A GPI processing phospholipase A2, PGAP6, modulates Nodal signaling in embryos by shedding CRIPTO

©2016 Gun-Hee Lee et al. Originally published in Journal of Cell Biology. https://doi.org/10.1083/jcb.20160512

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Urinary type IV collagen (U-Col4) and albumin excretion is evaluated to monitor the development of diabetic kidney disease. However, U-Col4 excretion in the general population without diabetes has not yet been fully elucidated. In this study, 1067 participants without diabetes and with urinary albumin-creatinine ratio <300 mg/gCr (normo- or microalbuminuria) who underwent an annual health examination in 2004 were enrolled and observed for 5 years. They were divided according to the amount of U-Col4 or urinary albumin excreted. The decline in estimated glomerular filtration rate (eGFR) was calculated. In participants with eGFR ≥80 mL/min, abnormal U-Col4 excretion was indicated as a significant independent risk factor for 10% eGFR change per year, which is one of the prognostic factors for the development of end-stage kidney disease. Moreover, in contrast to urinary albumin excretion, U-Col4 excretion was not related to age or kidney function, suggesting that some individuals with abnormal U-Col4 excretion can have an independent hidden risk for the development of kidney dysfunction. In conclusion, it is important to measure U-Col4 excretion in the general population without diabetes to determine changes in renal features in every individual and help detect future complications such as diabetic kidney disease. If U-Col4 excretion is abnormal, kidney manifestation should be carefully followed up, even if the kidney function and urinalysis findings are normal

Qualitative Simulation for Early-Stage Service Design

Currently, the importance of services is widely accepted in various industries. Given this background, fundamental research on service engineering is carried out quite actively. Service engineering seeks to provide design methodology for services from an engineering perspective. In product and service design, designers are generally forced to spend a lot of redesign works if design changes occur at a late stage of the design process. Thus, it is important for designers to validate design solutions in the early stage(s) of the design process by using simulation methods. However, simulation models in the existing methods are built with quantitative information. In the early stages of the service design process, most of the information about a design solution is still not defined; therefore, it is difficult to obtain sufficient quantitative information. For obtaining such quantitative information, service providers need to offer a designed service to their customers as a trial, which impose much effort for building quantitative simulation models. In order to reduce such risks, this research applies a qualitative simulation method, which can be used to analyze the behavior of systems with fuzzy qualitative information. In this paper, we propose a method to build a qualitative simulation model with the design information available at the early stage(s) of the service design process. This method would enable designers to evaluate a design solution in the early stage of a service design process and would increases quality of the service design.サービス学会主催 The 3rd International Conference on Serviceology (ICServ 2015) July 7-9, 2015 in San Jose, CA, USA

IVC diameter in patients undergoing HD

Background : IVC diameter on expiration (IVCdexp) is measured by echocardiography routinely. It is used to estimate volume status and designated as a definitive marker for determining dry weight (DW) in patients undergoing hemodialysis (HD). Methods : A cross-sectional study. Outpatients (n = 107), and inpatients (n = 35) undergoing HD were enrolled. IVCdexp was measured on non-dialysis days in outpatients and dialysis days before and after the dialysis session in inpatients. In outpatients, the relationship of IVCdexp with echocardiography findings and clinical characteristics was analyzed. IVCdexp was compared with the other DW markers as a predictive factor for intradialytic hypotension. In inpatients, IVCdexp was analyzed by dividing inpatients with or without fluid in extravascular space. Results : IVCdexp ranged from 5.4 to 16.9 mm in outpatients who had optimal DW. IVCdexp could reflect on volume status, but not predictive for intradialytic hypotension and not suggestive of fluid in extravascular space. Conclusions : IVCdexp was a rough marker to estimate volume status and only useful in suggesting apparent hypervolemia or hypovolemia. We should know that the IVCdexp value is affected by a lot of factors and not a definitive marker for estimating practical DW

Successful treatment of highly advanced immunoglobulin G4-related kidney disease presenting renal mass-like regions with end-stage kidney failure : a case study

Background: Immunoglobulin G4-related kidney disease characterized by immunoglobulin G4-positive plasma cell-rich tubulointerstitial nephritis has distinctive serological and radiological findings. Renal prognosis is good because of a good response to glucocorticoids. Here we report a case of successful treatment of highly advanced immunoglobulin G4-related kidney disease presenting renal mass-like regions with end-stage kidney failure. Case Presentation: A 59-year-old Japanese man was referred to our hospital because of uremia with a creatinine level of 12.36 mg/dL. Urinalysis revealed mild proteinuria and hyperβ2microglobulinuria, and blood tests showed hyperglobulinemia with an IgG level of 3243 mg/dL and an IgG4 level of 621 mg/dL. Non-contrast computed tomography revealed renal mass-like regions. Based on the findings, immunoglobulin G4-related kidney disease was suspected, however, further radiological examination showed unexpected results. Ga-67 scintigraphy showed no kidney uptake. T2-weighted magnetic resonance imaging revealed high-intensity signals which corresponded to mass-like regions and multiple patchy low-intensity signals in kidney cortex. Finally, the patient was diagnosed with immunoglobulin G4-related kidney disease by renal pathology of severe immunoglobulin G4-positive plasma cellrich tubulointerstitial nephritis and characteristic fibrosis. He received 50 mg oral prednisolone, which was tapered with a subsequent decrease of serum creatinine and IgG4 levels. One year after initiation of treatment, he achieved normalization of serum IgG4 level and proteinuria, and remained off dialysis with a creatinine level of 3.50 mg/dL. After treatment with steroids, repeat imaging suggested bilateral severe focal atrophy. However, mass-like regions did not show atrophic change although renal atrophy was evident in patchy low-intensity lesions on T2-weighted magnetic resonance imaging. These findings suggest that multiple patchy low-intensity signals and high-intensity mass-like regions were mildly atrophic lesions of immunoglobulin G4-related kidney disease due to severe fibrosis and normal parts of kidney, respectively. Conclusions: In immunoglobulin G4-related kidney disease with severe kidney failure, radiological findings should be carefully examined. In addition, renal prognosis may be good despite highly advanced tubulointerstitial nephritis and fibrosis

1-year tolvaptan efficacy in ADPKD

Autosomal dominant polycystic kidney disease (ADPKD) develops into end-stage kidney disease by 65 years of age in an estimated 45%-70% of patients. Recent trials revealed that tolvaptan inhibits disease progression both in early-stage or late-stage ADPKD ; however, stratified analysis showed a difference of favorable factors correlated with tolvaptan efficacy between early-stage and late-stage ADPKD. Thus, we examined the efficacy of tolvaptan in ADPKD with a wide range of estimated glomerular filtration rates (eGFR). We enrolled 24 patients with eGFR 35.3 (28.0-65.5) ml / min / 1.73m2 and evaluated treatment effect as ΔΔeGFR (ml / min / 1.73m2 / year) or ΔΔtotal kidney volume (TKV) (% / year) that was calculated as post-treatment annual change - pre-treatment annual change. Pre ΔeGFR was significantly low in eGFR responders, defined as ΔΔeGFR > 0 ml / min / 1.73m2 / year. In eGFR responders, pre ΔeGFR, post ΔeGFR, eGFR, TKV, and proteinuria were significantly correlated with ΔΔeGFR. In TKV responders defined as ΔΔTKV > 5 % / year, we identified hypertension history, proteinuria, TKV, and post ΔTKV as significantly correlated factors with ΔΔTKV. In conclusion, pre ΔeGFR may be a predictive factor of therapeutic efficacy on kidney function. Tolvaptan may have greater efficacy in early-stage ADPKD with rapid GFR decline or with well-controlled blood pressure

Urinary type IV collagen excretion in the Japanese general population without diabetes

Urinary type IV collagen (U-Col4) and albumin excretion is evaluated to monitor the development of diabetic kidney disease. However, U-Col4 excretion in the general population without diabetes has not yet been fully elucidated. In this study, 1067 participants without diabetes and with urinary albumin-creatinine ratio <300 mg/gCr (normo- or microalbuminuria) who underwent an annual health examination in 2004 were enrolled and observed for 5 years. They were divided according to the amount of U-Col4 or urinary albumin excreted. The decline in estimated glomerular filtration rate (eGFR) was calculated. In participants with eGFR ≥80 mL/min, abnormal U-Col4 excretion was indicated as a significant independent risk factor for 10% eGFR change per year, which is one of the prognostic factors for the development of end-stage kidney disease. Moreover, in contrast to urinary albumin excretion, U-Col4 excretion was not related to age or kidney function, suggesting that some individuals with abnormal U-Col4 excretion can have an independent hidden risk for the development of kidney dysfunction. In conclusion, it is important to measure U-Col4 excretion in the general population without diabetes to determine changes in renal features in every individual and help detect future complications such as diabetic kidney disease. If U-Col4 excretion is abnormal, kidney manifestation should be carefully followed up, even if the kidney function and urinalysis findings are normal

Depletion of Lipid Efflux Pump ABCG1 Triggers the Intracellular Accumulation of Extracellular Vesicles and Reduces Aggregation and Tumorigenesis of Metastatic Cancer Cells

The ATP-binding cassette transporter G1 (ABCG1) is a cholesterol lipid efflux pump whose role in tumor growth has been largely unknown. Our transcriptomics revealed that ABCG1 was powerfully expressed in rapidly metastatic, aggregative colon cancer cells, in all the ABC transporter family members. Coincidently, genetic amplification of ABCG1 is found in 10–35% of clinical samples of metastatic cancer cases. Expression of ABCG1 was further elevated in three-dimensional tumoroids (tumor organoids) within stemness-enhancing tumor milieu, whereas depletion of ABCG1 lowered cellular aggregation and tumoroid growth in vitro as well as hypoxia-inducible factor 1α in cancer cells around the central necrotic areas in tumors in vivo. Notably, depletion of ABCG1 triggered the intracellular accumulation of extracellular vesicles (EVs) and regression of tumoroids. Collectively, these data suggest that ABCG1 plays a crucial role in tumorigenesis in metastatic cancer and that depletion of ABCG1 triggers tumor regression with the accumulation of EVs and their derivatives and cargos, implicating a novel ABCG1-targeting therapeutic strategy by which redundant and toxic substances may be accumulated in tumors leading to their regression

Differentiation of murine B cells induced by chondroitin sulfate B

A two-step culture system was used to investigate the role of chondroitin sulfate (CS) B, which is mitogenic to B cells, in differentiation of B cells. Mouse spleen B cells were incubated for 3 days with CSB in the presence of interleukin (IL)-4 and IL-5. After washing, the cells were replated at 10(5) viable cells/well and recultured without CSB in the presence of IL-4 and IL-5. CSB dose-dependently increased IgM production, the greatest enhancement being 450%. Dextran sulfate had a similar effect, whereas other glycosaminoglycans, CSA, CSC, heparin and hyaluronic acid, were marginally effective. Treatment of B cells with CSB resulted in increases in the number of IgM-secreting cells and numbers of CD138-positive cells and CD45R/B220-negative cells. CSB-induced IgM production was inhibited by the protein kinase C (PKC) inhibitor GF109203X but not by the phosphatidylinositol 3-kinase (P13K) inhibitor wortmannin. These results demonstrated that CSB promoted differentiation of B cells in the presence of IL-4 and IL-5 and suggested that PKC but not P13K is crucial for CSB-induced IgM production.</p