記述言語：英語   掲載種別：研究論文（学術雑誌）  

Idiopathic nodular glomerulosclerosis has a poor renal prognosis and is characterized by diffuse nodular glomerulosclerotic lesions in the absence of diabetic mellitus. Here, we report the case of a 69-year-old woman with no smoking history who developed renal dysfunction and proteinuria in the absence of overt diabetes or obesity. A biopsy specimen showed nodular mesangial sclerosis with arteriolar hyalinosis and severe large-vessel arteriosclerosis, leading to a diagnosis of idiopathic nodular glomerulosclerosis. Addition of esaxerenone to her existing renin-angiotensin-aldosterone inhibitor therapy led to a rapid decrease in the proteinuria levels and the maintenance of renal function without any complications for more than a year. The results suggest that intensive renin-angiotensin-aldosterone blockade might be an effective treatment for idiopathic nodular glomerulosclerosis.

DOI： 10.1007/s13730-022-00766-3

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The benefits of dietary protein restriction in CKD remain unclear, largely due to inadequate adherence in most clinical trials. We examined whether low-protein rice (LPR) previously developed to reduce the protein content of rice, a major staple food, would help improve adherence to dietary protein restriction. METHODS: This open-label, multicenter, randomized, controlled trial evaluated the efficacy of LPR use for reducing dietary protein intake (DPI) in patients with CKD stages G3aA2-G4. Participants were randomly assigned in a 1:1 ratio to an LPR or control group and were followed up for 24 weeks. Both groups received regular counseling by dietitians to help achieve a target DPI of 0.7 g/kg ideal body weight (IBW) per day. The amount of protein in LPR is about 4% of that in ordinary rice, and the participants in the LPR group were instructed to consume LPR with at least two meals per day. The primary outcome was estimated dietary protein intake (eDPI) determined using the Maroni formula. The secondary outcomes included creatinine clearance (CCr) and urinary protein on the basis of 24-hour urine collection. RESULTS: In total, 51 patients were randomized to either the LPR group or the control group. At baseline, mean age was 62.5 years, 70% were men, mean CCr was 52.0 ml/min, and mean eDPI was 0.99 g/kg IBW per day. At 24 weeks, mean eDPI decreased to 0.80 g/kg IBW per day in the LPR group and to 0.91 g/kg IBW per day in the control group, giving a between-group difference of 0.11 g/kg IBW per day (95% confidence interval, 0.03 to 0.19 g/kg IBW per day; P=0.006). There was no significant between-group difference in CCr, but urinary protein was lower at 24 weeks in the LPR group than in the control group. CONCLUSIONS: LPR is a feasible tool for efficiently reducing DPI in patients with CKD. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Randomized, Multicenter, Controlled Study for the Efficacy of Low-Protein Rice Diet in Patients with Chronic Kidney Disease, UMIN000015630.

DOI： 10.34067/KID.0002982022

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS: Megalin, a proximal tubular endocytosis receptor, is excreted in urine in two forms: ectodomain (A-megalin) and full-length (C-megalin). We explored whether urinary megalin levels can be used as independent prognostic biomarkers in the progression of diabetic kidney disease (DKD). METHODS: The associations between baseline urinary A-megalin/creatinine (Cr) and/or C-megalin/Cr levels and the subsequent estimated glomerular filtration rate (eGFR) slope were analyzed using a generalized estimating equation. Patients were categorized into higher or lower groups based on the optimal cutoff values, obtained from a receiver operating characteristic curve, of the two forms of urinary megalin. RESULTS: We retrospectively analyzed 188 patients with type 2 diabetes. The eGFR slopes of the higher A-megalin/Cr and higher C-megalin/Cr groups were - 0.904 and -0.749 ml/min/1.73 m2/year steeper than those of the lower groups, respectively. Moreover, the eGFR slope was -1.888 ml/min/1.73 m2/year steeper in the group with both higher A- and higher C-megalin/Cr than in the other group. These results remained significant when adjusted for known urinary biomarkers (albumin, α1-microglobulin, β2-microglobulin, and N-acetyl-β-d-glucosaminidase). CONCLUSIONS: Urinary A- and C-megalin/Cr levels are likely to be prognostic biomarkers in the progression of DKD independent of other urinary biomarkers.

DOI： 10.1016/j.jdiacomp.2022.108312

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BMC  

Background Standard amino acid solutions have recently been removed from the contraindications for use in dialysis patients in Japan. However, the details of their safety and efficacy in these patients are still not known. In this study, we investigated the safety and efficacy of intradialytic parenteral nutrition (IDPN) using ENEFLUID (R) injection containing standard amino acids, glucose, electrolytes, fats, and water-soluble vitamins in maintenance hemodialysis patients with malnutrition. Methods This clinical trial was designed as a multicenter, prospective, non-randomized, open-label, single-arm, observational pilot study. The participants were patients on maintenance hemodialysis who were in the nutritional high-risk group according to the Nutritional Risk Index for Japanese Hemodialysis Patients. One bag of ENEFLUID (R) injection was administered during every hemodialysis session for 12 weeks. The primary endpoint was change in serum transthyretin levels between before and after the 12-week period. As safety endpoints, we evaluated changes in body fluid volume and blood biochemical tests, including blood urea nitrogen and electrolytes, as well as blood glucose variability using flash glucose monitoring (FGM). Results The mean age and body mass index of the 13 participants were 79.0 +/- 10.7 years and 18.0 +/- 1.7 kg/m(2), respectively. No significant changes were observed in nutritional parameters, including serum transthyretin, between before and after the start of the study. After IDPN initiation, there was no obvious fluid overload or significant changes in blood biochemical tests, including electrolytes, and the treatment could be safely continued for 12 weeks. In the FGM analysis, asymptomatic hypoglycemia during hemodialysis was observed at the beginning of the study, but there was a trend toward improvement after 12 weeks (area over the curve < 70 mg/dl per dialysis session: 747.5 +/- 1333.9 to 21.6 +/- 54.3, P = 0.09). Conclusions IDPN using ENEFLUID (R) injection can be safely continued, although it does not significantly improve markers of nutritional status. It also showed the potential to ameliorate asymptomatic hypoglycemia during hemodialysis sessions. More detailed studies of the improvement in nutritional indicators are needed. Trial registration: This study was registered with the University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR) on May 9, 2021 (registration ID, UMIN000044051).

DOI： 10.1186/s41100-022-00432-5

Web of Science

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BMC  

Background Dulaglutide is a once-weekly glucagon-like peptide-1 (GLP-1) receptor agonist approved for the treatment of type 2 diabetes mellitus (T2DM). However, the efficacy and safety of dulaglutide remain unclear in insulin-treated patients with T2DM on maintenance hemodialysis (HD). Methods Dulaglutide treatment was initiated, and the insulin dose was adjusted according to the needs of individual participants. Primary outcomes were changes in the mean and standard deviation (SD) of blood glucose (BG) levels and mean amplitude of glycemic excursions (MAGE) evaluated by continuous glucose monitoring (CGM) for six days, glycated albumin (GA), glycated hemoglobin (HbA1c), pre-dialysis blood glucose levels, and daily total insulin dose from the baseline over 24 weeks. Secondary outcomes were changes in treatment satisfaction and QOL levels from the baseline, measured by using the Diabetes Treatment Satisfaction Questionnaire (DTSQ) and the Diabetes Therapy-Related Quality of Life questionnaire (DTR-QOL) scores. Results The analysis was performed on the 12 participants who completed the study. The GA level (median - 1.8 [interquartile range - 6.6, - 0.3] %; p = 0.026) and daily total insulin dose (- 15.0 [- 24.5, - 9.4] U/day; p = 0.002) significantly decreased without increasing hypoglycemia (area over the glucose curve < 70 mg/dL: 0.0 [- 0.2, 0.0] mg center dot 24 h/dl; p = 0.917). Four patients successfully withdrew from insulin therapy. The levels of HbA1c, SD of BG, and MAGE showed a decreasing tendency, but no significant improvement. Regarding treatment satisfaction and QOL, the total scores of DTSQ (8.0 [0.3, 12.5]; p = 0.041) and DTR-QOL (15.5 [- 1.8, 42.0]; p = 0.023) significantly improved. Conclusion Dulaglutide may help improve glycemic control, treatment satisfaction, and QOL without increasing hypoglycemia in insulin-treated patients with T2DM on maintenance HD. Trial registration This study was registered with the University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR) on October 11, 2016 (registration ID, UMIN000024283).

DOI： 10.1186/s41100-022-00409-4

Web of Science

researchmap

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Although metabolic syndrome traits are risk factors for chronic kidney disease, few studies have examined their association with urinary biomarkers. METHODS: Urinary biomarkers, including A-megalin, C-megalin, podocalyxin, albumin, α1-microglobulin, β2-microglobulin, and N-acetyl-β-D-glucosaminidase, were cross-sectionally assessed in 347 individuals (52.7% men) with a urine albumin-to-creatinine ratio (ACR)  < 300 mg/g in a health checkup. Metabolic syndrome traits were adopted from the National Cholesterol Education Program (third revision) of the Adult Treatment Panel criteria modified for Asians. RESULTS: Participants had a mean body mass index, estimated glomerular filtration rate (eGFR), and median ACR of 23.0 kg/m2, 74.8 mL/min/1.73 m2, and 7.5 mg/g, respectively. In age- and sex-adjusted logistic regression analysis, A-megalin and albumin were significantly associated with the clustering number of metabolic syndrome traits (3 or more). After further adjustment with eGFR, higher quartiles of A-megalin and albumin were each independently associated with the clustering number of metabolic syndrome traits (adjusted odds ratio for A-megalin: 1.30 per quartile, 95% CI 1.03-1.64; albumin: 1.42 per quartile, 95% CI 1.12-1.79). CONCLUSIONS: Both urinary A-megalin and albumin are associated with the clustering number of metabolic syndrome traits. Further research on urinary A-megalin is warranted to examine its role as a potential marker of kidney damage from metabolic risk factors.

DOI： 10.1186/s13098-021-00779-5

PubMed

researchmap

記述言語：日本語   出版者・発行元：(有)科学評論社  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Chronic kidney disease (CKD) impairs the anti-inflammatory effects of high-density lipoprotein (HDL) and increases cardiovascular mortality. Though the potential role of dietary interventions to manage HDL is well studied, the clinical trials aimed to increase HDL levels have failed to reduce cardiovascular risk, rendering HDL function to be explored as a more relevant clinical parameter. This study investigates the effects of rice endosperm protein (REP), a plant-based protein, on the anti-inflammatory properties of HDL and renal injury-driven atherosclerosis in comparison with casein, an animal protein. Ten-week-old apolipoprotein E-deficient hyperlipidemic mice underwent uninephrectomy. The mice (n = 6 each) were pair-fed a normal casein-based diet or a REP-based diet (both with 20.0% protein content) for seven weeks. Atherosclerotic lesions were detected by en face Sudan IV staining of the aorta. The number and sizes of the atherosclerotic lesions were significantly lower in the REP-based diet-fed group than the casein-based diet-fed group (p = 0.038). However, the REP-based diet neither elicited an ameliorative effect on kidney function or histology nor impacted the cholesterol profiles. Furthermore, HDL from the REP-based diet-fed mice significantly suppressed the inflammatory cytokine response of human umbilical vein endothelial cells than that from the casein-based diet-fed mice (MCP-1, p = 0.010; IL-6, p = 0.011; IL-1β, p = 0.028). The REP-based diet has a higher potential to lessen the atherosclerotic lesions accelerated by renal mass reduction than a casein-based diet, which could be associated with the anti-inflammatory effects of HDL.

DOI： 10.1080/07315724.2021.1950584

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Recently, attention has been focused on the effect of glucagon on blood glucose variability. The dynamics of glucagon have attracted attention as a new target in the treatment of diabetes patients. However, the dynamics of glucagon in hemodialysis (HD) patients with type 2 diabetes mellitus (T2DM) remain unclear. OBJECTIVES: The aim of this study was to assess the dynamics of glucagon in HD patients with T2DM. MATERIALS AND METHODS: We measured plasma glucagon in HD patients with T2DM by liquid chromatography-high-resolution mass spectrometry (LC-HRMS), sandwich enzyme-linked immunosorbent assay (ELISA), and radioimmunoassay (RIA). The glucagon levels measured by each method were compared. We used the glucagon levels determined by our developed LC-HRMS method as the standard in this study. RESULTS: Plasma glucagon levels measured by LC-HRMS before HD were significantly higher than those measured after HD. Plasma glucagon levels measured using sandwich ELISA had a significantly higher correlation with those measured using LC-HRMS compared with RIA. CONCLUSIONS: This was the first study to assess glucagon levels in HD patients with T2DM using LC-HRMS, which is considered a highly accurate method. Sandwich ELISA was shown to measure glucagon levels accurately as well.

DOI： 10.1159/000518027

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Urinary fatty acid binding protein 1 (FABP1, also known as liver-type FABP) has been implicated as a biomarker of acute kidney injury (AKI) in humans. However, the precise biological mechanisms underlying its elevation remain elusive. Here, we show that urinary FABP1 primarily reflects impaired protein reabsorption in proximal tubule epithelial cells (PTECs). Bilateral nephrectomy resulted in a marked increase in serum FABP1 levels, suggesting that the kidney is an essential organ for removing serum FABP1. Injected recombinant FABP1 was filtered through the glomeruli and robustly reabsorbed via the apical membrane of PTECs. Urinary FABP1 was significantly elevated in mice devoid of megalin, a giant endocytic receptor for protein reabsorption. Elevation of urinary FABP1 was also observed in patients with Dent disease, a rare genetic disease characterized by defective megalin function in PTECs. Urinary FABP1 levels were exponentially increased following acetaminophen overdose, with both nephrotoxicity and hepatotoxicity observed. FABP1-deficient mice with liver-specific overexpression of FABP1 showed a massive increase in urinary FABP1 levels upon acetaminophen injection, indicating that urinary FABP1 is liver-derived. Lastly, we employed transgenic mice expressing diphtheria toxin receptor (DT-R) either in a hepatocyte- or in a PTEC-specific manner, or both. Upon administration of diphtheria toxin (DT), massive excretion of urinary FABP1 was induced in mice with both kidney and liver injury, while mice with either injury type showed marginal excretion. Collectively, our data demonstrated that intact PTECs have a considerable capacity to reabsorb liver-derived FABP1 through a megalin-mediated mechanism. Thus, urinary FABP1, which is synergistically enhanced by concurrent liver injury, is a biomarker for impaired protein reabsorption in AKI. These findings address the use of urinary FABP1 as a biomarker of histologically injured PTECs that secrete FABP1 into primary urine, and suggest the use of this biomarker to simultaneously monitor impaired tubular reabsorption and liver function. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

DOI： 10.1002/path.5775

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Fabry disease is an X-linked disorder of α-galactosidase A (GLA) deficiency. Our previous interim analysis (1 July 2014 to 31 December 2015) revealed plasma globotriaosylsphingosine as a promising primary screening biomarker for Fabry disease probands. Herein, we report the final results, including patients enrolled from 1 January to 31 December 2016 for evaluating the potential of plasma globotriaosylsphingosine and GLA activity as a combined screening marker. We screened 5691 patients (3439 males) referred from 237 Japanese specialty clinics based on clinical findings suggestive of Fabry disease using plasma globotriaosylsphingosine and GLA activity as primary screening markers, and GLA variant status as a secondary screening marker. Of the 14 males who tested positive in the globotriaosylsphingosine screen (≥2.0 ng/mL), 11 with low GLA activity (<4.0 nmol/h/mL) displayed GLA variants (four classic, seven late-onset) and one with normal GLA activity and no pathogenic variant displayed lamellar bodies in affected organs, indicating late-onset biopsy-proven Fabry disease. Of the 19 females who tested positive in the globotriaosylsphingosine screen, eight with low GLA activity displayed GLA variants (six classic, two late-onset) and five with normal GLA activity displayed a GLA variant (one classic) and no pathogenic variant (four late-onset biopsy-proven). The combination of plasma globotriaosylsphingosine and GLA activity can be a primary screening biomarker for classic, late-onset, and late-onset biopsy-proven Fabry disease probands.

DOI： 10.3390/cimb43010032

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Dipeptidyl peptidase 4 (DPP4) inhibitors are widely used in patients with type 2 diabetes mellitus (T2DM) on maintenance hemodialysis (HD), but the efficacy of the once-weekly DPP4 inhibitor omarigliptin is not known. METHODS: This prospective, randomized, open-label, parallel-group, non-inferiority/superiority, once-daily DPP4 inhibitor linagliptin-controlled, multicenter study examined glycemic control and safety of omarigliptin (UMIN000024284). Sample size was calculated to confirm non-inferiority in terms of changes in glycated hemoglobin (HbA1c). We enrolled 33 patients with T2DM on maintenance HD who had been treated with linagliptin for at least 3 months. The patients were randomized to receive omarigliptin (12.5 mg/week; n = 16) or linagliptin (5 mg/day; n = 17). Primary endpoints were changes in HbA1c and glycoalbumin (GA) over 24 weeks. RESULTS: Differences in the mean change in primary endpoint values between the omarigliptin and linagliptin groups were - 0.61% [- 1.14, - 0.09] for HbA1c, with a two-tailed upper 95% limit (i.e., one-tailed 97.5% upper limit) of 0.25%, below the non-inferiority limit, and - 1.67% [- 4.23, + 0.88] for GA, with a two-tailed upper 95% limit of 0.75%, above the non-inferiority limit. At 24 weeks, the omarigliptin group showed significantly greater reduction in HbA1c than the linagliptin group (- 0.2% ± 0.6% vs. 0.4% ± 0.8%, two-tailed p = 0.024) and significantly greater reduction in blood glucose after a single HD session (- 18.4 ± 31.4 mg/dL vs. 25.2 ± 59.5 mg/dL, respectively, two-tailed p = 0.019). No subjects in the omarigliptin group developed hypoglycemia. CONCLUSIONS: Our data showed that omarigliptin was non-inferior to linagliptin in glycemic control. Omarigliptin is feasible for glycemic control in patients with T2DM on maintenance HD. CLINICAL TRIALS REGISTRATION: UMIN000024284.

DOI： 10.1007/s13300-020-00991-y

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Cisplatin, one of the most active anticancer agents, is widely used in standard chemotherapy for various cancers. Cisplatin is more poorly tolerated than other chemotherapeutic drugs, and the main dose-limiting toxicity of cisplatin is its nephrotoxicity, which is dose-dependent. Although less toxic methods of cisplatin administration have been established, cisplatin-induced nephrotoxicity remains an unsolved problem. Megalin is an endocytic receptor expressed at the apical membrane of proximal tubules. We previously demonstrated that nephrotoxic drugs, including cisplatin, are reabsorbed through megalin and cause proximal tubular cell injury. We further found that cilastatin blocked the binding of cisplatin to megalin in vitro. In this study, we investigated whether cilastatin could reduce cisplatin-induced nephrotoxicity without influencing the antitumor effects of cisplatin. Nephrotoxicity was decreased or absent in mice treated with cisplatin and cilastatin, as determined by kidney injury molecule-1 staining and the blood urea nitrogen content. Combined with cilastatin, a twofold dose of cisplatin was used to successfully treat the mice, which enhanced the antitumor effects of cisplatin but reduced its nephrotoxicity. These findings suggest that we can increase the dose of cisplatin when combined with cilastatin and improve the outcome of cancer patients.

DOI： 10.1038/s41598-020-80853-6

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: The precise blood glucose (BG) profile of hemodialysis patients is unclear, as is the effectiveness of dipeptidyl peptidase-4 (DPP-4) inhibitors in hemodialysis patients with type 2 diabetes. Here, we used continuous glucose monitoring (CGM) to evaluate BG variability in these patients and to assess the efficacy of DPP-4 inhibitors, particularly during hemodialysis sessions and at nighttime (UMIN000012638). METHODS: We examined BG profiles using CGM in 31 maintenance hemodialysis patients with type 2 diabetes. Differences between patients with and without DPP-4 inhibitors (n = 15 and 16, respectively) were analyzed using a linear mixed-effects model to assess changes in glucose levels in 5-min intervals. RESULTS: The model revealed that DPP-4 inhibitor use was significantly associated with suppression of a rapid drop in glucose levels, both with and without adjustment for BG levels at the start of hemodialysis. Moreover, the model revealed that the two groups differed significantly in the pattern of changes in BG levels from 0:00 to 6:55 am. DPP-4 inhibitors suppressed the tendency for subsequent nocturnal hypoglycemia. CONCLUSIONS: This prospective observational exploratory study showed that DPP-4 inhibitors could suppress BG variability during hemodialysis sessions as well as subsequent nocturnal changes in patients with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov identifier, UMIN000012638.

DOI： 10.1007/s13300-020-00928-5

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.jff.2020.103981

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/s12885-019-6398-2

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3390/nu11122919

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/s12882-019-1591-8

PubMed

researchmap

掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/s12882-019-1352-8

PubMed

researchmap

その他リンク： http://link.springer.com/article/10.1186/s12882-019-1352-8/fulltext.html

掲載種別：研究論文（学術雑誌）  

A 60-year-old male presented with accelerated hypertension, renal insufficiency, proteinuria, and hematuria. Percutaneous kidney biopsy revealed membranoproliferative glomerulonephritis (MPGN) without any immunoglobulin and complement deposition. On performing electron microscopy, deposits with a tubular, organized structure and approximately 60 nm in diameter were detected in the glomerular subendothelial spaces and mesangial areas. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) demonstrated the significantly increased deposition of fibrinogen and fibronectin in glomeruli. Immunohistochemistry and immunoelectron microscopy demonstrated that the deposits were composed of fibrinogen. Here we report a case of cryofibrinogen -associated GN in which LC-MS/MS and immunoelectron microscopy were useful for diagnosis. When MPGN with organized deposits without the deposition of immunoglobulins and complements is diagnosed, we considered the cryofibrinogen-associated GN in one of the differential diagnosis, and even skin symptoms cannot be detected.

DOI： 10.1016/j.ehpc.2018.12.002

Scopus

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1155/2019/1394678

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Blackwell Munksgaard  

Background and Objectives: Previous reports suggest that several serum biomarkers play roles in the pathogenesis, inflammatory response, and oxidative stress in periodontitis caused by bacterial infections, linking chronic periodontitis to atherosclerotic vascular disease (ASVD). The aim of this preliminary study was to investigate, in a Japanese cross-sectional community survey, potential serum biomarkers of periodontitis that are associated with ASVD and chronic periodontitis. Material and Methods: The study cohort included a total of 108 male subjects who underwent annual health examinations. Serum biomarkers (high-sensitivity C-reactive protein [hs-CRP], proprotein convertase subtilisin/kexin type 9 [PCSK9], interleukin-6, tumor necrosis factor-α, soluble CD14, myeloperoxidase, matrix metalloproteinase-3, adiponectin, total bilirubin [TBIL], and serum lipids) were analyzed to determine their association (if any) with periodontal parameters. Aortic stiffness was evaluated using the brachial-ankle aortic pulse wave velocity (PWV) index and the cardio-ankle vascular index (CAVI). Results: The concentrations of PCSK9 and hs-CRP were increased (P =.001 and.042, respectively), and the concentration of TBIL was decreased (P =.046), in subjects with periodontal disease (determined as a probing depth of ≥4 mm in at least one site) compared with periodontally healthy subjects. The ratio of low-density lipoprotein cholesterol (LDL-C) to high-density lipoprotein cholesterol and the concentrations of triglycerides, remnant-like particles-cholesterol, and oxidized LDL were elevated in subjects with periodontal disease compared with periodontally healthy subjects (P =.038,.007,.002, and.049, respectively). Multivariate regression analyses indicated that the number of sites with a pocket depth of ≥4 mm was associated with the concentration of PCSK9 and inversely associated with the concentration of TBIL independently (standardized β =.243, P =.040
standardized β = −.443, P =.0002
respectively). Analysis of receiver operating characteristic curves of PCSK9 indicated moderate accuracy for predicting the presence of disease sites (probing depth ≥ 4 mm) (area under the curve = 0.740). No significance in the values of PWV and CAVI was observed between subjects with periodontal disease and periodontally healthy subjects. Conclusion: In Japanese male subjects, the concentrations of serum PCSK9 and TBIL were correlated with periodontal parameters. Moreover, PCSK9 could be a candidate biomarker for diagnosing chronic periodontitis, and may also have potential to evaluate the risk for periodontitis to cause ASVD. Longitudinal studies of larger populations are necessary to confirm the exact association of periodontitis with increased serum PCSK9 and decreased TBIL.

DOI： 10.1111/jre.12533

Scopus

PubMed

researchmap

記述言語：日本語   出版者・発行元：(株)日本メディカルセンター  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本病態栄養学会  

researchmap

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

In maintenance hemodialysis (MHD) patients, low protein intake is associated with protein-energy wasting, a risk factor that affects outcome. However, increased protein intake may lead to hyperphosphatemia and hyperkalemia, which are also mortality risk factors. Here, we evaluated the safety and effects of purified rice endosperm protein (REP), which contains less phosphorus and potassium than soy and casein proteins, as a supplemental protein source for MHD patients. This randomized, double-blind, placebo-controlled, crossover pilot study of REP supplementation (5 g/day x 4 weeks) was carried out in 50 Japanese adult MHD patients (1 dropped out); the primary outcome was the change in the urea kinetic-based normalized protein catabolic rate (nPCR), an indicator of protein intake in MHD patients. Intention-to-treat analyses of 24 patients in the REP-first group and 25 in the placebo-first group showed that REP supplementation increased nPCR significantly by 0.07 g/kg/day (95% confidence interval, 0.03-0.11), whereas changes in serum phosphorus and potassium concentrations were not different from the placebo. REP supplementation did not show a significant effect on other nutritional or metabolic parameters and no specific complications. In conclusion, purified REP with efficient bioavailability may be safe and useful for dietary supplementation in MHD patients.

DOI： 10.1038/s41598-017-18340-8

Web of Science

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER SOC NEPHROLOGY  

Nephrotoxicity induced by antimicrobial or anticancer drugs is a serious clinical problem. Megalin, an endocytic receptor expressed at the apical membranes of proximal tubules, mediates the nephrotoxicity of aminoglycosides and colistin, key antimicrobials for multidrug-resistant organisms. The mechanisms underlying the nephrotoxicity induced by vancomycin, an antimicrobial for methicillin-resistant Staphylococcus aureus, and cisplatin, an important anticancer drug, are unknown, although the nephrotoxicity of these drugs and gentamicin, an aminoglycoside, is suppressed experimentally with cilastatin. In the clinical setting, cilastatin has been used safely to suppress dehydropeptidase-I-mediated renal metabolism of imipenem, a carbapenem antimicrobial, and thereby limit tubular injury. Here, we tested the hypothesis that cilastatin also blocks megalin-mediated uptake of vancomycin, cisplatin, colistin, and aminoglycosides, thereby limiting the nephrotoxicity of these drugs. Quartz crystal microbalance analysis showed that megalin also binds vancomycin and cisplatin and that cilastatin competes with megalin for binding to gentamicin, colistin, vancomycin, and cisplatin. In kidney specific mosaic megalin knockout mice treated with colistin, vancomycin, or cisplatin, the megalin-replete proximal tubule epithelial cells exhibited signs of injury, whereas the megalin-deficient cells did not. Furthermore, concomitant cilastatin administration suppressed colistin-induced nephrotoxicity in C57BL/6J mice. Notably, cilastatin did not inhibit the antibacterial activity of gentamicin, colistin, or vancomycin in vitro, just as cilastatin did not affect the anticancer activity of cisplatin in previous studies. In conclusion, megalin blockade with cilastatin efficiently suppresses the nephrotoxicity induced by gentamicin, colistin, vancomycin, or cisplatin. Cilastatin may be a promising agent for inhibiting various forms of drug-induced nephrotoxicity mediated via megalin in the clinical setting.

DOI： 10.1681/ASN.2016060606

Web of Science

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER DIABETES ASSOC  

Efficient biomarkers for diabetic nephropathy (DN) have not been established. Using ELISA, we found previously that urinary levels of full-length megalin (C-megalin), a multiligand endocytic receptor in proximal tubules, was positively correlated with DN progression in patients with type 2 diabetes mellitus (T2DM). Here, we found that urinary extracellular vesicle (UEV) excretion and C-megalin content in UEVs or in their exosomal fraction increased along with the progression of the albuminuric stages in patients with T2DM. Cultured immortalized rat proximal tubule cells (IRPTCs) treated with fatty acid-free BSA or advanced glycation end product-modified BSA (AGE-BSA), endocytic ligands of megalin, increased EV excretion, and their C-megalin content. C-megalin excretion from IRPTCs via extracellular vesicles was significantly blocked by an exosome-specific inhibitor, GW4869, indicating that this excretion is mainly exocytosis-mediated. AGE-BSA treatment of IRPTCs caused apparent lysosomal dysfunction, which stimulated multivesicular body formation, resulting in increased exosomal C-megalin excretion. In a high-fat diet-induced, megalin-mediated kidney injury model in mice, urinary C-megalin excretion also increased via UEVs. Collectively, exocytosis-mediated urinary C-megalin excretion is associated with the development and progression of DN in patients with T2DM, particularly due to megalin-mediated lysosomal dysfunction in proximal tubules, and hence it could be a candidate biomarker linked with DN pathogenesis.

DOI： 10.2337/db16-1031

Web of Science

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

IgA nephropathy (IgAN) is a chronic glomerular disease that causes end-stage renal disease in 20-40 % of patients within 20 years. The efficacy of tonsillectomy combined with steroid pulse (SP) administration (TSP) for clinical remission of IgAN has been reported. Particularly in Japan, TSP has been performed widely. However, the optimum method for steroid administration in TSP has not been established.
We retrospectively compared clinical remission in IgAN patients treated with tonsillectomy combined with two different steroid administration methods: (1) three courses of SP therapy and oral prednisolone administered on alternate days (group 3A; n = 25); and (2) one course of SP therapy and oral prednisolone administered on consecutive days (group 1C; n = 22).
There was no significant difference in the clinical remission rates between the two groups at 12 (48.0 vs. 40.9 %, P = 0.77) and 24 months after starting treatment (68.0 vs. 72.7 %, P = 0.76) and at the final observation (76.0 vs. 81.8 %, P = 0.73). The mean period from starting treatment to remission of hematuria in group 3A was significantly shorter than that in group 1C (5.7 +/- 4.4 vs. 9.9 +/- 5.9 months, P = 0.03). Dyslipidemic patients treated for the first time with statin after the SP therapy were more present in group 3A at 24 months (P = 0.02).
In IgAN patients, treatment of group 3A may be effective for inducing rapid remission of hematuria. Further studies are needed to establish an appropriate protocol for TSP.

DOI： 10.1007/s10157-016-1282-8

Web of Science

PubMed

researchmap

記述言語：日本語   出版者・発行元：(一社)日本病態栄養学会  

SGLT2阻害薬は近位尿細管における糖の再吸収を抑制することで尿糖排泄を増加し血糖低下をもたらす糖尿病治療薬であり、食事療法が密接にその治療効果へ影響を及ぼすことが予想される。症例は40歳女性。SGLT2阻害薬のイプラグリフロジンを開始と同時に、1400kcal/日にて栄養指導を月1回、継続的に行った。連日の食事記録より、2000kcal/日以上であった摂取エネルギーは平均1700kcal/日程度に減少した。35週間で体重は97.6kgから83.4kgと減少、HbA1cは7.4%から6.0%と改善した。SGLT2阻害薬開始後にエネルギー摂取量が増加する可能性が示唆されている。本症例は指導量よりは過剰であったものの、SGLT2阻害薬開始後に減少を認めており、体重減少および血糖改善につながったと考えられる。SGLT2阻害薬を使用中の患者においては正確な食事内容の把握と継続的な栄養指導が重要である。(著者抄録)

researchmap

記述言語：英語   出版者・発行元：KARGER  

Web of Science

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MEDICAL TRIBUNE INC  

Purpose: This purpose of this prospective study was to use a continuous glucose monitoring (CGM) system to evaluate the suitability of our institution's glucose management protocol after cardiovascular surgery and to clarify the impact of glycemic variability on postoperative complications.
Methods: In all, 76 patients who underwent elective cardiovascular surgery and were monitored perioperatively using a CGM system were evaluated. Postoperative glucose management consisted of continuous intravenous insulin infusion (CIII) in the intensive care unit, and subcutaneous insulin injections (SQII) after oral food intake started. CIII and subcutaneous injections were initiated when blood glucose level exceeded 150 mg/dL. CGM data were used to analyze perioperative glycemic variability and association with postoperative complications.
Results: Target glucose levels (71-180 mg/dL) were achieved during 97.1 +/- 5.5% and 86.4 +/- 19.0% of the continuous insulin infusion and subcutaneous injection periods, respectively. Major postoperative complications were surgical site infections, found in 6.6% of total patients, and atrial fibrillation, found in 44% of patients with off-pump coronary artery bypass grafting. High glycemic variability during SQII was associated with increased risk for both complications.
Conclusion: Data analysis revealed that our glucose management protocol during CIII was adequate. However, the management protocol during SQII required improvement.

DOI： 10.5761/atcs.oa.17-00045

Web of Science

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

Objective The administration of glucocorticoids usually causes a mild increase in fasting glucose levels and a greater dose-dependent increase in postprandial values in patients without pre-existing diabetes mellitus. Patients with persistent hyperglycemia due to glucocorticoid therapy sometimes require insulin therapy, which might result in increased weight gain and more episodes of hypoglycemia, some of which are severe. On the other hand, scant evidence is available on the efficacy of oral hypoglycemic agents in treating glucocorticoid-induced diabetes. In this study, we evaluated the efficacy of dipeptidyl peptidase (DPP)-4 inhibitors in patients with glucocorticoid-induced diabetes by continuous glucose monitoring (CGM).
Methods We examined the glycemic profiles using CGM at baseline and 1-4 weeks after initiating DPP-4 inhibitor treatment in patients with newly developed glucocorticoid-induced diabetes.
Results Eleven patients who had been diagnosed with kidney disease or other diseases with renal involvement were recruited for the present retrospective study. After starting DPP-4 inhibitors, the mean and standard deviation (SD) of the glucose level, and the mean amplitude of glycemic excursion (MAGE) were significantly improved in comparison to baseline. Furthermore, the area over the curve (AOC) for the glucose levels &lt;70 mg/dL was not increased in comparison to baseline after the initiation of DPP-4 inhibitor treatment. The results indicate that the treatment of patients with glucocorticoid-induced diabetes using DPP-4 inhibitors can minimize the risk of hypoglycemia and reduce glucose variability.
Conclusion DPP-4 inhibitors are potentially useful for blood glucose control in patients with glucocorticoid-induced diabetes.

DOI： 10.2169/internalmedicine.8296-16

Web of Science

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：CAMBRIDGE UNIV PRESS  

We previously reported that rice endosperm protein (REP) has renoprotective effects in Goto-Kakizaki rats, a non-obese diabetic model. However, whether these effects occur in obese diabetes remains unclear. This study aimed to clarify the effects of REP on obese diabetes, especially on fatty liver and diabetic nephropathy, using the obese diabetic model Zucker diabetic fatty (ZDF) rats. In total, 7-week-old male ZDF rats were fed diets containing 20 % REP or casein (C) for 8 weeks. Changes in fasting blood glucose levels and urinary markers were monitored during the experimental period. Hepatic lipids and metabolites were measured and renal glomeruli were observed morphologically. HbA1c levels were significantly lower in rats fed REP, compared with C (P &lt; 005). Compared with C in the liver, REP prevented lipid accumulation (total lipid, TAG and total cholesterol, P &lt; 001). Liver metabolome analysis indicated that levels of metabolites associated with glycolysis, the pentose phosphate pathway and carnitine metabolism were significantly greater in the REP group than in the C group (P &lt; 005), suggesting activation of both glucose catabolism and fatty acid oxidation. The metabolite increases promoted by REP may contribute to suppression of liver lipid accumulation. Urinary excretion of albumin and N-acetyl--d-glucosaminidase was significantly reduced in rats fed REP for 8 weeks (P &lt; 001). In addition, there was a distinct suppression of mesangial matrix expansion and glomerular hypertrophy in response to REP (P &lt; 001). Thus, REP had preventive effects on obese diabetes, fatty liver and diabetic nephropathy.

DOI： 10.1017/S0007114516003512

Web of Science

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER SOC NEPHROLOGY  

Obesity, an important risk factor for metabolic syndrome (MetS) and cardiovascular disease, is often complicated by CKD, which further increases cardiovascular risk and causes ESRD. To elucidate the mechanism underlying this relationship, we investigated the role of the endocytic receptor megalin in proximal tubule epithelial cells (PTECs). We studied a high-fat diet (HFD)-induced obesity/MetS model using kidney-specific mosaic megalin knockout (KO) mice. Compared with control littermates fed a normal-fat diet, control litter mates fed an HFD for 12 weeks showed autolysosomal dysfunction with autophagy impairment and increased expression of hypertrophy, lipid peroxidation, and senescence markers in PTECs of the S2 segment, peritubular capillary rarefaction with localized interstitial fibrosis, and glomerular hypertrophy with mesangial expansion. These were ameliorated in HFD-fed megalin KO mice, even though these mice had the same levels of obesity, dyslipidemia, and hyperglycemia as HFD-fed control mice. Intravital renal imaging of HFD-fed wild-type mice also demonstrated the accumulation of autofluorescent lipofuscin-like substances in PTECs of the S2 segment, accompanied by focal narrowing of tubular lumens and peritubular capillaries. In cultured PTECs, fatty acid-rich albumin induced the increased expression of genes encoding PDGF-B and monocyte chemoattractant protein-1 via megalin, with large (auto)lysosome formation, compared with fatty acid-depleted albumin. Collectively, the megalin-mediated endocytic handling of glomerular-filtered (lipo)toxic substances appears to be involved primarily in hypertrophic and senescent PTEC injury with autophagy impairment, causing peritubular capillary damage and retrograde glomerular alterations in HFD-induced kidney disease. Megalin could be a therapeutic target for obesity/MetS-related CKD, independently of weight, dyslipidemia, and hyperglycemia modification.

DOI： 10.1681/ASN.2015020190

Web of Science

PubMed

researchmap

掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

DOI： 10.1186/s40795-016-0065-7

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：TAYLOR & FRANCIS LTD  

Thrombosis is the leading cause of mortality globally. It is not only a complication but also a risk factor for progression of diabetes. However, alternative oral therapies and prophylaxis with less adverse effect for thrombosis have not been well studied. In this study, composite powder containing earthworm (CEP) was used and its fibrinolytic activity was measured. CEP was found to have a high urokinase-type plasminogen activator like activity in an in vitro assay. It also had significantly shortened euglobulin clot lysis time (ECLT) at 4 and 24h after ingestion in Sprague Dawley rats. Zucker Diabetic Fatty rats were used to assess the effect of CEP on diabetes and diabetic nephropathy. After 10weeks of feeding, CEP significantly shortened ECLT and attenuated HbA1c, hepatic lipid accumulation, and urinary albumin excretion and improved glomerular mesangial matrix score. Therefore, CEP may have beneficial effects on diabetes and diabetic nephropathy.

DOI： 10.1080/09168451.2016.1166932

Web of Science

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

Background Albuminuria is a biomarker for chronic kidney disease and an independent predictor of cardiovascular and all-cause mortality. A recent meta-analysis concluded that these risks increase with urinary albumin concentration, even when below the microalbuminuria threshold. Thus, minimizing urinary albumin may be a valuable therapeutic goal regardless of disease status.
Methods We investigated the benefits and safety of a 12-week lifestyle modification program including diet and combined aerobic and resistance exercise for reducing albuminuria in 295 normoalbuminuric or microalbuminuric Japanese adults, including 30 with type 2 diabetes mellitus (T2DM), 104 with metabolic syndrome (MS), and 145 with hypertension (HT).
Results In the study population, the urinary albumin:creatinine ratio (UACR) was reduced significantly (Delta UACR -3.8 +/- A 16.8 mg/g, P &lt; 0.001) with no change in estimated glomerular filtration rate (eGFR) (Delta eGFR -0.4 +/- A 7.4 mL/min/1.73 m(2), P = 0.343). The reduction in UACR was associated with decreased fasting plasma glucose (P &lt; 0.05). The UACR was also reduced in the T2DM, MS, and HT groups with no change in eGFR. Reduced UACR was associated with decreased fasting plasma glucose in the MS group and decreased systolic blood pressure in the HT group. The UACR was also reduced in 46 subjects using renin-angiotensin system inhibitors with no change in eGFR. Conclusions Our 12-week lifestyle modification program reduced UACR, maintained eGFR, and improved multiple fitness findings in Japanese subjects including T2DM, MS, and HT patients.

DOI： 10.1007/s10157-015-1103-5

Web of Science

PubMed

researchmap

Web of Science

researchmap

記述言語：日本語   出版者・発行元：新潟医学会  

researchmap

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2015&ichushi_jid=J00990&link_issn=&doc_id=20150811080015&doc_link_id=%2Fdg3nigta%2F2015%2Fs12905%2F008%2F0290-0290%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdg3nigta%2F2015%2Fs12905%2F008%2F0290-0290%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：新潟急性血液浄化研究会  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OXFORD UNIV PRESS  

researchmap

Web of Science

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER DIABETES ASSOC  

OBJECTIVE-Megalin, an endocytic receptor in proximal tubule cells, is involved in the mechanisms of albuminuria in diabetic nephropathy (DN). To develop efficient novel biomarkers associated with the pathogenesis of DN, we investigated urinary megalin excretion in type 2 diabetes.
RESEARCH DESIGN AND METHODS-Sandwich enzyme-linked immunosorbent assay systems were established with monoclonal antibodies against the NH2 (amino [A]-megalin assay) and CO OH (C-megalin assay) termini of megalin to analyze urinary forms of megalin in 68 patients with type 2 diabetes.
RESULTS-The A-megalin assay mainly detected a megalin ectodomain form in the soluble urinary fraction, whereas the C-megalin assay identified a full-length form in both soluble and insoluble fractions. Urinary C-megalin levels were significantly high in patients with normoalbuminuria, were elevated in line with increased albuminuria, and showed a better association with estimated glomerular filtration rate (eGFR) (&lt;60 mL/min/1.73 m(2)) than did urinary albumin. In contrast, urinary A-megalin levels were increased in patients with normo- and microalbuminuria but not in those with macroalbuminuria. Urinary C-megalin levels were also positively associated with plasma inorganic phosphate and negatively with hemoglobin levels in those showing no features of bleeding and not taking vitamin D analogs, phosphate binders, or erythropoiesis-stimulating agents.
CONCLUSIONS-Urinary full-length megalin excretion as measured by the C-megalin assay is well associated with reduced eGFR and linked to the severity of DN, phosphate dysregulation, and anemia, whereas urinary excretion of megalin ectodomain as measured by the A-megalin assay may be associated with distinctive mechanisms of earlier DN in type 2 diabetes.

DOI： 10.2337/dc11-1684

Web of Science

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Vitamin D deficiency is associated with various medical conditions including musculoskeletal disorders, infection, metabolic diseases, and cardiovascular disease. Megalin and cubilin, endocytic receptors in proximal tubule cells, are involved in the reabsorption of vitamin D binding protein from glomerular filtrates and the subsequent intracellular conversion of 25-hydroxyvitamin D-3 to biologically active 1 alpha,25-dihydroxyvitamin D-3. Dysfunction of these receptors, which is commonly found in patients with diabetic nephropathy, even at early stages, may explain why vitamin D deficiency is often complicated in these patients. Therapeutic strategies to protect the functions of these receptors from injury could be used to prevent vitamin D deficiency and its related disorders.

DOI： 10.1111/j.1744-9987.2011.00920.x

Web of Science

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.bbrc.2011.02.118

Web of Science

PubMed

researchmap

DOI： 10.4061/2011/957164

PubMed

researchmap

記述言語：日本語   出版者・発行元：(株)癌と化学療法社  

症例は血液透析施行中の82歳、男性。2003年、進行食道癌に対し化学放射線療法(low-dose FP+放射線照射)を施行され経過良好であったが、2009年3月に頸部食道に再発し通過障害のため入院した。内視鏡的胃瘻造設術を行った後、docetaxel(18mg/m22週ごと)+nedaplatin(16mg/m22週ごと)併用療法を開始した。既往の洞不全症候群による頻脈発作やめまいを認めたのみで重篤な有害事象は認めず、2回目投与後に退院し外来化学療法に移行した。通過障害の改善がみられ飲水可能となり、4回目施行後の食道造影にて狭窄の改善を認めた。その後、急性心筋梗塞により2009年7月に永眠された。血液透析患者のようなハイリスク患者に対する化学療法は推奨される投与量やレジメンが確立されていないが、ハイリスクであってもリスクとベネフィットをよく説明した上で患者が希望された場合には化学療法を施行し得る。実際、本例においては患者のQOLの向上を認め有用であった。(著者抄録)

researchmap

その他リンク： https://search.jamas.or.jp/default/link?pub_year=2010&ichushi_jid=J00296&link_issn=&doc_id=20100524490021&doc_link_id=%2Fab8gtkrc%2F2010%2F003705%2F022%2F0883-0885%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fab8gtkrc%2F2010%2F003705%2F022%2F0883-0885%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

Megalin plays a critical role in the endocytosis of albumin and other filtered low-molecular-weight proteins. Here we studied the interaction between megalin and Disabled-2 (Dab2), an adaptor protein that binds to the cytoplasmic domain of megalin and appears to control its trafficking. We co-immunoprecipitated megalin and Dab2 from cultured proximal tubule cells and identified the proteins by liquid chromatography and tandem mass spectrometry. We found two proteins associated with the megalin/Dab2 complex, nonmuscle myosin heavy chain IIA (NMHC-IIA) and beta-actin. Subcellular fractionation followed by sucrose velocity gradient separation showed that megalin, Dab2, and NMHC-IIA existed as a complex in the same endosomal fractions. In vitro pull-down assays demonstrated that NMHC-IIA was bound to the carboxyl-terminal region of Dab2, but not to megalin&apos;s cytoplasmic domain. We then transfected COS-7 cells with plasmids that induced the expression of Dab2, NMHC-IIA, and the megalin minireceptor, a truncated form of megalin. Co-immunoprecipitation studies showed that the minireceptor and NMHC-IIA co-immunoprecipitated only with Dab2. Furthermore, the uptake of (125)I-lactoferrin, an endocytic ligand of megalin, by rat yolk sac-derived megalin-expressing L2 cells was inhibited by blebbistatin, a specific inhibitor of nonmuscle myosin II. Our study shows that NMHC-IIA is functionally linked to megalin by interaction with Dab2 and is likely involved in megalin-mediated endocytosis in proximal tubule cells. Kidney International (2009) 75, 1308-1315; doi:10.1038/ki.2009.85; published online 1 April 2009

DOI： 10.1038/ki.2009.85

Web of Science

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ENDOCRINE SOC  

Impairment of proximal tubular endocytosis of glomerular-filtered proteins including albumin results in the development of proteinuria/albuminuria in patients with chronic kidney disease. However, the mechanisms regulating the proximal tubular function are largely unknown. This study aimed to investigate the role of angiotensin II type 1A receptor (AT(1A)R)- and insulin-mediated signaling pathways in regulating the expression of megalin, a multiligand endocytic receptor in proximal tubule cells (PTCs). Opossum kidney PTC-derived OK cells that stably express rat AT(1A)R but are deficient in endogenous angiotensin II receptors (AT(1A)R-OK cells) were used for this study. Treatment of the cells with angiotensin II suppressed mRNA and protein expression of megalin at 3- and 24-h incubation time points, respectively. Cellular uptake and degradation of albumin and receptor-associated protein, megalin&apos;s endocytic ligands were suppressed 24 h after angiotensin II treatment. The AT(1A)R-mediated decrease in megalin expression was partially prevented by ERK inhibitors. Insulin competed with the AT(1A)R-mediated ERK activation and decrease in megalin expression. Inhibitors of phosphatidylinositol 3- kinase (PI3K), a major component of insulin signaling, also suppressed megalin expression, and activation of the insulin receptor substrate (IRS)/PI3K system was prevented by angiotensin II. Collectively the AT(1A)R-mediated ERK signaling is involved in suppressing megalin expression in the OK cell line, and insulin competes with this pathway. Conversely, the insulin-IRS/PI3K signaling, with which angiotensin II competes, tends to stimulate megalin expression. In conclusion, there is AT(1A)R- and insulin-mediated competitive signaling cross talk to regulate megalin expression in cultured PTCs. (Endocrinology 150: 871 - 878, 2009)

DOI： 10.1210/en.2008-0886

Web of Science

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE  

Serum levels of cystatin C, an endogenous cysteine protemase inhibitor, are often used as an indicator of glomerular filtration rate. Although it is known that cystatin C is filtered by glomeruli and metabolized in proximal tubule cells (PTC), the precise molecular mechanism underlying this process is undetermined. Using quartz-crystal microbalance analyses, we demonstrate that cystatin C binds directly to megalin, an endocytic receptor in PTC, in a Ca(+)-dependent manner. We also find that cystatin C is endocytosed specifically via megalin in rat yolk sac epithelium-derived L2 cells which share a variety of characteristics with PTC. Finally, it? vivo studies using kidney-specific megalin knockout mice provide evidence that megalin mediates proximal tubular uptake of cystatin C. We conclude that megalin is an endocytic receptor of cystatin C in PTC. (c) 2007 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bbrc.2007.04.072

Web of Science

PubMed

researchmap

DOI： 10.1159/000111253

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

Background/Aims: Mutations of the endosomal chloride/ proton exchanger gene, CLCN5, cause Dent's disease, an X-linked recessive proximal tubular disorder. The renal endocytic system was found to be affected in clcn5 knockout mice. However, the impaired endocytic machinery of Dent's disease patients has not been thoroughly investigated. Methods: The CLCN5 gene was sequenced in a Japanese patient with Dent's disease and his family. The loss-of-function phenotype of the missense CLCN5 mutation was investigated by gene expression in Xenopus oocytes and CHO cells. Immunohistochemical analysis was performed on kidney biopsy specimens for endocytic machinery proteins, megalin, cubilin, and disabled-2 (Dab2) in proximal tubules. Results: Genomic analysis revealed a novel G-to-A transition at the first nucleotide of the 333rd codon of CLCN5, causing a substitution of glycine with arginine. Inefficient expression of the mutant gene in Xenopus oocytes resulted in abolished chloride currents. Impaired N-glycosylation of the mutant protein was evident in the DNA-transfected CHO cells. Proximal tubular expression of megalin, cubilin, and Dab2 was markedly reduced and irregular staining in some portions was observed in the patient compared with controls. Conclusions: A novel G333R CLCN5 mutation caused defective expression of megalin, cubilin, and Dab2 in a patient with Dent's disease. Copyright (c) 2007 S. Karger AG, Basel.

DOI： 10.1159/000111253

Web of Science

researchmap

記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

researchmap

記述言語：日本語   出版者・発行元：(株)東京医学社  

researchmap

記述言語：日本語   出版者・発行元：新潟県医師会  

メガリンは糸球体濾過蛋白質の再吸収・代謝に関わるエンドサイトーシス受容体であるが、近位尿細管細胞におけるメガリンおよびその関連分子の発現や機能が、糖尿病性腎臓病(DKD)を含む慢性腎臓病の発症・進展に深く関与していると考えられる。著者らの研究から、1)メガリンを標的分子としたDKDの発症・進展機序の解明と新規のバイオマーカーの探索、2)DKDの発症および進展を目的とした新しい食事療法の開発について述べた。

researchmap

記述言語：日本語   出版者・発行元：(一社)日本臨床栄養代謝学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本糖尿病学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

researchmap

記述言語：日本語   出版者・発行元：(株)メディカ出版  

researchmap

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J02946&link_issn=&doc_id=20200528150009&doc_link_id=%2Fao7tousi%2F2020%2F002606%2F011%2F0514-0516%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fao7tousi%2F2020%2F002606%2F011%2F0514-0516%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(公財)臨床薬理研究振興財団  

軽度〜中等度腎機能障害を有する成人2型糖尿病患者(残存機能ネフロンに過剰代謝負荷がかかっていることが推測される)を対象に、エンパグリフロジンによる腎機能保護作用を検証するとともに尿中メガリン(およびメガリンリガンド分子)の動態を調べ、腎機能保護作用がメガリン機能に関連したものであるか検討した。さらに、尿中メガリンなどの検査がコンパニオン診断として有用であるか、探索的な検討を行った。また、SGLT2阻害薬がメガリンの発現・機能に及ぼす影響についても検討を継続した。臨床試験の被験者51名で、平均年齢は62歳であり、男性が32名であった。2名が有害反応のため脱落したが、6ヵ月後、HbA1cとBMIが減少した。現在、メガリンを含む尿中バイオマーカーの推移について解析を行っている。ダパグリフロジン、エンパグリフロジンを投与されたマウスでは尿中の糖排泄増加を認めたが血糖値に差は認められなかった。免疫組織化学染色では近位尿細管におけるメガリンの染色性が低下していることが確認された。またウエスタンブロット法において、メガリンの蛋白がvehicle群と比較して低下していることが認められた。リアルタイムRT-PCRにおいてもメガリンmRNAがvehicle群と比較して低下していることが確認された。ダパグリフロジンを添加されたIRPTCではメガリン蛋白の低下が認められ、mRNAの低下も認められた。

researchmap

記述言語：日本語   出版者・発行元：(株)メディカ出版  

researchmap

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J02946&link_issn=&doc_id=20200528150008&doc_link_id=issn%3D1341-1489%26volume%3D26%26issue%3D6%26spage%3D512&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D1341-1489%26volume%3D26%26issue%3D6%26spage%3D512&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

記述言語：日本語   出版者・発行元：医歯薬出版(株)  

これまでに、たんぱく質制限に関してさまざまな無作為化比較試験(RCT)とそのメタ解析が行われてきたが、その結果から、慢性腎臓病(CKD)患者に対するたんぱく質摂取制限は、とくに非糖尿病性腎症や1型糖尿病患者のGFR低下抑制に対して有効で、2型糖尿病患者でも有効な可能性があると考えられる。たんぱく質摂取指示量に関しては、『慢性腎臓病に対する食事療法基準2014年版』を参考に、個々の患者の病態やリスクなどを総合的に判断すべきであるが、すくなくとも0.6g/kg体重/dayを下回らない、0.8g/kg体重/day未満のたんぱく質の制限は、死亡のリスクを増やさずにGFR低下抑制に有効である可能性がある。なお、たんぱく質を制限する場合、低栄養の発症リスクを常に念頭におき、必要なエネルギー(25〜35kcal/kg標準体重/day)を確保することが必要である。たんぱく質制限においてはその遵守率(アドヒアランス)が末期腎不全のリスクに大きな影響を与え、遵守率の改善に多職種連携や低たんぱく質食品が有効であることが示唆されている。(著者抄録)

researchmap

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J00060&link_issn=&doc_id=20200316030004&doc_link_id=%2Faa7ayuma%2F2020%2F027211%2F005%2F1129-1132%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faa7ayuma%2F2020%2F027211%2F005%2F1129-1132%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(株)メディカ出版  

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：(公社)日本透析医会  

我が国では急速に高齢化が進展しており、加齢に伴い腎機能は低下するため、今後しばらくは、透析導入患者数は減少しないことが予想されている。超高齢社会における透析患者の高齢化も必発であり、その対策が急務である。高齢透析患者では、高齢者特有の生理機能の変化や併存疾患による嚥下機能の低下だけでなく、食欲低下からのエネルギー不足や腎不全特有の様々な要因が加わることで、protein energy wasting(PEW)と呼ばれるたんぱく質やエネルギーの貯蔵が減少している状態を招く。したがって高齢透析患者では栄養状態を適格に評価し、適切なタイミングで栄養介入することが必要である。経口栄養補助(oral nutrition supplement;ONS)は栄養状態の改善に寄与することが期待されているが、ONSでその改善が得られなかった症例や経口摂取が上手くいかない症例にとっては、透析中の静脈栄養(intradialytic parenteral nutrition;IDPN)は合理的な治療選択肢である。多くの問題点はあるが、今後、透析施設での透析中の食事提供、食事摂取についても再検討が必要である。(著者抄録)

researchmap

記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

researchmap

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J02822&link_issn=&doc_id=20190807240003&doc_link_id=10.4009%2Fjsdt.52.401&url=https%3A%2F%2Fdoi.org%2F10.4009%2Fjsdt.52.401&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本糖尿病学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本糖尿病学会  

researchmap

記述言語：日本語   出版者・発行元：(株)東京医学社  

researchmap

記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER DIABETES ASSOC  

DOI： 10.2337/db19-29-LB

Web of Science

researchmap

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

researchmap

記述言語：日本語   出版者・発行元：(株)東京医学社  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本糖尿病学会  

researchmap

記述言語：日本語   出版者・発行元：(株)東京医学社  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本糖尿病学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本病態栄養学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本病態栄養学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本病態栄養学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本病態栄養学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本病態栄養学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本病態栄養学会  

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：新潟急性血液浄化研究会  

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：(一社)日本糖尿病学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

researchmap

記述言語：日本語   出版者・発行元：(株)メディカ出版  

researchmap

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J05098&link_issn=&doc_id=20180705140009&doc_link_id=issn%3D1882-3343%26volume%3D11%26issue%3D7%26spage%3D610&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D1882-3343%26volume%3D11%26issue%3D7%26spage%3D610&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

記述言語：日本語   出版者・発行元：(株)メディカ出版  

researchmap

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J05098&link_issn=&doc_id=20180705140007&doc_link_id=issn%3D1882-3343%26volume%3D11%26issue%3D7%26spage%3D606&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D1882-3343%26volume%3D11%26issue%3D7%26spage%3D606&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

記述言語：日本語   出版者・発行元：(株)メディカ出版  

researchmap

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J05098&link_issn=&doc_id=20180705140008&doc_link_id=issn%3D1882-3343%26volume%3D11%26issue%3D7%26spage%3D608&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D1882-3343%26volume%3D11%26issue%3D7%26spage%3D608&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

researchmap

記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

researchmap

記述言語：日本語   出版者・発行元：(公社)日本栄養・食糧学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本糖尿病学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本糖尿病学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本糖尿病学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本糖尿病学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本糖尿病学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本糖尿病学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

researchmap

記述言語：日本語   出版者・発行元：(株)ジェフコーポレーション  

researchmap

記述言語：日本語   出版者・発行元：(株)ライフメディコム  

researchmap

記述言語：日本語  

DOI： 10.20837/4201802252

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

DOI： 10.19020/KB.0000000098

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：医歯薬出版(株)  

糖尿病性腎症は透析導入の原因疾患の第1位を占め、その早期診断や重症度判定は重要な課題である。微量アルブミン尿は早期診断のマーカーとして世界的にコンセンサスを得ているが、さまざまな問題点も指摘されており、よりその病因や病態に基づいた新しいバイオマーカーの開発が求められている。そのようななかで現在、日本医療研究開発機構における難治性疾患等実用化研究事業(腎疾患実用化研究事業)において「糖尿病性腎症の進展予防にむけた病期分類・病理・バイオマーカーを統合した診断法の開発」として、腎症の評価に有用なバイオマーカー開発の基盤研究が進行している。今後、病因および病態を反映したバイオマーカー開発がなされれば、それに基づいた創薬など、有効な治療法の確立につながる可能性もあり、この分野におけるさらなる研究の進展が期待されている。本稿では腎症における既存のバイオマーカーだけでなく、近年、多くのあらたな報告がなされている尿細管障害性マーカーなどの検討も含めながら概説する。(著者抄録)

researchmap

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J00060&link_issn=&doc_id=20171229030021&doc_link_id=%2Faa7ayuma%2F2017%2F026313%2F022%2F1123-1128%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faa7ayuma%2F2017%2F026313%2F022%2F1123-1128%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：新潟急性血液浄化研究会  

researchmap

記述言語：日本語   出版者・発行元：(有)フジメディカル出版  

体内の酸塩基平衡は食事の影響を受けることが知られている。食事に依存した酸負荷は食事性酸負荷と呼ばれ、食事摂取量の情報から算出することが可能であり、正味内因性酸産生量(net endogenous acid production:NEAP)や潜在的腎臓酸負荷(potential renal acid load:PRAL)などの指標が提唱されている。最近、その食事性酸負荷が動脈硬化や糖尿病など生活習慣に起因する疾患に対して影響を及ぼす可能性が示唆されている。一方、慢性腎臓病(CKD)の進行において代謝性アシドーシスは独立した末期腎不全の危険因子であるが、食事性酸負荷がCKDの発症および進展に関連しているとする多くの報告が集積されつつある。食塩やたんぱく質、脂質管理などとともに、食事性酸負荷を適切に管理することが新たなCKD対策の一つになる可能性があり、今後のさらなる研究の進展が期待される。(著者抄録)

researchmap

記述言語：日本語   出版者・発行元：(一社)日本老年医学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本老年医学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本老年医学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

researchmap

記述言語：日本語   出版者・発行元：新潟県医師会  

researchmap

記述言語：日本語   出版者・発行元：日本臨床検査医学会  

researchmap

記述言語：日本語   出版者・発行元：新潟医学会  

researchmap

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J00990&link_issn=&doc_id=20170929080018&doc_link_id=%2Fdg3nigta%2F2017%2Fs13105%2F013%2F0318-0318%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdg3nigta%2F2017%2Fs13105%2F013%2F0318-0318%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(一社)日本糖尿病学会  

researchmap

記述言語：日本語   出版者・発行元：(公社)日本栄養・食糧学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

researchmap

記述言語：日本語   出版者・発行元：(公社)日本栄養・食糧学会  

researchmap

記述言語：日本語   出版者・発行元：(有)科学評論社  

researchmap

記述言語：日本語   出版者・発行元：(NPO)日本心臓血管外科学会  

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：(一社)日本病態栄養学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本神経学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本神経学会  

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：(一社)日本神経学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本糖尿病学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

researchmap

記述言語：日本語   出版者・発行元：(株)東京医学社  

researchmap

記述言語：日本語   出版者・発行元：(有)科学評論社  

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

researchmap

記述言語：日本語   出版者・発行元：(公社)日本栄養・食糧学会  

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：(株)日本メディカルセンター  

症例は79歳男性で、40歳時に2型糖尿病と診断され、68歳時に糖尿病性腎症のため血液透析を導入された。78歳時に急性心筋梗塞に対し、冠動脈バイパス術が行われた。79歳時に閉塞性動脈硬化症に対しステント留置術が行われた。入院21日前より発熱を認め、透析とセフォチアムヘキセチルを使用したが解熱せず受診した。腹部CTで左尿管結石と腎盂の拡張を認め、血液検査ではCRP 16.9mg/dLと高値であった。尿管結石および尿路感染症と診断し、入院しメロペネム静脈内投与を開始した。血液培養よりSerratia marcescensが検出された。入院後もボグリボースを継続したが、空腹時血糖値が200mg/dLと高値で、尿路感染症の影響もあり、経口薬による血糖コントロールは困難と考え、超速効型インスリンに変更した。解熱傾向が得られ、インスリンからシタグリプチンに変更したが血糖コントロール悪化は認めず、第19病日から3日間持続血糖モニター(CGM)にて血糖変動を評価した。入院中はCGM中も含め、毎食前と就寝前の少なくとも1日4回の血糖測定を行った。シタグリプチンは糖尿病合併維持血液透析患者に対し、有用な選択肢となると思われる。

DOI： 10.19020/J01864.2016250031

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：(有)科学評論社  

researchmap

記述言語：日本語   出版者・発行元：(株)東京医学社  

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：(一社)日本病態栄養学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本病態栄養学会  

researchmap

記述言語：日本語   出版者・発行元：新潟急性血液浄化研究会  

researchmap

記述言語：日本語   出版者・発行元：(株)インフォノーツパブリッシング  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本アフェレシス学会  

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：(株)東京医学社  

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：(一社)日本糖尿病学会  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：(株)文光堂  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本外科学会  

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：日本アミノ酸学会  

researchmap

記述言語：日本語   出版者・発行元：(公財)日本腎臓財団  

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：(株)中外医学社  

タンパク質代謝は腎に負荷を与え,腎機能障害を増悪させると考えられてきた.タンパク質摂取制限が腎機能の低下速度を抑制するとする確証が十分に得られていないが,近年タンパク質摂取制限の有効性を示す報告がなされてきている.また,摂取タンパク質の種類が腎に与える影響についても検討が進んでいる.健常人では,糸球体を濾過する低分子量タンパク質が近位尿細管細胞によって再吸収・代謝されている.糸球体傷害をきたすと,本来糸球体を濾過しない物質やタンパク質の濾過が亢進し,その代謝負荷が近位尿細管の傷害を引き起こす可能性が考えられる.メガリンは近位尿細管におけるタンパク質代謝機構において重要な役割を担っている.Nrf2活性化薬バルドキソロンメチルは,2型糖尿病の糖尿病性腎症患者のeGFRを改善し,またサルにおいて,メガリンの発現低下とともにクレアチニンクリアランスの増大を認めることが報告されている.(著者抄録)

researchmap

記述言語：日本語   出版者・発行元：(株)東京医学社  

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：(一社)日本肥満学会  

肥満は世界的な問題であり、我が国においても増加傾向であると考えられる。肥満やメタボリックシンドローム(MetS)は慢性腎臓病(chronic kidney disease:CKD)とも深く関連しているが、肥満に伴うCKDはobesity-related glomerulopathy(ORG:肥満関連糸球体症)という概念で捉えられている。そして、その病因として、脂肪組織から分泌されるアディポカインの関与や腎血行動態の異常、さらに脂肪毒性(lipotoxicity)による腎傷害機序が想定されている。脂肪毒性とは、脂肪(脂質)による細胞・臓器障害を意味するが、腎臓においては、糸球体固有細胞(メサンギウム細胞、内皮細胞、上皮細胞)だけでなく、尿細管細胞への影響に関する報告も増加している。そのような意味で、肥満(あるいはMetS)に関連する腎症は、糸球体のみならず、尿細管や間質病変、あるいはネフロンの構築上の異常も含めた総合的な病態として捉えるべきであると考えられる。腎臓における脂肪毒性による傷害機序としては、大きく分けて2つあると考えられている。1つは、脂肪酸や中性脂肪の合成と分解のバランス異常から腎臓に脂肪が蓄積することによるものであり、もう1つは遊離脂肪酸(free fatty acids:FFA)などの細胞取り込みの増加によるものである。いずれの傷害機序においても、腎臓における脂肪毒性に関しては、尿細管細胞(特に近位尿細管細胞)への影響が重要である。特に、FFAの再吸収においては近位尿細管のエンドサイトーシス受容体であるメガリンが重要な役割を果たしている。肥満やMetSおよび糖尿病においては、メガリンによって再吸収される糸球体濾過タンパク質の質的・量的代謝負荷が、近位尿細管のみならず腎臓全体の機能障害の進展に影響を与えている可能性がある。メガリンはそのような病態の解明だけでなく、治療の標的候補分子のひとつとして重要であり、今後のさらなる研究が期待される。(著者抄録)

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：(株)メディカルレビュー社  

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：(NPO)日本高血圧学会  

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：新潟医学会  

CiNii Article

CiNii Books

researchmap

記述言語：日本語   出版者・発行元：(株)中外医学社  

メガリンは近位尿細管において糸球体濾過分子(主にタンパク質)の再吸収に関わるエンドサイトーシス受容体である.近年,その発現調節機構,新規リガンドの同定,リガンド結合機序,他分子との相互作用の解析などが進んでいる.またメガリンとその関連分子は,アルブミン尿の出現や腎機能障害の進展機序において重要な役割を担っていることが明らかになってきている.さらに尿中メガリンの測定系の開発が行われ,それが新規バイオマーカーとなる可能性が期待されている.またメガリンおよびその関連分子のgenome-wide association studyによる解析,腎内レニン・アンジオテンシン系活性化機序におけるメガリンの役割,経口抗酸化薬bardoxolne methylとメガリンの関わりなど,注目される知見が相次いでいる.今後,メガリンを標的とした腎臓病の新しい診断・治療法の開発が期待される.(著者抄録)

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：(一社)日本病態栄養学会  

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：(株)東京医学社  

小分子物質からアルブミン領域までの溶質除去性能の向上を目的として開発されたFB-210UHβ(以下UHβ)を維持透析患者6名に使用し、その溶質除去特性について、既存の透析器PES-21Sα(以下Sα)と比較検討した。結果、小分子物質からβ2-MG領域までの溶質除去性能には有意差を認めなかった。α1-MGについては、除去量でUHβが136±38.1mg、Sαが81±32.0mg、クリアランスでUHβが10±1.1mL/min、Sαが4±0.7mL/minであり、UHβのほうが有意に高値であった。透析排液中アルブミン漏出量の1透析あたり平均値は、Sαの0.80±0.24gに対してUHβは3.43±0.87gと有意に高値であった。血清アルブミン値は、Sα使用時の4.12±0.16g/dLに対し、UHβでは使用開始1週後3.90±0.17g/dL、1ヵ月後3.78±0.12gと低下したが、その後はほとんど変化なく推移した。

researchmap

記述言語：日本語   出版者・発行元：(株)先端医学社  

若年・中年期の非糖尿病高血圧患者20名を対象に、アジルサルタンの降圧効果に加え、尿中アルブミン排泄量およびインスリン抵抗性に及ぼす影響について検討した。その結果、ARB未処方への追加例およびバルサルタンからの変更例いずれの群においても、アジルサルタン処方2週後より血圧の有意な低下を認め、その降圧効果が確認された。また、アジルサルタン処方により、尿中アルブミン排泄量の低下、インスリン抵抗性の改善が示された。

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：(株)日本メディカルセンター  

腎臓は生体恒常性維持においてさまざまな役割を果たしている臓器である.なかでも近位尿細管は重要な役割をもつと考えられており,その上皮細胞にエンドサイトーシス受容体,メガリンが発現している.メガリンはさまざまなトランスポーターや受容体の機能調節にかかわるとともに,アルブミンを含む多くのタンパク質の代謝あるいは分解に関与する.近年の研究から細胞内シグナルに関与することや,さらにはメガリンを介する病的リガンドのエンドサイトーシスが近位尿細管障害発症のメカニズムに関与することなどが示唆されている.このように多岐にわたる役割をもつメガリンをCKDの診断や治療に応用することを目指した研究も行われている.(著者抄録)

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：(NPO)日本高血圧学会  

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：新潟医学会  

CiNii Article

CiNii Books

researchmap

その他リンク： http://search.jamas.or.jp/link/ui/2013193690

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：(株)日本医学館  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

researchmap

記述言語：日本語   出版者・発行元：(株)東京医学社  

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：(NPO)日本高血圧学会  

researchmap

記述言語：日本語   出版者・発行元：(株)ライフ・サイエンス  

2型糖尿病を有する透析施行患者に対するアログリプチンの有効性と安全性について検討した。2型糖尿病を有する透析施行患者7例で、アログリプチンの末期腎不全患者の用法・用量から6.25mgを1日1回投与し、投与前および投与後4週ごとのHbA1cを測定した。エリスロポエチン製剤の試験期間中の投与量には変化はなかった。4週後および8週後、12週後における平均HbA1cは、それぞれ6.2±0.4%および5.9±0.3%、5.6±0.3%と投与前に比較して有意に低下した。全例で良好な血糖低下の推移を認めた。投与開始12週後において有意な変化を認めたのは透析前の拡張期血圧のみであったが、わずかながら脂質の項目に低下がみられた。副作用としての低血糖症状は認めなかった。

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：(株)癌と化学療法社  

症例は慢性腎不全にて血液透析施行中の75歳、男性。多発肝転移を伴う進行胃癌(Stage IV)と診断した。化学療法を希望されたため、一次治療はtegafur-uracil(300mg/日、連日)+docetaxel(20mg/m2、3週毎)、二次治療はtegafur-uracil(同量)+CPT-11(64mg/m2、2週毎)併用療法とした。docetaxelとCPT-11は非透析日に投与した。その結果、一次治療は計3コース、二次治療は計9コース安全に施行可能であり、grade 3以上の重篤な有害事象は認めなかった。透析患者に対する抗癌剤の至適投与量はいまだ明確ではないため、その代謝特性を考慮しながら症例ごとに検討するしかないのが現状である。この点で本症例は示唆に富むと考え報告した。(著者抄録)

CiNii Article

researchmap

記述言語：日本語   出版者・発行元：(一社)日本臨床スポーツ医学会  

メタボリックシンドロームの主要な発症原因と考えられる内臓脂肪型肥満とインスリン抵抗性に対する有酸素性運動とレジスタンストレーニングを組み合わせた運動の効果を検討した。対象はメタボリックシンドローム診断基準に該当する男性27名であった。実践させた運動は、施設では有酸素性運動(40〜60%HRmax、15〜30分)とレジスタンストレーニング(15RMの重量、反復回数10〜15回/セット、3セット)であり、頻度は週1回程度であった。加えて、施設外では施設で実践している強度でのウォーキング等の有酸素性運動と自体重によるレジスタンストレーニングの実践を促した。期間は約3ヵ月間であった。評価項目は形態、体組成、血圧、血中脂質、糖代謝能であった。体重、体脂肪量、腹囲、収縮期血圧、拡張期血圧、インスリン、HOMA-IRは有意に減少したが、除脂肪量には有意な差を認めなかった。有酸素性運動とレジスタンストレーニングの併用は内臓脂肪型肥満とインスリン抵抗性を有意に改善させた。(著者抄録)

researchmap

記述言語：日本語   出版者・発行元：(株)中外医学社  

糖尿病性腎症は慢性腎不全に至る最も重要な原因疾患であり,その早期診断,病態把握,予後推定のため,微量アルブミン尿の測定が推奨されている.さらに微量アルブミン尿は,糖尿病の有無にかかわらず,心血管系イベントの危険因子としても知られている.しかしその機序や意義については未だ不明な点も多い.近年,糖尿病における微量アルブミン尿の機序について,糸球体・血管系と尿細管系の相互的関係をふまえ,ネフロン傷害の全体像を把握する重要性を示す報告が蓄積している.本稿では特に,近位尿細管上皮細胞におけるアルブミンの処理機構の問題,あるいはインスリン抵抗性やgenome-wide association studyなどの新しい知見をふまえて,その動向を紹介する.(著者抄録)

researchmap

記述言語：日本語   出版者・発行元：日本プロテオーム学会（日本ヒトプロテオーム機構）  

DOI： 10.14889/jhupo.2011.0.186.0

CiNii Article

researchmap

記述言語：日本語   出版者・発行元：新潟医学会  

CiNii Article

CiNii Books

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：長岡赤十字病院  

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：(一社)日本糖尿病・妊娠学会  

1型糖尿病による慢性腎不全に対する腎移植後に、結婚・妊娠・出産した症例を経験した。腎移植後の本邦出産例はこれまでいくつか報告されているが、原疾患が糖尿病腎症の例は本邦2例目である。[症例]37歳、初産婦。[既往歴]糖尿病性網膜症のため右眼は失明。[現病歴]8歳時に1型糖尿病を発症し、インスリン療法を開始した。20歳時に蛋白尿が出現し、腎生検にて糖尿病腎症と診断された。28歳頃より腎機能が低下し、29歳時、腎不全に伴う溢水のために血液透析が開始された。31歳時、父をドナーとして血液型一致の生体腎移植術を受けた。拒絶反応はなく、移植腎機能はCr 1.0-1.1mg/dl、尿蛋白陰性と安定しており、高血圧も認めなかった。36歳時に結婚し、2007年1月、妊娠6週であることが判明したが計画妊娠ではなかった。妊娠判明後は、妊娠前と同様インスリンリスプロおよびインスリングラルギンの強化インスリン療法にて、HbA1c7%以下にコントロールされた。妊娠30週頃から尿蛋白が出現した。妊娠36週に血圧上昇および尿蛋白の増加を認め、妊娠高血圧腎症を合併した。左眼の硝子体出血を考慮し、37週1日にて帝王切開を施行された。3168gの男児をApgar score 8/9点で分娩した。児に無呼吸発作、低血糖、高ビリルビン血症を認めたが、後遺症なく退院した。出産半年後の腎機能および蛋白尿は妊娠前に回復した。(著者抄録)

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：新潟医学会  

CiNii Article

CiNii Books

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：(一社)日本循環器学会  

researchmap

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：(一社)日本糖尿病・妊娠学会  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：(一社)日本糖尿病学会  

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

researchmap

記述言語：日本語  

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

researchmap

記述言語：日本語  

researchmap

記述言語：日本語  

researchmap

記述言語：日本語  

researchmap

記述言語：日本語  

researchmap

記述言語：日本語  

researchmap

記述言語：日本語  

researchmap

記述言語：日本語  

researchmap

記述言語：日本語  

researchmap

記述言語：日本語   会議種別：公開講演，セミナー，チュートリアル，講習，講義等  

researchmap

記述言語：英語  

researchmap

記述言語：英語  

researchmap

記述言語：英語  

researchmap

記述言語：英語  

researchmap

記述言語：英語  

researchmap

記述言語：英語  

researchmap

記述言語：日本語   会議種別：公開講演，セミナー，チュートリアル，講習，講義等  

researchmap

記述言語：日本語  

researchmap

記述言語：日本語  

researchmap

記述言語：日本語  

researchmap

記述言語：日本語  

researchmap