Combined Use of a Solid-Phase Hexapeptide Ligand Library with Liquid Chromatography and Two-Dimensional Difference Gel Electrophoresis for Intact Plasma Proteomics

The intact plasma proteome is of great interest in biomarker studies because intact proteins reflect posttranslational protein processing such as phosphorylation that may correspond to disease status. We examined the utility of a solid-phase hexapeptide ligand library in combination with conventional plasma proteomics modalities for comprehensive profiling of intact plasma proteins. Plasma proteins were sequentially fractionated using depletion columns for albumin and immunoglobulin, and separated using an anion-exchange column. Proteins in each fraction were treated with a solid-phase hexapeptide ligand library and compared to those without treatment. Two-dimensional difference gel electrophoresis demonstrated an increased number of protein spots in the treated samples. Mass spectrometric studies of these protein spots with unique intensity in the treated samples resulted in the identification of high- and medium-abundance proteins. Our results demonstrated the possible utility of a solid-phase hexapeptide ligand library to reveal greater number of intact plasma proteins. The characteristics of proteins with unique affinity to the library remain to be clarified by more extensive mass spectrometric protein identification, and optimized protocols should be established for large-scale plasma biomarker studies

外科的に切除しえた, 肝硬変を伴う維持透析患者に発症した右腎癌下大静脈腫瘍塞栓の1例

症例は54歳, 男性。1900年, CGNにて血液透析導入となった。2005年2月に肉眼的血尿が出現。CTにて右腎癌を指摘され, 3月9日当科紹介。当科にて施行したCTでは直径7cm大の右腎腫瘍とともに下大静脈内の肝静脈流入部まで達する腫瘍塞栓を認めた。右腎腫瘍, 下大静脈塞栓, T3bN0M0 stage IIIの診断で4月28日, 根治的右腎摘除ならびに腫瘍塞栓摘除術を施行した。手術時間4時間28分, 出血量1, 400ml, 摘出標本は重量800g, 病理所見はrenal cell carcinoma, G2, pT3bであった。術前の凝固系検査は異常を認めなかったが, 肝硬変が原因と考えられる出血時間の延長と血小板数の低下を認めたため, 周術期は血小板輸血などにて対応した。術後経過は良好で, 後出血などの術後合併症もなく, 術後18日目に退院した。現在IFNα投与にて後療法を施行中であるが, 再発を認めていない。透析患者における下大静脈腫瘍塞栓を伴う腎癌に対して外科的治療を施行した症例についての報告例については比較的少なく, 文献的考察も含めて報告する。(著者抄録)A 54-year-old man who had been under hemodialysis therapy for 16 years presented with gross hematuria at our department in February 2005. Imaging findings revealed right renal tumor of8.2 cm in diameter. In addition, the tumor extended into inferior vena cava at the level of the hepatic vein. There were no findings of distant metastasis. Right radical nephrectomy and thrombectomy were performed on April 2006. Histopathological analysis showed that the tumor was renal cell carcinoma of clear cell type, grade 2. Postoperative course was uneventful, and the adjuvant therapy with interferon alpha was initiated. He has been free from recurrence for 22 months after surgery

University Administrators’ Visions for the Recovery of International Student Exchange in a Post–COVID-19 World

Objectives: Little is known about how international functions of higher education, such as exchange programmes, can be resumed during recovery from a disruptive global crisis, such as COVID-19. We collected the opinions of administrators of international exchange programmes regarding their plans to resume their exchange programmes in the recovery phase and identified variations in the responses concerning institution type (public vs. private) and the presence or absence of a medical school. Method: We used multiple-choice survey questions in our study, resulting in 180 valid responses. We examined overall patterns using descriptive statistics and institutional uniqueness using Fisher’s exact test. Results: Governing organisations and domestic university networks are expected to initiate the resumption of student exchange programmes. Respondents indicate that they would rely on infection prevention experts at their institutions as sources of information for their decision-making. Public universities would rely more extensively on their staff’s opinions whilst private universities would consult with external experts. Universities with a medical school indicated a greater likelihood of referring to the opinions of experts at their institutions. Implication for Theory and/or Practice: Higher education systems vary across nations. However, extant studies have shown some shared features, and the findings may have implications for higher education institutions internationally. Policy incentives and support may encourage public universities to participate in the global recovery of international education. During global public health infectious crises, institutions without a medical school may require more government support. Conclusions: Institutional variations should be considered to effectively encourage universities to adapt to changing dynamics in the recovery of international education. Method: The study used multiple-choice survey questions, resulting in 180 valid responses. The study examined overall patterns using descriptive statistics and institutional uniqueness using Fisher\u27s exact test. Results: Governing organisations and domestic university networks are expected to initiate the resumption of student exchange. Respondents indicate that they would rely on infection prevention experts at their institutions as sources of information for their decision-making. Public universities would rely more extensively on their staff’s opinions whilst private universities would consult with external experts. Universities with a medical school indicated a greater likelihood of referring to the opinions of experts at their institutions. Implication for Theory and/or Practice: The higher education systems vary across nations. However, extant studies have shown some shared features, and the findings may have implications for higher education institutions internationally. Policy incentives and support may encourage public universities to participate in the global recovery of international education. During global public health infectious crises, institutions without a medical school may require more government support. Conclusions: Institutional variations should be considered to effectively encourage universities to adapt to changing dynamics in the recovery of international education

Novel bronchofiberscopic catheter spray device allows effective anesthetic spray and sputum suctioning

AbstractStudy objectives: To evaluate how serum lidocaine concentrations (SLC) rise when lidocaine is administered by a Bronchofiberscopic Catheter Spray Device (BCSD), and to demonstrate the effect on the aspiration speed of a substitute for sputum when a catheter spray remains in the channel of the bronchofiberscope (BF).Methods: This is a prospective randomized clinical study. After lidocaine ultrasonic nebulizer, the BF was inserted orally. During the procedure patients received 4% lidocaine by two methods. In Group 1, 11 patients received lidocaine by bronchofiberscopic (BF) injection. In Group 2, 15 patients received lidocaine by spraying from the ∅1.06mm catheter through the BF channel. SLC were measured at 40min from onset of nebulization. Separately, we examined how effectively sputum was aspirated through the BF channel with a catheter.Results: Total lidocaine dose (TLD) is the total dose used for nebulization and for the BF injection or spray. The TLD for Groups 1 and 2 were 698.2±162.1mg (mean±sd) and 498.7±103.8mg, respectively (P=0.03). The SLC for Groups 1 and 2 were 1.28±0.72 and 1.48±0.70mg/l, respectively (P=0.49).Conclusions: Using BCSD allows easier in administration of lidocaine and is not associated with a significant increase in SLC in comparison with BF injection. Although sputum aspiration using the BF inserted with our catheter was somewhat slow, we did not feel inconvenient so much. Compared to the conventional method, using BCSD may be preferable for patients and bronchoscopists

Urinary ACE2 in pediatric IgA nephropathy

Background : Our previous studies demonstrated that the intrarenal renin-angiotensin system (RAS) status was activated in pediatric patients with chronic glomerulonephritis. In the present study, we tested the hypothesis that angiotensin-converting enzyme 2 (ACE2) expression in the kidney is associated with the development of pediatric IgA nephropathy. Methods : We analyzed urinary ACE2 levels and ACE2 expression in the kidney tissues of pediatric patients with IgA nephropathy treated with RAS blockade. Paired tests were used to analyze changes from the first to the second biopsy. Results : Urinary ACE2 levels were significantly decreased after RAS blockade treatment, accompanied by decreased ACE2 expression levels in kidney tissues, urinary protein levels and mesangial hypercellularity scores. Urinary ACE2 levels at the first biopsy were positively correlated with the ACE2 expression levels. Conclusions : These data suggest that urinary ACE2 is associated with ACE2 expression in the diseased kidney, which correlates with the pathogenesis of IgA nephropathy in pediatric patients

NADPH oxidase and ROS in kidney growth

Ureteric bud branching and nephrogenesis are performed through large-scale proliferation and apoptosis events during renal development. Reactive oxygen species (ROS), produced by NADPH oxidase, may contribute to cell behaviors, including proliferation and apoptosis. We investigated the role of NADPH oxidase expression and ROS production in developing kidneys. Immunohistochemistry revealed that NADPH oxidase components were expressed on epithelial cells in ureteric bud branches, as well as on immature glomerular cells and epithelial cells in nephrogenic zones. ROS production, detected by dihydroethidium assay, was strongly observed in ureteric bud branches and nephrogenic zones, corresponding with NADPH oxidase localization. Organ culture of E14 kidneys revealed that the inhibition of NADPH oxidase significantly reduced the number of ureteric bud branches and tips, consistent with reduced ROS production. This was associated with reduced expression of phosphorylated ERK1/2 and increased expression of cleaved caspase-3. Organ culture of E18 kidneys showed that the inhibition of NADPH oxidase reduced nephrogenic zone size, accompanied by reduced ROS production, fewer proliferating cell nuclear antigen-positive cells, lower p-ERK1/2 expression, and increased expression of cleaved caspase-3. These results demonstrate that ROS produced by NADPH oxidase might play an important role in ureteric bud branching and nephrogenesis by regulating proliferation and apoptosis

Role of ERK1/2 and ERK5 in glomerulonephritis

Aim: Extracellular signal regulated kinase (ERK)1/2 and ERK5 are key kinases of the signaling pathways involved in various cellular responses to kidney injury; however, the mechanistic links between those kinase and renin-angiotensin system (RAS) activation in glomerulonephritis (GN) have not been fully elucidated. In this study, we sought to clarify the potential roles of ERK1/2 and ERK5 via RAS activation in the pathogenesis of GN. Methods: A rat model of progressive GN was induced by anti-glomerular basement membrane (GBM) injection and the signal transduction pathway in angiotensin II (Ang II)-induced glomerular pathologic alterations were investigated in primary cultured mesangial cells (MCs). Results: Rats developed typical cellular crescents in glomeruli on day 7 that progressed to severe fibrocellular crescents and glomerulosclerosis on day 28. Strong expression of phospho-ERK1/2 was observed on day 7 and phospho-ERK5 expression was markedly increased on day 28 of GN. An angiotensin II type 1 receptor blocker (ARB) suppressed those augmentations. Moreover, ARB treatment attenuated the increases in macrophage infiltration and PCNA-positive cells observed on day 7 in GN rats, as well as the increase in collagen type 1 expression on day 28. Consistently, MCs stimulated by Ang II showed significant increases in proliferation and the expression of MCP-1 and collagen type 1. Interestingly, while the ERK1/2 inhibitor PD98059 abolished the elevations in MCP-1 expression and cell proliferation, the ERK5 inhibitor BIX02189 abrogated the elevation in collagen type 1 expression. Conclusion: Altogether, these data suggest that ERK1/2 regulates acute inflammatory reactions, while ERK5 promotes the development of RAS-induced chronic glomerular fibrosis activation in GN

First Detection of NaI D lines in High-Redshift Damped Lyman-alpha Systems

A Near-infrared (1.18-1.35 micron) high-resolution spectrum of the gravitationally-lensed QSO APM 08279+5255 was obtained with the IRCS mounted on the Subaru Telescope using the AO system. We detected strong NaI D 5891,5897 doublet absorption in high-redshift DLAs at z=1.062 and 1.181, confirming the presence of NaI, which was first reported for the rest-frame UV NaI 3303.3,3303.9 doublet by Petitjean et al. This is the first detection of NaI D absorption in a high-redshift (z>1) DLA. In addition, we detected a new NaI component in the z=1.062 DLA and four new components in the z=1.181 DLA. Using an empirical relationship between NaI and HI column density, we found that all "components" have large HI column density, so that each component is classified as DLA absorption. We also detected strong NaI D absorption associated with a MgII system at z=1.173. Because no other metal absorption lines were detected in this system at the velocity of the NaI absorption in previously reported optical spectra (observed 3.6 years ago), we interpret this NaI absorption cloud probably appeared in the line of sight toward the QSO after the optical observation. This newly found cloud is likely to be a DLA based upon its large estimated HI column density. We found that the N(NaI)/N(CaII) ratios in these DLAs are systematically smaller than those observed in the Galaxy; they are more consistent with the ratios seen in the Large Magellanic Cloud. This is consistent with dust depletion generally being smaller in lower metallicity environments. However, all five clouds of the z=1.181 system have a high N(NaI)/N(CaII) ratio, which is characteristic of cold dense gas. We tentatively suggest that the host galaxy of this system may be the most significant contributor to the gravitational-lens toward APM 08279+5255.Comment: 22 pages, 6 Postscript figures, 3 tables, ApJ in press (Vol.643, 2 June 2006

Comprehensive Prospective Analysis of the Factors Contributing to Aspiration Pneumonia Following Endoscopic Submucosal Dissection in Patients with Early Gastric Neoplasms

Endoscopic submucosal dissection (ESD) has become the first-line treatment for early gastric neoplasms; however, a subset of patients treated by this method develop aspiration pneumonia. We conducted a comprehensive prospective analysis of the factors contributing to post-ESD aspiration pneumonia in early gastric neoplasms in this study, with special focus on whether pre-treatment oral care can prevent aspiration pneumonia. Sixty-one patients who underwent ESD for gastric neoplasms were randomly assigned to the oral care or control groups. ESD was performed under deep sedation. Of 60 patients whose data were available for analysis, 5 (8.3%) experienced pneumonia confirmed either by chest radiography or computed tomography. Although no difference in the rate of pneumonia was found between the control and oral care groups, the post-oral care bacteria count was significantly higher in the saliva of patients who developed pneumonia compared to those without pneumonia. In addition, the presence of vascular brain diseases and the dose of meperidine were also significantly associated with the occurrence of pneumonia. These results suggest that the number of oral bacteria as well as pre-existing vascular brain diseases and high-dose narcotics can affect the incidence of post-ESD pneumonia