Papers by Hidekazu Ikeuchi
Rheumatology International
Anti-neutrophil cytoplasmic antibodies-associated vasculitis (AAV) occurs in elderly people, and ... more Anti-neutrophil cytoplasmic antibodies-associated vasculitis (AAV) occurs in elderly people, and patients with anti-myeloperoxidase autoantibodies (MPO-ANCA)-positive AAV are often complicated with interstitial lung disease (ILD). This study aimed to evaluate the age-related clinical features of elderly patients with MPO-ANCA-positive AAV-ILD. This study retrospectively investigated 63 patients with MPO-ANCA-positive AAV-ILD, all of whom were 65 years or older at diagnosis. Clinical characteristics, causes of death and survival rates among three groups stratified by age (65–74 years, n = 29; 75–79 years, n = 18; over 80 years, n = 16) were compared. This study also examined the association with severe infections in these patients. Among the three age groups, there were significant differences in sex (P = 0.032), serum Krebs von den Lungen-6 (P < 0.01), and total ground-glass opacity score (P = 0.011). The causes of death were mainly severe infections and complications of ILD. Kaplan–Meier curve analysis showed a significantly lower 5-year survival rate in the oldest group (P < 0.01). Regarding severe infections in these patients, the 5-year cumulative incidence of severe infections was higher in the patients receiving steroid pulse therapy (P = 0.034). The clinical characteristics of MPO-ANCA-positive AAV-ILD differ with age in elderly patients, with age being an important poor prognostic factor in these patients. The administration of steroid pulse therapy is a significant risk factor of severe infection in MPO-ANCA-positive elderly patients with AAV-ILD.
Journal of Nephrology
Minimal change disease (MCD) is characterized by a nephrotic syndrome usually steroid-sensitive a... more Minimal change disease (MCD) is characterized by a nephrotic syndrome usually steroid-sensitive and a high incidence of relapse of proteinuria. Previous cohort studies have reported conflicting results regarding the association between the time to remission and incidence of relapse. This multicenter prospective cohort study included 102 adult patients with steroid-sensitive MCD or focal segmental glomerulosclerosis from a 5-year cohort study of primary nephrotic syndrome, the Japan Nephrotic Syndrome Cohort Study, who achieved remission of proteinuria within 2 months of immunosuppressive therapy (IST). The association between the time to remission of proteinuria after immunosuppressive therapy and incidence of relapse was assessed using Cox proportional hazards models adjusted for clinically relevant factors. Remission was observed at 3–7, 8–14, 15–21, 22–28, and 30–56 days after initiation of immunosuppressive therapy in 17 (16.7%), 37 (36.3%), 21 (20.6%), 13 (12.7%), and 14 (13.7%) patients, respectively. During a median observation period of 2.3 years after the end of the 2nd month after initiation of immunosuppressive therapy, 46 (45.1%) patients relapsed. The time to remission was associated with the incidence of relapse in an inverse U-shaped pattern (multivariable-adjusted hazard ratios [95% confidence intervals] of the time to remission of 3–7, 8–14, 15–21, 22–28, 30–56 days: 1.00 [reference], 1.76 [0.56, 5.51], 6.06 [1.85, 19.80], 5.46 [1.44, 20.64], and 2.19 [0.52, 9.30], respectively). The time to remission was identified as a significant predictor of relapse in steroid-sensitive patients.
Clinical and Experimental Nephrology
Arthritis & Rheumatism, 2011
CIN: Computers, Informatics, Nursing, 2022
Nurses need to increase patient education opportunities so that more people with chronic kidney d... more Nurses need to increase patient education opportunities so that more people with chronic kidney disease can understand the disease accurately from its early stages. We developed an e-learning course based on the Dick and Carey system approach model and the attention, relevance, confidence, satisfaction model for people with chronic kidney disease. People with chronic kidney disease, on average, are aged around 50 to 60 years, and this population tends to lack perceived susceptibility toward and concern for the disease owing to the asymptomatic nature of early chronic kidney disease. Therefore, e-learning should be easy to use and motivate learning. This study aimed to evaluate the usability and learning motivation of this course. The participants included 10 outpatients (mean age, 51.2 years) with chronic kidney disease whose mastery percentage of learning objectives was compared by the knowledge tests immediately before and after the course. We also observed the participants' operation status and measured their motivation for using instructional materials with a questionnaire. The results demonstrated that this course facilitates independent operation, improves postcourse performance, and motivates participants in all areas of learning motivation. Thus, this e-learning course can be recommended as easy to use and motivating for people with chronic kidney disease.
The Journal of Dermatology, 2020
Anti‐transcription intermediary factor 1γ (anti‐TIF1γ) antibody (Ab) is significantly associated ... more Anti‐transcription intermediary factor 1γ (anti‐TIF1γ) antibody (Ab) is significantly associated with internal malignancies in adult patients with dermatomyositis (DM). Although pathogenesis of cancer‐associated DM is unknown, TIF1γ overexpression in tumors has been considered to be critical for the development of DM. The objective of this study was to investigate clinical characteristics of patients with anti‐TIF1γ Ab‐positive DM and elucidate risk factors that are potentially associated with internal malignancy. In addition, we compared the expression of TIF1γ in tumor tissues of patients with anti‐TIF1γ Ab‐positive DM, anti‐TIF1γ Ab‐negative DM and without DM in order to investigate the pathogenesis of cancer‐associated DM. We analyzed 77 Japanese patients with DM, and found 19 patients to be positive for anti‐TIF1γ Ab. Patients with anti‐TIF1γ Ab‐positive DM were older and presented heliotrope rash and flagellate erythema more frequently than patients without anti‐TIF1γ Ab (P < 0.05). Interstitial lung disease (ILD) and rapidly progressive ILD, as well as palmar violaceous erythema, were less frequent in patients with anti‐TIF1γ Ab than in patients without. Furthermore, internal malignancy and dysphagia were significantly more frequent in the anti‐TIF1γ Ab‐positive group (P < 0.01). Male sex and dysphagia were significantly associated with internal malignancy in patients with anti‐TIF1γ Ab‐positive DM (P < 0.01 and <0.05, respectively). Using immunohistochemistry, we examined the TIF1γ expression in tumors of 11 patients with cancer‐associated DM (anti‐TIF1γ Ab‐positive, nine; anti‐TIF1γ Ab‐negative, two) and 25 patients without DM. TIF1γ was highly expressed in all tumors, and there was no significant difference in TIF1γ expression between patients with and without DM. Furthermore, TIF1γ expressions in tumors were similar irrespective of the presence of anti‐TIF1γ Ab. These results suggest that anti‐TIF1γ antibody may not be simply induced by overexpression of TIF1γ in tumors in patients with DM, but that other mechanisms may exist.
Mesangial cells stimulate differentiation of endothelial cells to form capillary-like networks in... more Mesangial cells stimulate differentiation of endothelial cells to form capillary-like networks in a three-dimensional culture system
Nihon Naika Gakkai Zasshi, 2012
Annals of the Rheumatic Diseases, 2016
Background: Granulomatosis with polyangiitis (GPA) is characterized by extravascular necrotizing ... more Background: Granulomatosis with polyangiitis (GPA) is characterized by extravascular necrotizing granulomatous inflammation and systemic anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis. The pathogenic mechanisms, especially of the granulomatous inflammation, are still not fully understood. Cell death and tissue damage could be a driving force for chronic inflammation in GPA. Objectives: To investigate the role of the damage-associated molecular patterns (DAMPs) IL-33 and high-mobility group box 1 (HMGB1) in the granulomatous inflammation of GPA. Methods: Tissue expression of HMGB1, IL-33 and their corresponding DAMP receptors "receptor for advanced glycation end products" (RAGE) and "suppression of tumorigenicity 2" (ST2), respectively, were analyzed in nasal GPA biopsies compared to chronic rhinosinusitis (CRS) by immunostaining. Circulating soluble RAGE (sRAGE) and soluble ST2 (sST2) were measured in GPA sera compared to CRS or healthy controls (HC) using ELISA. Expression of HMGB1 and the autoantigen proteinase 3 (PR3) in nasal GPA tissues and on isolated neutrophils was determined by immunofluorescence staining. Full-length IL-33 was cleaved in vitro by either activated, necrotic or NETotic neutrophils. The biological activity of these IL-33-cleavage fragments was tested by subsequent stimulation of human mast cells (HMC-1). The resulting activation of mitogen-activated protein kinases (MAPK) was determined by western blot. Results: Increased tissue expression of extranuclear HMGB1 (p<0.01) and strong upregulation of RAGE was observed in the necrotizing granulomatous inflammation compared to CRS. In addition, substantial numbers of IL-33 and ST2 expressing cells were found in close proximity to necrotic areas and lymphoid structures in the granulomatous inflammation compared to CRS. However, neither sRAGE nor sST2 were elevated in GPA sera compared to controls. In GPA tissue co-localization of HMGB1 and PR3 was detected on neutrophils. This co-localization could be induced on isolated neutrophils by apoptosis in vitro. Full-length IL-33 was processed by activated, necrotic or NETotic neutrophils into different cleavage products. IL-33 fragments produced by necrotic GPA neutrophils induced a significantly stronger MAPK activity in HMC-1 compared to those from HC. Conclusions: In this study, we demonstrate a direct link between dying neutrophils and necrosis-derived DAMPs HMGB1 and IL-33 in the granulomatous inflammation of GPA. Differential cleavage of IL-33 by dying neutrophils, IL-33-dependent MAPK activation and high tissue expression of RAGE and ST2 suggest a considerable role of these DAMPs in sustaining chronic inflammation in GPA. Moreover, HMGB1/PR3 co-localization on apoptotic neutrophils reveals a possible adjuvant function of HMGB1 for the autoimmune response against PR3.
International journal of rheumatic diseases, Jan 29, 2014
To evaluates the pregnancy outcomes in systemic lupus erythematosus (SLE) patients in South Korea... more To evaluates the pregnancy outcomes in systemic lupus erythematosus (SLE) patients in South Korea and determine the predictive factors for adverse fetal and maternal outcomes. All pregnancies in SLE patients who were seen at the Samsung Medical Center between November 1994 and December 2010 were included and retrospectively analyzed. SLE flares were determined by the Lupus Activity Index-Pregnancy (LAI-P) score. Sixty-two pregnancies were observed in 50 patients. Fifty-one (82.3%) live births and 11 (17.7%) fetal losses were observed. Thirty-eight of the live births (74.5%) were full-term and 13 (25.5%) were preterm births. Fetal losses included three spontaneous abortions, two stillbirths and six therapeutic abortions. Proteinuria during pregnancy was a predictive factor for adverse fetal outcomes (adjusted odds ratio [OR] 12.50; P = 0.032). An LAI-P score was obtained in 36 pregnancies, and SLE flares occurred in 12 pregnancies (33.3%), primarily during the second trimester (46.2%...
Cancer Prevention Research, 2011
Inflammation contributes to the development of papillomas and squamous cell carcinomas in the wel... more Inflammation contributes to the development of papillomas and squamous cell carcinomas in the well-established 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-l3-acetate (TPA) model of skin carcinogenesis. Synthetic oligonucleotides (ODN) containing repetitive TTAGGG motifs have been shown to block deleterious inflammatory reactions in murine models of autoimmunity, pneumonitis, and shock. This article examines whether treatment with suppressive (Sup) ODN can interfere with DMBA/TPA-induced inflammation, thereby reducing papilloma formation. Results indicate that Sup ODN block TPA-dependent skin hyperplasia, edema, and leukocytic infiltration. Sup ODN also inhibit the upregulation of genes encoding pro-oncogenic chemokines and other markers of inflammation including CXCL2, CCL2, COX-2, and ODC (ornithine decarboxylase). Of greatest import, Sup ODN reduce papilloma formation in a dose- and sequence-dependent manner. These findings suggest that Sup ODN may provide a no...
American Journal of Physiology-Renal Physiology, 2011
Renal proximal tubular epithelium can regenerate after various insults. To examine whether the tu... more Renal proximal tubular epithelium can regenerate after various insults. To examine whether the tubular repair process is regulated by surrounding peritubular capillaries, we established an in vitro human tubulogenesis model that mimics in vivo tubular regeneration after injury. In this model, HGF, a potent renotropic factor, dose dependently induced tubular structures in human renal proximal tubular epithelial cells cultured in gels. Consistent with regenerating tubular cells after injury, HGF-induced tubular structures expressed a developmental gene, Pax-2, and a mesenchymal marker, vimentin, and formed a lumen with aquaporin-1 expression. Electron microscopic analysis showed the presence of microvilli on the apical site of the lumen, suggesting that these structures are morphologically equivalent to renal tubules in vivo. When cocultured with human umbilical vein endothelial cells (HUVEC), HGF-induced tubular formation was significantly enhanced. This could not be reproduced by th...
American Journal of Physiology-Renal Physiology, 2011
Recovery after acute kidney injury is impaired in the elderly, but the precise mechanism for such... more Recovery after acute kidney injury is impaired in the elderly, but the precise mechanism for such age-related incompetence remains unclear. By in vivo bromodeoxyuridine (BrdU) labeling, renal progenitor cells (label-retaining cells; LRCs) were identified in tubules of normal rat kidney and were shown to be the origin of proliferating cells after injury. In the present study, the involvement of LRCs in the age-related decline of tubular recovery after injury was examined. After 1 wk of BrdU labeling followed by a 2-wk chase period, ischemia-reperfusion injury was induced in 7-wk-, 7-mo-, and 12-mo-old rats. Age-related decreases in DNA synthesis and cell proliferation in renal tubules after injury were found. The number of LRCs also significantly declined with age. At 24 h after reperfusion, the number of LRCs significantly increased in all ages of rats tested. There was no significant difference in the ratio of LRC division among rats of different ages. The area of the rat endotheli...
Modern Rheumatology, 2017
Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine, Jan 10, 2012
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Papers by Hidekazu Ikeuchi