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ABSTRACT We demonstrate the use of an aldehyde scrubber system to resolve isobaric aldehyde/alkene interferences in a proton transfer reaction mass spectrometer (PTR-MS) by selectively removing the aldehydes from the [...]

Background. The importance of crescent formation in glomerulonephritis has increased. However, detailed analysis of crescentic glomerulonephritis in Asia is scarce. In addition, advances in serological diagnostic techniques (antineutrophil cytoplasmic and antiglomerular basement membrane autoantibodies) and early diagnosis have reduced the number of cases meeting the strict definition of crescentic glomerulonephritis (>50% of glomeruli are crescentic). Therefore, we analyzed the clinicopathological features and renal prognosis of glomerulonephritis cases that exhibited at least one crescentic lesion. Methods. We retrospectively evaluated 265 adult patients diagnosed with glomerulonephritis with at least one crescent formation based on the results of renal biopsy. We divided the patients into two groups based on the four types of glomerulonephritis, namely, the immune-complex (type II: IgA nephropathy, IgA vasculitis with nephritis, and lupus nephritis) and pauci-immune (type III: microscopic polyangiitis) groups. Factors affecting renal prognosis (end-stage renal failure requiring renal replacement therapy) were examined in a multivariate analysis using the Cox proportional hazards model. Kaplan–Meier curves and log-rank test were used to analyze and compare time from entry to renal death. Results. Renal prognosis differed significantly between the immune-complex and pauci-immune groups. Among the four types of glomerulonephritis, IgA nephropathy was the most prevalent. Multivariate analysis showed that renal function at renal biopsy and the ratio of global sclerosis independently predicted renal prognosis, but the type of glomerulonephritis was not a factor. Conclusions. Renal dysfunction at renal biopsy and the ratio of global sclerosis predicted renal prognosis, because it reflects the degree of irreversible renal damage. We also suspect that the formation of at least one crescentic lesion led to the development of these predictive factors, regardless of the type of glomerular disease and degree of crescent formation. [ABSTRACT FROM AUTHOR]

Background: In patients with systemic lupus erythematosus (SLE), disease activity can persist even after initiating dialysis. However, guidelines for the treatment of patients with SLE after dialysis is initiated have not yet been established. Case Presentation: We describe the case of a 54-year-old Japanese woman who was diagnosed with SLE at age 12, progressed to end-stage renal disease (ESRD), and initiated hemodialysis for lupus nephritis. However, SLE activity persisted after hemodialysis. Cyclophosphamide and mycophenolate mofetil were administered in addition to prednisolone and immunoadsorption, but this treatment strategy was limited by side effects. The patient was subsequently treated with belimumab, and the activity of SLE decreased rapidly. Conclusions: ESRD patients with SLE show no significant decrease in transitional B cells and have elevated levels of B-cell activating factor (BAFF). Both transitional B cells and BAFF are important therapeutic targets for belimumab, indicating that patients with ESRD may benefit from belimumab therapy. However, the effects of belimumab may be potentiated in patients with uremia, who may be more susceptible to adverse events such as infections. Patients with SLE who receive belimumab after initiation of hemodialysis therefore require careful follow-up. Here, we report the first case of belimumab administration in a patient with SLE after initiation of hemodialysis. [ABSTRACT FROM AUTHOR]

Calciprotein particles (CPPs) are a new biological marker of chronic kidney disease-mineral and bone disorder (CKD-MBD). CPPs consist of phosphate, calcium, and some proteins, with phosphate being the major contributor to the level and biological activity of CPPs. Recent studies have shown the physiological and pathological significance of CPPs, including contributions to bone and mineral metabolism, and to tissue and organ impairments such as cardiovascular damage and inflammatory responses. These actions are well known as important aspects of CKD-MBD. Fibroblast growth factor 23 (FGF23), which is secreted from the bone as the phosphaturic hormone, is markedly elevated in CKD-MBD. Many clinical studies have shown significant relationships between the level of FGF23 and outcomes such as mortality, prevalence of cardiovascular disease, bone fracture, and levels of inflammatory markers. Basic and clinical studies have suggested that CPPs contribute to synthesis and secretion of FGF23. Surgical treatments such as renal transplantation and parathyroidectomy for patients with CKD-MBD suppress excess levels of phosphate, calcium, parathyroid hormone (PTH), and FGF23, which are related to the CPP level. Therefore, suppression of CPPs might also contribute to improved clinical outcomes after these treatments. [ABSTRACT FROM AUTHOR]

Recently, the usefulness of multi-target therapy, which combines steroids with mycophenolate mofetil (MMF) and tacrolimus (Tac), a common treatment for LN, has been reported. To determine the effects of multi-target therapy in this case, a third kidney biopsy was performed after treatment initiation. Membranous lupus nephritis (MLN) accounts for approximately 10%-20% of all lupus nephritis (LN) cases. [Extracted from the article]

We have developed two types of innovative LCD displays: a 5-inch FHD and a 7-inch WQXGA. Both feature 0.96mm module thickness with 1mm narrow border, a 50% less backlight power consumption by adopting a unique RGBW display technology. They are also equipped with an in-cell touch panel system which achieves stylus input. [ABSTRACT FROM AUTHOR]

Abstract: Aerosol particles have important effects on human health, climate, regional visibility, and the deposition of acidic and toxic substances. The aerosols also have significant pharmaceutical and industrial applications. Trials of gas chromatographic analysis of extracts composition of diesel exhaust particles and aerosol mass spectrometer measurement of diesel exhaust particles composition are introduced in this paper. Usually, organic fraction of automotive exhaust particles are concentrated to 1mL by Kuderna-Danish concentrator after extracted into dichloromethane by soxhlet extraction. Then, these extracts are analyzed by GC/MS. In the extracts from the diesel exhaust particles, there are over several thousands of components, for example paraffinic hydrocarbons, aromatics, oxygenates and other hydrocarbons. [Copyright &y& Elsevier]

Mice deficient for paired immunoglobulin (Ig)-like receptor B (PIR-B) show defective regulation of receptor-mediated activation in antigen-presenting cells. Older PIR-B-/- mice had an increased number of peritoneal B1 cells. Splenic PIR-B-/- B2 cells were constitutively activated and proliferated much more than those from wild-type mice upon B cell receptor ligation. T helper type 2 (TH2)-prone humoral responses were augmented in PIR-B-/- mice upon immunization with T-dependent antigens, including increased interleukin 4 and decreased interferon-? responses, as well as enhanced IgG1 and IgE production. Impaired maturation of dendritic cells (DCs), possibly due to perturbed intracellular signaling, was responsible for the skewed responses. Thus, PIR-B is critical for B cell suppression, DC maturation and for balancing TH1 and TH2 immune responses. [ABSTRACT FROM AUTHOR]

Atmospheric aerosols are measured by recording PM mass because ambient standards are written in mass concentrations. However, in order to better understand how means of transportation contribute to ambient PM, many researchers are extending their investigations to include particle speciation measurement. An Aerosol Mass Spectrometer (Aerodyne Research type) has been designed to analyze the chemical components present on aerosol particles. This study continuously measured the chemical composition of automotive exhaust particles using an improved aerosol mass spectrometer. It found that the diesel exhaust particle size dependent composition changes according to the driving conditions. [ABSTRACT FROM AUTHOR]

Aim This study aimed to examine the roles of fibroblast growth factor 23 (FGF23) and soluble Klotho in phosphate metabolism in autosomal-dominant polycystic kidney disease (ADPKD) patients. Methods We measured these two factors and phosphate metabolism parameters in 80 patients with ADPKD and 53 patients with non-diabetic chronic kidney disease (CKD). Results The mean serum FGF23 level in the ADPKD group was significantly (twofold) higher than in the non-diabetic CKD patients, but the mean soluble Klotho level in the ADPKD group was significantly lower in the non-diabetic CKD group. The mean serum phosphate levels of the two groups were similar. The estimated glomerular filtration rate (eGFR) was approximately 45 mL/min per 1.73 m2 in both groups, and their serum vitamin D metabolite levels were in the normal range. Conclusion The serum FGF23 levels were significantly higher and soluble Klotho levels significantly lower in the ADPKD group than in the non-diabetic CKD group matched for eGFR, and these findings may be associated with resistance of renal phosphate excretion. [ABSTRACT FROM AUTHOR]

The intracellular trafficking pathway of albumin in podocytes remains controversial. We therefore analysed albumin endocytosis through caveolae, subsequent transcytosis, and exocytosis. In Western blot and immunofluorescence analysis in vitro , methyl-beta-cyclodextrin (MBCD) treatment significantly decreased the expression of caveolin-1 and albumin in cultured human podocytes after incubation with albumin; additionally, MBCD interfered with albumin endocytosis through caveolae in the experiment using Transwell plates. In the immunofluorescence analysis, albumin was incubated with cultured human podocytes, and colocalisation analysis with organelles and cytoskeletons in the podocytes showed that albumin particles colocalised with caveolin-1 and Fc-receptor but not clathrin in endocytosis, colocalised with actin cytoskeleton but not microtubules in transcytosis, and colocalised with early endosomes and lysosomes but not proteasome, endoplasmic reticulum, or Golgi apparatus. In the electron microscopic analysis of podocytes in nephrotic syndrome model mice, gold-labelled albumin was shown as endocytosis, transcytosis, and exocytosis with caveolae. These results indicate the intracellular trafficking of albumin through podocytes. Albumin enters through caveolae with the Fc-receptor, moves along actin, and reaches the early endosome, where some of them are sorted for lysosomal degradation, and others are directly transported outside the cells through exocytosis. This intracellular pathway may be a new aetiological hypothesis for albuminuria. • Intracellular trafficking of albumin through podocytes is shown. • Albumin enters podocytes through caveolae via Fc receptor endocytosis. • Albumin moves along actin but not microtubules in transcytosis. • At early endosomes, albumin is either lysosomally degraded or excreted. [ABSTRACT FROM AUTHOR]

It is well established that activating-type Fc receptors for IgG (FcγR), such as FcγRI and FcγRIII, are essential for inducing inflammatory responses, whereas a unique inhibitory FcγR, FcγRIIB, inhibits intracellular signaling upon ligation of IgG-immune complexes, and can suppress inflammation and autoimmunity. Although antigen presentation is a crucial step for evoking inflammatory responses, the contribution of FcγRIIB to antigen presentation is controversial as to whether it regulates antigen-presenting cells (APC), particularly dendritic cells (DC), positively or negatively. In the present report, we show that the antigen targeting to both activating-type FcγRs, FcγRI/III, and inhibitory FcγRIIB on bone marrow-derived DC and macrophages and primary epidermal Langerhans’ cells augmented T cell proliferation in vitro and elicited humoral responses upon adoptive transfer of the antigen-pulsed DC. The DC lacking FcγRIIB showed a reduction in IC-uptake ability and a decreased T-cell stimulation, and induced less efficient IgG production than those of DC from wild-type mice. On the other hand, the DC lacking FcR common γ subunit, which only expresses FcγRIIB, showed significant up-regulations of IC-uptake, T-cell proliferation, and IgG production compared to those of FcγR null DC, demonstrating a positive regulation of FcγRIIB for the efficient antigen presentation of IgG-complexed antigens. These results support the therapeutic benefits of antigen-targeting to FcγR on APC in the various inflammatory disorders. [Copyright &y& Elsevier]

Background: Tonsillectomy may treat IgA nephropathy (IgAN) by reducing the levels of galactose-deficient IgA1. Therefore, we aimed to analyze the long-term effects of tonsillectomy on patients with IgAN, as an initial treatment and as a treatment at any time in their lives., Methods: In this retrospective cohort analysis, 1147 patients with IgAN were grouped according to whether they had undergone tonsillectomy at any time, >1 year after renal biopsy (study 1), or within 1 year after renal biopsy (study 2). The patients were propensity-score matched or divided into four groups according to their proteinuria and renal function. The 20-year renal survival rates were evaluated until serum creatinine levels doubled (primary end point) and ESKD occurred (secondary end point)., Results: Patients in both studies had similar background characteristics after propensity score matching. In study 1, the renal survival rates for the primary and secondary end points were significantly higher for patients who underwent tonsillectomy at any time or >1 year after renal biopsy compared with those who did not. In study 2, the renal survival rates for the primary and secondary end points were significantly higher for patients who underwent tonsillectomy soon after renal biopsy compared with those who did not (primary end point, 98% versus 69%, P =0.001; secondary end point, 100% versus 75%, P =0.0001). A stratified analysis showed that significant treatment efficacy was observed for patients with proteinuria >1.0 g/d. Multivariate Cox regression analyses showed that tonsillectomy was associated with disease progression (hazard ratio, 0.27; P =0.04). Complications associated with tonsillectomy occurred in 8% of patients., Conclusions: Among patients with IgAN, tonsillectomy at any time of life, or soon after renal biopsy, prevents disease progression, and the procedure is relatively safe., Competing Interests: All authors have nothing to disclose., (Copyright © 2020 by the American Society of Nephrology.)

Renal disease is a common complication of rheumatoid arthritis (RA) and can occur secondary to RA or be induced by therapeutic agents. Recently, glomerular deposition of galactose-deficient IgA1 (Gd-IgA1) was identified as a feature of primary IgA vasculitis with nephritis (IgA-VN). We herein report a case of IgA-VN in an RA patient whose disease activity was controlled by treatment with etanercept. To distinguish between primary IgA-VN and secondary IgA-VN caused by RA or etanercept, we performed immunostaining of renal biopsy sections with the Gd-IgA1-specific antibody KM55. Positive KM55 staining confirmed the diagnosis of primary IgA-VN in a patient with RA.

According to the current status of chronic dialysis therapy in Japan 2016, the average age at the time of dialysis initiation is 68.57 years for males and 71.19 years for females, which has been rising continuously. Frailty is a geriatric syndrome that is frequently seen in the elderly. It is known that frailty among dialysis patients are more common than the general population of the same age, and that frailty is associated with life prognosis. As eGFR decreases, BMD decreases and fracture risk increase, and dialysis patients are at the highest risk of fracture in CKD patients. Various factors such as frailty, sarcopenia, PEW(protein-energy wasting), dynapenia, uremic osteoporosis, diabetes, AGEs(advanced glycation end products), oxidative stress, falls are involved in the increased risk of fracture in dialysis patients, and consequently, fragile fractures occur frequently in dialysis patients. Fragile fracture is a common complication in dialysis patients, and it is reported that the hospitalization for fracture, and the subsequent course is associated with poor prognosis. In diabetes, bone quality declines without loss of BMD, so the conventional DXA method may be insufficient in predicting fracture risk among dialysis patients, and the evaluation method using HR-pQCT or FRAXR may be useful. It has been reported that bisphosphonate is an established therapy in patients with primary osteoporosis, but many bisphosphonates cannot be used at eGFR of less than 30 mL/min per 1.73 m2. Bisphosphonate-related adverse effects such as accumulation, ossification, osteomalacia, ADB(adynamic bone), and jaw bone necrosis were reported, there are few reports of usefulness in CKD patients. Denosumab administration trial results for women with osteoporosis in dialysis patients have been waited(NCT 01464931). In this article, we outline the relation, diagnosis, and treatment of fragile fractures and frailty in dialysis patients.

We report a patient treated with rituximab for interstitial pneumonia (IP) associated with microscopic polyangiitis (MPA) and who was undergoing hemodialysis. A 59-year-old woman who had been treated with tacrolimus for 1 year for rheumatic arthritis was referred to the Department of Nephrology for fatigue, fever, weight loss, and rapidly developing renal dysfunction. On the first admission, severe renal dysfunction, proteinuria, hematuria, and an elevated titer of MPO-ANCA were observed, and the woman was diagnosed with rapidly progressive glomerulonephritis because of MPA. At that point, IP was found to be present but not active. Although steroid semipulse therapy following an initial prednisolone (PSL) administration of 40 mg/day, IVCY, and plasma exchange were administered, renal dysfunction did not recover, and the patient required maintenance hemodialysis. Upon discharge, a high titer of MPO-ANCA was continuously observed. Nine months after the initiation of hemodialysis, respiratory discomfort and desaturation developed. Interstitial shadow and ground glass opacity were seen on a CT scan, and the patient was diagnosed with exacerbation of interstitial pneumonia caused by MPA recurrence. At the second admission, acute findings identified by imaging techniques had improved. However, the high titer of MPO-ANCA continued in spite of the steroid semi-pulse therapy following PSL administration, and rituximab corresponding to 200 mg/weekly for 1 month was also administered. The dose of rituximab was decreased subsequently because the patient was judged to be compromised by the hemodialysis. At the same time, internal administration of sulfamethoxazole/trimethoprim was initiated. After the rituximab treatment, MPO-ANCA antibodies gradually decreased, and the respiratory condition improved. Five months after the rituximab treatment, respiratory dysfunction recurred. Based on the CT findings and a high level of β-D-glycan, the patient was diagnosed with ARDS due to pneumocystis pneumonia. In this case, rituximab was effective for IP due to MPA, but pneumocystis pneumonia could not be prevented in spite of prophylactic antibiotics. This case suggests that deliberative dose adjustments, careful patient observation, and prophylactic measures for infection are critical in rituximab treatment.

We report a case of nephrotic syndrome associated with MALT lymphoma. The patient was a 66-year-old woman who had a 21-year history of MALT lymphoma. She was admitted to our hospital for the evaluation of systemic edema and purpura during two months. Urinary protein excretion was quantified at 3.3 g/24h. Serum creatinine was elevated to 1.63 mg/dL. An immunoserological investigation showed the presence of IgM-kappa type monoclonal cryoglobulin accompanied by a decreased serum complement level. HCV infection was negative. A renal biopsy specimen revealed membranoproliferative glomerulonephritis (MPGN) with cryoglobulin deposition and focal atypical lymphoid cells infiltration in the renal interstitium. Immunoperoxidase staining of the atypical lymphoid cell population was positive for CD20 and CD79. Combined therapy with prednisolone, plasma exchange and rituximab was commenced. Her proteinuria disappeared and renal function improved after rituximab therapy. In our case, nephrotic syndrome due to cryoglobulinemic glomerulonephritis was successfully treated mainly by rituximab.

Immune activation and inhibitory receptors play an important role in the maintenance of an adequate activation threshold of various cells in our immune system. Analyses of murine models show that the inhibitory Fcreceptor, FcgammaRIIB plays an indispensable role in the suppression of anti-body-mediated allergy and autoimmunity. In contrast, the activating-type Fcreceptors (FcRs) are essential for the development of these diseases, suggesting that regulation of inhibitory or activating FcR is an ideal target as a therapeutic agent. In addition, recent crystal structural analyses of FcR-Ig-Fc fragment complexes provide an effective approach for developing FcR-targeting drugs. This review summarises recent advances of FcR, which were mainly obtained by murine studies, and highlights novel antibodies as possible FcR-targeting therapies for allergy, autoimmune diseases and cancer.

Cancer immunotherapy by fusion of antigen-presenting cells and tumor cells has been shown to induce potent antitumor immunity. In this study, we characterized syngeneic and allogeneic, murine macrophage/dendritic cell (DC)-cancer fusion cells for the antitumor effects. The results showed the superiority of allogeneic cells as fusion partners in both types of antigen-presenting cells in an in vivo immunotherapy model. A potent induction of tumor-specific CTLs was observed in these immunized conditions. In addition, the immunization with DC-cancer fusion cells was better than that with macrophage-cancer fusion cells. Both syngeneic and allogeneic DC-cancer fusion cells induced higher levels of IFN-gamma production than macrophage-cancer fusion cells. Interestingly, allogeneic DC-cancer fusion cells were superior in that they efficiently induced Th1-type cytokines but not the Th2-type cytokines interleukin (IL)-10 and IL-4, whereas syngeneic DC-cancer fusion cells were powerful inducers of both Th1 and Th2 cytokines. These results suggest that allogeneic DCs are suitable as fusion cells in cancer immunotherapy. To further enhance the antitumor immunity in the clinical setting, we prepared DCs fused with IL-12 gene-transferred cancer cells and thus generated IL-12-secreting DC-cancer fusion cells. Immunization with these gene-modified DC-cancer fusion cells was able to elicit a markedly enhanced antitumor effect in the in vivo therapeutic model. This novel IL-12-producing fusion cell vaccine might be one promising intervention for future cancer immunotherapy.

The activation threshold of various cells in the immune system is tuned by immune inhibitory receptors. The inhibitory Fc receptor, FcgammaRIIB, is one of the critical elements for keeping immune cells silent. Murine models for allergic responses and autoimmune diseases illustrate the indispensable roles of FcgammaRIIB in the suppression of these immune disorders. On the contrary, activating-type Fc receptors are crucial for the onset and exacerbation of such diseases. In addition, recent reports have revealed the pivotal roles of Fc receptors in enhancing antigen presentation by dendritic cells, which leads to efficient major histocompatibility complex class I- and class II-restricted T cell activation. In this context, anti-cancer immunopotentiation could be augmented by targeting the tumor antigens to Fc receptors on dendritic cells. This review summarizes recent advances in Fc receptor biomedicine in light of exploiting them as potential therapeutic targets for allergy, autoimmune disease and cancer.

Dendritic cells (DCs) loaded with tumor-associated Ags (TAAs) act as potent adjuvant that initiates antitumor immune responses in vivo. However, TAA-based DC vaccination requires prior identification of TAAs. Apoptotic tumor cells (ATCs) can be an excellent source for DC loading because their potential uncharacterized Ags would be efficiently presented to T cells without any prior characterization and isolation of these Ags. However, ATCs alone are considered to be inefficient for activating antitumor immunity, possibly because of their inability to induce DC maturation. In this study, the aim was to enhance antitumor immune response by taking advantage of ATCs that have been opsonized with IgG (ATC-immune complexes, ATC-ICs) so as to target them to FcR for IgG (FcgammaRs) on DCs. It was found that when compared with ATCs, ATC-ICs were efficiently internalized by DCs via FcgammaRs, and this process induced maturation of DCs, which was more efficient than that of ATCs. Importantly, ATC-IC loading was shown to be more efficient than ATCs alone in its capacity for inducing antitumor immunity in vivo, in terms of cytotoxic T cell induction and tumor rejection. These results show that using ATC-ICs may overcome the limitations and may enhance the immune response of current ATC-based DC vaccination therapy.

Mice deficient for paired immunoglobulin (Ig)-like receptor B (PIR-B) show defective regulation of receptor-mediated activation in antigen-presenting cells. Older PIR-B(-/-) mice had an increased number of peritoneal B1 cells. Splenic PIR-B(-/-) B2 cells were constitutively activated and proliferated much more than those from wild-type mice upon B cell receptor ligation. T helper type 2 (T(H)2)-prone humoral responses were augmented in PIR-B(-/-) mice upon immunization with T-dependent antigens, including increased interleukin 4 and decreased interferon-gamma responses, as well as enhanced IgG1 and IgE production. Impaired maturation of dendritic cells (DCs), possibly due to perturbed intracellular signaling, was responsible for the skewed responses. Thus, PIR-B is critical for B cell suppression, DC maturation and for balancing T(H)1 and T(H)2 immune responses.