http://hdl.handle.net/10564/3715 2020年度博士論文 2026-04-10T13:50:52Z http://hdl.handle.net/10564/3935 タイトル: Molecular and Epidemiological Characteristics of Carbapenemase-Producing Klebsiella pneumoniae Clinical Isolates in Japan. 著者: Yonekawa, Shinsuke; Mizuno, Tomoki; Nakano, Ryuichi; Nakano, Akiyo; Suzuki, Yuki; Asada, Tomoko; Ishii, Ayako; Kakuta, Naoki; Tsubaki, Kosuke; Mizuno, Sayaka; Ogawa, Miho; Yano, Hisakazu; Kasahara, Kei; Mikasa, Keiichi 抄録: Carbapenemase-producing Enterobacteriaceae represent a serious public health threat worldwide. Carbapenemase genes, harbored on a transferable plasmid, have been isolated globally with distinct geographical features. Klebsiella pneumoniae, included in Enterobacteriaceae, also produces carbapenemase and often shows hypervirulence. Overlapping carbapenem resistance and hypervirulence in K. pneumoniae have been reported, but such strains have not yet been found in Japan. Here, we screened 104 carbapenemase-producing K. pneumoniae isolates collected from 37 hospitals and outpatient clinics in Japan between September 2014 and July 2015. PCR and DNA sequencing demonstrated IMP-1 in 21 isolates and IMP-6 in 83 isolates, 77 of which coharbored CTX-M-2. Most of the isolates showed low MICs toward imipenem and meropenem but high MICs toward penicillin and cephalosporins. Conjugation experiments with an Escherichia coli J53 recipient showed that most of the plasmids in IMP-6 producers were transferable, whereas only one-half of the plasmids in IMP-1 producers were transferable. PCR-based replicon typing and multiplex PCR identified five isolates belonging to the CG258 non-tonB79 cluster and no isolate belonging to the CG258-tonB79 cluster or sequence type 307 (ST307). Four K1-ST23 isolates, 10 K2-ST65 isolates, and 7 K2-ST86 isolates were detected that harbored virulence genes. The resistance genes in 85 isolates were transferable, but the virulence genes were not transferred. These results demonstrate the acquisition of IMP-type carbapenemase genes and CTX-M-type genes among hypervirulence isolates in Japan, warranting further attention and countermeasures. In this study, we have determined the molecular characteristics and epidemiology of IMP-6 producers that coharbored various CTX-M genes in Japan.IMPORTANCE Carbapenems serve as a last resort for the clinical treatment of multidrug-resistant infections. Therefore, the rapid spread of carbapenemase-producing strains represents a serious public health threat, further limiting antibiotic choices. The current findings of hypervirulent carbapenemase-producing Klebsiella pneumoniae clinical isolates in Japan demonstrate the potential broad spread and transfer of these genes, necessitating close surveillance. 内容記述: 博士（医学）・乙第1509号・令和3年3月15日; Copyright © 2020 Yonekawa et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license(https://creativecommons.org/licenses/by/4.0/). 2020-10-20T15:00:00Z http://hdl.handle.net/10564/3934 タイトル: Evaluation of background parenchymal enhancement in breast contrast-enhanced ultrasound with Sonazoid. ® 著者: Haga, Masayo; Hirai, Toshiko; Nakai, Tokiko; Kobayashi, Toyoki; Nakamura, Takashi; Marugami, Aki; Ito, Takahiro; Takewa, Megumi; Marugami, Nagaaki; Kichikawa, Kimihiko 抄録: Purpose: The objective of this study was to retrospectively evaluate the association between background parenchymal enhancement (BPE) on contrast-enhanced ultrasound (CEUS) with Sonazoid® and patient characteristics. Additionally, background parenchymal tissues with the high-contrast effect were pathologically observed compared to those showing the low-contrast effect. Methods: A total of 65 patients who underwent breast CEUS with Sonazoid® between January 2010 and November 2013 were enrolled. Regions of interest (ROIs) were put on the tumor and on the background parenchymal tissue. The dB values during the nonenhanced time and at peak contrast enhancement were measured based on the time intensity curve (TIC) drawn by the ROI. The differences in the dB values of pre- and post-enhanced time were obtained separately for ROIs on the tumor and ROIs on the parenchymal tissue. The patient characteristics studied were age, menstrual status, mammographic density, BPE on magnetic resonance imaging (MRI), and pathological diagnoses of breast tumors. Results: There was a weak negative correlation between BPE on CEUS and age. As for the contrast effect of parenchymal tissue, there was a significant difference between the menstruating and menopausal groups. There was no significant difference among the levels of mammographic density, and among the degrees of contrast effect on MRI. BPE on CEUS was the same between those with a malignant tumor and those with a benign tumor in each menstrual status. The parenchymal tissue with the low-contrast effect showed pathological atrophy. Conclusion: The degree of BPE on CEUS appeared related to age, menstruating or menopausal, and atrophy of breast tissue. BPE on CEUS was the same between those with a malignant tumor and those with a benign tumor in each menstrual status. 内容記述: 博士（医学）・乙第1508号・令和3年3月15日; © Springer Nature Singapore Pte Ltd. 2020.; © The Japan Society of Ultrasonics in Medicine 2020.; This is a post-peer-review, pre-copyedit version of an article published in Journal of medical ultrasonics. The final authenticated version is available online at: https://doi.org/10.1007/s10396-020-01052-4. 2020-09-30T15:00:00Z http://hdl.handle.net/10564/3933 タイトル: Daily salt intake is associated with leg edema and nocturnal urinary volume in elderly men. 著者: Yoshikawa, Motokiyo; Torimoto, Kazumasa; Hirayama, Akihide; Kiba, Keisuke; Yamamoto, Yutaka; Akashi, Yasunori; Shimizu, Nobutaka; Tanaka, Nobumichi; Uemura, Hirotsugu; Fujimoto, Kiyohide 抄録: Aims: There is accumulating evidence that excessive salt intake contributes to nocturnal polyuria. We aimed to investigate the relationship between salt intake, leg edema, and nocturnal urine volume (NUV) to assess the etiology of nocturnal polyuria. Methods: A total of 56 men aged ≥60 years who were hospitalized for benign prostatic hyperplasia or with suspected prostatic cancer were enrolled. Urine frequency-volume charts of the patients were maintained, and they underwent bioelectrical impedance analysis twice daily (at 5:00 pm and 6:00 am) and examination of blood (brain natriuretic peptide levels) and urine (sodium and creatinine levels and osmotic pressure) samples once daily (at 6:00 am). Free-water clearance, solute clearance, and sodium clearance at night were measured, and daily salt intake was estimated. Results: The data of 52 patients were analyzed. Daily salt intake positively correlated with leg edema at 5:00 pm, differences in leg extracellular fluid levels between 5:00 pm and 6:00 am, and NUV, but not with diurnal urine volume. Partial correlation coefficients showed that salt intake was a factor of the correlation between NUV and change in extracellular volume in the legs between 5:00 pm and 6:00 am. A multivariate logistic model showed that sleep duration and sodium clearance were independent predictive factors for nocturnal polyuria. Conclusions: Sodium intake correlates with diurnal leg edema and NUV in elderly men. These results provide evidence supporting sodium restriction as an effective treatment for nocturnal polyuria. 内容記述: 博士（医学）・乙第1507号・令和3年3月15日; © 2020 Wiley Periodicals LLC.; This is the peer reviewed version of the following article: https://onlinelibrary.wiley.com/doi/10.1002/nau.24401, which has been published in final form at https://doi.org/10.1002/nau.24401. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. 2020-05-31T15:00:00Z http://hdl.handle.net/10564/3932 タイトル: Inhibition of Heparanase Expression Results in Suppression of Invasion, Migration and Adhesion Abilities of Bladder Cancer Cells. 著者: Tatsumi, Yoshihiro; Miyake, Makito; Shimada, Keiji; Fujii, Tomomi; Hori, Shunta; Morizawa, Yosuke; Nakai, Yasushi; Anai, Satoshi; Tanaka, Nobumichi; Konishi, Noboru; Fujimoto, Kiyohide 抄録: Heparan sulfate proteoglycan syndecan-1, CD138, is known to be associated with cell proliferation, adhesion, and migration in malignancies. We previously reported that syndecan-1 (CD138) may contribute to urothelial carcinoma cell survival and progression. We investigated the role of heparanase, an enzyme activated by syndecan-1 in human urothelial carcinoma. Using human urothelial cancer cell lines, MGH-U3 and T24, heparanase expression was reduced with siRNA and RK-682, a heparanase inhibitor, to examine changes in cell proliferation activity, induction of apoptosis, invasion ability of cells, and its relationship to autophagy. A bladder cancer development mouse model was treated with RK-682 and the bladder tissues were examined using immunohistochemical analysis for Ki-67, E-cadherin, LC3, and CD31 expressions. Heparanase inhibition suppressed cellular growth by approximately 40% and induced apoptosis. The heparanase inhibitor decreased cell activity in a concentration-dependent manner and suppressed invasion ability by 40%. Inhibition of heparanase was found to suppress autophagy. In N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced bladder cancer mice, treatment with heparanase inhibitor suppressed the progression of cancer by 40%, compared to controls. Immunohistochemistry analysis showed that heparanase inhibitor suppressed cell growth, and autophagy. In conclusion, heparanase suppresses apoptosis and promotes invasion and autophagy in urothelial cancer. 内容記述: 博士（医学）・乙第1506号・令和3年3月15日; © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). 2020-05-26T15:00:00Z