishimura B, Hiyama T, Kuno H, Shinozaki T, Sakamoto N, and Nakajima T
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- Humans, Positron Emission Tomography Computed Tomography, Neoplasm Recurrence, Local, Free Tissue Flaps, Mouth Neoplasms diagnostic imaging, Mouth Neoplasms surgery, Carcinoma, Squamous Cell
- Abstract
Fibroepithelial polyp (FEP) is a common benign tumor occurring in the skin and genitourinary tract, and there are no reports of multiple FEPs occurring on the myocutaneous flap. We report two cases of FEPs occurring diffusely on the skin tissue of the free anterolateral thigh flap after surgical reconstruction for oral squamous cell carcinoma. Clinically, multiple papillary nodules on the myocutaneous flap gradually increased. CT and MRI showed multiple papillary nodules on an enhanced layer covering the entire myocutaneous flap. PET/CT showed high uptake. One case was diagnosed with FEPs by surgery, the other by biopsy. The tumor-limited localization on the myocutaneous flap, characteristic morphology showing multiple papillary projection with an enhanced layer, and MRI signal showing patchy mild elevation of the apparent diffusion coefficient value may help in differential diagnosis from tumor recurrence or secondary carcinoma of the myocutaneous flap on diagnostic imaging., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2023
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12. Genomic Comparative Analysis of Two Multi-Drug Resistance (MDR) Acinetobacter baumannii Clinical Strains Assigned to International Clonal Lineage II Recovered Pre- and Post-COVID-19 Pandemic.
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Traglia GM, Pasteran F, Escalante J, Nishimura B, Tuttobene MR, Subils T, Nuñez MR, Rivollier MG, Corso A, Tolmasky ME, and Ramirez MS
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Background: After the emergence of COVID-19, numerous cases of A. baumannii /SARS-CoV-2 co-infection were reported. Whether the co-infecting A. baumannii strains have distinctive characteristics remains unknown., Methods and Results: A. baumannii AMA_NO was isolated in 2021 from a patient with COVID-19. AMA166 was isolated from a mini-BAL used on a patient with pneumonia in 2016. Both genomes were similar, but they possessed 337 (AMA_NO) and 93 (AMA166) unique genes that were associated with biofilm formation, flagellar assembly, antibiotic resistance, secretion systems, and other functions. The antibiotic resistance genes were found within mobile genetic elements. While both strains harbored the carbapenemase-coding gene bla
OXA-23 , only the strain AMA_NO carried blaNDM-1 . Representative functions coded for by virulence genes are the synthesis of the outer core of lipooligosaccharide (OCL5), biosynthesis and export of the capsular polysaccharide (KL2 cluster), high-efficiency iron uptake systems (acinetobactin and baumannoferrin), adherence, and quorum sensing. A comparative phylogenetic analysis including 239 additional sequence type (ST) 2 representative genomes showed high similarity to A. baumannii ABBL141. Since the degree of similarity that was observed between A. baumannii AMA_NO and AMA166 is higher than that found among other ST2 strains, we propose that they derive from a unique background based on core-genome phylogeny and comparative genome analysis., Conclusions: Acquisition or shedding of specific genes could increase the ability of A. baumannii to infect patients with COVID-19.- Published
- 2023
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13. The Iron Content of Human Serum Albumin Modulates the Susceptibility of Acinetobacter baumannii to Cefiderocol.
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Escalante J, Nishimura B, Tuttobene MR, Subils T, Mezcord V, Actis LA, Tolmasky ME, Bonomo RA, and Ramirez MS
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The mortality rates of patients infected with Acinetobacter baumannii who were treated with cefiderocol (CFDC) were not as favorable as those receiving the best available treatment for pulmonary and bloodstream infections. Previous studies showed that the presence of human serum albumin (HSA) or HSA-containing fluids, such as human serum (HS) or human pleural fluid (HPF), in the growth medium is correlated with a decrease in the expression of genes associated with high-affinity siderophore-mediated iron uptake systems. These observations may explain the complexities of the observed clinical performance of CFDC in pulmonary and bloodstream infections, because ferric siderophore transporters enhance the penetration of CFDC into the bacterial cell. The removal of HSA from HS or HPF resulted in a reduction in the minimal inhibitory concentration (MIC) of CFDC. Concomitant with these results, an enhancement in the expression of TonB-dependent transporters known to play a crucial role in transporting iron was observed. In addition to inducing modifications in iron-uptake gene expression, the removal of HSA also decreased the expression of β-lactamases genes. Taken together, these observations suggest that environmental HSA has a role in the expression levels of select A. baumannii genes. Furthermore, the removal of iron from HSA had the same effect as the removal of HSA upon the expression of genes associated with iron uptake systems, also suggesting that at least one of the mechanisms by which HSA regulates the expression of certain genes is through acting as an iron source.
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- 2023
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14. Human serum albumin (HSA) regulates the expression of histone-like nucleoid structure protein (H-NS) in Acinetobacter baumannii.
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Escalante J, Nishimura B, Tuttobene MR, Subils T, Pimentel C, Georgeos N, Sieira R, Bonomo RA, Tolmasky ME, and Ramirez MS
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- Anti-Bacterial Agents, Bacterial Proteins, Biofilms, Gene Expression Regulation, Bacterial, Histones, Humans, Quorum Sensing, Serum Albumin, Human, Acinetobacter baumannii
- Abstract
According to the Centers for Disease Control and Prevention, Acinetobacter baumannii is listed among the most threatening pathogens. A. baumannii is mainly a nosocomial pathogen with a distinctive ability to survive in multiple environments. These characteristics together with this bacterium's ability to acquire antibiotic resistance determinants make it a notorious pathogen. The presence of human serum albumin (HSA) is associated with modification of expression levels in numerous genes. The presence of HSA in the culture medium is also correlated with a reduction in levels of the global suppressor histone-like nucleoid structure protein, H-NS. Comparative transcriptome analysis of the wild type and isogenic Δhns strains cultured in lysogeny broth (LB) in the presence or absence of HSA revealed that the expression of a subset of eleven genes are modified in the Δhns cultured in LB and the wild-type strain in the presence of HSA, pointing out these genes as candidates to be regulated by the presence of HSA through H-NS. Six and five of these genes were up- or down-regulated, respectively. Three of these genes have functions in quorum sensing (acdA, kar and fadD), one in quorum quenching (aidA), two in stress response (katE, ywrO), three in metabolism (phaC, yedL1, and yedL2), one in biofilm formation (csuAB), and one in β-oxidation of fatty acids (fadA). The regulation of these genes was assessed by: (i) transcriptional analysis and qPCR at the transcriptional level; and (ii) by determining the phenotypic characteristics of each function. The results of these studies support the hypothesis that HSA-mediated reduction of H-NS levels may be one very important regulatory circuit utilized by A. baumannii to adapt to selected environments, such as those where HSA-containing human fluids are abundant., (© 2022. The Author(s).)
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- 2022
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15. Inflammation-Based Score (Combination of Platelet Count and Neutrophil-to-Lymphocyte Ratio) Predicts Pharyngocutaneous Fistula After Total Laryngectomy.
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Matsumoto S, Nakayama M, Gosho M, Nishimura B, Takahashi K, Yoshimura T, Senarita M, Ohara H, Akizuki H, Wada T, and Tabuchi K
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- Humans, Inflammation, Laryngectomy adverse effects, Lymphocyte Count, Lymphocytes, Neutrophils, Platelet Count, Prognosis, Retrospective Studies, Cutaneous Fistula epidemiology, Cutaneous Fistula etiology, Pharyngeal Diseases epidemiology, Pharyngeal Diseases etiology
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Objectives/hypothesis: Postoperative complications may depend on the systemic inflammatory response. We evaluated the predictive potential of the combination of platelet count and neutrophil-to-lymphocyte ratio (COP-NLR) for the incidence of pharyngocutaneous fistula (PCF) in patients who have undergone total laryngectomy., Study Design: Retrospective cohort study., Methods: Patients who underwent total laryngectomy between 2000 and 2020 were recruited from four hospitals. The correlations between the incidence of PCF and several risk factors, including the COP-NLR, were examined. Patients with both elevated platelet count and elevated neutrophil-to-lymphocyte ratio (NLR) were categorized as COP-NLR 2, and patients with either one or no abnormal values of both parameters were assigned as COP-NLR 1 and COP-NLR 0, respectively., Results: A total of 235 patients were identified. The overall incidence of PCF was 12.3%. The cut-off value for NLR before surgery was set at 3.95 (sensitivity = 58.6%, specificity = 69.4%, area under the curve [AUC] = 0.635), and the platelet count was set at 320 × 10
9 /L (sensitivity = 27.6%, specificity = 87.9%, AUC = 0.571). Multivariate analysis revealed that COP-NLR was an independent risk factor for PCF (COP-NLR 1 vs. COP-NLR 0: odds ratio [OR], 4.17; 95% confidence interval [CI], 1.64 to 10.59; and COP-NLR 2 vs. COP-NLR 0: OR, 5.33; 95% CI, 1.38 to 20.56)., Conclusions: COP-NLR is a novel predictive factor for the development of PCF in patients undergoing total laryngectomy., Level of Evidence: 4 Laryngoscope, 132:1582-1587, 2022., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)- Published
- 2022
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16. Acinetobacter baumannii response to cefiderocol challenge in human urine.
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Nishimura B, Escalante J, Tuttobene MR, Subils T, Mezcord V, Pimentel C, Georgeos N, Pasteran F, Rodriguez C, Sieira R, Actis LA, Tolmasky ME, Bonomo RA, and Ramirez MS
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- Albumins pharmacology, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Carbapenems pharmacology, Cephalosporins, Humans, Iron pharmacology, Microbial Sensitivity Tests, Siderophores, beta-Lactamases genetics, Cefiderocol, Acinetobacter baumannii
- Abstract
Cefiderocol (CFDC) is a novel chlorocatechol-substituted siderophore antibiotic approved to treat complicated urinary tract infections (cUTI) and hospital-acquired and ventilator-acquired pneumonia (HAP/VAP). Previous work determined that albumin-rich human fluids increase the minimum inhibitory concentration (MICs) of Acinetobacter baumannii against CFDC and reduce the expression of genes related to iron uptake systems. This latter effect may contribute to the need for higher concentrations of CFDC to inhibit growth. The presence of human urine (HU), which contains low albumin concentrations, did not modify MIC values of two carbapenem-resistant A. baumannii. Levels of resistance to CFDC were not modified by HU in strain AMA40 but were reduced in strain AB5075. Expanding the studies to other carbapenem-resistant A. baumannii isolates showed that the presence of HU resulted in unmodified or reduced MIC of CDFC values. The expression of piuA, pirA, bauA, and bfnH determined by qRT-PCR was enhanced in A. baumannii AMA40 and AB5075 by the presence of HU in the culture medium. All four tested genes code for functions related to recognition and transport of ferric-siderophore complexes. The effect of HU on expression of pbp1, pbp3, bla
OXA-51-like , blaADC , and blaNDM-1 , genes associated with resistance to β-lactams, as well as genes coding for efflux pumps and porins was variable, showing dependence with the strain analyzed. We conclude that the lack of significant concentrations of albumin and free iron in HU makes this fluid behave differently from others we tested. Unlike other albumin rich fluids, the presence of HU does not impact the antibacterial activity of CFDC when tested against A. baumannii., (© 2022. The Author(s).)- Published
- 2022
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17. Efficacy of the pretreatment geriatric nutritional risk index for predicting severe adverse events in patients with head and neck cancer treated with chemoradiotherapy.
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Nakayama M, Ohnishi K, Adachi M, Ii R, Matsumoto S, Nakamura M, Miyamoto H, Hirose Y, Nishimura B, Tanaka S, Wada T, and Tabuchi K
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- Aged, Geriatric Assessment, Humans, Nutrition Assessment, Nutritional Status, Retrospective Studies, Squamous Cell Carcinoma of Head and Neck therapy, Chemoradiotherapy adverse effects, Head and Neck Neoplasms therapy
- Abstract
Objective: The Geriatric Nutritional Risk Index (GNRI) is a simple and well-established nutritional assessment tool. Although concurrent chemoradiotherapy (CCRT), particularly cisplatin-based CCRT, is a standard treatment for locoregional advanced head and neck squamous cell carcinoma (HNSCC), the predictive factors of adverse events related to CCRT remain to be elucidated. The present study aimed to determine the association between GNRI and CCRT-related adverse events in patients of all ages with head and neck cancer (HNC) who underwent CCRT., Methods: We retrospectively analyzed and compared the clinical characteristics and adverse events of 82 patients with HNC treated with CCRT according to their GNRI at the Department of Otolaryngology, Head and Neck Surgery, University of Tsukuba Hospital, between May 2014 and November 2019. The GNRI was calculated according to the equation: 1.489 × serum albumin (g/L) + 41.7 × (body weight/ideal body weight). We compared two groups: low GNRI (GNRI < 98) and normal GNRI (GNRI ≥ 98) groups., Results: Eighty-two patients were enrolled in this study. There were 61 (76%) and 21 (26%) patients in the normal GNRI group and low GNRI group, respectively. There were significant differences in the incidence of grade ≥ 3 radiation mucositis, radiation dermatitis, and leukopenia between the low GNRI group and the normal GNRI groups., Conclusions: Patients with low GNRI scores were more likely to have severe adverse events. Pretreatment GNRI predicted severe CCRT-related adverse events in patients of all ages with HNC undergoing CCRT., Competing Interests: Declaration of Competing Interest The authors have no financial disclosures or conflicts of interest to declare., (Copyright © 2021. Published by Elsevier B.V.)
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- 2022
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18. Human Serum Proteins and Susceptibility of Acinetobacter baumannii to Cefiderocol: Role of Iron Transport.
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Le C, Pimentel C, Pasteran F, Tuttobene MR, Subils T, Escalante J, Nishimura B, Arriaga S, Carranza A, Mezcord V, Vila AJ, Corso A, Actis LA, Tolmasky ME, Bonomo RA, and Ramírez MS
- Abstract
Cefiderocol, a recently introduced antibiotic, has a chemical structure that includes a cephalosporin that targets cell wall synthesis and a chlorocatechol siderophore moiety that facilitates cell penetration by active iron transporters. Analysis of the effect that human serum, human serum albumin, and human pleural fluid had on growing Acinetobacter baumannii showed that genes related to iron uptake were down-regulated. At the same time, β-lactamase genes were expressed at higher levels. The minimum inhibitory concentrations of this antimicrobial in A. baumannii cells growing in the presence of human serum, human serum albumin, or human pleural fluid were higher than those measured when these fluids were absent from the culture medium. These results correlate with increased expression levels of β-lactamase genes and the down-regulation of iron uptake-related genes in cultures containing human serum, human serum albumin, or human pleural fluid. These modifications in gene expression could explain the less-than-ideal clinical response observed in patients with pulmonary or bloodstream A. baumannii infections. The exposure of the infecting cells to the host's fluids could cause reduced cefiderocol transport capabilities and increased resistance to β-lactams. The regulation of genes that could impact the A. baumannii susceptibility to cefiderocol, or other antibacterials, is an understudied phenomenon that merits further investigation.
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- 2022
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19. Interplay between Meropenem and Human Serum Albumin on Expression of Carbapenem Resistance Genes and Natural Competence in Acinetobacter baumannii.
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Le C, Pimentel C, Tuttobene MR, Subils T, Nishimura B, Traglia GM, Perez F, Papp-Wallace KM, Bonomo RA, Tolmasky ME, and Ramirez MS
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- Anti-Bacterial Agents pharmacology, Carbapenems pharmacology, Humans, Meropenem pharmacology, Microbial Sensitivity Tests, Serum Albumin, Human, Acinetobacter baumannii genetics
- Abstract
Acinetobacter baumannii A118, a carbapenem-susceptible strain, and AB5075, carbapenem resistant, were cultured in lysogeny broth (LB) or LB with different supplements, such as 3.5% human serum albumin (HSA), human serum (HS), meropenem, or meropenem plus 3.5% HSA. Natural transformation levels were enhanced in A. baumannii A118 and AB5075 cultured in medium supplemented with 3.5% HSA. Addition of meropenem plus 3.5% HSA caused synergistic enhancement of natural transformation in A. baumannii A118. Medium containing 3.5% HSA or meropenem enhanced the expression levels of the competence and type IV pilus-associated genes. The combination meropenem plus 3.5% HSA produced a synergistic enhancement in the expression levels of many of these genes. The addition of HS, which has a high content of HSA, was also an inducer of these genes. Cultures in medium supplemented with HS or 3.5% HSA also affected resistance genes, which were expressed at higher or lower levels depending on the modification required to enhance resistance. The inducing or repressing activity of these modulators also occurred in three more carbapenem-resistant strains tested. An exception was the A. baumannii AMA16 bla
NDM-1 gene, which was repressed in the presence of 3.5% HSA. In conclusion, HSA produces an enhancement of natural transformation and a modification in expression levels of competence genes and antibiotic resistance. Furthermore, when HSA is combined with carbapenems, which may increase the stress response, the expression of genes involved in natural competence is increased in A. baumannii. This process may favor the acquisition of foreign DNA and accelerate evolution.- Published
- 2021
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20. Histone-like nucleoid-structuring protein (H-NS) regulatory role in antibiotic resistance in Acinetobacter baumannii.
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Rodgers D, Le C, Pimentel C, Tuttobene MR, Subils T, Escalante J, Nishimura B, Vescovi EG, Sieira R, Bonomo RA, Tolmasky ME, and Ramirez MS
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- Acinetobacter baumannii genetics, Biofilms growth & development, Gene Expression Regulation, Bacterial, Genotype, Microbial Sensitivity Tests, Phenotype, Quorum Sensing genetics, Acinetobacter baumannii metabolism, Bacterial Proteins metabolism, Drug Resistance, Multiple, Bacterial genetics, Histones metabolism
- Abstract
In the multidrug resistant (MDR) pathogen Acinetobacter baumannii the global repressor H-NS was shown to modulate the expression of genes involved in pathogenesis and stress response. In addition, H-NS inactivation results in an increased resistance to colistin, and in a hypermotile phenotype an altered stress response. To further contribute to the knowledge of this key transcriptional regulator in A. baumannii behavior, we studied the role of H-NS in antimicrobial resistance. Using two well characterized A. baumannii model strains with distinctive resistance profile and pathogenicity traits (AB5075 and A118), complementary transcriptomic and phenotypic approaches were used to study the role of H-NS in antimicrobial resistance, biofilm and quorum sensing gene expression. An increased expression of genes associated with β-lactam resistance, aminoglycosides, quinolones, chloramphenicol, trimethoprim and sulfonamides resistance in the Δhns mutant background was observed. Genes codifying for efflux pumps were also up-regulated, with the exception of adeFGH. The wild-type transcriptional level was restored in the complemented strain. In addition, the expression of biofilm related genes and biofilm production was lowered when the transcriptional repressor was absent. The quorum network genes aidA, abaI, kar and fadD were up-regulated in Δhns mutant strains. Overall, our results showed the complexity and scope of the regulatory network control by H-NS (genes involved in antibiotic resistance and persistence). These observations brings us one step closer to understanding the regulatory role of hns to combat A. baumannii infections., (© 2021. The Author(s).)
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- 2021
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21. Involvement of the Histone-Like Nucleoid Structuring Protein (H-NS) in Acinetobacter baumannii's Natural Transformation.
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Le C, Pimentel C, Tuttobene MR, Subils T, Escalante J, Nishimura B, Arriaga S, Rodgers D, Bonomo RA, Sieira R, Tolmasky ME, and Ramírez MS
- Abstract
Most Acinetobacter baumannii strains are naturally competent. Although some information is available about factors that enhance or reduce the frequency of the transformation of this bacterium, the regulatory elements and mechanisms are barely understood. In this article, we describe studies on the role of the histone-like nucleoid structuring protein, H-NS, in the regulation of the expression of genes related to natural competency and the ability to uptake foreign DNA. The expression levels of the natural transformation-related genes pilA , pilT , pilQ , comEA , comEC , comF , and drpA significantly increased in a Δ hns derivative of A. baumannii A118. The complementation of the mutant with a recombinant plasmid harboring hns restored the expression levels of six of these genes ( pilT remained expressed at high levels) to those of the wild-type strain. The transformation frequency of the A. baumannii A118 Δ hns strain was significantly higher than that of the wild-type. Similar, albeit not identical, there were consequences when hns was deleted from the hypervirulent A. baumannii AB5075 strain. In the AB5075 complemented strain, the reduction in gene expression in a few cases was not so pronounced that it reached wild-type levels, and the expression of comEA was enhanced further. In conclusion, the expression of all seven transformation-related genes was enhanced after deleting hns in A. baumannii A118 and AB5075, and these modifications were accompanied by an increase in the cells' transformability. The results highlight a role of H-NS in A. baumannii's natural competence.
- Published
- 2021
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22. Case Report: Complete Response of Recurrent and Metastatic Cystadenocarcinoma of the Parotid Gland With a Single Course of Combined Nivolumab and Ipilimumab Therapy.
- Author
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Nakamura Y, Nakayama M, Nishimura B, Okiyama N, Tanaka R, Ishitsuka Y, Matsumoto S, and Fujisawa Y
- Abstract
Although cystadenocarcinoma is classified as a low-grade histological subtype of salivary gland carcinoma (SGC), recurrence and metastases sometimes develop. However, standard treatments for advanced cases have not yet been established. Here, we present a case of unresectable local recurrence and cervical lymph node metastases of cystadenocarcinoma of the parotid gland with multiple lung nodules, all of which showed complete response with only a single course of combined nivolumab and ipilimumab therapy. The patient's medical history of metastatic melanoma roused our suspicions that the multiple lung nodules were cystadenocarcinoma metastases or malignant melanoma. Combination therapy was used based on our suspected diagnosis of lung metastases of melanoma although histological examination of the lung nodules could not be performed. While various chemotherapies are used for advanced SGCs including cystadenocarcinoma, overall, the results are unsatisfactory. In contrast, there have not yet been any reports of advanced cystadenocarcinoma of the salivary gland treated with immune checkpoint inhibitors (ICIs). Given that, in our case, a single course of combined ICI therapy induced a complete response in the unresectable and lymph node metastases from the cystadenocarcinoma and the multiple lung nodules, ICIs, including combined therapy, could be a promising treatment for advanced cystadenocarcinoma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Nakamura, Nakayama, Nishimura, Okiyama, Tanaka, Ishitsuka, Matsumoto and Fujisawa.)
- Published
- 2021
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23. The Geriatric Nutritional Risk Index as a Prognostic Factor in Patients with Advanced Head and Neck Cancer.
- Author
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Nakayama M, Gosho M, Adachi M, Ii R, Matsumoto S, Miyamoto H, Hirose Y, Nishimura B, Tanaka S, Wada T, and Tabuchi K
- Subjects
- Adult, Aged, Aged, 80 and over, Cohort Studies, Female, Head and Neck Neoplasms pathology, Humans, Male, Middle Aged, Neoplasm Staging, Prognosis, Retrospective Studies, Risk Assessment, Squamous Cell Carcinoma of Head and Neck pathology, Survival Rate, Geriatric Assessment, Head and Neck Neoplasms mortality, Nutrition Assessment, Squamous Cell Carcinoma of Head and Neck mortality
- Abstract
Objective: The Geriatric Nutritional Risk Index (GNRI) is a simple and well-established nutritional assessment tool and is a significant prognostic factor in various cancers. However, the role of the GNRI in predicting clinical outcomes in patients with advanced head and neck cancer (AHNC) has not been investigated. The aim of the present study was to examine the association between the GNRI and prognosis in patients with AHNC., Study Design: Retrospective cohort study., Methods: Data collected between 2002 and 2013 from Tsukuba University Hospital were reviewed. The GNRI was calculated according to the equation, 1.489 × serum albumin (g/l) + 41.7 × (body weight/ideal body weight). Characteristics and prognosis were compared among three risk groups: high (GNRI <82); intermediate (GNRI 82-98); and normal (GNRI >98). The primary endpoint was overall survival., Results: A total of 248 AHNC patients were enrolled, among whom 134 (54%) exhibited no nutritional risk, 53 (21%) had an intermediate risk for malnutrition, and 61 (25%) exhibited a high risk for malnutrition. Three-year survival rates according to the three-group GNRI scores for normal, intermediate, and high risk were 76.6%, 56.3%, and 19.5%, respectively. As the three-group GNRI score increased, the risk for mortality significantly increased (adjusted hazard ratio [HR] for intermediate to normal, 1.73 [95% CI, 1.02-2.92]; adjusted HR for high to normal, 4.31 [95% CI, 2.71-6.84])., Conclusions: The GNRI could be considered a useful prognostic factor in patients with AHNC., Level of Evidence: 4 Laryngoscope, 131:E151-E156, 2021., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)
- Published
- 2021
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24. Modified combination of platelet count and neutrophil "to" lymphocyte ratio as a prognostic factor in patients with advanced head and neck cancer.
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Nakayama M, Gosho M, Hirose Y, Nishimura B, Tanaka S, Tabuchi K, Okubo H, Wada T, and Hara A
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- Aged, Female, Head and Neck Neoplasms mortality, Humans, Male, Middle Aged, Neoplasm Staging, Prognosis, Survival Rate, Head and Neck Neoplasms blood, Head and Neck Neoplasms pathology, Lymphocyte Count, Neutrophils
- Abstract
Background: We evaluated the prognostic potential of the combination of platelet count and neutrophil to lymphocyte ratio (COP-NLR) in patients with advanced head and neck cancer., Methods: We proposed a modified COP-NLR scoring system defined as follows: score 0 (platelet count level <300 × 10
9 /L and NLR <3); score 1 (platelet count level ≥300 × 109 /L and NLR <3); and score 2 (NLR ≥3). We assessed whether the modified scoring system had better performance as an indicator of prognosis than the existing COP-NLR scoring system (original and 4-group scores)., Results: A total of 248 patients were enrolled. The Akaike Information Criterion value with the modified COP-NLR score was the smallest among the 3 models. The 3-year survival rates according to the modified COP-NLR scores of 0, 1, and 2 were 80.6%, 59.9%, and 23.8%, respectively., Conclusion: The modified COP-NLR score is a useful prognostic marker in patients with advanced head and neck cancer., (© 2018 Wiley Periodicals, Inc.)- Published
- 2018
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25. A case of refractory Kimura disease with a buccal bulky mass successfully treated with low-dose cyclosporine A: report and review of the literature.
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Miki H, Tsuboi H, Kaneko S, Takahashi H, Yokosawa M, Asashima H, Hirota T, Hagiwara S, Umeda N, Kondo Y, Nishimura B, Sugano M, Matsumoto I, and Sumida T
- Subjects
- Adult, Biopsy, Cyclosporine administration & dosage, Cytokines blood, Humans, Immunoglobulin E blood, Immunoglobulin E immunology, Immunosuppressive Agents administration & dosage, Magnetic Resonance Imaging, Male, Treatment Outcome, Angiolymphoid Hyperplasia with Eosinophilia diagnosis, Angiolymphoid Hyperplasia with Eosinophilia drug therapy, Cyclosporine therapeutic use, Immunosuppressive Agents therapeutic use, Mouth Mucosa pathology
- Published
- 2016
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26. Ceramide/sphingomyelin cycle involvement in gentamicin-induced cochlear hair cell death.
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Chi le NU, Tabuchi K, Nakamagoe M, Nakayama M, Nishimura B, and Hara A
- Subjects
- Aniline Compounds pharmacology, Animals, Animals, Newborn, Benzylidene Compounds pharmacology, Cell Death drug effects, Cells, Cultured, Fatty Acids, Monounsaturated pharmacology, Hair Cells, Auditory enzymology, Hair Cells, Auditory metabolism, Hair Cells, Auditory pathology, Oleic Acids pharmacology, Rats, Sprague-Dawley, Serine C-Palmitoyltransferase antagonists & inhibitors, Serine C-Palmitoyltransferase metabolism, Sphingomyelin Phosphodiesterase antagonists & inhibitors, Sphingomyelin Phosphodiesterase metabolism, Transferases (Other Substituted Phosphate Groups) antagonists & inhibitors, Transferases (Other Substituted Phosphate Groups) metabolism, Ceramides biosynthesis, Gentamicins toxicity, Hair Cells, Auditory drug effects, Sphingomyelins biosynthesis
- Abstract
Ceramide, a sphingolipid metabolite, regulates diverse cellular processes including apoptosis, cell senescence, the cell cycle, and cellular differentiation. Exogenously administered ceramide reportedly increased cochlear hair cell death due to gentamicin-induced ototoxicity. Ceramide is mainly generated via a ceramide/sphingomyelin cycle by sphingomyelinase and sphingomyelin synthase or via de novo synthesis by serine palmitoyltransferase and ceramide synthase. This study was designed to investigate the possible involvement of neutral sphingomyelinase, sphingomyelin synthase, or serine palmitoyltransferase in hair cell death due to gentamicin. The basal turns of the organ of Corti of Sprague-Dawley rats were dissected on postnatal days 3-5. Cochlear cultures were exposed to media containing 35 μM gentamicin for 48 h to assess the effects of GW4869 (a neutral sphingomyelinase inhibitor), 2-hydroxyoleic acid (a sphingomyelin synthase activator), and myriocin (a serine palmitoyltransferase inhibitor). Hair cell loss was significantly decreased in the presence of GW4869 or 2-hydroxyoleic acid. Myriocin had no significant effects against gentamicin-induced hair cell loss. In addition, neutral sphingomyelinase was activated by gentamicin exposure. The present findings strongly suggest that the ceramide/sphingomyelin cycle plays an important role in the protection of hair cells against gentamicin-induced ototoxicity.
- Published
- 2015
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27. The influence of sphingosine-1-phosphate receptor antagonists on gentamicin-induced hair cell loss of the rat cochlea.
- Author
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Nakayama M, Tabuchi K, Hoshino T, Nakamagoe M, Nishimura B, and Hara A
- Subjects
- Animals, Apoptosis drug effects, Cell Count, Cochlea cytology, Cochlea drug effects, Cochlea metabolism, Hair Cells, Auditory cytology, Hair Cells, Auditory metabolism, In Vitro Techniques, Rats, Sprague-Dawley, Receptors, Lysosphingolipid metabolism, Anti-Bacterial Agents toxicity, Gentamicins toxicity, Hair Cells, Auditory drug effects, Receptors, Lysosphingolipid antagonists & inhibitors
- Abstract
Sphingosine-1-phosphate (S1P) is a sphingolipid metabolite that regulates various critical biological processes, such as cell proliferation, survival, migration, and angiogenesis. The action of S1P is exerted by its binding to 5 specific G protein-coupled S1P receptors (S1PR), S1PR1-S1PR5. Aminoglycoside antibiotics including gentamicin induce cochlear hair cell loss and sensorineural hearing loss. Apoptotic cell death is considered to play a key role in this type of cochlear injury. S1P acts as a cochlear protectant against gentamicin ototoxicity. In the present study, expression of S1PRs in the cochlea was examined. In addition, the effects of S1PR antagonists on gentamicin ototoxicity were investigated using tissue culture techniques. Cochleas were dissected from Sprague-Dawley rats on postnatal days 3-5. Basal turn organ of Corti explants were exposed to 35 μM gentamicin for 48 h with or without S1PR antagonists. S1PR(1-3) were expressed in the organ of Corti and spiral ganglion. The S1PR2 antagonist increased gentamicin-induced hair cell loss, while the S1PR1 and S1PR3 antagonists did not affect gentamicin ototoxicity. These results indicate the possibility that S1P act as a cochlear protectant against gentamicin ototoxicity via activation of S1PR2., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2014
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28. The effects of A1 and A2A adenosine receptor agonists on kainic acid excitotoxicity in the guinea pig cochlea.
- Author
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Tabuchi K, Sakai S, Nakayama M, Nishimura B, Hayashi K, Hirose Y, and Hara A
- Subjects
- Action Potentials drug effects, Action Potentials physiology, Adenosine pharmacology, Animals, Dendrites drug effects, Guinea Pigs, Receptor, Adenosine A1 metabolism, Receptors, Purinergic P1 drug effects, Receptors, Purinergic P1 physiology, Adenosine analogs & derivatives, Adenosine A1 Receptor Agonists pharmacology, Adenosine A2 Receptor Agonists pharmacology, Cochlea drug effects, Kainic Acid toxicity, Neuroprotective Agents pharmacology
- Abstract
The present study aimed to clarify the protective effect of adenosine receptors against the excitotoxicity of cochlear afferent dendrites. The effects of 2-chloro-N6-cyclopentyladenosine (CCPA), an A1 adenosine receptor agonist, and 5'-N-cyclopropyl-carboxamidoadenosine (CPCA), an A2A adenosine receptor agonist, on cochlear excitotoxicity induced by kainic acid (KA) were examined using guinea pigs. KA was applied to the round window membrane at a concentration of 10mM for 30 min. CCPA or CPCA was given at the onset of KA application. KA morphologically induced the swelling of cochlear afferent dendrites and significantly elevated the threshold of the compound action potential (CAP) of the cochlea. CCPA inhibited the KA-induced CAP threshold shift and swelling of the cochlear afferent dendrites. However, CPCA did not affect cochlear excitotoxicity induced by KA. The results suggest that adenosine A1 receptor activation could prevent the excitotoxicity of cochlear afferent dendrites., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2012
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29. Effects of neuroactive steroids on cochlear hair cell death induced by gentamicin.
- Author
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Nakamagoe M, Tabuchi K, Nishimura B, and Hara A
- Subjects
- Animals, Anti-Bacterial Agents adverse effects, Dehydroepiandrosterone pharmacology, Estradiol pharmacology, Estrogens pharmacology, Gene Expression Regulation drug effects, Hair Cells, Auditory metabolism, Hair Cells, Auditory, Outer cytology, Hair Cells, Auditory, Outer drug effects, Hair Cells, Auditory, Outer metabolism, Progesterone pharmacology, Rats, Rats, Sprague-Dawley, Receptors, Estrogen antagonists & inhibitors, Receptors, Estrogen metabolism, Cell Death drug effects, Cochlea cytology, Cytoprotection drug effects, Gentamicins adverse effects, Hair Cells, Auditory cytology, Hair Cells, Auditory drug effects, Steroids pharmacology
- Abstract
As neuroactive steroids, sex steroid hormones have non-reproductive effects. We previously reported that 17β-estradiol (βE2) had protective effects against gentamicin (GM) ototoxicity in the cochlea. In the present study, we examined whether the protective action of βE2 on GM ototoxicity is mediated by the estrogen receptor (ER) and whether other estrogens (17α-estradiol (αE2), estrone (E1), and estriol (E3)) and other neuroactive steroids, dehydroepiandrosterone (DHEA) and progesterone (P), have similar protective effects. The basal turn of the organ of Corti was dissected from Sprague-Dawley rats and cultured in a medium containing 100 μM GM for 48h. The effects of βE2 and ICI 182,780, a selective ER antagonist, were examined. In addition, the effects of other estrogens, DHEA and P were tested using this culture system. Loss of outer hair cells induced by GM exposure was compared among groups. βE2 exhibited a protective effect against GM ototoxicity, but its protective effect was antagonized by ICI 182,780. αE2, E1, and E3 also protected hair cells against gentamicin ototoxicity. DHEA showed a protective effect; however, the addition of ICI 182,780 did not affect hair cell loss. P did not have any effect on GM-induced outer hair cell death. The present findings suggest that estrogens and DHEA are protective agents against GM ototoxicity. The results of the ER antagonist study also suggest that the protective action of βE2 is mediated via ER but that of DHEA is not related to its conversion to estrogen and binding to ER. Further studies on neuroactive steroids may lead to new insights regarding cochlear protection., (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Published
- 2011
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30. Protective role of Nrf2 in age-related hearing loss and gentamicin ototoxicity.
- Author
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Hoshino T, Tabuchi K, Nishimura B, Tanaka S, Nakayama M, Ishii T, Warabi E, Yanagawa T, Shimizu R, Yamamoto M, and Hara A
- Subjects
- Animals, Ear, Inner drug effects, Gene Expression Regulation, Developmental, Hair Cells, Auditory drug effects, Hair Cells, Auditory enzymology, Heme Oxygenase-1 genetics, Mice, Mice, Knockout, NAD(P)H Dehydrogenase (Quinone) genetics, NF-E2-Related Factor 2 genetics, Response Elements, Spiral Ganglion drug effects, Spiral Ganglion enzymology, Superoxide Dismutase genetics, Superoxide Dismutase-1, Aging, Anti-Bacterial Agents adverse effects, Ear, Inner enzymology, Gentamicins adverse effects, Hearing Loss chemically induced, Hearing Loss genetics, NF-E2-Related Factor 2 physiology
- Abstract
Expression of antioxidant enzymes is regulated by transcription factor NF-E2-related factor (Nrf2) and induced by oxidative stress. Reactive oxygen species contribute to the formation of several types of cochlear injuries, including age-related hearing loss and gentamicin ototoxicity. In this study, we examined the roles of Nrf2 in age-related hearing loss and gentamicin ototoxicity by measuring auditory brainstem response thresholds in Nrf2-knockout mice. Although Nrf2-knockout mice maintained normal auditory thresholds at 3 months of age, their hearing ability was significantly more impaired than that of age-matched wild-type mice at 6 and 11 months of age. Additionally, the numbers of hair cells and spiral ganglion cells were remarkably reduced in Nrf2-knockout mice at 11 months of age. To examine the importance of Nrf2 in protecting against gentamicin-induced ototoxicity, 3-day-old mouse organ of Corti explants were cultured with gentamicin. Hair cell loss caused by gentamicin treatment was enhanced in the Nrf2-deficient tissues. Furthermore, the expressions of some Nrf2-target genes were activated by gentamicin treatment in wild-type mice but not in Nrf2-knockout mice. The present findings indicate that Nrf2 protects the inner ear against age-related hearing injuries and gentamicin ototoxicity by up-regulating antioxidant enzymes and detoxifying proteins., (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Published
- 2011
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31. Age-related hearing loss and expression of antioxidant enzymes in BDF1 mice.
- Author
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Tabuchi K, Hoshino T, Hirose Y, Hayashi K, Nishimura B, Nakayama M, and Hara A
- Subjects
- Animals, Evoked Potentials, Auditory, Brain Stem, Hair Cells, Auditory pathology, Hearing Loss pathology, Mice, Mice, Inbred C57BL, Mice, Inbred DBA, RNA, Messenger metabolism, Spiral Ganglion pathology, Superoxide Dismutase-1, Aging metabolism, Hearing Loss enzymology, Heme Oxygenase-1 metabolism, NAD(P)H Dehydrogenase (Quinone) metabolism, Superoxide Dismutase metabolism
- Abstract
Conclusion: Our data suggest that the changes in expression of antioxidant enzymes may cause age-related hearing loss (AHL)., Objectives: AHL is an aging process of the inner ear, and oxidant stressors are considered to be one of the leading causes. We investigated the hearing level and expression profile of antioxidant enzymes in aged mice., Methods: Mice aged 3, 6, and 11 months were used. Hearing levels of the mice were examined using the auditory brainstem response (ABR). After measuring the ABR threshold, cochleae were dissected. RNA was isolated from the cochleae, and cDNA was synthesized using the retro-transcription enzyme. Expression of the antioxidant enzymes was measured by quantitative real-time PCR., Results: The ABR thresholds of the BDF1 mice were elevated by 6 months of age. The expression of superoxide dismutase 1 (SOD1) and heme oxygenase 1 (HO1) at 11 months of age significantly decreased compared with that of those at 6 months of age. In contrast, a decrease in the expression level was not observed regarding NAD(P)H-quinone oxidoreductase 1 (NQO1).
- Published
- 2011
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32. Protective effects of corticosteroids and neurosteroids on cochlear injury.
- Author
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Tabuchi K, Nakamagoe M, Nishimura B, Hayashi K, Nakayama M, and Hara A
- Subjects
- Animals, Cochlea injuries, Cochlea physiopathology, Hearing Loss, Sensorineural physiopathology, Humans, Adrenal Cortex Hormones pharmacology, Cochlea drug effects, Hearing Loss, Sensorineural prevention & control, Neurotransmitter Agents pharmacology
- Abstract
Dysfunction of the cochlea causes sensorineural hearing loss. Glucocorticoids have been clinically applied for sensorineural hearing loss of sudden onset, including idiopathic sudden sensorineural hearing loss, acoustic injury, Meniere's disease, and immune-mediated hearing loss. However, clinical studies on sudden sensorineural hearing loss have revealed conflicting results regarding the efficacy of glucocorticoids. The findings obtained from animal experiments have demonstrated that glucocorticoids exhibited protective effects on some types of cochlear injury, but there were limitations regarding glucocorticoid therapy. Recently, the actions of neurosteroids in the cochlea have drawn much attention from auditory researchers. Clinical and experimental studies of the auditory system have indicated that estrogens affect auditory perception. Furthermore, estrogens and dehydroepiandrosterone (DHEA) exhibit protective effects on cochlear injury. This article was aimed to give an overview of steroid treatment for protection of the inner ear against various cochlear injuries. Findings obtained from animal studies are focused on.
- Published
- 2011
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33. Early detection of nasopharyngeal carcinoma.
- Author
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Tabuchi K, Nakayama M, Nishimura B, Hayashi K, and Hara A
- Abstract
Nasopharyngeal carcinoma (NPC) is a unique disease with a clinical presentation, epidemiology, and histopathology differing from other squamous cell carcinomas of the head and neck. NPC is an Epstein-Barr virus-associated malignancy with a marked racial and geographic distribution. Specifically, it is highly prevalent in southern China, Southeast Asia, and the Middle East. To date, most NPC patients have been diagnosed in the advanced stage, but the treatment results for advanced NPC are not satisfactory. This paper provides a brief overview regarding NPC, with the focus on the early detection of initial and recurrent NPC lesions.
- Published
- 2011
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34. The influences of sphingolipid metabolites on gentamicin-induced hair cell loss of the rat cochlea.
- Author
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Nishimura B, Tabuchi K, Nakamagoe M, and Hara A
- Subjects
- Animals, Apoptosis, Cell Count, Ceramides metabolism, Ceramides pharmacology, G(M3) Ganglioside metabolism, G(M3) Ganglioside pharmacology, Hair Cells, Auditory cytology, Hair Cells, Auditory metabolism, In Vitro Techniques, Lysophospholipids metabolism, Lysophospholipids pharmacology, Rats, Rats, Sprague-Dawley, Sphingolipids pharmacology, Sphingosine analogs & derivatives, Sphingosine metabolism, Sphingosine pharmacology, Anti-Bacterial Agents toxicity, Gentamicins toxicity, Hair Cells, Auditory drug effects, Sphingolipids metabolism
- Abstract
Sphingolipid metabolites inducing ceramide, sphingosine, and sphingosine-1-phosphate (S1P) play important roles in the regulation of cell proliferation, survival, and death. Aminoglycoside antibiotics including gentamicin induce inner ear hair cell loss and sensorineural hearing loss. Apoptotic cell death is considered to play a key role in this injury. The present study was designed to investigate the possible involvement of ceramide and S1P in hair cell death due to gentamicin. In addition, the effects of other metabolites of ceramide, gangliosides GM1 (GM1) and GM3 (GM3), on gentamicin ototoxicity were also investigated. Basal turn organ of Corti explants from p3 to p5 rats were maintained in tissue culture and exposed to 20 or 35μM gentamicin for 48h. The effects of ceramide, S1P, GM1, and GM3 on gentamicin-induced hair cell loss were examined. Gentamicin-induced hair cell loss was increased by ceramide but was decreased by S1P. GM1 and GM3 exhibited protective effects against gentamicin-induced hair cell death at the limited concentrations. These results indicate that ceramide enhances gentamicin ototoxicity by promoting apoptotic hair cell death, and that S1P, GM1, and GM3 act as cochlear protectants. In conclusion, sphingolipid metabolites influence the apoptotic reaction of hair cells to gentamicin ototoxicity., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2010
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35. Ischemia-reperfusion injury of the cochlea: pharmacological strategies for cochlear protection and implications of glutamate and reactive oxygen species.
- Author
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Tabuchi K, Nishimura B, Tanaka S, Hayashi K, Hirose Y, and Hara A
- Abstract
A large amount of energy produced by active aerobic metabolism is necessary for the cochlea to maintain its function. This makes the cochlea vulnerable to blockade of cochlear blood flow and interruption of the oxygen supply. Although certain forms of human idiopathic sudden sensorineural hearing loss reportedly arise from ischemic injury, the pathological mechanism of cochlear ischemia-reperfusion injury has not been fully elucidated. Recent animal studies have shed light on the mechanisms of cochlear ischemia-reperfusion injury. It will help in the understanding of the pathology of cochlear ischemia-reperfusion injury to classify this injury into ischemic injury and reperfusion injury. Excitotoxicity, mainly observed during the ischemic period, aggravates the injury of primary auditory neurons. On the other hand, oxidative damage induced by hydroxyl radicals and nitric oxide enhances cochlear reperfusion injury. This article briefly summarizes the generation mechanisms of cochlear ischemia-reperfusion injury and potential therapeutic targets that could be developed for the effective management of this injury type.
- Published
- 2010
- Full Text
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36. Estradiol protects the cochlea against gentamicin ototoxicity through inhibition of the JNK pathway.
- Author
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Nakamagoe M, Tabuchi K, Uemaetomari I, Nishimura B, and Hara A
- Subjects
- Animals, Anti-Bacterial Agents toxicity, Apoptosis physiology, Caspases physiology, Cells, Cultured, Cochlea cytology, Cochlea physiology, Dose-Response Relationship, Drug, Gentamicins toxicity, Hair Cells, Auditory cytology, Hair Cells, Auditory drug effects, Hair Cells, Auditory physiology, MAP Kinase Kinase 4 physiology, Models, Animal, Rats, Rats, Sprague-Dawley, Signal Transduction physiology, Anti-Bacterial Agents pharmacology, Apoptosis drug effects, Cochlea drug effects, Estradiol pharmacology, Gentamicins pharmacology, MAP Kinase Kinase 4 antagonists & inhibitors, Signal Transduction drug effects
- Abstract
Gentamicin induces outer hair cell death through the apoptotic pathway. It has been reported that this death pathway of outer hair cells is mediated by specific apoptotic enzymes including c-jun N-terminal kinase (JNK) and caspases. 17beta-Estradiol (E2), the most potent estrogen, is known to function as an antiapoptotic agent to prevent the death of various cell types. The purpose of the present study was to examine the effects of E2 on gentamicin-induced apoptotic cell death in outer hair cells. The basal turn organ of Corti explants from p3 or p4 rats were maintained in a tissue culture and exposed to 100muM gentamicin for 48h. The effects of E2 on gentamicin-induced outer hair cell loss, JNK activation, and staining for terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick-end labeling (TUNEL) were examined. E2 significantly decreased gentamicin-induced outer hair cell loss in a dose-dependent manner. JNK activation and TUNEL staining were observed in organ of Corti explants exposed to gentamicin, and staining levels were significantly decreased by E2 treatment. The results indicate that, through the inhibition of JNK and subsequent apoptotic reactions, E2 decreases outer hair cell loss induced by gentamicin ototoxicity., (2010 Elsevier B.V. All rights reserved.)
- Published
- 2010
- Full Text
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37. Epiglottic cyst in an infant.
- Author
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Nishimura B, Tabuchi K, Aoyagi Y, Tobita T, Wada T, Kohanawa R, Nagata C, Morishita Y, and Hara A
- Subjects
- Child, Preschool, Cysts complications, Cysts surgery, Female, Humans, Laryngeal Diseases complications, Laryngeal Diseases diagnosis, Laryngeal Diseases surgery, Laryngoscopy, Respiratory Sounds etiology, Sleep Apnea Syndromes etiology, Tomography, X-Ray Computed, Cysts diagnosis, Epiglottis
- Abstract
Epiglottic cyst is a rare cause of stridor and respiratory distress in newborns and infants. A 2-year-old girl was referred to our department for the treatment of an epiglottic cyst causing inspiratory stridor. Flexible fiberoptic laryngoscopy and a computed tomography (CT) scan revealed a cystic lesion on the lingual surface of the epiglottis. Frequent episodes of sleep apnea accompanied by desaturation had been observed during her sleep. Endoscopic deroofing was performed under general anesthesia. After the operation, stridor and sleep apnea disappeared.
- Published
- 2008
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38. Involvement of poly(ADP-ribose) synthetase in acoustic trauma of the cochlea.
- Author
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Tabuchi K, Hoshino T, Murashita H, Oikawa K, Uemaetomari I, Nishimura B, Tobita T, and Hara A
- Subjects
- Acoustic Stimulation adverse effects, Action Potentials physiology, Aminobenzoates administration & dosage, Aminobenzoates metabolism, Animals, Benzamides administration & dosage, Benzamides chemistry, Benzamides metabolism, Enzyme Activation, Guinea Pigs, Neuroprotective Agents chemistry, Neuroprotective Agents metabolism, Niacinamide administration & dosage, Niacinamide metabolism, Otoacoustic Emissions, Spontaneous, Poly(ADP-ribose) Polymerase Inhibitors, meta-Aminobenzoates, Cochlea pathology, Hearing Loss, Noise-Induced metabolism, Poly(ADP-ribose) Polymerases metabolism
- Abstract
We investigated effects of poly(ADP-ribose) synthetase (PARS) inhibitors on acoustic trauma. Albino guinea pigs were intravenously given 3-aminobenzamide, nicotinamide or 3-aminobenzoic acid (an inactive analog of 3-aminobenzamide) just prior to exposure to a 2 kHz pure tone of 120 dB sound pressure level (SPL) for 10 minutes. The threshold of the compound action potential (CAP) and the amplitude of distortion-product otoacoustic emissions (DPOAEs) were measured before and 4 hours after the acoustic overexposure. Statistically significant decreases in the CAP threshold shifts and significant increases in the DPOAE amplitudes were observed 4 hours after the acoustic overexposure in the animals treated with 3-aminobenzamide or nicotinamide, whereas 3-aminobenzoic acid did not exert any protective effect. These results strongly suggest that excessive activation of PARS is involved in generation of the acoustic trauma.
- Published
- 2003
- Full Text
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39. Costs of poor birth outcomes among privately insured.
- Author
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Adams EK, Nishimura B, Merritt RK, and Melvin C
- Subjects
- Adult, Cesarean Section economics, Cesarean Section statistics & numerical data, Employer Health Costs statistics & numerical data, Female, Humans, Infant, Newborn, Infant, Premature, Pregnancy, Pregnancy Complications epidemiology, Pregnancy Outcome economics, United States epidemiology, Delivery, Obstetric economics, Health Expenditures statistics & numerical data, Hospital Costs statistics & numerical data, Insurance, Hospitalization statistics & numerical data, Intensive Care Units, Neonatal economics, Pregnancy Complications economics
- Abstract
Despite expansions in the public insurance coverage of pregnant women, concerns over poor birth outcomes remain. Poor birth outcomes occur among publicly and privately insured women, however, thereby imposing excess costs on employers and their insurers. Data from a large sample of privately insured for 1996 are used to examine these outcomes and costs. Almost one-fourth (24.3 percent) of the infants in our matched sample of 12,020 deliveries was premature or had other problems at birth. Costs for these infants accounted for 82 percent of the total $56 million spent on sample infants. The incremental cost of infants with poor birth outcomes versus those with normal, full-terms was approximately $14,600. We found that these relative costs had increased over time due perhaps to the increased technology and intensity of services used to save infant lives. We also found that factors other than maternal and infant complications affected cost variations. For example, employers located in the Northeast, hiring older mothers, and in unionized sectors have higher prenatal, delivery, and infant costs.
- Published
- 2003
40. The criteria for early use of nonvocal communication systems with nonspeaking autistic children.
- Author
-
Nishimura B, Watamaki T, Sato M, and Wakabayashi S
- Subjects
- Autistic Disorder psychology, Child, Child Development, Concept Formation, Form Perception, Humans, Language Development Disorders psychology, Male, Phonetics, Prognosis, Speech Production Measurement, Stereotyped Behavior, Autistic Disorder diagnosis, Language Development Disorders diagnosis, Nonverbal Communication
- Abstract
Criteria to differentiate nonspeaking subjects from speaking autistic preschool-age children were examined. The data on several developmental features previously recorded at 4 1/2 years of age were compared between 10 nonspeaking and 10 speaking children who were followed until late childhood. Total DQ, subscale DQs of intellectual, self-care, and motor ability, and several speech production features (variety of phone categories, distortion in vowels, and disappearance of babbling) were the most distinctive indices between the two groups. We believe that an early use of a nonvocal communication system by autistic children with these features results in more successful outcomes than before.
- Published
- 1987
- Full Text
- View/download PDF
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