University of the Ryukyus University Hospital

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    熱帯インドネシアにおける伝統的住宅の熱環境制御に関する研究

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    琉球大学博士(工学)学位論

    Characterization of CTX-M-type-extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae isolated from Indonesian undergraduate medical students of a university in Surabaya, Indonesia

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    琉球大学博士(保健学)Enterobacteriaceae isolates producing CTX-M-type extended-spectrum b-lactamase (ESBL) has been found in hospitalized patients and healthy individuals in communities of the Southeast Asian countries. Medical students might have more risk of ESBL-producing Enterobacteriaceae contagion, because medical students who belong to communities have direct and indirect contacts with workers and patients in healthcare facilities. The aim of this study was to collect information for evaluation of the potential risk of ESBL-producing Enterobacteriaceae contagion in Indonesian undergraduate medical students by characterizing genotypic properties of Escherichia coli isolates-producing CTX-M-type ESBL. A total 141 fecal samples collected from 207 medical students of a university in Surabaya, Indonesia were subjected to PCR, XbaI and S1 nuclease-pulsed-field gel electrophoresis (PFGE), Southern blotting, and sequencing analysis. Eighty-two ESBL-producing Enterobacteriaceae, including 75 E. coli and 7 Klebsiella pneumoniae were isolated from 79 (56.0%) students. Among 75 ESBL-producing E. coli, blaCTX-M-15 was the most prevalent type (44.0%). Although XbaI-PFGE results showed genetic background of the E. coli isolates producing CTX-M-type ESBL were diverse, five clonal spread cases of certain E. coli producing CTX-Mtype ESBL isolates were observed among the medical students. Our results suggested that ESBLproducing Enterobacteriaceae might be circulating among the medical students through contaminated environment such as in a university or communities they belonged.学位論

    Proteomic profiling of HTLV-1 carriers and ATL patients reveals sTNFR2 as a novel diagnostic biomarker for acute ATL

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    琉球大学博士(保健学)AdultT-cell leukemia/lymphoma (ATL) is ahuman T-cell leukemia virus type 1 (HTLV-1)–associated T-cell malignancy with generally poor prognosis. Although only ;5% of HTLV-1 carriers progress to ATL, early diagnosis is challenging because of the lack of ATL biomarkers. In this study, we analyzed blood plasma profiles of asymptomatic HTLV-1 carriers (ACs); untreated ATL patients, including acute, lymphoma, smoldering, and chronic types; and ATL patients in remission. Through SOMAscan, expression levels of 1305 plasma proteins were analyzed in 85 samples (AC, n 5 40; ATL, n 5 40; remission, n 5 5). Using gene set enrichment analysis and gene ontology, overrepresented pathways in ATL vs AC included angiogenesis, inflammation by cytokines and chemokines, interleukin-6 (IL-6)/JAK/STAT3, and notch signaling. In selecting candidate biomarkers, we focused on soluble tumor necrosis factor receptor 2 (sTNFR2) because of its active role in enriched pathways, extreme significance (Welch’s t test P , .00001), high discrimination capacity (area under the curve .0.90), and novelty in ATL research. Quantification of sTNFR2 in 102 plasma samples (AC, n530; ATL, n568; remission, n54) using enzyme-linked immunosorbent assay showed remarkable elevations in acute ATL, at least 10 times those of AC samples, and return of sTNFR2 to AC state levels after achieving remission. Flow cytometry and immunostaining validated the expression of TNFR2 in ATL cells. No correlation between sIL-2 and sTNFR2 levels in acute ATL was found, suggesting the possibility of sTNFR2 as an independent biomarker. Our findings represent the first extensive blood-based proteomic analysis of ATL, suggesting the potential clinical utility of sTNFR2 in diagnosing acute ATL.学位論

    北西太平洋産ウミヅタ類の分類,系統,多様性に関する研究

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    琉球大学博士(学術)学位論

    The prognostic impact of a concentric left ventricular structure evaluated by transthoracic echocardiography in patients with acute decompensated heart failure : A retrospective study

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    琉球大学博士(医学)Background Left ventricular (LV) wall thickening relative to the LV radius, known as a concentric LV structure, is a mechanism that compensates for pressure overload and is related to the risk of cardiovascular events and heart failure. The prognostic value of a concentric LV structure, however, has not been examined in acute decompensated heart failure (ADHF). Methods This single-center, observational, retrospective, cohort study analyzed 385 consecutive patients hospitalized due to ADHF. On hospital admission, relative wall thickness (RWT) and the ratio of LV mass to LV end-diastolic volume (LVM/LVEDV) were measured by transthoracic echocardiography as markers of a concentric LV structure. The association of either RWT or LVM/LVEDV with all-cause death as the primary outcome was analyzed. Results During the follow-up period (median, 235 days), 95 (25%) patients died. The high-RWT group had a poorer prognosis than the low-RWT group (log-rank test, P = 0.009). High RWT was a significant risk (HR: 1.95, 95% CI: 1.28–2.97, P = 0.002) in the Cox proportional hazard model analysis adjusted by the Get With The Guideline score, which is an established risk score. In contrast, there was no significant difference in survival between the low and high-LVM/LVEDV groups (P = 0.42). In the non-severe valvular disease subgroup, patients with high RWT consistently showed worse survival than the low- RWT group (P = 0.028 by log-rank test, HR: 1.96, 95% CI: 1.24–3.11, P = 0.004). There was no significant difference in survival between the low and high-LVM/LVEDV groups (P = 0.42). Conclusions A concentric LV structure represented by a high RWT was associated with a poor prognosis in ADHF. The lack of association between LVM/LVEDV and mortality may result from methodological issues.学位論

    Development and persistence of neuropathic pain through microglial activation and KCC2 decreasing after mouse tibial nerve injury

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    琉球大学博士(医学)学位論

    沿岸工事とサンゴ礁 : 沖縄における人工護岸の伸長、生息地の消失、海洋生態系への影響

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    琉球大学博士(理学)学位論

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