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Find video protocols related to scientific articles indexed in Pubmed.
Characteristics of eosinophilic and non-eosinophilic asthma during treatment with inhaled corticosteroids.
J Asthma
PUBLISHED: 10-21-2014
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Abstract Objective: Eosinophilic inflammation in the respiratory tract is a hallmark of bronchial asthma. In naïve cases, the inflammatory profile is associated with disease severity and reactivity to inhaled corticosteroids (ICS). Sustained airway eosinophilia has been reported during ICS treatment. However, the immunological characteristics of these cases are not known and it is unclear if this situation contributes to asthma control. This study was performed to determine the answer of these questions. Methods: To compare phenotypes of eosinophilic and non-eosinophilic asthma (EA and NEA, respectively) under ICS treatment, clinical data were obtained from asthmatic subjects (n?=?22) and healthy controls (n?=?10), and the leukocyte compositions of induced sputum and peripheral blood were determined. T lymphocyte profiles in systemic blood were assessed by flow cytometry. Results: A higher frequency of emergency room visits was observed in the NEA group, which had a higher neutrophil count relative to the total inflammatory cell population in induced sputum than the EA group (59.5 versus 36.6%; p?
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Intact parathyroid hormone and whole parathyroid hormone assay results disagree in hemodialysis patients under cinacalcet hydrochloride therapy.
Clin. Exp. Nephrol.
PUBLISHED: 10-17-2014
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The parathyroid gland secretes 1-84 and 7-84 parathyroid hormone (PTH) fragments, and its regulation is dependent on stimulation of the extracellular calcium-sensing receptor. While the intact PTH system detects both PTH fragments, the whole PTH system detects the 1-84PTH but not the 7-84PTH. Cinacalcet hydrochloride (CH) binds to calcium-sensing receptor as a calcimimetic. Here we investigated the role of CH treatment in the assessment of parathyroid gland function.
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Characterization of anti-P monoclonal antibodies directed against the ribosomal protein •RNA complex antigen and produced using MRL autoimmune-prone mice.
Clin. Exp. Immunol.
PUBLISHED: 09-23-2014
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Autoantibodies, including anti-ribosomal P proteins (anti-P), are thought to be produced by an antigen-driven immune response in SLE. To test this hypothesis, we reconstituted the ribosomal antigenic complex in vitro using human P0, phosphorylated P1 and P2, and a 28S rRNA fragment covering the P0 binding site, and immunized MRL/lrp lupus mice with this complex without any added adjuvant to generate anti-P antibodies. By using hybridoma technology, we subsequently obtained 34 clones, each producing an anti-P monoclonal antibody (mAb) that recognized the conserved C-terminal tail sequence common to all three P proteins. We also obtained two P0-specific monoclonal antibodies, but not any antibody specific to P1, P2, or rRNA fragment. Two types of mAbs were found among these anti-P antibodies: one type (e.g., 9D5) reacted more strongly with the phosphorylated P1 and P2 than that with their non-phosphorylated forms, whereas the other type (e.g., 4H11) reacted with both phosphorylated and non-phosphorylated forms of P1/P2 equally. Both 9D5 and 4H11 inhibited the ribosome/eEF-2-coupled GTPase activity. However, preincubation with a synthetic peptide corresponding to the C-terminal sequence common to all three P proteins, but not the peptide that lacked the last three C-terminal amino acids, mostly prevented the mAb-induced inhibition of GTPase activity. Thus, at least two types of anti-P were preferentially produced following the immunization of MRL mice with the reconstituted antigenic complex. Presence of multiple copies of the C-termini, particularly that of the last three C-terminal amino acid residues, in the antigenic complex appears to contribute to the immunogenic stimulus.
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Nephrotic syndrome and end-stage kidney disease accompanied by bicytopenia due to copper deficiency.
Intern. Med.
PUBLISHED: 09-15-2014
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A 69-year-old man presented with proteinuria and hematuria. He had received total parenteral nutrition for massive small bowel resection. However, due to the iatrogenic lack of trace elements for the next four years, he developed severe copper-deficiency anemia and neutropenia. In addition, his proteinuria and kidney dysfunction worsened concurrently with the development of nephrotic syndrome and end-stage kidney disease. After receiving trace elements, the patient's anemia and neutropenia improved, and the anuria dramatically resolved. Copper-containing enzymes, including ceruloplasmin have an antioxidant activity. In patients with various types of glomerular injuries, the ceruloplasmin expression is known to be increased. Copper deficiency can worsen nephrotic syndrome by decreasing the ceruloplasmin activity, which protects the glomeruli.
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Higher Mortality Due to Intracerebral Hemorrhage in Dialysis Patients: A Comparison with the General Population in Japan.
Ther Apher Dial
PUBLISHED: 09-09-2014
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Cerebrovascular diseases, including intracerebral hemorrhage, cerebral infarction, and subarachnoid hemorrhage, remain prevalent causes of morbidity and mortality among dialysis patients. Their mortality rate for cerebrovascular diseases is roughly three times higher than that in the general population. However, whether mortality rates for all subtypes of cerebrovascular diseases are equally higher has not been evaluated. The aim of this study was to determine the mortality rate for each stroke subtype, comparing dialysis patients and the general population in Japan. We used mortality data reported by the Japanese Society for Dialysis Therapy and national Vital Statistics data between 2008 and 2009. We calculated standardized mortality ratios and compared the mortality rates for stroke subtypes including intracerebral hemorrhage, cerebral infarction, and subarachnoid hemorrhage. During the 2-year study period, 51?994 and 933 deaths from intracerebral hemorrhage, 79?124 and 511 deaths from cerebral infarction, and 24?957 and 147 deaths from subarachnoid hemorrhage were recorded per 252 million person-years and per 546?474 dialysis patient-years, respectively. Standardized mortality ratios among dialysis patients relative to the general population were 3.8 (95% confidence interval, 3.6-4.1), 1.3 (1.2-1.4), and 1.3 (1.1-1.6) for intracerebral hemorrhage, cerebral infarction, and subarachnoid hemorrhage, respectively. Intracerebral hemorrhage was the highest cause of mortality in the dialysis population, although cerebral infarction was the highest in the general population. Relative to the general population in Japan, Japanese dialysis patients had higher mortality rates, especially for intracerebral hemorrhage.
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Effects of direct hemoperfusion with polymyxin B-immobilized fiber on rapidly progressive interstitial lung diseases.
Intern. Med.
PUBLISHED: 09-01-2014
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Direct hemoperfusion with polymyxin B-immobilized fiber columns (PMX-DHP) has been used for the treatment of septic shock. It was recently suggested that PMX-DHP may also be effective in acute exacerbations of idiopathic pulmonary fibrosis (IPF). However, all previous reports are case series without controls. The aim of the study was to determine the effects of PMX-DHP on the prognosis of the patients with rapidly progressive interstitial lung diseases (ILDs) in a case-control setting.
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Depression's Influence on the Asthma Control Test, Japanese Version.
Allergol Int
PUBLISHED: 08-25-2014
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Background: Depression has been linked to poorer asthma control in asthmatic patients. Although the Japanese version of the Asthma Control Test (ACT-J) is frequently used as a simple, practical evaluation tool in clinical care settings in Japan, knowledge regarding its efficacy for assessing asthma control in asthmatic patients with depression is limited. Thus, we retrospectively investigated cut-off values of the ACT-J for well-controlled asthma, and explored depression's influence on the test with a questionnaire survey. Methods: Data were analyzed on 1,962 adult asthmatic patients who had completed both the ACT-J and the Japanese version of the Patient Health Questionnaire-9 (J-PHQ-9) in 2008 questionnaire survey conducted by the Niigata Asthma Treatment Study Group. Patients were classified into low (LD: J-PHQ-9 score of 0-4) or high depression (HD: J-PHQ-9 score of 5-27) groups. In both groups, the efficacy of the ACT-J was confirmed. We then compared the optimal cut-off points for uncontrolled asthma in both groups by performing a receiver operating characteristic (ROC) analysis, using the original classification referred to the GINA classification as the "true" classification. Results: Cronbach's alpha in the LD and HD group was 0.808 and 0.740 respectively. In both groups, the sub-group with existence of work absenteeism or frequent attacks during the previous 12 months scored lower on the ACT-J. The area under the curve and optimal cut-off point for patients with LD and HD were 0.821 and 0.846, and 23 and 20 respectively. Conclusions: The efficacy of the ACT-J was confirmed in depressive patients with asthma. Because asthma control as evaluated with the ACT-J can be worse than actual control under depressive states, physicians should also pay attention to a patient's depressive state at evaluation. Further investigations focus on the association between the ACT-J and depression are required.
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A slight increase within the normal range of serum uric acid and the decline in renal function: associations in a community-based population.
Nephrol. Dial. Transplant.
PUBLISHED: 07-24-2014
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Hyperuricemia is a risk factor for adverse renal outcomes in patients with chronic kidney disease. This study investigated the effect of uric acid on renal function in a community-based population.
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Serum magnesium concentration is inversely associated with fibroblast growth factor 23 in haemodialysis patients.
Nephrology (Carlton)
PUBLISHED: 06-01-2014
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Fibroblast growth factor 23 is reported to be a pivotal regulator for the chronic kidney disease-mineral bone disorders, working in coordinated ways with phosphate, calcium, and parathyroid hormone. However, whether there is a relationship between fibroblast growth factor 23 and magnesium is currently unclear. To address this, we performed a cross-sectional observational study in haemodialysis patients.
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Annual decline in estimated glomerular filtration rate is a risk factor for cardiovascular events independent of proteinuria.
Nephrology (Carlton)
PUBLISHED: 06-01-2014
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Chronic kidney disease is a risk factor of the development of cardiovascular disease (CVD). However, it is not clear whether decline of glomerular filtration rate (GFR), not reduced GFR, is a risk factor for the incidence of CVD independent of proteinuria.
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Periodontal and serum protein profiles in patients with rheumatoid arthritis treated with tumor necrosis factor inhibitor adalimumab.
J. Periodontol.
PUBLISHED: 05-26-2014
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Tumor necrosis factor (TNF)-? inhibitor has been shown to affect the periodontal condition of patients with rheumatoid arthritis (RA). The aim of the present study is to assess the effect of a fully humanized anti-TNF-? monoclonal antibody, adalimumab (ADA), on the periodontal condition of patients with RA and to compare serum protein profiles before and after ADA therapy.
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Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens.
Krzysztof Kiryluk, Yifu Li, Francesco Scolari, Simone Sanna-Cherchi, Murim Choi, Miguel Verbitsky, David Fasel, Sneh Lata, Sindhuri Prakash, Samantha Shapiro, Clara Fischman, Holly J Snyder, Gerald Appel, Claudia Izzi, Battista Fabio Viola, Nadia Dallera, Lucia Del Vecchio, Cristina Barlassina, Erika Salvi, Francesca Eleonora Bertinetto, Antonio Amoroso, Silvana Savoldi, Marcella Rocchietti, Alessandro Amore, Licia Peruzzi, Rosanna Coppo, Maurizio Salvadori, Pietro Ravani, Riccardo Magistroni, Gian Marco Ghiggeri, Gianluca Caridi, Monica Bodria, Francesca Lugani, Landino Allegri, Marco Delsante, Mariarosa Maiorana, Andrea Magnano, Giovanni Frasca, Emanuela Boer, Giuliano Boscutti, Claudio Ponticelli, Renzo Mignani, Carmelita Marcantoni, Domenico Di Landro, Domenico Santoro, Antonello Pani, Rosaria Polci, Sandro Feriozzi, Silvana Chicca, Marco Galliani, Maddalena Gigante, Loreto Gesualdo, Pasquale Zamboli, Giovanni Giorgio Battaglia, Maurizio Garozzo, Dita Maixnerová, Vladimir Tesar, Frank Eitner, Thomas Rauen, Jürgen Floege, Tibor Kovacs, Judit Nagy, Krzysztof Mucha, Leszek Pączek, Marcin Zaniew, Małgorzata Mizerska-Wasiak, Maria Roszkowska-Blaim, Krzysztof Pawlaczyk, Daniel Gale, Jonathan Barratt, Lise Thibaudin, Francois Berthoux, Guillaume Canaud, Anne Boland, Marie Metzger, Ulf Panzer, Hitoshi Suzuki, Shin Goto, Ichiei Narita, Yasar Caliskan, Jingyuan Xie, Ping Hou, Nan Chen, Hong Zhang, Robert J Wyatt, Jan Novak, Bruce A Julian, John Feehally, Bénédicte Stengel, Daniele Cusi, Richard P Lifton, Ali G Gharavi.
Nat. Genet.
PUBLISHED: 05-13-2014
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We performed a genome-wide association study (GWAS) of IgA nephropathy (IgAN), the most common form of glomerulonephritis, with discovery and follow-up in 20,612 individuals of European and East Asian ancestry. We identified six new genome-wide significant associations, four in ITGAM-ITGAX, VAV3 and CARD9 and two new independent signals at HLA-DQB1 and DEFA. We replicated the nine previously reported signals, including known SNPs in the HLA-DQB1 and DEFA loci. The cumulative burden of risk alleles is strongly associated with age at disease onset. Most loci are either directly associated with risk of inflammatory bowel disease (IBD) or maintenance of the intestinal epithelial barrier and response to mucosal pathogens. The geospatial distribution of risk alleles is highly suggestive of multi-locus adaptation, and genetic risk correlates strongly with variation in local pathogens, particularly helminth diversity, suggesting a possible role for host-intestinal pathogen interactions in shaping the genetic landscape of IgAN.
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Comparison of predictive value for first cardiovascular event between Japanese GFR equation and coefficient-modified CKD-EPI equation.
Clin. Exp. Nephrol.
PUBLISHED: 05-08-2014
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The most superior GFR-estimating equation from the viewpoint of cardiovascular disease (CVD) prediction remains unclear. Thus, we performed cross-sectional comparison between two GFR-estimating equations (Japanese GFR equation and coefficient-modified CKD-EPI equation) and CVD incidence using Japanese nationwide "specific health checkup" data.
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A case of severe thrombocytopenia associated with acute HIV-1 infection.
Int J STD AIDS
PUBLISHED: 04-17-2014
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A 23-year-old man was admitted to our hospital with severe thrombocytopenia. He had unprotected sexual contact 6 weeks earlier. He was diagnosed with acute HIV infection by means of HIV RNA viral load testing and HIV-associated thrombocytopenia. Although thrombocytopenia improved immediately with short-term dexamethasone therapy, this effect was not sustained after cessation of therapy. Antiretroviral therapy including raltegravir was initiated, and the patient recovered from severe thrombocytopenia within several days. The findings from this case suggest that acute HIV infection should be suspected with unexplained thrombocytopenia, and that antiretroviral therapy is the treatment of choice for severe HIV-associated thrombocytopenia, even when in the early period following acquisition of the virus.
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Regional variation in hip fracture incidence among Japanese hemodialysis patients.
Ther Apher Dial
PUBLISHED: 04-12-2014
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Hip fracture incidence in Japanese hemodialysis patients is five-fold higher than in the general population, although the mechanisms underlying this difference are not fully understood. Substantial regional variation exists in hip fracture incidence in the general Japanese population, despite a uniform health care and insurance system and lack of ethnic and racial variation. In this study, we determined whether the regional variation seen in the general population also applies to hemodialysis patients in Japan. Standardized incidence ratios were calculated for each regional district, and regional variations of hip fracture incidence among hemodialysis patients were evaluated using data obtained from the Japanese Society for Dialysis Therapy registry (data collected from December 2007 to December 2008). Standardized hip fracture incidence ratios across the districts ranged from 0.71 to 1.29 for male and 0.49 to 1.36 for female hemodialysis patients. Incidence ratios tended to be higher in western Japan and lower in eastern Japan, suggesting that regional variation also exists among hemodialysis patients. Our findings suggest that common risk factors for hip fracture may be shared among the general population and hemodialysis patients. Further research aimed at identifying factors, including those associated with regional variation, may help decrease hip fracture incidence in both the general population and hemodialysis patients in Japan.
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Outcomes of primary nephrotic syndrome in elderly Japanese: retrospective analysis of the Japan Renal Biopsy Registry (J-RBR).
Clin. Exp. Nephrol.
PUBLISHED: 04-03-2014
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There are very little data available regarding nephrotic syndrome (NS) in elderly (aged ?65 years) Japanese. The aim of this study was to examine the causes and outcomes of NS in elderly patients who underwent renal biopsies between 2007 and 2010.
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Effects of a biologic agent in a patient with rheumatoid arthritis after treatment for methotrexate-associated B-cell lymphoma: a case report.
BMC Res Notes
PUBLISHED: 03-31-2014
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Several studies have suggested an increased risk of malignant tumor in patients with rheumatoid arthritis. It has been also reported that rheumatoid arthritis patients have a high incidence of lymphoma compared with the general population, and that patients receiving methotrexate, which is the anchor drug for rheumatoid arthritis treatment, can develop lymphoproliferative disease. Nevertheless, management of rheumatoid arthritis after treatment for methotrexate-associated lymphoma has not been fully investigated. We here report a patient with rheumatoid arthritis who developed malignant lymphoma associated with methotrexate therapy. Moreover, we describe the use of a biologic agent for a rheumatoid arthritis patient after treatment for lymphoma associated with methotrexate.
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An observational study of giant cell interstitial pneumonia and lung fibrosis in hard metal lung disease.
BMJ Open
PUBLISHED: 03-29-2014
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Hard metal lung disease has various pathological patterns including giant cell interstitial pneumonia (GIP) and usual interstitial pneumonia (UIP). Although the UIP pattern is considered the prominent feature in advanced disease, it is unknown whether GIP finally progresses to the UIP pattern.
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Role of the p.E66Q variant of GLA in the progression of chronic kidney disease.
Clin. Exp. Nephrol.
PUBLISHED: 03-25-2014
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The p.E66Q variant of the ?-galactosidase A gene (GLA) is frequently found during screening for Fabry disease in dialysis patients in Japan. However, recent reports suggest that the p.E66Q variant is not a disease-causing mutation but is a risk factor for cerebral small-vessel occlusion. To evaluate the role of the p.E66Q in the progression of renal diseases, we performed a genetic association study in patients with chronic kidney disease (CKD).
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Tocilizumab treatment safety in rheumatoid arthritis in a patient with multiple sclerosis: a case report.
BMC Res Notes
PUBLISHED: 01-30-2014
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Multiple sclerosis is a relatively rare disease, and complications of multiple sclerosis and rheumatoid arthritis are much rarer. Since anti-tumor necrosis factor therapy increases exacerbations of multiple sclerosis, complications of demyelinating diseases contraindicate anti-tumor necrosis factor therapy. There have been few reports of anti-interleukin-6 receptor therapy for patients with rheumatoid arthritis complicated with multiple sclerosis.
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Effect of donor-recipient age difference on long-term graft survival in living kidney transplantation.
Int Urol Nephrol
PUBLISHED: 01-28-2014
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We aimed to examine the influence of donor age on living-donor kidney transplantation (KTx), particularly with regard to long-term graft survival in young recipients with aged kidney grafts.
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Novel assay to detect increased level of neutralizing anti-interferon gamma autoantibodies in non-tuberculous mycobacterial patients.
J. Infect. Chemother.
PUBLISHED: 01-28-2014
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Subjects exposed to non-tuberculous mycobacterium (NTM) species do not always develop an active disease, which likely reflects underlying host susceptibility factors. Recent reports have shown that anti interferon gamma (IFN-?) neutralizing autoantibodies (IFN-? Ab) are associated with the development of disseminated NTM in patients without known evidence of immunodeficiency. The purpose of this study is to establish the screening method if subjects have IFN-? Ab. Whole blood was obtained from patients with disseminated NTM, those with pulmonary NTM, and healthy controls. The neutralizing capacity to IFN-? activity was assessed as an inhibition of Signal Transducer and Activation of Transcription 1 (STAT-1) phosphorylation in leukocyte after stimulation with exogenous IFN-? by flow cytometer. The strength of phosphorylation was described as STAT1 phosphorylation index. Antigen capture assay was performed to measure the relative titer of Immunoglobulin-G fraction of IFN-? Ab. STAT1 phosphorylation by IFN-? was significantly inhibited in the leukocytes from patients with disseminated NTM compared to that in healthy subjects, while this inhibition was not observed in patients with pulmonary NTM. All subjects with inhibited STAT1 phosphorylation had high titer of Immunoglobulin-G that reacted with IFN-? in the antigen capture assay. The measurement of STAT1 phosphorylation index in whole blood leukocytes and antigen capture assay are simple and useful method for detection of anti-IFN-? neutralizing autoantibodies, and is valuable in the pathophysiological diagnosis of disseminated NTM patients without obvious immunodeficiency.
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Analysis of the influenza A (H1N1) 2009 pandemic infection in Japanese asthmatic patients: using a questionnaire-based survey.
Allergol Int
PUBLISHED: 01-25-2014
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Influenza infection is known to be an exacerbating factor in the control of asthma, therfore its prevention is critical in managing asthma. The aim of this study was to investigate the influenza A H1N1 2009 pandemic virus (H1N1 pdm09) infection in adult asthmatic patients.
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Budget impact analysis of chronic kidney disease mass screening test in Japan.
Clin. Exp. Nephrol.
PUBLISHED: 01-15-2014
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Our recently published cost-effectiveness study on chronic kidney disease mass screening test in Japan evaluated the use of dipstick test, serum creatinine (Cr) assay or both in specific health checkup (SHC). Mandating the use of serum Cr assay additionally, or the continuation of current policy mandating dipstick test only was found cost-effective. This study aims to examine the affordability of previously suggested reforms.
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DDX3X Induces Primary EGFR-TKI Resistance Based on Intratumor Heterogeneity in Lung Cancer Cells Harboring EGFR-Activating Mutations.
PLoS ONE
PUBLISHED: 01-01-2014
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The specific mechanisms how lung cancer cells harboring epidermal growth factor receptor (EGFR) activating mutations can survive treatment with EGFR-tyrosine kinase inhibitors (TKIs) until they eventually acquire treatment-resistance genetic mutations are unclear. The phenotypic diversity of cancer cells caused by genetic or epigenetic alterations (intratumor heterogeneity) confers treatment failure and may foster tumor evolution through Darwinian selection. Recently, we found DDX3X as the protein that was preferentially expressed in murine melanoma with cancer stem cell (CSC)-like phenotypes by proteome analysis. In this study, we transfected PC9, human lung cancer cells harboring EGFR exon19 deletion, with cDNA encoding DDX3X and found that DDX3X, an ATP-dependent RNA helicase, induced CSC-like phenotypes and the epithelial-mesenchymal transition (EMT) accompanied with loss of sensitivity to EGFR-TKI. DDX3X expression was associated with upregulation of Sox2 and increase of cancer cells exhibiting CSC-like phenotypes, such as anchorage-independent proliferation, strong expression of CD44, and aldehyde dehydrogenase (ALDH). The EMT with switching from E-cadherin to N-cadherin was also facilitated by DDX3X. Either ligand-independent or ligand-induced EGFR phosphorylation was inhibited in lung cancer cells that strongly expressed DDX3X. Lack of EGFR signal addiction resulted in resistance to EGFR-TKI. Moreover, we found a small nonadherent subpopulation that strongly expressed DDX3X accompanied by the same stem cell-like properties and the EMT in parental PC9 cells. The unique subpopulation lacked EGFR signaling and was highly resistant to EGFR-TKI. In conclusion, our data indicate that DDX3X may play a critical role for inducing phenotypic diversity, and that treatment targeting DDX3X may overcome primary resistance to EGFR-TKI resulting from intratumor heterogeneity.
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Association between combined lifestyle factors and non-restorative sleep in Japan: a cross-sectional study based on a Japanese health database.
PLoS ONE
PUBLISHED: 01-01-2014
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Although lifestyle factors such as cigarette smoking, excessive drinking, obesity, low or no exercise, and unhealthy dietary habits have each been associated with inadequate sleep, little is known about their combined effect. The aim of this study was to quantify the overall impact of lifestyle-related factors on non-restorative sleep in the general Japanese population.
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Expression of tight junction protein claudin-1 in human crescentic glomerulonephritis.
Int J Nephrol
PUBLISHED: 01-01-2014
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The origin of crescent forming cells in human glomerulonephritis (GN) remains unknown. Some animal studies demonstrated that parietal epithelial cells of Bowman's capsule (PECs) were the main component of proliferating cells and PEC-specific tight junction protein claudin-1 was expressed in crescentic lesions. We investigated the expression of claudin-1 in human GN. Immunohistochemistry for claudin-1 was performed on 17 kidney biopsy samples with crescent formation. Colocalization of claudin-1 with intracellular tight junction protein ZO-1 was also evaluated by immunofluorescence double staining. Claudin-1 is expressed mainly at the cell to cell contact site of proliferating cells in cellular crescentic lesions in patients with these forms of human GN. Small numbers of crescent forming cells showed extrajunctional localization of claudin-1. Colocalization of claudin-1 with ZO-1 was found at cell to cell contact sites of adjacent proliferating cells. In control samples, staining of claudin-1 was positive in PECs, but not in podocytes. Our findings suggest that claudin-1 contributes to crescent formation as a component of the tight junction protein complex that includes ZO-1. Co-localization of claudin-1 with ZO-1 implies the formation of functional tight junction complexes in crescentic lesions to prevent the interstitial damage caused by penetration of filtered molecules from Bowman's space.
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A Case of Membranous Glomerulonephropathy Associated with Takayasu's Arteritis.
Case Rep Nephrol Urol
PUBLISHED: 01-01-2014
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Glomerulonephropathy is a rare complication of Takayasu's arteritis (TA). To date, most glomerulonephropathies associated with TA show the histological feature of mesangial proliferation. Membranous glomerulonephropathy (MG) is a form of glomerulonephropathy in which the mesangial proliferation is not conspicuous and its association with TA is extremely rare. A 54-year-old man was referred to our hospital due to progressive edema in the lower limbs and nephrotic range proteinuria. Five years previously, he underwent percutaneous angioplasty for left subclavian artery stenosis. Kidney biopsy revealed stage II MG. General examination including enhanced CT scan confirmed the presence of TA. He started oral prednisolone therapy at a dose of 40 mg daily. The C-reactive protein level normalized 7 days after the prednisolone therapy. Three months later, proteinuria had remitted. Though the true relationship between MG and TA was not revealed in present case, considering the fact that complete remission of nephrotic syndrome occurred following the improvement of C-reactive protein level in response to steroid therapy, TA might be the secondary cause of MG. To our best knowledge, only two case reports described the association of MG and TA previously. Those two patients, however, also demonstrated the feature of systemic lupus erythematosus in addition to TA. This is the first case report that describes a patient who presented as MG associated with TA, but not complicated by systemic lupus erythematosus.
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Cluster analysis identifies characteristic phenotypes of asthma with accelerated lung function decline.
J Asthma
PUBLISHED: 11-04-2013
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Abstract Objective: While the majority of individuals with asthma retain normal lung function over time, some exhibit accelerated lung function decline. Preservation of lung function is an important aspect of asthma management. Whether the asthma guidelines can prevent lung function decline remains controversial. This study was performed to determine the distribution of asthmatic subjects with greater lung function decline and to identify characteristic clinical features of such subjects treated in accordance with clinical guidelines by using hierarchical cluster analysis. Methods: Eighty-six asthmatic subjects without a history of smoking were assessed with respect to eight variables selected from clinical phenotypes by using step-wise multiple regression analysis. Hierarchical cluster analysis using Wards method generated a dendrogram for estimation of the number of clusters within the population and the differences between them. Results: Three distinct clusters were identified. Cluster 1 (n?=?40) comprised women with late-onset asthma. Cluster 2 (n?=?17) comprised subjects with early-onset asthma, atopy and long disease duration. Cluster 3 (n?=?29) predominantly comprised older men who had late-onset asthma, a lower prevalence of exacerbation and a lower predicted % forced expiratory volume in 1?s (FEV1) at baseline. Subjects in cluster 3 showed a mean decline in FEV1 of 69?mL/year, which was the greatest lung function decline among the three clusters. Conclusion: We identified a subgroup of patients with accelerated lung function decline despite appropriate asthma treatment based on guidelines constructed by using subjective symptoms.
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Dialysis disequilibrium syndrome induced by neoplastic meningitis in a patient receiving maintenance hemodialysis.
BMC Nephrol
PUBLISHED: 09-13-2013
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Dialysis disequilibrium syndrome is characterized by neurological symptoms resulting from cerebral edema, which occurs as a consequence of hemodialysis. Dialysis disequilibrium syndrome most often occurs in patients who have just started hemodialysis, during hemodialysis, or soon after hemodialysis; although it may also occur in patients who are under maintenance hemodialysis with pre-existing neurological disease.
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Persistent metabolic acidosis in a hemodialyzed patient with short bowel syndrome.
Intern. Med.
PUBLISHED: 06-19-2013
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Short bowel syndrome (SBS) is characterized by a malabsorptive state. It is conceivable that the coexistence of SBS and end-stage renal disease can lead to severe metabolic acidosis; however, such a condition has rarely been documented. We herein describe the case of a 64-year-old man with SBS who required maintenance hemodialysis. Persistent metabolic acidosis and mineral and bone disorders should be of particular concern in hemodialyzed patients with SBS.
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DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked is an immunogenic target of cancer stem cells.
Cancer Immunol. Immunother.
PUBLISHED: 05-21-2013
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Accumulating evidence suggests that most solid malignancies consist of heterogeneous tumor cells and that a relatively small subpopulation, which shares biological features with stem cells, survives through potentially lethal stresses such as chemotherapy and radiation treatment. Since the survival of this subpopulation of cancer stem cells (CSC) plays a critical role in recurrence, it must be eradicated in order to cure cancer. We previously reported that vaccination with CD133(+) murine melanoma cells exhibiting biological CSC features induced CSC-specific effector T cells. These were capable of eradicating CD133(+) tumor cells in vivo, thereby curing the parental tumor. In the current study, we indicated that DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked (DDX3X) is an immunogenic protein preferentially expressed in CD133(+) tumor cells. Vaccination with DDX3X primed specific T cells, resulting in protective and therapeutic antitumor immunity. The DDX3X-primed CD4(+) T cells produced CD133(+) tumor-specific IFN? and IL-17 and mediated potent antitumor therapeutic efficacy. DDX3X is expressed in various human cancer cells, including lung, colon, and breast cancer cells. These results suggest that anti-DDX3X immunotherapy is a promising treatment option in efforts to eradicate CSC in the clinical setting.
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Association between warfarin use and incidence of ischemic stroke in Japanese hemodialysis patients with chronic sustained atrial fibrillation: a prospective cohort study.
Clin. Exp. Nephrol.
PUBLISHED: 05-19-2013
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Although generally recommended for atrial fibrillation (AF) in the general population, the efficacy and safety of warfarin in hemodialysis patients remains controversial. Warfarin use in hemodialysis patients may confer an additional risk of bleeding that is not appreciated in patients without renal failure because hemodialysis patients have platelet defects and receive anticoagulation agents during dialysis. The incidence of major bleeding was reported to be higher in Japanese AF patients on warfarin therapy compared to patients in other countries, suggesting that racial differences may influence bleeding tendency. Thus, examining risks and benefits of warfarin therapy in Japanese hemodialysis patients with AF is important.
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Upregulation of prolactin receptor in proximal tubular cells was induced in cardiac dysfunction model mice.
Clin. Exp. Nephrol.
PUBLISHED: 05-12-2013
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BACKGROUND: In order to clarify the interaction between cardiac dysfunction and sodium homeostasis in the kidney, we used a murine model of cardiac dysfunction and investigated the effect on sodium transporters in renal tubular cells. METHODS: Cardiac function was deteriorated by abdominal aortic banding, and the gene expression of sodium transporters in the kidneys was evaluated by real-time RT-PCR and compared with that in the kidneys of control mice. RESULTS: Gene expression of all three variants of the murine prolactin receptor was enhanced by aortic banding. Upregulated prolactin receptor was distributed in the proximal tubular cells of the pars recta in the deep inner cortex and the outer stripe of the outer medulla. Prolactin has been reported to be a natriuretic hormone that inhibits proximal tubular Na(+)/K(+)-ATPase activity, resulting in reduced sodium reabsorption and the acceleration of natriuresis. Inhibition of endogenous prolactin secretion by bromocriptine administration decreased the urine sodium excretion in both aortic banding and control mice. On the other hand, excess exogenous prolactin administration enhanced urine potassium excretion in aortic banding mice. Furthermore, a high-sodium diet accelerated urinary sodium excretion, which was also significantly decreased by inhibition of endogenous prolactin secretion in aortic banding mice. CONCLUSION: We reported that the prolactin receptor was upregulated by aortic banding treatment. Prolactin-prolactin receptor interaction in the proximal tubular cells of the pars recta should involve a different mechanism of kaliuresis other than inhibition of Na(+)/K(+)-ATPase.
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A single injection of a sustained-release prostacyclin analog (ONO-1301MS) suppresses airway inflammation and remodeling in a chronic house dust mite-induced asthma model.
Eur. J. Pharmacol.
PUBLISHED: 03-27-2013
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ONO-1301, a novel prostacyclin agonist with thromboxane A2 synthase inhibitory activity, is a useful agent for ameliorating airway allergic inflammation; however, its short-action feature implies a requirement for the frequent administration of this drug. Therefore, we investigated the effects of ONO-1301-loaded poly (d,l-lactic-co-glycolic acid) microspheres (ONO-1301MS; to release ONO-1301 for 3 weeks) on the airway inflammation and remodeling in chronic house dust mite (HDM)-induced model. Balb/c mice were exposed to an HDM extract intranasally for 5 days/week for 5 consecutive weeks. The mice received a single subcutaneous injection of ONO-1301MS or vehicle after 3 weeks of HDM exposure, followed by 2 additional weeks of HDM exposure. Forty-eight hours after the last HDM exposure, airway hyperresponsiveness to methacholine was assessed and bronchoalveolar lavage was performed. Lung specimens were excised and stained to check for goblet cell metaplasia, airway smooth muscle hypertrophy, and submucosal fibrosis. Mice receiving ONO-1301MS showed significantly lower airway hyperresponsiveness, airway eosinophilia, and induced T helper 2 cytokine production compared with mice receiving the vehicle. Histological findings such as goblet cell metaplasia, airway smooth muscle hypertrophy, and submucosal fibrosis were decreased in ONO-1301MS-treated mice compared with vehicle-treated mice. A single administration of ONO-1301MS achieved sustained elevation of its circulating level for 3 weeks. These data suggest that a single administration of ONO-1301MS may suppress airway hyperresponsiveness, airway allergic inflammation, and development of airway remodeling in chronic HDM-induced asthma model. This agent may be effective as an anti-inflammatory and remodeling drug in the practical treatment of asthma.
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Two susceptibility loci to Takayasu arteritis reveal a synergistic role of the IL12B and HLA-B regions in a Japanese population.
Am. J. Hum. Genet.
PUBLISHED: 03-23-2013
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Takayasu arteritis (TAK) is an autoimmune systemic vasculitis of unknown etiology. Although previous studies have revealed that HLA-B*52:01 has an effect on TAK susceptibility, no other genetic determinants have been established so far. Here, we performed genome scanning of 167 TAK cases and 663 healthy controls via Illumina Infinium Human Exome BeadChip arrays, followed by a replication study consisting of 212 TAK cases and 1,322 controls. As a result, we found that the IL12B region on chromosome 5 (rs6871626, overall p = 1.7 × 10(-13), OR = 1.75, 95% CI 1.42-2.16) and the MLX region on chromosome 17 (rs665268, overall p = 5.2 × 10(-7), OR = 1.50, 95% CI 1.28-1.76) as well as the HLA-B region (rs9263739, a proxy of HLA-B*52:01, overall p = 2.8 × 10(-21), OR = 2.44, 95% CI 2.03-2.93) exhibited significant associations. A significant synergistic effect of rs6871626 and rs9263739 was found with a relative excess risk of 3.45, attributable proportion of 0.58, and synergy index of 3.24 (p ? 0.00028) in addition to a suggestive synergistic effect between rs665268 and rs926379 (p ? 0.027). We also found that rs6871626 showed a significant association with clinical manifestations of TAK, including increased risk and severity of aortic regurgitation, a representative severe complication of TAK. Detection of these susceptibility loci will provide new insights to the basic mechanisms of TAK pathogenesis. Our findings indicate that IL12B plays a fundamental role on the pathophysiology of TAK in combination with HLA-B(?)52:01 and that common autoimmune mechanisms underlie the pathology of TAK and other autoimmune disorders such as psoriasis and inflammatory bowel diseases in which IL12B is involved as a genetic predisposing factor.
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Preventive effect of irbesartan on bleomycin-induced lung injury in mice.
Respir Investig
PUBLISHED: 03-22-2013
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Idiopathic pulmonary fibrosis is a specific form of chronic fibrosing interstitial pneumonia that is limited to the lung. Angiotensin receptor blockers (ARBs) and peroxisome proliferator-activated receptor (PPAR) ? ligands have anti-inflammatory and anti-fibrotic effects. We investigated the effects of irbesartan-an ARB with PPAR ? activity-on the development of bleomycin-induced pulmonary fibrosis in mice.
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Assessment of interleukin-6 receptor inhibition therapy on periodontal condition in patients with rheumatoid arthritis and chronic periodontitis.
J. Periodontol.
PUBLISHED: 03-14-2013
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Background: Overproduction of interleukin (IL)-6 may play a pathologic role in rheumatoid arthritis (RA) and chronic periodontitis (CP). The present study assesses IL-6 receptor (IL-6R) inhibition therapy on the periodontal condition of patients with RA and CP. Methods: The study participants were 28 patients with RA and CP during treatment with IL-6R inhibitor, and 27 patients with RA and CP during treatment without IL-6R inhibitor. Periodontal and rheumatologic parameters and serum levels of cytokine and inflammatory markers and immunoglobulin G against periodontopathic bacteria were examined after medication with IL-6R inhibitor for 20.3 months on average (T1) and again 8 weeks later (T2). Results: No differences were observed between the groups in any parameter values at T1, except for serum IL-6 levels. The anti-IL-6R group showed a significantly greater decrease in gingival index, bleeding on probing (BOP), probing depth (PD), clinical attachment level (CAL), and serum levels of IL-6 and matrix metalloproteinase (MMP)-3 from T1 to T2 than the control group (P <0.05). A significant correlation was found between changes in serum anticyclic citrullinated peptide levels and those in PD and CAL in the anti-IL-6R group (P <0.05), whereas both groups exhibited a significant association between changes in serum MMP-3 levels and those in BOP (P <0.05). Conclusion: Changes in periodontal and serum parameter values were different between the patients with RA and CP during treatment with and without IL-6R inhibitor.
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Development of IgG4-related disease in a patient diagnosed with idiopathic membranous nephropathy.
Clin Kidney J
PUBLISHED: 03-03-2013
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We report a case of IgG4-related disease (IgG4-RD) diagnosed after 3 years of follow-up for idiopathic membranous nephropathy (MN). MN has been considered as glomerular lesion of IgG4-related kidney diseases in recent years and was diagnosed simultaneously with or after a diagnosis of IgG4-RD in previously reported cases. In the present case, IgG4-RD developed 3 years after the diagnosis of idiopathic MN, indicating a possible relationship between idiopathic MN and IgG4-RD through common underlying mechanisms of development.
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Distribution of amyloid deposits in the kidneys of a patient with reactive amyloidosis associated with rheumatoid arthritis.
BMC Res Notes
PUBLISHED: 02-25-2013
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We previously reported that the amount of amyloid A (AA) amyloid deposited in renal biopsy specimens was highly correlated with parameters of renal function. However, the distribution of amyloid deposits throughout the kidneys of these patients, and the degree of renal abnormality, remained unclear. Therefore, we describe the features of reactive amyloidosis associated with rheumatoid arthritis (RA) in an autopsied patient.
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Immunoglobulin G4-related disease with several inflammatory foci.
Intern. Med.
PUBLISHED: 02-15-2013
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We herein report the case of a 62-year-old Japanese man who presented with jaundice, dry eyes and abdominal discomfort. Imaging studies revealed swelling of the periorbital tissue, parotid and submandibular glands, pulmonary hilar lymph nodes, pancreas, bile ducts, gall bladder walls, bilateral kidneys, arterial walls and prostate. A significant increase in the serum level IgG4 was seen, and the patient was diagnosed with IgG4-related disease after undergoing a biopsy of the pancreas and prostate. We herein report a case of IgG4-related disease with multiple ten organ involvement at the onset of the disease that was successfully treated with prednisolone (PSL) therapy.
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The clinical course of patients with IgG4-related kidney disease.
Kidney Int.
PUBLISHED: 02-13-2013
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Long-term follow-up for IgG4-related kidney disease, including relapse information, is sparse. To gather data on this we retrospectively examined the clinical course of 43 patients with IgG4-related kidney disease, in which most patients were treated with, and maintained on, corticosteroids. One month after the start of treatment, most of the abnormal serology and radiology parameters had improved. In 34 of the steroid-treated patients whose follow-up period was more than 12 months (median 34 months), excluding one hemodialysis patient, the estimated glomerular filtration rate (eGFR) before treatment was over 60?ml/min in 14 patients (group A) and under 60?ml/min in 20 patients (group B). In group A, there was no difference between the eGFR before therapy and at the last review. In group B, the mean eGFR before treatment (34.1?ml/min) was significantly improved after 1 month (45.0?ml/min), and renal function was maintained at a similar level through last follow-up. Among 24 evaluated patients at the last review, however, renal atrophy had developed in 2 of 9 in group A and in 9 of 15 in group B. Relapse of IgG4-related lesions occurred in 8 of 40 treated patients. Thus, the response of IgG4-related kidney disease to corticosteroids is rapid, not total, and the recovery of renal function persists for a relatively long time under low-dose maintenance. A large-scale prospective study to formulate more useful treatment strategies is necessary.
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The efficacy of triplet antiemetic therapy with 0.75 mg of palonosetron for chemotherapy-induced nausea and vomiting in lung cancer patients receiving highly emetogenic chemotherapy.
Support Care Cancer
PUBLISHED: 01-21-2013
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Chemotherapy-induced nausea and vomiting (CINV) are some of the most problematic symptoms for cancer patients. Triplet therapy consisting of a 5HT3 receptor antagonist, aprepitant, and dexamethasone is a guideline-recommended antiemetic prophylaxis for highly emetogenic chemotherapy (HEC). The efficacy and safety of triplet therapy using a 0.75-mg dose of palonosetron have not yet been investigated. We performed a prospective phase II study using triplet antiemetic therapy with 0.75 mg of palonosetron.
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Screening of male dialysis patients for fabry disease by plasma globotriaosylsphingosine.
Clin J Am Soc Nephrol
PUBLISHED: 01-10-2013
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Previous reports of Fabry disease screening in dialysis patients indicate that ?-galactosidase A activity alone cannot specifically and reliably identify appropriate candidates for genetic testing; a marker for secondary screening is required. Elevated plasma globotriaosylsphingosine is reported to be a hallmark of classic Fabry disease. The purpose of this study was to examine the usefulness of globotriaosylsphingosine as a secondary screening target for Fabry disease.
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Increased risk of hip fracture among Japanese hemodialysis patients.
J. Bone Miner. Metab.
PUBLISHED: 01-06-2013
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Incidence of hip fracture in dialysis patients is significantly higher than that in the general population. As information is lacking about Asian dialysis patients, we compared the incidence of hip fracture in hemodialysis patients with that in the general population in Japan. We conducted a retrospective cohort study using panel data from the Japanese Society for Dialysis Therapy registry. The study included patients without history of hip fracture who received hemodialysis three times per week as of December 31, 2007. We compared the observed number of hip fractures to the expected number derived from a national survey, and calculated standardized incidence ratios (SIRs) and the incidence rate difference. Subgroup analysis was performed according to vintage and diabetic status. During the one-year study period, 1,437 hip fractures were recorded in the 128,141 hemodialysis patients (61.9 % male). The overall incidence was 7.57 and 17.43 per 1,000 person-years in men and women, respectively. The SIRs for male and female patients were 6.2 [95 % confidence interval (CI) 5.7-6.8] and 4.9 (95 % CI 4.6-5.3) compared to the general population, and remained nearly constant until 16 years vintage, but increased steeply thereafter. The incidence rate difference of hip fracture increased with age. The SIRs for diabetics of both genders were higher than those for non-diabetics. Our study provides additional evidence that hip fracture risk among Asian dialysis patients is also significantly higher than in the general population.
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The Asthma Control Test, Japanese version (ACT-J) as a predictor of Global Initiative for Asthma (GINA) guideline-defined asthma control: analysis of a questionnaire-based survey.
Allergol Int
PUBLISHED: 01-04-2013
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The 2006 Global Initiative for Asthma (GINA 2006) guidelines emphasize the importance of evaluating the control rather than the severity of asthma. The Asthma Control Test (ACT) is well known to be an excellent tool for evaluating asthma control in the clinical setting. This study aimed to evaluate the ACT, Japanese version (ACT-J) as a predictor of asthma control as defined by the GINA 2006 guidelines in actual clinical practice.
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A case of podocytic infolding glomerulopathy with focal segmental glomerulosclerosis.
Case Rep Nephrol Urol
PUBLISHED: 01-01-2013
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Podocytic infolding glomerulopathy (PIG) has been proposed as a new disease entity. A 14-year-old girl underwent renal biopsy at our institution because of a chance finding of proteinuria. Light microscopic findings revealed a minor glomerular abnormality, but under a higher magnification, after periodic acid methenamine silver staining, a bubbling appearance in the glomerular basement membrane (GBM) was observed. An electron microscopic examination revealed microspheres in the GBM, which were sparse but global. The patient was diagnosed as having PIG. After 3 years, her urinary protein had increased and a second biopsy was performed, showing focal segmental glomerulosclerosis in addition to a lesser degree of podocytic infolding than at the first biopsy. This is the first report of a case complicated by a different type of glomerulonephritis after being diagnosed as PIG. A few cases of PIG are complicated by focal segmental glomerulosclerosis, suggesting several mechanisms for the disorder.
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Chronic portal-systemic shunt encephalopathy in a hemodialysis patient treated with balloon-occluded retrograde transvenous obliteration.
Case Rep Nephrol Urol
PUBLISHED: 01-01-2013
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We report a case of chronic portal-systemic shunt encephalopathy in a 79-year-old female hemodialysis patient with end-stage renal disease. Approximately 1 month before admission, she occasionally had a discrepant conversation. It was considered that hepatic encephalopathy was caused by an increase in the ammonia level in the blood flow of the shunt, which had been diagnosed 7 years previously between the splenic vein and the left renal vein. On admission, disturbed consciousness and an elevated serum ammonia level (221 ?g/dl) were observed. No change in the shunt diameter was noted. Consciousness improved with conservative treatment, whereas hyperammonemia remained. Balloon-occluded retrograde transvenous obliteration (B-RTO) was performed on the shunt. As a result, hyperammonemia resolved immediately, and the level of ammonia was maintained at approximately 60 ?g/dl. The patient often complained of drug-induced constipation; therefore, an increase in the intra-abdominal pressure in addition to ammonia production in the intestinal tract was suspected as the cause of encephalopathy. More than 23 months have passed since the B-RTO therapy, and no symptoms of encephalopathy have been observed yet.
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Three cases of gastric antral vascular ectasia in chronic renal failure.
Case Rep Nephrol Urol
PUBLISHED: 10-03-2011
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Gastric antral vascular ectasia (GAVE) is currently recognized as an important cause of gastrointestinal bleeding. Chronic kidney disease (CKD) is associated with a high incidence of GAVE. We report 3 patients with CKD who presented with severe anemia and were diagnosed with GAVE; they were resistant to endoscopic argon plasma coagulation. However, remission of anemia and improvement in GAVE lesions were observed after the initiation of hemodialysis. The pathogenesis of GAVE remains largely unknown, but mechanical stress of the antrum could play an important role. This stress may be reduced by hemodialysis through improvement of uremia-associated gastrointestinal symptoms. Therefore, the initiation of hemodialysis might be effective for intractable GAVE in CKD patients.
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Influence of obesity on control in asthmatic Japanese patients defined by the Japanese definition of obesity.
Intern. Med.
PUBLISHED: 09-15-2011
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BACKGROUND Despite the use of inhaled corticosteroid (ICS) becoming increasingly widespread, many problems related to asthma management still need to be addressed. One of them, obesity, has been reported to exert a harmful influence on asthma control. However, there have been few reports focusing not only on both obesity and its influence on Japanese asthma patients but also on the Japanese definition of obesity, as defined by the Japan Society for the Study of Obesity (JASSO). AIMS & METHODS The aim of this study was to confirm the influence of obesity, as defined by the JASSO, on asthma management in Japanese asthmatic patients. Using data from the Niigata Asthma Treatment Study Group 2008 questionnaire survey, differences between the "normal" group (18.5 kg/m(2) ? BMI <25 kg/m(2)) and the "obese" group (25 kg/m(2) ? BMI) were analyzed. RESULTS There was a significantly lower step 1 rate (19.4% v.s. 26.8%) and a higher proportion of patients using inhaled salmeterol (43.6% v.s. 35.8%) and leukotriene receptor antagonist (49.8% v.s. 40.8%) in the obese group relative to the normal group, although there were no significant differences in indicators of asthma control, including asthma control test scores. CONCLUSION This study investigated influences of JASSO-defined obesity on asthma severity and management in a clinical setting in Japan. It is possible that there are strong interactions between asthma and obesity, such as obesity causing decreased ICS therapy efficacy and leukotriene (LT)-related inflammation, although further investigation is necessary.
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The effect of renal administration of a selective cyclooxygenase-2 inhibitor or stable prostaglandin I2 analog on the progression of sclerotic glomerulonephritis in rats.
Clin. Exp. Nephrol.
PUBLISHED: 07-21-2011
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There is increasing evidence that a change in glomerular hemodynamics may promote the development of glomerulosclerosis. In this study, we focused on the pharmacological effects of 2 contrasting agents, etodolac, a preferential cyclooxygenase-2 inhibitor, and beraprost sodium (BPS), a prostaglandin I(2) analog, delivered renally, on the disease course of progressive anti-Thy-1 (ATS) glomerulonephritis.
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[Effects of anticoagulant therapy for rapidly progressive interstitial pneumonias].
Nihon Kokyuki Gakkai Zasshi
PUBLISHED: 07-09-2011
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To clarify the effects of anticoagulant therapy, we investigated patients with rapidly progressive interstitial pneumonias, retrospectively. We defined rapidly progressive pneumonia as idiopathic or secondary interstitial pneumonia with acute exacerbation of respiratory symptoms within 2 months, without infection or heart failure. A total of 20 cases admitted to our hospital between April 1999 and January 2010 met our criteria. Of those 20 cases, 6 were non-idiopathic pulmonary fibrosis (non-IPF), 3 were IPF, 6 were amyopathic dermatomyositis (ADM), 2 were DM, 2 were rheumatoid arthritis, and 1 was mixed connective-tissue disease. We divided the 20 cases into two groups according to whether they were treated with anticoagulant therapy (dalteparin and/or warfarin) (group A, n = 11) or not (group B, n = 9), and compared their outcomes. They were all given standard therapy. There was significantly better survival time in group A than in group B by the Kaplan-Meier survival curve (p = 0.0389). Anticoagulant therapy may improve the survival of patients with rapidly progressive interstitial pneumonias.
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Weight gain after 20 years of age is associated with prevalence of chronic kidney disease.
Clin. Exp. Nephrol.
PUBLISHED: 07-01-2011
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Weight gain after maturity is a risk factor for diabetes, coronary heart disease, and stroke, even in individuals with a normal body mass index; however, there is little information about the influence of weight gain after maturity on chronic kidney disease (CKD). Therefore, we examined the association between weight gain after 20 years of age and the prevalence of CKD.
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Henoch Schönlein purpura associated with pulmonary adenocarcinoma.
J Med Case Rep
PUBLISHED: 06-22-2011
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Henoch-Schönlein purpura is a common immunoglobulin A-mediated vasculitis syndrome in children. Henoch-Schönlein purpura can also affect adults and is probably related to malignancy.
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The case of BK virus infection in which it was difficult to differentiate from acute rejection.
Clin Transplant
PUBLISHED: 06-01-2011
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BK virus (BKV) nephropathy is one of the major causes of allograft dysfunction or graft loss in kidney transplant recipients. Early diagnosis and timely reduction in immunosuppressant is important for proper treatment. We report a 35-yr-old male case of cadaveric renal transplantation with BK viral related tubulointerstitial nephritis complicated by acute rejection. The diagnostic biopsy showed severe inflammatory infiltrates, tubulitis, and peritubular capillaritis. Discontinuation of mycophenolate mofetil, prednisone pulse therapy, and r-globulin was successful in relieving allograft dysfunction.
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Nuclear chromatin-concentrated osteoblasts in renal bone diseases.
Ther Apher Dial
PUBLISHED: 05-21-2011
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The morphological appearance of an osteoblast largely alters with its differentiation and maturation, along with the change of cell function. We quantitatively observed the osteoblast morphology and compared it with bone metabolism. Biopsied iliac bone samples obtained from 77 dialysis patients (14 mild change, 37 osteitis fibrosa, 2 osteomalacia, 8 mixed, and 16 adynamic bone) were included in the study. Osteoblast appearances were classified into three groups: (i) type II and III osteoblasts, namely, active osteoblasts characterized by cuboidal or columnar shapes with or without a nuclear clear zone; (ii) type IV osteoblasts, lining osteoblasts characterized by extremely thin cytoplasm; and (iii) type V osteoblasts, apoptotic osteoblasts characterized by nuclear chromatin concentration. The results were quantitatively expressed as the length of bone surface covered by each type of osteoblasts. The type II and III osteoblasts were predominant in osteitis fibrosa, mixed, and mild change. The type IV osteoblasts were overwhelmingly predominant in adynamic bone. The type V osteoblasts appeared most frequently in osteitis fibrosa, followed by mixed and mild change. Both absolute and relative lengths of bone surface covered by the type V osteoblasts were significantly higher in the high-turnover bone group (osteitis fibrosa and mixed) than the low-turnover bone group (adynamic bone and osteomalacia). The type V osteoblasts were slightly correlated with serum intact parathyroid hormone levels. In conclusion, a high bone-turnover condition seems to be associated with the promotion of osteoblastic apoptosis in dialysis patients. This finding may explain the fact that osteopenia develops faster in CKD patients with high turnover of bone.
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Quantitative histological analysis of SM22? (transgelin) in an adriamycin-induced focal segmental glomerulosclerosis model.
Nephron Exp. Nephrol.
PUBLISHED: 04-29-2011
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SM22?, transgelin, has been revealed to be specifically expressed in glomerular epithelial cells and interstitial cells, according to the nature of the renal injury. In this study, quantitative analyses of SM22? positivity were performed to investigate the pathological significance of its expression.
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A severe form of Churg-Strauss syndrome complicated with acute cardiac failure and rapidly progressive peripheral neuropathy--a possible effect of intravenous immunoglobulin therapy.
Intern. Med.
PUBLISHED: 04-15-2011
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We report a case of Churg-Strauss syndrome (CSS) complicated by severe cardiac failure and peripheral neuropathy. Two courses of methylprednisolone pulse therapy were unable to control the disease activity. Repeated intravenous administration of high-dose human immunoglobulin (IVIg) was added together with intravenous cyclophosphamide pulse therapy (IVCY), and the patients cardiac function and neurological symptoms were gradually ameliorated without any adverse event. Although glucocorticoid and cyclophosphamide comprise the standard therapy for patients with CSS, a number of patients with severe complications appear to be resistant to such conventional treatment. IVIg is thought to be an effective therapeutic option for such patients.
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Significant association between renal function and area of amyloid deposition in kidney biopsy specimens in reactive amyloidosis associated with rheumatoid arthritis.
Rheumatol. Int.
PUBLISHED: 04-03-2011
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The kidney is a major target organ for systemic amyloidosis, resulting in proteinuria and an elevated serum creatinine level. In patients with reactive amyloidosis associated with rheumatoid arthritis, a correlation between the amount of amyloid deposits and clinical parameters is not known. The purpose of this study was to clarify the association between various factors including renal function and the area of amyloid deposition in these patients. Fifty-eight patients with an established diagnosis of reactive AA amyloidosis were studied. We retrospectively investigated the correlation between clinical data and the area occupied by amyloid in renal biopsy specimens. All the patients showed amyloid deposits in renal tissues, and the percentage of the area occupied by amyloid was <10% in 54 of them. Mesangial proliferative glomerulonephritis and membranous nephropathy were frequently combined with renal amyloidosis. For statistical analyses, the percentage of the area occupied by amyloid was transformed to a common logarithmic value (Log(10) % amyloid), as the histograms showed a log-normal distribution. Log(10) % amyloid was found to be correlated with age, creatinine (Cr) level, creatinine clearance (Ccr), blood urea nitrogen (BUN) level, and the estimated glomerular filtration rate (eGFR). Multiple linear regression analyses were then performed to examine the sex- and age-adjusted association between Log(10) % amyloid and each of the clinical variables. Cr, Ccr, BUN, UA, CRP, and eGFR were significantly correlated with Log(10) % amyloid, but urinary protein was not. There was a significant correlation between the area of amyloid deposition in renal tissue and parameters of renal function, especially Cr and Ccr. If amyloid deposition in renal tissue can be arrested or prevented, then it may be possible to maintain renal function at an acceptable level.
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Fatal acute pancreatitis associated with reactive AA amyloidosis in rheumatoid arthritis with end-stage renal disease: a report of three cases.
Intern. Med.
PUBLISHED: 04-01-2011
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We report three cases of fatal pancreatitis associated with systemic AA amyloidosis in rheumatoid arthritis (RA). All of the patients showed end-stage renal failure, and hemodialysis was introduced during the course of treatment. Autopsy was performed on two of the three patients, and this revealed amyloid deposition on the vascular walls in the pancreas. It was strongly suggested that the acute pancreatitis in all three patients was attributable to deposition of amyloid in vascular and pancreatic tissues. Acute pancreatitis is considered to be a rare complication of end-stage amyloidosis associated with RA, and is frequently fatal. It is important to treat RA patients intensively to avoid such deposition of amyloid.
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Megalin is downregulated via LPS-TNF-?-ERK1/2 signaling pathway in proximal tubule cells.
Biochem. Biophys. Res. Commun.
PUBLISHED: 02-19-2011
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Expression and function of megalin, an endocytic receptor in proximal tubule cells (PTCs), are reduced in diabetic nephropathy, involved in the development of proteinuria/albuminuria. Lipopolysaccharide (LPS) is chronically increased in diabetic sera, by the mechanism called metabolic endotoxemia. We investigated low-level LPS-mediated signaling that regulates megalin expression in immortalized rat PTCs (IRPTCs). Incubation of the cells with LPS (10 ng/ml) for 48 h suppressed megalin protein expression and its endocytic function. TNF-? mRNA expression was increased by LPS treatment, and knockdown of the mRNA with siRNA inhibited LPS-mediated downregulation of megalin mRNA expression at the 24-h time point. Incubation of IRPTCs with exogenous TNF-? also suppressed megalin mRNA and protein expression at the 24- and 48-h time points, respectively. MEK1 inhibitor PD98059 competed partially but significantly TNF-?-mediated downregulation of megalin mRNA expression. Collectively, low-level LPS-mediated TNF-?-ERK1/2 signaling pathway is involved in downregulation of megalin expression in IRPTCs.
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Identification of alternatively activated macrophages in new-onset paediatric and adult immunoglobulin A nephropathy: potential role in mesangial matrix expansion.
Histopathology
PUBLISHED: 02-18-2011
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New onset of the clinical symptoms of immunoglobulin A (IgA) nephropathy (IgAN) manifests with proliferative glomerular lesions in children, whereas adults exhibit mesangial matrix expansion and interstitial fibrosis. Alternatively, activated (M2) macrophages have been implicated in promoting tissue fibrosis in some settings. Therefore, the aim of this study was to investigate whether M2 macrophages are present in new-onset IgAN and if they are related to pathological differences between paediatric and adult disease.
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Clinical and microbiological evaluation of hemodialysis-associated pneumonia (HDAP): should HDAP be included in healthcare-associated pneumonia?
J. Infect. Chemother.
PUBLISHED: 02-07-2011
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Although hemodialysis-associated pneumonia (HDAP) was included among the healthcare-associated pneumonias (HCAP) in the 2005 American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) guideline, little information relevant to clinical epidemiology, especially microbiological characteristics, is available. This study aimed to reveal microbiological characteristics and clinical outcomes of HDAP and to assess whether HDAP should be included in the HCAP category. We retrospectively analyzed 69 HDAP patients [42 with moderate and 27 with severe disease based on A-DROP (age, dehydration, respiratory failure, orientation disturbance, and low blood pressure)] in whom sputum cultures were performed at our hospital between 2007 and 2009. The most common pathogens were Staphylococcus aureus (37.7%), which were composed of methicillin-resistant S. aureus (MRSA) (27.5%) and methicillin-sensitive S. aureus (MSSA) (10.1%), followed by Streptococcus pneumoniae (10.1%), Klebsiella pneumoniae (8.7%), Haemophilus influenzae (7.2%), and Moraxella catarrhalis (5.8%). This distribution mostly resembled the microbiological characteristics of HCAP reported previously, except that the frequency of multi-drug-resistant (MDR) gram negatives such as Pseudomonas aeruginosa (2.9%) was clearly lower and that of MRSA was higher. There were no significant differences in microbiological findings, including the incidence of MDR pathogens, between the two severity groups. Despite most cases (82.6%) receiving only monotherapy, the prognosis (30-day survival and in-hospital mortality rates were 88.4% and, 17.4%, respectively) was similar to the past HCAP reports, but there were no significant correlations between prognosis and presence of MDR pathogens (30-day mortality rates 18.2% in MDR positive vs. 8.5% in MDR negative; p = 0.242). Assessment for not only MDR pathogens, but also severity of illness by the A-DROP system made it possible to conduct stratification based on prognosis. Our results suggest that HDAP should be included in the HCAP category, while understanding that there are some differences.
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Assessment of bone status in inhaled corticosteroid user asthmatic patients with an ultrasound measurement method.
Allergol Int
PUBLISHED: 02-01-2011
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The effect of inhaled corticosteroid (ICS) on the bone status of asthmatic patients is still uncertain, because it can differ by race and because there have been few cases in Japan. In this study, the bone status of ICS users with asthma was evaluated in an actual clinical setting in Japan.
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Injured kidney cells express SM22? (transgelin): Unique features distinct from ?-smooth muscle actin (?SMA).
Nephrology (Carlton)
PUBLISHED: 01-29-2011
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SM22? (transgelin) has been focused upon as a player in the process of phenotypic changes of types of cells. The SM22? expression in the rat anti-glomerular basement membrane (GBM) nephritis model and differences from an established phenotypic marker for the myofibroblast, ?-smooth muscle actin (?SMA), were investigated.
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Novel expression of claudin-5 in glomerular podocytes.
Cell Tissue Res.
PUBLISHED: 01-27-2011
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Tight junctions are the main intercellular junctions of podocytes of the renal glomerulus under nephrotic conditions. Their requisite components, claudins, still remain to be identified. We have measured the mRNA levels of claudin subtypes by quantitative real-time PCR using isolated rat glomeruli. Claudin-5 was found to be expressed most abundantly in glomeruli. Mass spectrometric analysis of membrane preparation from isolated glomeruli also confirmed only claudin-5 expression without any detection of other claudin subtypes. In situ hybridization and immunolocalization studies revealed that claudin-5 was localized mainly in glomeruli where podocytes were the only cells expressing claudin-5. Claudin-5 protein was observed on the entire surface of podocytes including apical and basal domains of the plasma membrane in the normal condition and was inclined to be concentrated on tight junctions in puromycin aminonucleoside nephrosis. Total protein levels of claudin-5 in isolated glomeruli were not significantly upregulated in the nephrosis. These findings suggest that claudin-5 is a main claudin expressed in podocytes and that the formation of tight junctions in the nephrosis may be due to local recruitment of claudin-5 rather than due to total upregulation of the claudin protein levels.
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Vaccination with CD133(+) melanoma induces specific Th17 and Th1 cell-mediated antitumor reactivity against parental tumor.
Cancer Immunol. Immunother.
PUBLISHED: 01-15-2011
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Accumulating evidence suggests that cancer cells possess a small subpopulation that survives during potentially lethal stresses, including chemotherapy, radiation treatment, and molecular-targeting therapy. CD133 is a putative marker that distinguishes a minor subpopulation from normal differentiated tumor cells in many cancers. Although it is necessary to eradicate all cancer cells to obtain a cure, effective treatment to eliminate the CD133(+) treatment-tolerant cells has not been elucidated. In this study, we demonstrated that a CD133(+) subpopulation in murine melanoma is immunogenic and that effector T cells specific for the CD133(+) melanoma cells mediated potent antitumor reactivity, curing the mice of the parental melanoma. CD133(+) melanoma antigens preferentially induced type 17 T helper (Th17) cells and Th1 cells but not Th2 cells. CD133(+) melanoma cell-specific CD4(+) T-cell treatment eradicated not only CD133(+) tumor cells but also CD133(-) tumor cells while inducing long-lasting accumulation of lymphocytes and dendritic cells with upregulated MHC class II in tumor tissues. Further, the treatment prevented regulatory T-cell induction. These results indicate that T-cell immunotherapy is a promising treatment option to eradicate CD133(+) drug-tolerant cells to obtain a cure for cancer.
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Association between clinical parameters and amyloid-positive area in gastroduodenal biopsy in reactive amyloidosis associated with rheumatoid arthritis.
Rheumatol. Int.
PUBLISHED: 01-15-2011
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Our study was aimed to clarify an association between gastrointestinal (GI) amyloid-positive area and various kinds of factors including renal function in reactive amyloidosis associated with rheumatoid arthritis (RA). Twenty-five patients with an established diagnosis of reactive AA amyloidosis participated in the study between January 1989 and December 2009. Each patient satisfied the 1987 American Rheumatism Association criteria for RA. All patients showed amyloid deposits in both of GI and renal tissues. The average amyloid-deposited area was 2.2% in renal tissues and 3.7% in GI tissues although the difference was not statistically significant. Twenty-two patients out of 25 patients showed less than 5% of amyloidosis in renal tissues and nineteen patients showed 5% of amyloidosis in GI tissues. In 5 out of a total of 25 cases, the amyloid-deposited area in GI tissues was lesser than that in renal tissues. Mesangial proliferative glomerulonephritis, thin basement membrane disease (TBMD) and membranous nephropathy were frequently combined with renal amyloidosis. For statistical analyses, renal and GI tissues of % amyloid-positive areas were transformed to common logarithmic values (Log(10)%amyloid), since the histograms showed log-normal distribution. Clinical data were assessed by patient record at the time of GI biopsy. The correlation between Log(10)%GI-amyloid and age, creatinine (Cr), creatinine clearance (Ccr), blood urea nitrogen (BUN), and estimated glomerular filtration rate (eGFR) were not significantly associated with Log(10)%GI-amyloid in crude correlation analyses and also in sex- and age-adjusted linear regression analyses. Although GI biopsy was not correlated with clinical factors, GI amyloid-positive areas were larger than renal amyloid-positive areas. Endoscopic screening of the upper GI tract is common in Japan, and amyloid-deposited area in GI tissues was sufficient to use for the diagnosis of amyloidosis compared with renal tissues in terms of convenience and sensitivity.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.