55 results on '"Fumiaki Nogaki"'
Search Results
2. Remission inductive efficacy of the combination of <scp>ARB</scp> , <scp>MRA</scp> , and saireito for nephrotic syndrome of membranous nephropathy
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Takahiko Ono, Hiroyuki Nagai, Noriyuki Suzuki, and Fumiaki Nogaki
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General Medicine - Published
- 2022
3. Two-step puncture technique in percutaneous peritoneal dialysis catheter placement
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Fumiaki Nogaki
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Nephrology ,General Medicine - Published
- 2023
4. An 89-year-old man who underwent percutaneous peritoneal dialysis catheter placement and had peritoneal dialysis introduced
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Naoki Washida, Fumiaki Nogaki, Kazuya Sugita, Tomohiko Urano, and Noriyuki Suzuki
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Male ,medicine.medical_specialty ,Catheters ,Activities of daily living ,Percutaneous ,Barthel index ,medicine.medical_treatment ,Peritoneal dialysis ,Japan ,Renal Dialysis ,Activities of Daily Living ,Peritoneal dialysis catheter ,Humans ,Medicine ,Dialysis ,Aged ,Aged, 80 and over ,business.industry ,Monitoring system ,Emergency medicine ,Quality of Life ,Kidney Failure, Chronic ,Hemodialysis ,Geriatrics and Gerontology ,business ,Peritoneal Dialysis - Abstract
The number of elderly patients requiring dialysis is continuously increasing. In Japan, many patients undergo hemodialysis; however, it has been associated with huge stress-mainly on the cardiovascular system-and requires frequent hospital visits. Conversely, peritoneal dialysis is much less invasive with a much lower frequency of hospital visits than that of hemodialysis; therefore, it is suitable for elderly patients. In addition, peritoneal dialysis, which originally had a high affinity for home care, has become more useful for elderly patients with renal failure thanks to the recent introduction of a cloud-based remote monitoring system at home. We performed percutaneous placement of a peritoneal dialysis catheter to reduce physical invasiveness and initiate peritoneal dialysis. The Barthel Index before hospitalization was 0 but increased to 65 at discharge. Further technology advancements in peritoneal dialysis are expected in the future. The cloud-based remote monitoring system is also expected to maintain or increase activities of daily living and the quality of life in elderly patients with renal failure with decreased activities of daily living.
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- 2021
5. Late relapse of IgM nephropathy‐associated nephrotic syndrome after repeated administration of immune checkpoint inhibitor against pulmonary adenocarcinoma
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Yutaka Tsutsumi, Fumiaki Nogaki, Kentaro Odani, and Mitsuhiro Tachibana
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medicine.medical_specialty ,Medicine (General) ,IgM nephropathy ,acute pancreatitis ,Immune checkpoint inhibitors ,Pulmonary adenocarcinoma ,immune checkpoint inhibitor ,Case Report ,pulmonary adenocarcinoma ,Disease ,Case Reports ,030204 cardiovascular system & hematology ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,R5-920 ,Usual interstitial pneumonia ,Internal medicine ,Medicine ,interstitial pneumonia ,Lung ,business.industry ,Cancer ,General Medicine ,respiratory system ,medicine.disease ,respiratory tract diseases ,immune‐related adverse events ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Adenocarcinoma ,Acute pancreatitis ,business ,Late Relapse ,Pancreas ,Nephrotic syndrome - Abstract
ICPIs were effective for primary and metastatic foci of lung adenocarcinoma, but their repeated use provoked a late relapse of IgM nephropathy and lethal lesions in pancreas and lung. ICPIs should be used carefully in cases of immune‐related disease.
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- 2021
6. Retrospective analysis of percutaneous peritoneal dialysis catheter placement using the Seldinger technique
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Kazuya Sugita, Fumiaki Nogaki, and Noriyuki Suzuki
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medicine.medical_specialty ,Percutaneous ,business.industry ,medicine ,Peritoneal dialysis catheter ,Retrospective analysis ,Seldinger technique ,business ,Surgery - Published
- 2019
7. Usefulness of mineralocorticoid receptor antagonists, rather than angiotensin II receptor blockers, for the prevention and treatment of licorice-induced pseudoaldosteronism
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Noboru Otsuka, Yoshinori Asahara, Takahiko Ono, Tasuku Yokoyama, and Fumiaki Nogaki
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endocrine system diseases ,business.industry ,medicine.drug_class ,Kampo ,nutritional and metabolic diseases ,Negative control ,Angiotensin II Receptor Blockers ,Pharmacology ,urologic and male genital diseases ,030226 pharmacology & pharmacy ,Hypokalemia ,03 medical and health sciences ,0302 clinical medicine ,Mineralocorticoid receptor ,030220 oncology & carcinogenesis ,Concomitant ,Medicine ,Shakuyakukanzoto ,medicine.symptom ,business ,Antihypertensive drug - Abstract
Aim The influence of angiotensin II receptor blockers (ARB) on licorice-induced pseudoaldosteronism remains unclear and the antihypertensive drug selection of prescribers, when they encounter hypokalemia and hypertension in licorice-treated patients, has not been surveyed. Methods We examined the occurrence of hypokalemia, concomitant drugs, and treatment for hypokalemia and hypertension in 42, 26 and 27 patients prescribed the licorice-containing traditional Japanese kampo medicines shakuyakukanzoto (SKT; containing 6 g licorice/day), rikkunshito (RKT; 1 g licorice/day), and goshajinkigan (GJG; without licorice), respectively. Results Seven (16.7%; P
- Published
- 2017
8. A patient with diabetic nephropathy who developed bilateral emphysematous pyelonephritis during peritoneal dialysis
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Yuichi Uemura, Noriyuki Suzuki, Keika Kou, Fumiaki Nogaki, Hiroko Kimura, Shigeki Fukuzawa, and Ken Megumi
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medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,030232 urology & nephrology ,Urology ,medicine.disease ,Peritoneal dialysis ,Diabetic nephropathy ,03 medical and health sciences ,0302 clinical medicine ,Emphysematous pyelonephritis ,030220 oncology & carcinogenesis ,medicine ,business - Published
- 2017
9. Percutaneous peritoneal dialysis catheter placement combined with the SMAP technique
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Fumiaki Nogaki, Noriyuki Suzuki, Keika Ko, and Izumi Amano
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03 medical and health sciences ,medicine.medical_specialty ,0302 clinical medicine ,Percutaneous ,business.industry ,030232 urology & nephrology ,Peritoneal dialysis catheter ,Medicine ,business ,030218 nuclear medicine & medical imaging ,Surgery - Published
- 2017
10. Efficacy of Indapamide for Glomerular Hypertrophy due to Salt Loading in Mice with Angiotensin II Receptor Overexpression
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Fumiaki Nogaki, Chunmo Wu, Yoko Ogata, Kozue Kato, Michihiro Shino, Ono Takahiko, Tetsuo Kume, Masaki Ito, and Kazuhide Uemura
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Kidney ,medicine.medical_specialty ,Angiotensin receptor ,Chemistry ,Glomerular Mesangial Cell ,Indapamide ,Wild type ,Glomerular Hypertrophy ,Excretion ,medicine.anatomical_structure ,Endocrinology ,Blood pressure ,Internal medicine ,medicine ,medicine.drug - Abstract
It is well known that salt excess accelerates organ injury when the renin-angiotensin system is activated.In the present study,we investigated the mechanisms by which salt excess causes glomerular injury using AT1A receptor overexpression mice,and evaluated the preventive effect of indapamide,a thiazide-like diuretic.Young AT1A receptor overexpression mice and C57BL/6 mice (wild type normal control) were salt-loaded from 8 to 14 weeks old using 1.5% NaCl in drinking water,and kidney specimens were collected.In the indapamide treatment group,10 mg/kg body weight of indapamide was administered concomitantly in the drinking water,and the dose adjusted weekly according to body weight measurements.Although neither strain of mice exhibited a significant increase in blood pressure after such salt loading during the specified period,increased urinary protein excretion was observed in the AT1A receptor overexpression mice,and indapamide blocked this influence of salt loading.There was a slight increase in the number of glomerular cells due to salt loading in the wild type and a marked increase in the AT1A receptor overexpression mice,which was suppressed by indapamide.Immunostaining of angiotensin II receptors revealed a strong reaction in the glomerular mesangial cells in the latter as opposed to a mild reaction in the former.Furthermore,salt loading induced an increase in collagen IV,a major component of the extracellular matrix (ECM),which was suppressed by indapamide.The present findings suggest that blood pressure and glomerular hypertrophy/ECM deposition are not necessarily connected in young AT1A receptor overexpression mice,and that glomerular injury is accelerated by salt loading.Also indapamide appears to be a promising therapy in the case of a salt excess and an activated renin-angiotensin system.
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- 2010
11. Contents Vol. 112, 2009
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Ying Zhang, Hidetaka Otsuka, Nobutaka Kato, Kazuhide Uemura, Kohei Kamikado, Hisayo Kitamura, Yutaka Yoshida, Masaaki Nameta, Eri Muso, Ning Liu, Fumiaki Nogaki, Haruyoshi Yoshida, Linning Zhao, Koji Sakamoto, Noriko Mori, Eishin Yaoita, Yuki Tomari, Tadashi Yamamoto, Makiko Shimosawa, Bo Xu, Hidehiko Fujinaka, and Takahiko Ono
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Nephrology ,Physiology ,Genetics ,General Medicine - Published
- 2009
12. Lipopolysaccharide-Triggered Acute Aggravation of Mesangioproliferative Glomerulonephritis through Activation of Coagulation in a High IgA Strain of ddY Mice
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Takahiko Ono, Yuki Tomari, Haruyoshi Yoshida, Kazuhide Uemura, Hisayo Kitamura, Koji Sakamoto, Kohei Kamikado, Eri Muso, Ning Liu, Fumiaki Nogaki, Hidetaka Otsuka, Noriko Mori, and Makiko Shimosawa
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Lipopolysaccharides ,medicine.medical_specialty ,Lipopolysaccharide ,Glomerulonephritis, Membranoproliferative ,Physiology ,Blotting, Western ,Dermatan Sulfate ,Gene Expression ,Thromboplastin ,Nephropathy ,Proinflammatory cytokine ,Mice ,chemistry.chemical_compound ,Tissue factor ,Proliferating Cell Nuclear Antigen ,Internal medicine ,Genetics ,medicine ,Animals ,Receptor, PAR-2 ,Blood Coagulation ,Chemokine CCL2 ,Protease-activated receptor 2 ,Fibrin ,Mice, Inbred BALB C ,Reverse Transcriptase Polymerase Chain Reaction ,business.industry ,Factor X ,Chondroitin Sulfates ,Anticoagulants ,Factor V ,Glomerulonephritis ,General Medicine ,medicine.disease ,Immunohistochemistry ,Glomerular Mesangium ,Immunoglobulin A ,Toll-Like Receptor 4 ,Endocrinology ,Microscopy, Fluorescence ,chemistry ,Nephrology ,Mesangium ,Female ,Heparitin Sulfate ,business ,Injections, Intraperitoneal - Abstract
Background: The high IgA (HIGA) strain of ddY mice represents an inbred model of IgA nephropathy that shows mesangioproliferative glomerulonephritis with mesangial IgA deposition. In this study, aggravation of glomerulonephritis in HIGA mice through lipopolysaccharide (LPS)-triggered activation of coagulation was investigated. Methods: Twelve-week-old HIGA and BALB/c mice were intraperitoneally injected with LPS twice at an interval of 3 days, and kidney specimens were collected 7 days after the second LPS injection. In an intervention experiment, the factor Xa inhibitor danaparoid was injected intraperitoneally every day for 7 days after the first LPS injection. Results: LPS injection induced macrophage infiltration and cellular proliferation in the mesangium together with fibrin deposition and monocyte chemoattractant protein 1 mRNA expression, as well as antigen deposition of tissue factor, factor V, factor X, and protease-activated receptor 2. These phenomena were obvious in HIGA mice when compared to BALB/c mice. Interestingly, toll-like receptor 4 was intensely expressed in HIGA mice before LPS injection and subsequently decreased. Danaparoid treatment significantly ameliorated proteinuria, cellular proliferation, and fibrin deposition. Conclusions: The present data suggest that tissue factor and factor V induction by LPS may in part accelerate mesangioproliferative glomerulonephritis through activation of factor X and downstream proinflammatory and procoagulant mechanisms.
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- 2009
13. Tissue Factor and Factor V Involvement in Rat Peritoneal Fibrosis
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Fumiaki Nogaki, Kazuhide Uemura, Noriko Mori, Takahiko Ono, Ning Liu, Hisayo Kitamura, Kozue Kato, Masayuki Kitamoto, Hiroki Saito, and Toshiya Takeda
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medicine.medical_specialty ,Pathology ,biology ,business.industry ,Factor X ,medicine.medical_treatment ,Factor V ,General Medicine ,medicine.disease ,Peritoneal dialysis ,Tissue factor ,chemistry.chemical_compound ,medicine.anatomical_structure ,Endocrinology ,Peritoneum ,chemistry ,Nephrology ,Fibrosis ,Internal medicine ,biology.protein ,Medicine ,business ,Peritoneal Fibrosis ,Kidney disease - Abstract
Objective Fibrin deposition on the peritoneum has been frequently observed in peritoneal fibrosis induced by long-term peritoneal dialysis. The present study was conducted to clarify the contribution of factor Xa through tissue factor and factor V expression in peritoneal fibrosis. Methods Wistar rats were intraperitoneally injected with chlorhexidine gluconate (CG) every day. For the interventional study, the factor Xa inhibitor fondaparinux was subcutaneously administered. After 28 days of CG injection, peritoneal specimens were examined by immunohistochemical analyses and in situ hybridization. Results The peritoneal submesothelial compact zone was observed to be markedly thicker in the CG-injected groups than in the normal group, and that thickness was dose dependent. Immunohistochemical study revealed massive fibrin, fibronectin, and type IV collagen depositions in the CG-injected groups, which was markedly higher than that in the normal group. Macrophage infiltration and staining for tissue factor, factor V, factor X, and protease-activated receptor-2 were intense in the CG-injected groups and negative/trace in the normal group. Tissue factor and factor V mRNAs were abundant in cells in the thickened peritoneum. A double-labeling experiment revealed that tissue factor was observed mainly in macrophages, and factor V was abundantly distributed in the fibrotic tissue together with macrophages. Fondaparinux treatment decreased the thickness of submesothelial fibrotic tissue, and size and number of CD31-positive vessels. Conclusion These results suggest that expression of tissue factor and factor V in infiltrated macrophages, together with factor X deposition, may progress angiogenesis and accumulation of extracellular matrix components, partly via profibrotic and procoagulant mechanisms in the peritoneum after inflammatory stimulation.
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- 2009
14. Renal redox dysregulation in AKI: application for oxidative stress marker of AKI
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Hajime Nakamura, Hideki Kimura, Kazuko Uno, Fumiaki Nogaki, Yasunari Nobukawa, Takahiko Ono, Kiichi Shirakawa, Junji Yodoi, Takaaki Koshiji, Naoki Takahashi, Haruyoshi Yoshida, Kenji Kasuno, Masayuki Iwano, Narihisa Yamada, Kenji Shigemi, Hitoshi Kusano, Kiyoshi Mori, Sawaka Tanabe, and Eri Muso
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Adult ,Male ,medicine.medical_specialty ,Pathology ,Time Factors ,Physiology ,Enzyme-Linked Immunosorbent Assay ,Biology ,urologic and male genital diseases ,medicine.disease_cause ,Kidney ,law.invention ,Diagnosis, Differential ,Mice ,Thioredoxins ,law ,Predictive Value of Tests ,Internal medicine ,medicine ,Oxidative stress marker ,Cardiopulmonary bypass ,Animals ,Humans ,Renal Insufficiency, Chronic ,Renal ischemia reperfusion ,Aged ,Aged, 80 and over ,urogenital system ,Acute kidney injury ,Acute Kidney Injury ,Middle Aged ,medicine.disease ,Up-Regulation ,Disease Models, Animal ,Oxidative Stress ,ROC Curve ,Area Under Curve ,Case-Control Studies ,Reperfusion Injury ,Cardiology ,Female ,Oxidation-Reduction ,Oxidative stress ,Biomarkers - Abstract
Oxidative stress is a major determinant of acute kidney injury (AKI); however, the effects of an AKI on renal redox system are unclear, and few existing AKI markers are suitable for evaluating oxidative stress. We measured urinary levels of the redox-regulatory protein thioredoxin 1 (TRX1) in patients with various kinds of kidney disease and in mice with renal ischemia-reperfusion injury. Urinary TRX1 levels were markedly higher in patients with AKI than in those with chronic kidney disease or in healthy subjects. In a receiver operating characteristic curve analysis to differentiate between AKI and other renal diseases, the area under the curve for urinary TRX1 was 0.94 (95% confidence interval, 0.90–0.98), and the sensitivity and specificity were 0.88 and 0.88, respectively, at the optimal cutoff value of 43.0 μg/g creatinine. Immunostaining revealed TRX1 to be diffusely distributed in the tubules of normal kidneys, but to be shifted to the brush borders or urinary lumen in injured tubules in both mice and humans with AKI. Urinary TRX1 in AKI was predominantly in the oxidized form. In cultured human proximal tubular epithelial cells, hydrogen peroxide specifically and dose dependently increased TRX1 levels in the culture supernatant, while reducing intracellular levels. These findings suggest that urinary TRX1 is an oxidative stress-specific biomarker useful for distinguishing AKI from chronic kidney disease and healthy kidneys.
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- 2014
15. Quantitative trait loci (QTL) analysis reveals a close linkage between the hinge region and trimeric IgA dominancy in a high IgA strain (HIGA) of ddY mice
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Emi Oida, Takahiko Ono, Tadashi Kamata, Ikei Kobayashi, Toru Kita, Fumiaki Nogaki, Shigeki Miyawaki, Tadao Serikawa, Haruyoshi Yoshida, and Eri Muso
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Genetics ,Genetic Linkage ,Blotting, Western ,Kidney Glomerulus ,Molecular Sequence Data ,Quantitative Trait Loci ,Immunology ,Quantitative trait locus ,Biology ,medicine.disease ,Molecular biology ,Immunoglobulin A ,Nephropathy ,Mice ,Mesangium ,medicine ,Animals ,Immunology and Allergy ,Immunoglobulin heavy chain ,Amino Acid Sequence ,Peptide sequence ,Gene ,Chromosome 12 ,Dominance (genetics) - Abstract
Polymerization of IgA has been suggested as one of the causes of mesangial deposition in IgA nephropathy. HIGA mice are an inbred model of IgA nephropathy, established by selective mating of ddY mice. This strain is characterized by a unique profile of the IgA molecule that is dominantly polymeric and has high serum levels with intense IgA deposition on the mesangium. We carried out quantitative trait loci (QTL) analysis, using F2 generations by crossing HIGA with BALB/c mice. Significant linkage of polymeric IgA in serum samples was identified around D12Mit263, which is close to the gene of the immunoglobulin heavy chain on chromosome 12. The amino acid sequence of the alpha heavy chain revealed marked differences between BALB/c and HIGA mice. Furthermore, most differences were focussed on the hinge region. The DBA/2J strain, which has the same amino acid sequence in the hinge region as the HIGA strain, also showed polymeric IgA dominance but low IgA levels in sera. Size fraction analysis revealed that these polymeric IgA showed trimer dominance in both DBA/2J and HIGA mice. In conclusion, the hinge region plays a key role in trimeric IgA formation in HIGA mice.
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- 2004
16. Hepatitis C virus-associated tubulointerstitial injury
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Akira Matsumori, Junji Yodoi, Kenji Kasuno, Fumiaki Nogaki, Takahiko Ono, Hitomi Watanabe, Eri Muso, and Hitoshi Kusano
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Adult ,Male ,Pathology ,medicine.medical_specialty ,Adolescent ,Biopsy ,Hepatitis C virus ,Interstitial nephritis ,Kidney Glomerulus ,Hepacivirus ,medicine.disease_cause ,Glomerulonephritis, Membranous ,Glomerulonephritis ,Japan ,Membranous nephropathy ,Glomerulopathy ,Prevalence ,medicine ,Humans ,Aged ,Retrospective Studies ,Aged, 80 and over ,medicine.diagnostic_test ,business.industry ,virus diseases ,Hepatitis C Antibodies ,Middle Aged ,medicine.disease ,Hepatitis C ,digestive system diseases ,Nephrology ,Case-Control Studies ,Nephritis, Interstitial ,RNA, Viral ,Female ,Renal biopsy ,Hepatitis C Antigens ,business ,Kidney disease - Abstract
Background: Tubulointerstitial damage is recognized as a determinant of the prognosis of kidney disease. Various types of viral infection have been reported to induce tubulointerstitial lesions; however, that caused by hepatitis C virus (HCV) remains unclear, although glomerular lesions caused by this viral infection have been well documented. Methods: To identify any association, we retrospectively investigated 320 patients who underwent renal biopsy and did not have extrarenal diseases causing tubulointerstitial nephritis. Results: Of these patients, 13 patients had HCV infection and 307 patients did not. In a case-control study, HCV infection showed a significant association with the prevalence of tubulointerstitial injury. To offset the secondary tubulointerstitial change caused by advanced glomerulopathy, we performed a glomerular stage-matched comparison of patients with membranous nephropathy (MN). Nine patients with MN among the 13 HCV-infected patients and 18 HCV-negative patients with electron microscopic glomerular stage-matched MN were randomly selected from the overall pool of patients. Comparing areas of interstitial fibrosis and inflammatory cell infiltration, both were greater in HCV-infected than HCV-negative patients. In biopsy tissues from HCV-infected patients, positive signal for HCV was observed in the perinuclear area of tubular epithelial cells and infiltrating cells on immunohistochemistry and in situ hybridization. By a strand-specific reverse-transcription polymerase chain reaction for HCV, both genomic- and replicative-strand RNA were detected in renal tissues. Conclusion: These results suggest that HCV infection is a potent pathogenic factor of tubulointerstitial injury.
- Published
- 2003
17. Suppressive effects of Perilla frutescens on IgA nephropathy in HIGA mice
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Fumiaki Nogaki, Takahiko Ono, Shigeki Miyawaki, Toshiaki Makino, Kotone Matsuyama, Gisho Honda, and Eri Muso
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medicine.medical_specialty ,Kampo ,Spleen ,Depsides ,Nephropathy ,Mice ,Random Allocation ,Immune system ,Internal medicine ,medicine ,Animals ,Transplantation ,Kidney ,Perilla frutescens ,biology ,Plant Extracts ,business.industry ,Anti-Inflammatory Agents, Non-Steroidal ,Glomerulonephritis, IGA ,Glomerulonephritis ,medicine.disease ,Perilla ,biology.organism_classification ,Immunoglobulin A ,Plant Leaves ,Disease Models, Animal ,medicine.anatomical_structure ,Endocrinology ,Cinnamates ,Nephrology ,Female ,business ,Digestive System ,Phytotherapy - Abstract
Background. Perilla frutescens (perilla) is a herbal medicine used in Japanese traditional Kampo medicine. The present study was conducted to evaluate the anti-nephritic effects of perilla in HIGA mice that spontaneously develop high levels of serum immunoglobulin A (IgA) along with mesangial IgA deposition. Methods. A perilla decoction and its major active constituent, rosmarinic acid (RsA), were orally administrated to 10-week-old HIGA mice for 16 weeks. At study completion, we measured proteinuria and serum IgA levels and generated histological scores from kidney specimens. In addition, we measured concentrations of IgA in culture media of intestinal Peyer’s patch cells and spleen cells obtained from the HIGA mice. Results. Perilla suppressed proteinuria, proliferation of glomerular cells, serum levels of IgA, glomerular IgA and IgG depositions in HIGA mice. Cultured Peyer’s patch cells and spleen cells from perilla-treated mice produced significantly less IgA than controls. Rosmarinic acid, by itself, suppressed serum IgA levels and glomerular IgA deposition in HIGA mice. Cultured spleen cells from RsA-treated mice produced less IgA than controls. Conclusions. The perilla decoction may suppress IgA nephropathy, in part, through modulation of the intestinal mucosal immune system. These effects were caused by RsA acting synergistically with other constituents.
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- 2003
18. Interleukin-12 alters the physicochemical characteristics of serum and glomerular IgA and modifies glycosylation in a ddY mouse strain having high IgA levels
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Eri Muso, Ikei Kobayashi, Hitoshi Kusano, Haruyoshi Yoshida, Takahiko Ono, Shigeki Miyawaki, and Fumiaki Nogaki
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medicine.medical_specialty ,Glycosylation ,Chemical Phenomena ,Polymers ,Ratón ,medicine.medical_treatment ,Kidney Glomerulus ,Mice, Inbred Strains ,Nephropathy ,Mice ,chemistry.chemical_compound ,Internal medicine ,Animals ,Medicine ,chemistry.chemical_classification ,Mice, Inbred BALB C ,Transplantation ,Chemistry, Physical ,business.industry ,Interleukin ,Glomerulonephritis ,Hydrogen-Ion Concentration ,medicine.disease ,Interleukin-12 ,Immunoglobulin A ,Blood ,Cytokine ,Endocrinology ,chemistry ,Nephrology ,Immunology ,Interleukin 12 ,business ,Glycoprotein - Abstract
Background We recently developed a ddY mouse strain having high IgA levels (HIGA) that provided a murine model of IgA nephropathy. We additionally showed that administration of interleukin (IL)-12, a potent helper T (Th)1-inducing cytokine, induced an apparent reduction in serum IgA levels. In the present study, we assessed the influence of IL-12 administration on several physicochemical characteristics of nephritogenic IgA molecules in HIGA mice. Methods HIGA mice received daily intraperitoneal injections of IL-12 or control injections of phosphate-buffered saline for 3 weeks. Crescent formation and levels of circulating and glomerular IgA were analysed. Moreover, potential changes in charge, size, and glycosylation of serum and glomerular IgA were investigated. Results In the IL-12 group, glomerular IgA deposition was faint, although crescent formation was more marked than in the control group. Serum IgA levels in IL-12 mice were significantly lower than in controls. IL-12-treated mice also showed markedly decreased acidic and polymeric IgA both in sera and in glomerular eluate. A lectin-binding study revealed a markedly reduced ratio of sialylated and galactosylated IgA in the sera and in glomerular eluate from HIGA mice kidneys. IL-12 treatment significantly increased sialylation and galactosylation of circulating IgA, although glycosylation of IgA in glomerular eluate remained low. Conclusions In HIGA mice showing under-glycosylation, IL-12 administration may lead to changes in the physicochemical characteristics of IgA, and this may occur through a shift to Th1. These results suggest that the Th1 and Th2 balance might play a role in the development of immunopathologic lesions in this model of IgA nephropathy.
- Published
- 2002
19. Broad Antiproliferative Effects of Benidipine on Cultured Human Mesangial Cells in Cell Cycle Phases
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Ning Liu, Hitoshi Kusano, Shigetake Sasayama, Fumiaki Nogaki, Toshiaki Makino, Eri Muso, and Takahiko Ono
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Dihydropyridines ,medicine.medical_specialty ,Nifedipine ,Cell Survival ,medicine.drug_class ,Calcium channel blocker ,Biology ,Diltiazem ,chemistry.chemical_compound ,Internal medicine ,medicine ,Humans ,Cells, Cultured ,Mesangial cell ,Calcium channel ,Glomerulonephritis ,Cell cycle ,Calcium Channel Blockers ,Flow Cytometry ,medicine.disease ,In vitro ,Glomerular Mesangium ,Cell biology ,Endocrinology ,chemistry ,Nephrology ,Cell culture ,Benidipine ,Cell Division - Abstract
Background and Purpose: Recently, in vitro studies have shown that some calcium channel blockers inhibit the proliferation of mesangial cells. In the present study, we evaluated the antiproliferative effects of benidipine, a calcium channel blocker, in comparison with other calcium channel blockers, and attempted to further clarify its mechanism of action on cultured human mesangial cells in relation to cell cycle. Methods: Human mesangial cells were cultured in medium containing 5% fetal calf serum (FCS), with or without benidipine, or other calcium channel blockers for 20 h, and [3H]thymidine incorporation were measured. Analysis of cell cycle dependency was carried out, using platelet-derived growth factor as a competence factor, which transfers cells from the G0 to the G1 (G0/G1) phase, and insulin as a progression factor, which transfers cells from the G1 to the S (G1/S) phase. Cells were also analyzed by flow cytometry. Results: Benidipine and nifedipine showed significant inhibitory effects on FCS-induced proliferation (p < 0.001 and p < 0.01, respectively, by ANOVA), with 3.8 and 41.9% of the control level of [3H]thymidine incorporation at the concentration of 10 µM of the blockers, respectively. Diltiazem had no inhibitory effect at this concentration. Benidipine was found to inhibit cells in both the boundaries of G0/G1 and G1/S phases (p < 0.001 and p < 0.0001, respectively), whereas nifedipine inhibited only cells in G1/S phase (p < 0.05). The effects of benidipine (10 µM) on cells in G1/S were stronger than those on cells in the G0/G1 phase (p < 0.0001). Furthermore, flow cytometry showed that 10 mM benidipine significantly inhibited the G1 to S phase transition of FCS-stimulated mesangial cells (p < 0.03). Conclusions: Benidipine markedly inhibited the proliferation of mesangial cells, at both the G0/G1 and G1/S phases, and it might be effective to suppress the progression of mesangioproliferative glomerular diseases.
- Published
- 2002
20. Coagulation process proceeds on cultured human mesangial cells via expression of factor V
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Eri Muso, Ning Liu, Takahiko Ono, Hitoshi Kusano, Katsuo Suyama, Shigetake Sasayama, Tadashi Kamata, Fumiaki Nogaki, and Kenji Kasuno
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medicine.medical_specialty ,Antibodies ,Fibrin ,chemistry.chemical_compound ,Tissue factor ,Thrombin ,Internal medicine ,medicine ,Humans ,RNA, Messenger ,mesangioproliferative glomerulonephritis ,Cells, Cultured ,biology ,Mesangial cell ,Tumor Necrosis Factor-alpha ,business.industry ,Factor X ,Factor V ,IgA nephropathy ,Immunohistochemistry ,Molecular biology ,Glomerular Mesangium ,intraglomerular coagulation ,Endocrinology ,Models, Chemical ,chemistry ,Coagulation ,Nephrology ,Cell culture ,Factor Xa ,biology.protein ,cross-linked fibrin ,tumor necrosis factor-α ,factor X ,business ,medicine.drug - Abstract
Coagulation process proceeds on cultured human mesangial cells via expression of factor V.BackgroundIn a previous clinicopathological study, we observed mesangial factor V expression accompanied by the intact form of cross-linked fibrin deposition in the active type of IgA nephropathy. The conversion of prothrombin to thrombin by factor Xa is potently accelerated more than 104-fold by the presence of factor V, which is a membrane-bound cofactor. Another membrane-bound cofactor, tissue factor, is known to play an initiating role in the coagulation cascade and to be synthesized in mesangial cells (MCs) by the stimulation of tumor necrosis factor-α (TNF-α). However, the synthesis of factor V, which plays on the terminating stage of prothrombin activation, has not been reported previously in MCs by in vitro study. Our current study tested the coagulation process via expression of factor V by the stimulation of proinflammatory cytokine, TNF-α, in cultured human MCs.MethodsTo evaluate factor V protein expression, immunoperoxidase staining with densitometric evaluation and Western blot analysis were conducted after stimulation of TNF-α. To test factor V activity, stimulated MCs were incubated in combination with factor Xa, prothrombin, fibrinogen and factor XIII, and fibrin production on MCs was assessed after immunoperoxidase staining on the cell surface. In a blocking test using an antibody against factor V, suppression of fibrin production was evaluated to clarify the role of factor V activity. For the evaluation of factor V mRNA expression in cultured human MCs, in situ hybridization and Northern blot analysis were performed.ResultsFactor V protein expression in MCs after TNF-α stimulation increased both time- and dose-dependently. As a marker of factor V activity with exogenous factor Xa, fibrin production on TNF-α–stimulated MCs was increased in a time-dependent manner and was inhibited by the addition of anti-factor V antibody. Factor V mRNA was identified in MCs by in situ hybridization and showed an increase after stimulation with TNF-α on Northern blot analysis.ConclusionsOur data suggest that the coagulation process proceeds on MCs as the result of increased expression of endogenous factor V activity on its cell surface in cooperation with exogenous factor Xa.
- Published
- 2001
21. Direct effects of simvastatin on proliferation and matrix accumulation in cultured murine mesangial cells
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Tadashi Kamata, Fumiaki Nogaki, Takahiko Ono, Shigetake Sasayama, Eri Muso, Masatomo Yashiro, and Kenji Kasuno
- Subjects
medicine.medical_specialty ,Platelet-derived growth factor ,DNA synthesis ,biology ,Physiology ,business.industry ,Growth factor ,medicine.medical_treatment ,Molecular biology ,Type IV collagen ,chemistry.chemical_compound ,Endocrinology ,chemistry ,Nephrology ,Physiology (medical) ,Internal medicine ,Plasminogen activator inhibitor-1 ,medicine ,biology.protein ,business ,Plasminogen activator ,Platelet-derived growth factor receptor ,Transforming growth factor - Abstract
Background. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have been demonstrated to suppress glomerular injuries in various renal diseases. However, it is not fully clear whether HMG-CoA reductase inhibitors directly regulate matrix protein accumulation in mesangial cells. Methods. We investigated the effect of simvastatin (SIM), an HMG-CoA reductase inhibitor, on DNA synthesis in cultured murine mesangial cells stimulated by fetal calf serum (FCS). We then determined whether SIM affected the expression of regulatory factors of cell growth and matrix protein accumulation, using Northern analysis. Results. SIM dose-dependently inhibited FCS-induced DNA synthesis after 24 h of incubation. SIM treatment for 24 h suppressed the mRNA expression of platelet-derived growth factor (PDGF)-B chain, PDGF receptor β-subunit and c-myc, while the expression of transforming growth factor β (TGF-β) was not affected. Concerning matrix protein synthesis, the mRNA expression of type IV collagen was suppressed, whereas that of type III collagen was markedly upregulated. As for matrix turnover proteins, SIM had a markedly suppressive effect on the mRNA expression of plasminogen activator inhibitor-1 (PAI-1), with a constant expression of tissue-type plasminogen activator (tPA). Conclusions. These results indicate that SIM may sup-press mesangial cell proliferation in part through the downregulation of PDGF, PDGF-receptor, and c-myc mRNA expressions. In addition, the suppression of the synthesis of collagen IV and PAI-1 appears to be a direct inhibitory effect of SIM on glomerular matrix accumulation.
- Published
- 2001
22. Notch1 and Notch3 Instructively Restrict bFGF-Responsive Multipotent Neural Progenitor Cells to an Astroglial Fate
- Author
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Kenji Tanigaki, Tasuku Honjo, Kei Tashiro, Fumiaki Nogaki, Hisanori Kurooka, and Jun Takahashi
- Subjects
STAT3 Transcription Factor ,Neuroscience(all) ,Cellular differentiation ,Notch signaling pathway ,Receptors, Cell Surface ,Biology ,Ciliary neurotrophic factor ,Hippocampus ,Proto-Oncogene Proteins ,Animals ,Cell Lineage ,Ciliary Neurotrophic Factor ,Receptor, Notch1 ,Progenitor cell ,Cells, Cultured ,Gliogenesis ,Neurons ,Stem Cells ,General Neuroscience ,Membrane Proteins ,Cell Differentiation ,Neural stem cell ,Clone Cells ,Rats ,DNA-Binding Proteins ,nervous system ,Astrocytes ,Trans-Activators ,biology.protein ,Fibroblast Growth Factor 2 ,Signal transduction ,Stem cell ,Neuroscience ,Signal Transduction ,Transcription Factors - Abstract
Notch1 has been shown to induce glia in the peripheral nervous system. However, it has not been known whether Notch can direct commitment to glia from multipotent progenitors of the central nervous system. Here we present evidence that activated Notch1 and Notch3 promotes the differentiation of astroglia from the rat adult hippocampus-derived multipotent progenitors (AHPs). Quantitative clonal analysis indicates that the action of Notch is likely to be instructive. Transient activation of Notch can direct commitment of AHPs irreversibly to astroglia. Astroglial induction by Notch signaling was shown to be independent of STAT3, which is a key regulatory transcriptional factor when ciliary neurotrophic factor (CNTF) induces astroglia. These data suggest that Notch provides a CNTF-independent instructive signal of astroglia differentiation in CNS multipotent progenitor cells.
- Published
- 2001
23. Alymphoplasia (aly)-Type Nuclear Factor κB–Inducing Kinase (Nik) Causes Defects in Secondary Lymphoid Tissue Chemokine Receptor Signaling and Homing of Peritoneal Cells to the Gut-Associated Lymphatic Tissue System
- Author
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Tasuku Honjo, Tadashi Kamata, Koichi Ikuta, Kei Tashiro, Sidonia Fagarasan, Reiko Shinkura, and Fumiaki Nogaki
- Subjects
Chemokine ,Lymphoid Tissue ,animal diseases ,Plasma Cells ,Immunology ,Protein Serine-Threonine Kinases ,Recombination-activating gene ,Mice ,Peyer's Patches ,Peritoneal cavity ,Intestine, Small ,medicine ,Animals ,Immunology and Allergy ,chemotaxis assay ,RAG-2−/− mice ,lamina propria ,CXCL13 ,biology ,Chemotaxis ,respiratory system ,Mice, Mutant Strains ,respiratory tract diseases ,Cell biology ,DNA-Binding Proteins ,Immunoglobulin Isotypes ,B-1 cell ,Lymphatic system ,medicine.anatomical_structure ,biology.protein ,Receptors, Chemokine ,Original Article ,Lymph Nodes ,peritoneal cavity cell transfer ,Chemokines ,Peritoneum ,Signal transduction ,Signal Transduction ,IgA plasma cells ,Homing (hematopoietic) - Abstract
Alymphoplasia (aly) mice, which carry a point mutation in the nuclear factor κB–inducing kinase (NIK) gene, are characterized by the systemic absence of lymph nodes and Peyer's patches, disorganized splenic and thymic architectures, and immunodeficiency. Another unique feature of aly/aly mice is that their peritoneal cavity contains more B1 cells than normal and aly/+ mice. Transfer experiments of peritoneal lymphocytes from aly/aly mice into recombination activating gene (RAG)-2−/− mice revealed that B and T cells fail to migrate to other lymphoid tissues, particularly to the gut-associated lymphatic tissue system. In vivo homing defects of aly/aly peritoneal cells correlated with reduction of their in vitro chemotactic responses to secondary lymphoid tissue chemokine (SLC) and B lymphocyte chemoattractant (BLC). The migration defect of aly/aly lymphocytes was not due to a lack of expression of chemokines and their receptors, but rather to impaired signal transduction downstream of the receptors for SLC, indicating that NIK is involved in the chemokine signaling pathway known to couple only with G proteins. The results showed that the reduced serum levels of immunoglobulins (Igs) and the absence of class switch to IgA in aly/aly mice are due, at least in part, to a migration defect of lymphocytes to the proper microenvironment where B cells proliferate and differentiate into Ig-producing cells.
- Published
- 2000
24. Direct inhibitory effects of simvastatin on matrix accumulation in cultured murine mesangial cells
- Author
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Eri Muso, Takahiko Ono, Tadashi Kamata, Fumiaki Nogaki, Shigetake Sasayama, Kenji Kasuno, and Masatomo Yashiro
- Subjects
Simvastatin ,medicine.medical_specialty ,Platelet-derived growth factor ,extracellular matrix ,medicine.medical_treatment ,Gene Expression ,Receptor, Platelet-Derived Growth Factor beta ,Mice ,chemistry.chemical_compound ,Type IV collagen ,Internal medicine ,Plasminogen Activator Inhibitor 1 ,medicine ,Animals ,Receptors, Platelet-Derived Growth Factor ,RNA, Messenger ,Cells, Cultured ,Platelet-Derived Growth Factor ,Extracellular Matrix Proteins ,Mice, Inbred BALB C ,biology ,Growth factor ,Urokinase-Type Plasminogen Activator ,Molecular biology ,Fibronectins ,Glomerular Mesangium ,Fibronectin ,Endocrinology ,chemistry ,Nephrology ,Plasminogen activator inhibitor-1 ,biology.protein ,plasminogen activator inhibitor-1 ,Collagen ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Plasminogen activator ,Platelet-derived growth factor receptor ,medicine.drug - Abstract
Direct inhibitory effects of simvastatin on matrix accumulation in cultured murine mesangial cells Background 3-Hydroxy-3-methylglutarylcoenzymeA(HMG-CoA) reductase inhibitors have been demonstrated to suppress glomerular injuries in various renal diseases. These agents inhibit in vitro proliferation of several cell types, including mesangial cells. This effect indicates the ability to ameliorate mesangioproliferative lesions, independent of the improvement of hypercholesterolemia. On the other hand, it is not clear whether HMG-CoA reductase inhibitors directly regulate extracellular matrix (ECM) accumulation from mesangial cells. Methods In this study, to examine the in vitro effects of simvastatin, an HMG-CoA reductase inhibitor, on mRNA expressions of matrix proteins, growth factors, and matrix turnover proteins, we incubated cultured murine mesangial cells stimulated by fetal calf serum (FCS) with or without simvastatin for 24 hours, and Northern analysis was performed. Results Simvastatin showed a slightly suppressive effect on mRNA expression of type IV collagen and fibronectin and a slightly up-regulative effect on that of type I collagen, whereas mRNA expression of type III collagen was markedly up-regulated. mRNA expression of platelet-derived growth factor (PDGF)-B chain and PDGF receptor β-subunit was suppressed, whereas that of transforming growth factor-β (TGF-β) was not affected by simvastatin. Concerning matrix turnover proteins, simvastatin markedly reduced mRNA expression of plasminogen activator inhibitor-1 (PAI-1) without affecting the expression of tissue-type plasminogen activator (tPA). Conclusion These results suggest type-specific modulation of matrix protein production independent of TGF-β and the suppressive effects of autocrine PDGF by administration of HMG-CoA reductase inhibitors in mesangial cells. Moreover, the beneficial effects of these agents on matrix protein accumulation may be through promoting ECM degradation derived from PAI-1 suppression.
- Published
- 1999
25. A hemodialysis patient with massive ascites, pleural effusion, hypercalcemia and low levels of i-PTH
- Author
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Takahide Kawamura, Kiichi Shirakawa, Eri Muso, Kojiro Makibayashi, Seiji Ohashi, Takahiko Ono, Teruhisa Kawamura, Mari Maeda, Fumiaki Nogaki, Toshio Doi, Shigetake Sasayama, Kenji Kasuno, and Hitoshi Fukushima
- Subjects
medicine.medical_specialty ,Pleural effusion ,business.industry ,medicine.medical_treatment ,Internal medicine ,medicine ,Hemodialysis ,medicine.disease ,business ,Gastroenterology - Published
- 1999
26. Serial renal biopsy findings in a case of POEMS syndrome with recurrent acute renal failure
- Author
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Atsushi Fukatsu, Takahiko Ono, Fumiaki Nogaki, Isoroku Kato, and Atsuko Y. Higashi
- Subjects
Nephrology ,Male ,Vascular Endothelial Growth Factor A ,Pathology ,medicine.medical_specialty ,Physiology ,medicine.medical_treatment ,Biopsy ,Plasma cell dyscrasia ,Ischemia ,urologic and male genital diseases ,Kidney ,Recurrence ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,POEMS syndrome ,Aged ,Peripheral Blood Stem Cell Transplantation ,medicine.diagnostic_test ,business.industry ,Glomerulosclerosis ,Immunosuppression ,Acute Kidney Injury ,medicine.disease ,POEMS Syndrome ,Renal biopsy ,business - Abstract
This report describes a patient presenting with recurrent acute renal failure occurring in the course of POEMS syndrome, a multisystem disease associated with plasma cell dyscrasia. Several combined immunosuppression therapies failed to resolve recurrent acute renal failure; autologous peripheral blood stem cell transplantation was therefore applied. A renal biopsy was performed on each of four occasions when he developed renal dysfunction. The renal biopsy showed typical renal histology of POEMS, membranoproliferative glomerulonephritis-like lesions and narrowing of vessel lumina of various sizes caused by endothelial injury, which progressed to glomerulosclerosis and vessel occlusion. Recurrent acute renal failure might be caused by ischemia due to arterial occlusion. Serum levels of vascular epithelial growth factor (VEGF), which is considered to be a causative factor of endothelial lesions in POEMS syndrome, were not elevated throughout the course of this case.
- Published
- 2010
27. Churg-Strauss syndrome with severe granulomatous angiitis and crescentic glomerulonephritis, which developed during therapy with a leukotriene receptor antagonist
- Author
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Takahiko Ono, Hiroji Nishihara, Takahiro Kanda, Hitoshi Tanio, Chunmo Wu, and Fumiaki Nogaki
- Subjects
Nephrology ,Cyclopropanes ,medicine.medical_specialty ,Physiology ,Prednisolone ,Acetates ,Churg-Strauss Syndrome ,Sulfides ,urologic and male genital diseases ,Gastroenterology ,Antibodies, Antineutrophil Cytoplasmic ,chemistry.chemical_compound ,Physiology (medical) ,Internal medicine ,Medicine ,Eosinophilia ,Humans ,Vasculitis, Central Nervous System ,Montelukast ,Aged ,Creatinine ,Proteinuria ,medicine.diagnostic_test ,Leukotriene receptor ,business.industry ,medicine.disease ,Asthma ,respiratory tract diseases ,Endocrinology ,C-Reactive Protein ,chemistry ,Granuloma ,Quinolines ,Leukotriene Antagonists ,Female ,Renal biopsy ,medicine.symptom ,business ,medicine.drug - Abstract
A 77-year-old Japanese female developed Churg-Strauss syndrome (CSS), showing fever and numbness in bilateral hands. She was being treated for bronchial asthma with combination inhalant of corticosteroid with beta(2)-agonist, and an oral leukotriene receptor antagonist (LTRA), montelukast, for 15 months. She presented fever up to 38°C with microscopic hematuria and proteinuria, serum creatinine level of 0.7 mg/dl, and C-reactive protein of 11 mg/dl. After referral to our hospital, eosinophilia and high myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA) level were observed together with hematuria and proteinuria; renal biopsy examination was performed to clarify the disorder. Renal biopsy specimens showed necrotizing crescent formation, severe granulomatous angiitis in an interlobular artery, and interstitial eosinophilic infiltration. It was noted that nearly intact glomeruli were infiltrated with eosinophils. After treatment with oral prednisolone at initial dose of 40 mg (1 mg/kg body weight), urinary findings rapidly became normal with mild elevation of serum creatinine to 1.5 mg/dl and trace level of serum C-reactive protein in 1 month. Because she was previously treated with montelukast without oral corticosteroid, linkage between CSS and LTRA was highly suspected.
- Published
- 2010
28. [Case of kidney failure with thrombotic microangiopathy lesions in renal biopsy caused by accelerated hypertension in young adult]
- Author
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Atsuko Y, Higashi, Fumiaki, Nogaki, Takahiko, Ono, and Atsushi, Fukatsu
- Subjects
Male ,Young Adult ,Treatment Outcome ,Thrombotic Microangiopathies ,Biopsy ,Hypertension ,Disease Progression ,Humans ,Renal Insufficiency ,Kidney ,Antihypertensive Agents ,Platelet Aggregation Inhibitors - Abstract
A 19-year-old male was admitted to our hospital for the treatment of severe hypertension with renal dysfunction. Two years before admission, his hypertension had been diagnosed as essential hypertension based on a series of examinations when his renal function was not impaired. Visits to his primary physician ended when he developed severe hypertension of 210/140 mmHg, at which time renal dysfunction and serum creatinine of 2.25 mg/dL were discovered. Renin and antidiuretic hormone were slightly elevated, but renal artery stenosis or other abnormalities were not detected by magnetic resonance imaging and computer tomography. After the hypertension was controlled by medication, a renal biopsy was performed to assess renal impairment. Histology demonstrated lesions compatible with thrombotic microangiopathy (TMA) and ischemic lesions, including fibrinoid necrosis, intimal thickening, occlusion in the small arteries, wrinkling and duplication of the glomerular basement membrane with microthrombi, and focal interstitial fibrosis. Renal function ameliorated after the hypertension was controlled. This case suggests that severe and accelerated hypertension can cause TMA with renal impairment even in young people.
- Published
- 2009
29. Sairei-to ameliorates rat peritoneal fibrosis partly through suppression of oxidative stress
- Author
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Takahiko Ono, Kazuhide Uemura, Kozue Kato, Masayuki Kitamoto, Chunmo Wu, Hisayo Kitamura, Tatsuya Morimoto, Akihisa Sugimoto, Fumiaki Nogaki, and Toshiya Takeda
- Subjects
Nephrology ,Male ,medicine.medical_specialty ,Physiology ,Angiogenesis ,Traditional Chinese medicine ,medicine.disease_cause ,Neovascularization ,Internal medicine ,Genetics ,medicine ,Animals ,Rats, Wistar ,Peritoneal Fibrosis ,Flavonoids ,Dose-Response Relationship, Drug ,Neovascularization, Pathologic ,business.industry ,Superoxide Dismutase ,General Medicine ,Rats ,Platelet Endothelial Cell Adhesion Molecule-1 ,Oxidative Stress ,Endocrinology ,Sairei to ,medicine.symptom ,business ,Oxidative stress ,Drugs, Chinese Herbal - Abstract
Background: Sairei-to is a herbal prescription originating from traditional Chinese medicine. We conducted an experimental study on rat peritoneal fibrosis to clarify the suppressive mechanisms of sairei-to. Methods: Wistar rats were intraperitoneally injected with chlorhexidine gluconate (CG) every day. Peritoneal specimens were collected after 28 days of CG injection and oral administration of sairei-to. Macrophage infiltration, extracellular matrix accumulation, and angiogenesis were evaluated by immunostaining for ED-1, fibronectin, and CD-31, respectively. To observe oxidative stress in the tissue, 4-hydroxy-2-noneal (HNE) accumulation and plasma levels of superoxide dismutase (SOD) activity were detected. As a candidate of antioxidative components in sairei-to, plasma levels of baicalin were determined by high-performance liquid chromatography. Results: Compared with the disease control group, serum total protein levels were significantly recovered in the sairei-to treatment group. Thickness of the submesothelial compact zone, trichrome-stained area, ED-1-positive cells, fibronectin-staining area, and HNE accumulation were suppressed in the treatment group. Concurrently, decreased plasma levels of SOD activity were recovered by sairei-to treatment. Increased CD-31-positive vessel number and area were also suppressed in the sairei-to group. Baicalin was detected in the plasma samples of the sairei-to group at 0.29 ± 0.11 µg/ml (mean±SEM). Conclusion: These results suggest that sairei-to ameliorates peritoneal fibrosis, partly through suppressing oxidative stress and macrophage infiltration.
- Published
- 2009
30. Tissue factor and factor v involvement in rat peritoneal fibrosis
- Author
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Hiroki, Saito, Masayuki, Kitamoto, Kozue, Kato, Ning, Liu, Hisayo, Kitamura, Kazuhide, Uemura, Fumiaki, Nogaki, Toshiya, Takeda, Noriko, Mori, and Takahiko, Ono
- Subjects
Male ,Chlorhexidine ,Factor V ,Fibrosis ,Extracellular Matrix ,Rats ,Thromboplastin ,Disease Models, Animal ,Fondaparinux ,Polysaccharides ,Factor Xa ,Macrophages, Peritoneal ,Animals ,Peritoneum ,Rats, Wistar ,Factor Xa Inhibitors - Abstract
Fibrin deposition on the peritoneum has been frequently observed in peritoneal fibrosis induced by long-term peritoneal dialysis. The present study was conducted to clarify the contribution of factor Xa through tissue factor and factor V expression in peritoneal fibrosis.Wistar rats were intraperitoneally injected with chlorhexidine gluconate (CG) every day. For the interventional study, the factor Xa inhibitor fondaparinux was subcutaneously administered. After 28 days of CG injection, peritoneal specimens were examined by immunohistochemical analyses and in situ hybridization.The peritoneal submesothelial compact zone was observed to be markedly thicker in the CG-injected groups than in the normal group, and that thickness was dose dependent. Immunohistochemical study revealed massive fibrin, fibronectin, and type IV collagen depositions in the CG-injected groups, which was markedly higher than that in the normal group. Macrophage infiltration and staining for tissue factor, factor V, factor X, and protease-activated receptor-2 were intense in the CG-injected groups and negative/trace in the normal group. Tissue factor and factor V mRNAs were abundant in cells in the thickened peritoneum. A double-labeling experiment revealed that tissue factor was observed mainly in macrophages, and factor V was abundantly distributed in the fibrotic tissue together with macrophages. Fondaparinux treatment decreased the thickness of submesothelial fibrotic tissue, and size and number of CD31-positive vessels.These results suggest that expression of tissue factor and factor V in infiltrated macrophages, together with factor X deposition, may progress angiogenesis and accumulation of extracellular matrix components, partly via profibrotic and procoagulant mechanisms in the peritoneum after inflammatory stimulation.
- Published
- 2009
31. Roles of coagulation pathway and factor Xa in rat mesangioproliferative glomerulonephritis
- Author
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Misa Tanaka, Toru Kita, Fumiaki Nogaki, Hidenori Arai, Ikei Kobayashi, Takahiko Ono, Atsushi Fukatsu, Keiko Nomura, Takamichi Hasegawa, Ning Liu, and Kojiro Nagai
- Subjects
Male ,medicine.medical_specialty ,Time Factors ,medicine.drug_mechanism_of_action ,Glomerulonephritis, Membranoproliferative ,Factor Xa Inhibitor ,Blotting, Western ,Biology ,Naphthalenes ,Pathology and Forensic Medicine ,Proinflammatory cytokine ,Tissue factor ,chemistry.chemical_compound ,Internal medicine ,medicine ,Animals ,Receptor, PAR-2 ,Rats, Wistar ,Molecular Biology ,Blood Coagulation ,Mitogen-Activated Protein Kinase 1 ,Analysis of Variance ,Mitogen-Activated Protein Kinase 3 ,Factor X ,Factor V ,Antibodies, Monoclonal ,Glomerulonephritis ,Cell Biology ,medicine.disease ,Immunohistochemistry ,Rats ,Proteinuria ,Endocrinology ,Coagulation ,chemistry ,Factor Xa ,biology.protein ,Mesangial proliferative glomerulonephritis ,Propionates ,Factor Xa Inhibitors - Abstract
Tissue factor initiates the extrinsic coagulation pathway by activating coagulation factor X to factor Xa, and factor V is a cofactor for the prothrombin activation by factor Xa. As factor Xa is known to promote the proliferation of mesangial cells in culture, the roles of the coagulation pathway and factor Xa were studied in an animal model of mesangioproliferative glomerulonephritis (MsPGN). MsPGN was induced in Wistar rats by an intravenous injection of anti-Thy 1.1 monoclonal antibody, OX-7. To clarify the role of factor Xa in MsPGN, a specific factor Xa inhibitor, DX-9065a, was injected intravenously at 2.5 or 10 mg/kg at the same time as OX-7, and kidney involvement was assessed by immunohistological analyses. We also examined p44/42 mitogen-activated protein (MAP) kinase activation. Time-course study revealed that expressions of tissue factor, factor V, and protease-activated receptor 2 (PAR2) were peaked on day 3, followed by factor X accumulation and mesangial proliferation. DX-9065a treatment significantly ameliorated proteinuria in a dose-dependent manner on day 8. Histological analyses showed a significant reduction in the size of glomeruli, the total number of glomerular cells, and crescent formation by DX-9065a treatment. Macrophage infiltration, which was rapidly observed on day 1 in disease control rats was not inhibited on days 1-3 by DX-9065a treatment, however it was suppressed on days 5-8. The deposition of fibrin, the number of PCNA-positive cells, and phosphorylation of p44/42 MAP kinase were markedly increased in the disease control group, whereas they were significantly reduced in the treatment group. Tissue factor and factor V induction may accelerate MsPGN through the activation and accumulation of factor X via proinflammatory and procoagulant mechanisms, and the inhibition of factor Xa would be a promising method to regulate the disease process.
- Published
- 2006
32. Chromosomal mapping of hyperserum IgA and glomerular IgA deposition in a high IgA (HIGA) strain of DdY mice
- Author
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Eri Muso, Haruyoshi Yoshida, Emi Oida, Takahiko Ono, Tadao Serikawa, Tadashi Kamata, Shigeki Miyawaki, Toru Kita, Sachiko Tahara, Fumiaki Nogaki, Ikei Kobayashi, Keiko Nomura, and Katsuo Suyama
- Subjects
Immunoglobulin A ,Renal glomerulus ,Kidney Glomerulus ,Quantitative Trait Loci ,Locus (genetics) ,Quantitative trait locus ,Nephropathy ,Mice ,Gene mapping ,Species Specificity ,medicine ,Animals ,HIGA mice ,Mice, Inbred BALB C ,biology ,Chromosome Mapping ,Glomerulonephritis ,Glomerulonephritis, IGA ,IgA nephropathy ,medicine.disease ,Mice, Mutant Strains ,Genetic marker ,Nephrology ,Immunology ,biology.protein ,Female ,Microsatellite Repeats - Abstract
Chromosomal mapping of hyperserum IgA and glomerular IgA deposition in a high IgA (HIGA) strain of DdY mice. Background The high IgA (HIGA) strain of ddY mice is an inbred model of IgA nephropathy (IgAN), established by selective mating of outbred ddY mice. HIGA mice show high levels of serum IgA and glomerulonephritis with mesangial IgA deposition. To identify the genetic loci responsible for hyperserum IgA and glomerular IgA deposition in this strain, quantitative trait loci analysis was carried out. Methods By crossing HIGA with BALB/c mice, 244 F2 generations were produced. Serum IgA levels and glomerular IgA deposition were examined at 40 weeks of age. Genetic markers were typed at 105 microsatellites and the quantitative trait loci of hyperserum IgA and glomerular IgA deposition were confirmed using Map Manager QTX software. Results Two significant quantitative trait loci of hyperserum IgA were identified on chromosome 2 [logarithm of odds (LOD) = 5.01] and chromsome 4 (LOD = 4.45), and a suggestive quantitative trait locus of hyperserum IgA was located on chromosome 1 (LOD = 3.49). On chromosome 15, a significant quantitative trait locus of glomerular IgA deposition was identified (LOD = 4.40) without the hyperserum IgA locus. Serum IgA level was weakly correlated with the intensity of glomerular IgA in 244 F2 mice; however, the quantitative trait loci of hyperserum IgA were not significantly associated with glomerular IgA deposition. Conclusion These findings indicate that, in HIGA mice, glomerular IgA deposition is mainly regulated by a quantitative trait locus on chromosome 15, and hyperserum IgA synergistically but weakly affect glomerular IgA deposition. The immune disturbance similar to IgAN was revealed to be under multigenic control in HIGA mice.
- Published
- 2005
33. Clinical efficacy of intravenous immunoglobulin for patients with MPO-ANCA-associated rapidly progressive glomerulonephritis
- Author
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Toshiko Ito-Ihara, Takahiko Ono, Toru Kita, Fumiaki Nogaki, Kazuo Suzuki, Mari Tanaka, Atsushi Fukatsu, Katsuo Suyama, Satomi Yonemoto, and Eri Muso
- Subjects
Male ,Prednisolone ,urologic and male genital diseases ,Immunoglobulin E ,Kidney ,Antibodies, Antineutrophil Cytoplasmic ,Leukocyte Count ,Glomerulonephritis ,immune system diseases ,medicine ,Rapidly progressive glomerulonephritis ,Humans ,Immunologic Factors ,cardiovascular diseases ,skin and connective tissue diseases ,Cyclophosphamide ,Glucocorticoids ,Anti-neutrophil cytoplasmic antibody ,Aged ,Peroxidase ,Aged, 80 and over ,biology ,business.industry ,Tumor Necrosis Factor-alpha ,Remission Induction ,Immunoglobulins, Intravenous ,General Medicine ,Middle Aged ,medicine.disease ,Creatine ,respiratory tract diseases ,C-Reactive Protein ,Nephrology ,Myeloperoxidase ,Immunology ,biology.protein ,Disease Progression ,Cytokines ,Drug Therapy, Combination ,Female ,Antibody ,business ,Immunosuppressive Agents ,Kidney disease ,medicine.drug - Abstract
Background: To determinewhether intravenous immunoglobulin (IVIg) cancontrol disease activity in patients with myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-associated rapidly progressive glomerulonephritis (RPGN). Methods: Twelve patients with serologically and histologically confirmed MPO-ANCA-associated RPGN (7 men, 5 women; mean age 71 ± 3 years) received IVIg (400 mg/kg/day) alone for 5 days. The effects of IVIg were evaluated by white blood cell counts, serum C-reactive protein levels, Birmingham Vasculitis Activity Score, rate of change in reciprocal creatinine (1/Cre), and plasma tumor necrosis factor-α levels after IVIg administration. Corticosteroids with or without cyclophosphamide were commenced after IVIg. Results:After IVIg treatment, a significant decrease was observed in white blood cell count (p < 0.05), C-reactive protein values (p < 0.001), and Birmingham Vasculitis Activity Score (p < 0.001) concomitant with the amelioration of systemic symptoms. The rate of change in 1/Cre significantly improved (p < 0.05). Plasma tumor necrosis factor-α levels that were significantly elevated in patients before IVIg compared with normal controls (p < 0.0001), rapidly declined after IVIg with a significant reduction(p < 0.05). Three months post-treatment with IVIg, all patients showed improvement of disease without serious infectious complications. Conclusion: IVIg is a potential component of remission induction therapy for patients with MPO-ANCA-associated RPGN.
- Published
- 2005
34. The Na+-excreting efficacy of indapamide in combination with furosemide in massive edema
- Author
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Keiko Nomura, Takahiko Ono, Kazuhide Uemura, Misa Tanaka, Eri Muso, Fumiaki Nogaki, Emi Oida, Atsushi Fukatsu, Masatomo Yashiro, and Takeshi Kimura
- Subjects
Adult ,Male ,medicine.medical_specialty ,Nephrotic Syndrome ,Physiology ,medicine.drug_class ,medicine.medical_treatment ,Urology ,Diuresis ,Excretion ,Furosemide ,Physiology (medical) ,Internal medicine ,Edema ,medicine ,Humans ,Diuretics ,Thiazide ,Aged ,Aged, 80 and over ,business.industry ,Indapamide ,Sodium ,Loop diuretic ,Middle Aged ,Endocrinology ,Treatment Outcome ,Nephrology ,Drug Therapy, Combination ,Female ,Diuretic ,medicine.symptom ,business ,medicine.drug - Abstract
Massive systemic edema is often observed in patients with severe nephrotic syndrome, including diabetic nephropathy. Although furosemide, a loop diuretic, is often administered to these patients, some patients do not respond to this treatment, still showing massive edema.The efficacy of indapamide which has a thiazide-like effect on distal convoluted tubules in combination with furosemide, was evaluated in eight patients with massive edema, in regard to both Na+ excretion and diuresis. Indapamide 2 mg was administered once a day, in the morning, to patients in whom it was considered that furosemide treatment of 40-120 mg a day for 1 week was ineffective.Urinary Na+ excretion was markedly increased, from 83.7 +/- 82.2 mEq/day to 140.7 +/- 33.8 mEq/day after 1 week of the combination therapy compared with furosemide alone (P0.01); urine volume was also increased, from 1070 +/- 230 ml to 1359 +/- 296 ml after 1 week of the combination therapy (P0.05). In this context, body weight was significantly decreased, from 57.2 +/- 12.3 kg to 53.4 +/- 12.8 kg, after the combination therapy (P = 0.01). Indapamide in combination with furosemide was well tolerated, and no significant changes in serum levels of creatinine and potassium were observed.This combination therapy appears to be effective in patients with massive edema, as it increased diuresis, and achieved potent Na+ excretion.
- Published
- 2004
35. Role of mesangial Factor V expression in crescent formation in rat experimental mesangioproliferative glomerulonephritis
- Author
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Takahiko Ono, Keiko Nomura, Ning Liu, Fujio Shimizu, Toshiaki Makino, Eri Muso, Gisho Honda, Toru Kita, and Fumiaki Nogaki
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Time Factors ,Glomerulonephritis, Membranoproliferative ,Immunoelectron microscopy ,urologic and male genital diseases ,Fibrin ,Antibodies ,Basement Membrane ,Pathology and Forensic Medicine ,Thrombin ,medicine ,Animals ,RNA, Messenger ,Rats, Wistar ,Microscopy, Immunoelectron ,biology ,urogenital system ,Chemistry ,Reverse Transcriptase Polymerase Chain Reaction ,Glomerular basement membrane ,Factor V ,Glomerulonephritis ,medicine.disease ,female genital diseases and pregnancy complications ,Glomerular Mesangium ,Rats ,medicine.anatomical_structure ,Mesangiolysis ,Mesangium ,Immunology ,biology.protein ,Mesangial proliferative glomerulonephritis ,Rabbits ,medicine.drug - Abstract
It has been suggested that fibrin deposition participates in the development of crescents in active glomerulonephritis (GN). In human IgA nephropathy, which is a common form of mesangioproliferative GN (MsPGN), crescent formation is occasionally observed in active disease, leading to end-stage renal failure. Factor V is a membrane-bound potent cofactor for the conversion of prothrombin to thrombin by Factor Xa. An in vivo study was conducted to clarify the contribution of local fibrin production to crescent formation in MsPGN through mesangial Factor V expression. Wistar rats were injected intravenously with rabbit anti-rat thymocyte serum. Three days after injection, mesangiolysis with intense mesangial Factor V expression was observed and immunoelectron microscopy revealed fibrin localization in mesangiolytic lesions, which had spread into the glomerular basement membrane adjacent to the destroyed mesangium, accompanied by clots in Bowman's space. Marked glomerular fibrin deposition, together with its deposition in Bowman's space and cellular crescent formation, was noted with mesangial proliferation on day 8. Specific bands for Factor V mRNA were also detected from isolated glomeruli. Fibrin deposition and cellular crescent formation were significantly suppressed by treatment with anti-Factor V antibody. These results suggest that local fibrin production, following mesangial Factor V expression, together with mesangiolysis that spreads to the adjacent glomerular basement membrane, plays a role in crescent formation in MsPGN.
- Published
- 2004
36. Coagulation in the mesangial area promotes ECM accumulation through factor V expression in MsPGN in rats
- Author
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Ning Liu, Hitoshi Kusano, Gisho Honda, Katsuo Suyama, Toru Kita, Takahiko Ono, Fumiaki Nogaki, Eri Muso, and Toshiaki Makino
- Subjects
Collagen Type IV ,Male ,medicine.medical_specialty ,Physiology ,Nitric Oxide Synthase Type II ,Immediate-Early Proteins ,Tissue factor ,chemistry.chemical_compound ,Thrombin ,Glomerulonephritis ,Transforming Growth Factor beta ,Internal medicine ,Proliferating Cell Nuclear Antigen ,medicine ,Animals ,Humans ,RNA, Messenger ,Antigens ,Rats, Wistar ,Blood Coagulation ,biology ,Mesangial cell ,Factor X ,Macrophages ,Factor V ,Connective Tissue Growth Factor ,Blotting, Northern ,Actins ,Extracellular Matrix ,Fibronectins ,Glomerular Mesangium ,Rats ,CTGF ,Fibronectin ,Endocrinology ,chemistry ,biology.protein ,Prothrombin Time ,Intercellular Signaling Peptides and Proteins ,Nitric Oxide Synthase ,medicine.drug ,Transforming growth factor - Abstract
It is well known that tissue factor starts the extrinsic coagulation pathway, which activates factor X to Xa, and factor V is a membrane-bound potent cofactor for the terminating stage of prothrombin activation by factor Xa. In a previous in vitro study, factor V was induced in cultured mesangial cells by inflammatory stimulation and increased expression of factor V promoted fibrin generation on the cultured mesangial cell surface. We report that extracellular matrix (ECM) accumulation is increased in association with coagulation in the mesangial area through factor V expression in mesangioproliferative glomerulonephritis (MsPGN). Wistar rats were intravenously injected with rabbit anti-rat thymocyte serum accompanied with or without simultaneous injection of rabbit anti-factor V antibody. Time course study in immunohistochemistry revealed that factor V expression was prominent on day 3 and fibrin-related antigen (FRA) deposition, then ECM accumulation, followed from day 3 to day 8. Massive fibronectin depositions and transforming growth factor (TGF)-β expression were also noted in glomeruli from the disease control group, markedly higher than those in the normal group, and these depositions and expressions were significantly decreased in the anti-factor V neutralizing antibody-injected group. Northern blot analysis revealed that factor V mRNA expression was prominent on day 3 and was weak on day 8. Double-labeling experiments revealed the frequent colocalization of α-smooth muscle actin with factor V, FRA, and fibronectin in the same mesangial areas of glomeruli. TGF-β, connective tissue growth factor (CTGF), collagen type IV, and fibronectin mRNA were upregulated in the disease control group, and anti-factor V-neutralizing antibody injection suppressed these mRNA expressions in glomeruli. The present results suggest that ECM components accumulation may progress in accordance with coagulation in the mesangial area through mesangial factor V expression and upregulated expression of TGF-β and CTGF in MsPGN.
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- 2004
37. Glomerulonephritis induced by methicillin-resistant Staphylococcus aureus infection that progressed during puerperal period
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Toshiko Ito-Ihara, Atsushi Fukatsu, Takahiko Ono, Eri Muso, Motomu Hashimoto, Ning Liu, Toru Kita, Fumiaki Nogaki, Emi Oida, Keiko Nomura, and Misa Tanaka
- Subjects
Nephrology ,Adult ,medicine.medical_specialty ,Staphylococcus aureus ,Endocapillary proliferative glomerulonephritis ,Physiology ,medicine.disease_cause ,Anasarca ,Gastroenterology ,Glomerulonephritis ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,medicine.diagnostic_test ,business.industry ,Staphylococcal Infections ,medicine.disease ,Methicillin-resistant Staphylococcus aureus ,Immunology ,Puerperal Infection ,Female ,Methicillin Resistance ,Renal biopsy ,medicine.symptom ,business ,Nephritis ,Nephrotic syndrome - Abstract
A 28-year-old Japanese woman developed fever, leg edema, purpura, and abdominal pain during the puerperal period, showing nephrotic syndrome with microscopic hematuria. At first she was thought to have Henoch-Shonlein purpura nephritis and was given steroids at another hospital. Because anasarca and massive urinary protein excretion developed, she was referred to our hospital. Renal biopsy specimens showed endocapillary proliferative glomerulonephritis with massive IgA and C3d deposition along the capillary loops and in the mesangium. A bacteriological study detected methicillin-resistant Staphylococcus aureus (MRSA) in cultures of vaginal secretions, urine, stool, and pharyngeal mucus samples. Based on the diagnosis of MRSA nephritis, anti-MRSA therapy with antibiotics was started, and MRSA became negative for each culture, and urinary protein decreased. Two months after the first renal biopsy, a second renal biopsy was performed, which revealed feeble endocapillary proliferation with mild IgA and C3d deposition in the mesangium. This case showed that the delivery procedure can cause MRSA nephritis after MRSA infection, and that steroid therapy should be avoided in the early phase of this type of nephritis.
- Published
- 2003
38. Heminephrectomy causes the progression of glomerulosclerosis and apoptosis in high IgA strain ddY mice
- Author
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Takahiko Ono, Toshiya Takeda, Keiko Nomura, Shigeki Miyawaki, Shigetake Sasayama, Hitoshi Kusano, Fumiaki Nogaki, Eri Muso, Haruyoshi Yoshida, and Akira Matsumori
- Subjects
Immunoglobulin A ,medicine.medical_specialty ,Renal cortex ,Apoptosis ,Nephron ,urologic and male genital diseases ,Kidney ,Nephrectomy ,Nephropathy ,Renin-Angiotensin System ,Mice ,Transforming Growth Factor beta ,Internal medicine ,medicine ,Animals ,Humans ,Extracellular Matrix Proteins ,biology ,business.industry ,Glomerulosclerosis, Focal Segmental ,Kidney metabolism ,Glomerulosclerosis ,Glomerulonephritis ,Glomerulonephritis, IGA ,Transforming growth factor beta ,medicine.disease ,Disease Models, Animal ,Endocrinology ,medicine.anatomical_structure ,biology.protein ,business - Abstract
Background: The reduction in nephrons in IgA nephropathy is critical to the prognosis of this disease. However, the immunopathological mechanism of the modifications seen in glomerular lesions is not clear. We thus investigated the influence of nephron reduction by heminephrectomy on renal lesions in a high immunoglobulin A inbred strain of ddY mouse (HIGA mouse), which shows progressive mesangial sclerosis with elevated renal expression of transforming growth factor (TGF)-β. Methods: Five-week-old HIGA mice were heminephrectomized (Nx), and were evaluated in comparison with a sham-operated group (S) at 40 weeks old. Histological findings, immunoglobulin depositions (IgG, IgA, and IgM), and expressions of cytokine and extracellular matrix proteins (TGF-β, fibronectin, collagen type I and IV) were analysed. PCNA and TUNEL stainings were performed with electron microscopic detection of apoptosis. Tissue renin-angiotensin systems (RAS) were also investigated by real-time quantitative RT-PCR. Results: In the Nx group, the glomerular tuft area and ratio of mesangial matrix area per tuft were significantly increased, and the glomerular cell count per tuft area was significantly decreased. Glomerular immunoglobulin deposits of IgG, IgA, and IgM in Nx were all significantly expanded in the paramesangium. The glomerular expressions of TGF-β and the extracellular matrix proteins were significantly increased in Nx mice. In contrast to the significant decrease of PCNA-positive cells, TUNEL-positive cells were significantly increased in Nx. Angiotensin-converting enzyme (ACE) was significantly increased in the renal cortex of Nx. Conclusion: Simple heminephrectomy, other than 5/6 renal ablation, of HIGA mice may be a potential model for research into the progressive glomerulosclerosis of human IgA nephropathy. The pathological role of apoptosis is apparently involved in these disease processes, possibly through upregulated RAS.
- Published
- 2002
39. Correlation between the severity of clinicopathological parameters and whole blood interferon-alpha production capacity in active phase IgA nephropathy patients
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Takahiko Ono, Fumiaki Nogaki, Kiichi Shirakawa, Kazuko Uno, Eri Muso, Takahide Kawamura, Miwa Yoshimoto, Tsunatarou Kishida, Mari Maeda, and Shigetake Sasayama
- Subjects
Adult ,Male ,business.industry ,Macrophages ,Statistics as Topic ,Alpha interferon ,Interferon-alpha ,Glomerulonephritis ,Glomerulonephritis, IGA ,Middle Aged ,medicine.disease ,Kidney ,Nephropathy ,Immune system ,Immunopathology ,Immunology ,Medicine ,Humans ,Female ,business ,Interferon alfa ,Kidney disease ,medicine.drug ,Whole blood - Abstract
Background/Aims: Patients with IgA nephropathy (IgA-N) are thought to have immune system disorders that frequently result in high serum IgA levels and a relatively high susceptibility to upper respiratory infections. Aims: To clarify the influence of the specific immune response of IgA-N patients on the clinicopathological features of the disease, we measured the whole-blood-producing capacity of interferon-α (IFNα-PC). We then compared these findings with clinical and histopathological parameters, including tissue macrophage infiltration, during both histologically active and latent phases. Patients and Methods: Fifty-one inpatients with IgA-N and 70 healthy controls were examined. According to the histological findings, 32 patients had disease in the active phase (AP), and 19 were in the latent phase (LP). Results: In AP patients, IFNα-PC showed positive correlations to serum creatinine, blood urea nitrogen, serum β2-microglobulin (s-β2MG), urinary total protein (U-TP), and urinary β2MG, in addition to the number of infiltrated macrophages per area of interstitium. In LP patients, negative correlations were shown between IFNα-PC and s-β2MG, U-TP, and U-N-acetyl-β-D-glucosaminidase. Conclusion: A significant positive relationship exists between IFNα-PC and the clinicopathological parameters of deteriorated renal lesions in the AP but not in the LP. Thus, the immune status influencing the functional damage may differ between these two phase.
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- 2001
40. Mesangial factor V expression colocalized with fibrin deposition in IgA nephropathy
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Tadashi Kamata, Kiichi Shirakawa, Mari Maeda, Katsuo Suyama, Shigetake Sasayama, Eri Muso, Fumiaki Nogaki, Atsushi Oyama, Takahide Kawamura, Ning Liu, and Takahiko Ono
- Subjects
Adult ,Male ,medicine.medical_specialty ,Plasmin ,Immunoelectron microscopy ,Biopsy ,Fibrin ,Immunoenzyme Techniques ,Thrombin ,renal biopsy ,Internal medicine ,medicine ,Humans ,Microscopy, Immunoelectron ,biology ,Factor V ,Glomerulonephritis, IGA ,inflammatory response ,Middle Aged ,medicine.disease ,Molecular biology ,Actins ,Glomerular Mesangium ,Endocrinology ,Cross-Linking Reagents ,Coagulation ,Mesangium ,Nephrology ,α-smooth muscle actin ,biology.protein ,cross-linked fibrin ,Mesangial proliferative glomerulonephritis ,Female ,glomerulonephritis ,medicine.drug - Abstract
Mesangial factor V expression colocalized with fibrin deposition in IgA nephropathy.BackgroundFactor V in its active form (Va) plays a key role at the termination of the intrinsic coagulation pathway, serving as a membrane-bound cofactor for the conversion of prothrombin to thrombin by factor Xa. Cross-linked fibrin (XFb) is often observed in mesangial areas in active types of human glomerulonephritis. In this study, to clarify contribution of factor V in intramesangial coagulation, mesangial factor V expression and its relationship to mesangial proliferation and fibrin deposition in IgA nephropathy (IgAN) were investigated.MethodsTwenty-two patients with IgAN were studied. XFb was detected in renal biopsy specimens using anti–d-dimer antibody combined with plasmin exposure, and factor V was detected with rabbit antibody against human factor V. Double-labeling immunohistochemistry was used to investigate the relationship of the glomerular distribution of factor V to XFb. The relationship of factor V staining to the activity index or XFb deposition was evaluated. The expression of factor V mRNA was assessed by in situ hybridization in relationship to the antigen staining of α-smooth muscle actin (α-SMA). The ultrastructural distribution of factor V in glomeruli was studied by immunoelectron microscopy.ResultsXFb and factor V were observed in the mesangium and along capillary loops in seven and nine specimens, respectively. Factor V had intense, frequent expression in the proliferating and necrotizing areas, showing a significant relationship to XFb (P < 0.05). Furthermore, XFb deposition and factor V expression were markedly correlated with disease activity (P = 0.005 and P = 0.008, respectively). By double-labeling experiments, XFb and factor V were often seen colocalized in mesangial areas of the glomeruli, which showed necrotizing lesions and/or intense cellular proliferation. By in situ hybridization, factor V mRNA was detected mainly in the mesangial cells, which were positive for α-SMA, and partly in the endothelial cells. By immunoelectron microscopy, factor V presence was confirmed in the mesangium and endothelium.ConclusionThe present findings suggest that factor V is strongly expressed in mesangial cells in active IgAN accompanied with mesangial proliferation and may exert procoagulant activity, leading to intramesangial coagulation.
- Published
- 2000
41. Interleukin 12 induces crescentic glomerular lesions in a high IgA strain of ddY mice, independently of changes in IgA deposition
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Tadashi Kamata, Shigeki Miyawaki, Kiichi Shirakawa, Fumiaki Nogaki, Hitoshi Kusano, Takahiko Ono, Eri Muso, Shigetake Sasayama, Atsushi Oyama, Ikei Kobayashi, and Haruyoshi Yoshida
- Subjects
CD4-Positive T-Lymphocytes ,medicine.medical_treatment ,T cell ,Kidney Glomerulus ,Fluorescent Antibody Technique ,Kidney ,Nephropathy ,Mice ,Immune system ,Transforming Growth Factor beta ,medicine ,Animals ,RNA, Messenger ,Transplantation ,Mice, Inbred BALB C ,business.industry ,Macrophages ,Interleukin ,Glomerulonephritis ,medicine.disease ,Interleukin-12 ,Immunoglobulin A ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Cytokine ,Nephrology ,Immune System ,Immunology ,Interleukin 12 ,Kidney Diseases ,business ,Spleen - Abstract
BACKGROUND Our recently established high immunoglobulin (Ig)A inbred strain (HIGA) of ddY mice showed constantly high serum IgA levels, progressive mesangial sclerosis accompanied by IgA deposits, and elevated renal expression of transforming growth factor (TGF)-beta, mimicking IgA nephropathy. In the present study, we assessed the role of the immune system, especially of T cells, in this strain. METHODS The in vitro production of interferon (IFN)-gamma, interleukin (IL)-4 and TGF-beta1 by splenic CD4+ T cells was assessed in HIGA mice at 14 and 28 weeks of age by comparison with age-matched C57BL/6 and BALB/c mice, T-helper (Th) 1, and Th2 prone controls respectively. Moreover, recombinant murine IL-12 was administered intraperitoneally to HIGA mice and serum IgA and renal lesions were analysed. RESULTS The production of IFN-gamma by splenic CD4+ T cells was markedly upregulated in HIGA mice at both ages as compared with age-matched C57BL/6 and BALB/c mice. Although splenic CD4+ T cells from HIGA mice produced less IL-4 than those from BALB/c mice at both ages, the former produced significantly more IL-4 with age, which contrasted with the age-associated decrease in the latter. Moreover, TGF-beta1 production of these cells in HIGA mice was equal to or greater than that in the two groups of control mice at both ages. Daily intraperitoneal administration of IL-12 for 1 week significantly enhanced crescent formation with glomerular macrophage accumulation and interstitial cell infiltration, whereas it reduced the serum IgA level. CONCLUSIONS In HIGA mice, Th1 is markedly upregulated from a young age and there is an age-associated Th2 increase with TGF-beta1 upregulation in helper T cells. The former may be related to the exacerbation of inflammatory renal lesions on IL-12 administration, while the latter may contribute to increased IgA production, leading to glomerular IgA deposition and progressive glomerulosclerosis in HIGA mice. The pathogenic role of T cell function and fluctuation of these subsets, especially the Th1/Th2 balance, is crucial to the immunopathological phenotype of the renal lesions in HIGA mice.
- Published
- 2000
42. Increased frequency of surface IgA-positive plasma cells in the intestinal lamina propria and decreased IgA excretion in hyper IgA (HIGA) mice, a murine model of IgA nephropathy with hyperserum IgA
- Author
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Tadashi Kamata, Fumiaki Nogaki, Ikei Kobayashi, Sidonia Fagarasan, Eri Muso, Koichi Ikuta, Haruyoshi Yoshida, Shigeki Miyawaki, Toshio Sakiyama, Tasuku Honjo, and Shigetake Sasayama
- Subjects
medicine.medical_specialty ,Immunology ,Plasma Cells ,Receptors, Antigen, B-Cell ,Biology ,CD19 ,Nephropathy ,Excretion ,Feces ,Mice ,Antigen ,Species Specificity ,Internal medicine ,medicine ,Immunology and Allergy ,Animals ,Secretion ,Lymphocyte Count ,RNA, Messenger ,Intestinal Mucosa ,Receptor ,Kidney ,Mice, Inbred BALB C ,Cell Cycle ,Receptors, Polymeric Immunoglobulin ,Glomerulonephritis ,Glomerulonephritis, IGA ,medicine.disease ,Lymphocyte Subsets ,Immunoglobulin A ,Mice, Inbred C57BL ,Endocrinology ,medicine.anatomical_structure ,biology.protein ,Leukocyte Common Antigens ,Female - Abstract
Because abnormalities of mucosal immunity have been suggested in human IgA nephropathy, we examined the involvement of mucosal immunity in IgA deposition to the kidney in hyper IgA (HIGA) mice, which was established as a mouse model for human IgA nephropathy with hyperserum IgA. The number of surface IgA+B220− lymphocytes in the intestinal lamina propria (LP) of HIGA mice increased 2.7-fold at 30 wk of age as compared with those at 10 wk of age, whereas normal mice did not show such increase. The surface IgA+B220− LP lymphocytes spontaneously secreted IgA in culture. Morphological studies showed that the surface IgA+B220− lymphocytes of murine intestinal LP are identical with plasma cells (PCs). About 20% of IgA+B220− PC in LP expressed both Mac-1 and CD19, suggesting that they may derive from peritoneal B-1 cells. Cell cycle study on intestinal IgA-PCs using bromodeoxyuridine revealed no difference between HIGA mice and normal mice, suggesting that the high frequency of IgA-producing PCs in HIGA mice is not due to enhanced proliferation or prolonged survival of IgA-producing PCs in LP. In addition, IgA secretion into the gut lumen of HIGA mice decreased drastically (to one forth) with aging. These data suggest that the increased number of intestinal IgA-producing PCs and the down-regulation of IgA excretion into the intestinal lumen might synergistically contribute to the hyperserum IgA in HIGA mice and resultant IgA deposition to the kidney.
- Published
- 2000
43. Mechanism of B1 cell differentiation and migration in GALT
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Koichi Ikuta, Tasuku Honjo, Reiko Shinkura, Fumiaki Nogaki, Sidonia Fagarasan, and Tadashi Kamata
- Subjects
Lymphatic system ,Mechanism (biology) ,Cellular differentiation ,Immunology ,Biology ,Cell biology - Published
- 2000
44. Subject Index Vol. 88, 2001
- Author
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Hiroko Yamasaki, David A. Sampson, Aydan Ikinciogullari, Janice Green, Gavin J. Becker, Cüneyt Ensari, Hassane Izzedine, Hiroshi Shibahara, Yoshihiko Kawarada, Yuji Nagura, Masahiro Hiraoka, F. Grases, Kazuo Fujisawa, Seiki Ito, Chikahide Hori, Katsuo Suyama, Mitsufumi Mayumi, Yusei Ohshima, D. Grekas, Norishige Yoshikawa, Tim D. Hewitson, Kazuo Tsuzuki, Muhammad Salmanullah, Masatomo Yashiro, Tadashi Kamata, Nigel Wardle, Takuma Narita, O. Söhnel, Z. Wang, Koichi Matsumoto, Adrian Williams, Michael K. Hise, Toshiko Yaginuma, Hiroki Fujita, Hirofumi Makino, Yoshihiko Onishi, Kathleen M. Nicholls, D. Stratakis, Eri Muso, Olivier Pajot, Sydney Benchetrit, Terumi Higuchi, Gilbert Deray, Toshihiro Sugiyama, Shigetake Sasayama, Masami Kawagoe, Jacques Bernheim, Hiroyuki Ohi, Eugenia Pedagogos, Donald Richardson, A. Makedou, H. Schiffl, Hélène Beaufils, Erina Okawa, Yoshiyuki Yoshida, A. Tourkantonis, Richard B. Parsons, Mariko Tamano, Arzu Ensari, E. Kassimatis, Kazuyoshi Okada, Mesiha Ekim, Shigeki Miyawaki, Fumiaki Nogaki, Chihiro Hagi, Kazuo Yoshioka, G. Bamichas, Sahare Fongoro, Haruyoshi Yoshida, Atsushi Oyama, Kyoko Aoki, Katsuo Kanmatsuse, Richard M. Rohan, D. Bacharaki, David B. Ramsden, S.M. Lang, Bernard Katz, A. Costa-Bauzá, Ikei Kobayashi, Necmiye Tümer, M. Ramis, Yoshio Nagake, Hurokazu Tsukahara, Susumu Takahashi, Velibor Tasic, Takahiko Ono, Eduardo Podjarny, Gloria S. Tannenbaum, Petar Korneti, Hiroyuki Matsushima, Yoshiko Takahashi, Rosemary H. Waring, and Cerys C. Huggins
- Subjects
Index (economics) ,business.industry ,Statistics ,Medicine ,Subject (documents) ,business - Published
- 2001
45. Relationship between the immunological background and the induction of inflammatory renal lesions by IL-12 in a high IgA strain of ddY mice
- Author
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Eri Muso, Hitoshi Kusano, Shigeki Miyawaki, Ikei Kobayashi, Shigetake Sasayama, Fumiaki Nogaki, Tadashi Kamata, Kiichi Shirakawa, Takahiko Ono, and Haruyoshi Yoshida
- Subjects
Pathology ,medicine.medical_specialty ,Strain (chemistry) ,Nephrology ,business.industry ,Interleukin 12 ,Medicine ,General Medicine ,business - Published
- 2000
46. Subject Index Vol. 112, 2009
- Author
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Hidetaka Otsuka, Bo Xu, Noriko Mori, Yuki Tomari, Kazuhide Uemura, Masaaki Nameta, Tadashi Yamamoto, Nobutaka Kato, Linning Zhao, Eishin Yaoita, Koji Sakamoto, Makiko Shimosawa, Fumiaki Nogaki, Hisayo Kitamura, Hidehiko Fujinaka, Eri Muso, Kohei Kamikado, Haruyoshi Yoshida, Yutaka Yoshida, Ning Liu, Ying Zhang, and Takahiko Ono
- Subjects
Index (economics) ,Nephrology ,Physiology ,Statistics ,Genetics ,Subject (documents) ,General Medicine ,Mathematics - Published
- 2009
47. Renal redox dysregulation in AKI: application for oxidative stress marker of AKI.
- Author
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Kenji Kasuno, Kiichi Shirakawa, Haruyoshi Yoshida, Kiyoshi Mori, Hideki Kimura, Naoki Takahashi, Yasunari Nobukawa, Kenji Shigemi, Sawaka Tanabe, Narihisa Yamada, Takaaki Koshiji, Fumiaki Nogaki, Hitoshi Kusano, Takahiko Ono, Kazuko Uno, Hajime Nakamura, Junji Yodoi, Eri Muso, and Masayuki Iwano
- Subjects
OXIDATIVE stress ,ACUTE kidney failure ,THIOREDOXIN ,REPERFUSION injury ,CHRONIC kidney failure ,IMMUNOSTAINING - Abstract
Oxidative stress is a major determinant of acute kidney injury (AKI); however, the effects of an AKI on renal redox system are unclear, and few existing AKI markers are suitable for evaluating oxidative stress. We measured urinary levels of the redox-regulatory protein thioredoxin 1 (TRX1) in patients with various kinds of kidney disease and in mice with renal ischemiareperfusion injury. Urinary TRX1 levels were markedly higher in patients with AKI than in those with chronic kidney disease or in healthy subjects. In a receiver operating characteristic curve analysis to differentiate between AKI and other renal diseases, the area under the curve for urinary TRX1 was 0.94 (95% confidence interval, 0.90-0.98), and the sensitivity and specificity were 0.88 and 0.88, respectively, at the optimal cutoff value of 43.0 μg/g creatinine. Immunostaining revealed TRX1 to be diffusely distributed in the tubules of normal kidneys, but to be shifted to the brush borders or urinary lumen in injured tubules in both mice and humans with AKI. Urinary TRX1 in AKI was predominantly in the oxidized form. In cultured human proximal tubular epithelial cells, hydrogen peroxide specifically and dose dependently increased TRX1 levels in the culture supernatant, while reducing intracellular levels. These findings suggest that urinary TRX1 is an oxidative stress-specific biomarker useful for distinguishing AKI from chronic kidney disease and healthy kidneys. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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48. Genetic analysis in a high IgA strain of ddY (HIGA) mice
- Author
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Tadashi Kamata, Takahiko Ono, Shigeki Miyawaki, Tasuku Honjo, Ikei Kobayashi, Eri Muso, Fumiaki Nogaki, Haruyoshi Yoshida, and Emi Oida
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Genetics ,business.industry ,Nephrology ,Strain (biology) ,Medicine ,General Medicine ,business ,Genetic analysis - Published
- 2008
49. Genetic locus of high serum IgA: Quantitative trait loci (QTL) analysis in high serum IgA ddY (HIGA) mice
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Eri Muso, Takahiko Ono, Ikei Kobayashi, Emi Oida, Keiko Nomura, Katsuo Suyama, Toru Kita, Fumiaki Nogaki, Shigeki Miyawaki, and Haruyoshi Yoshida
- Subjects
Genetics ,Qtl analysis ,Nephrology ,business.industry ,High serum ,Expression quantitative trait loci ,Medicine ,General Medicine ,Quantitative trait locus ,business - Published
- 2003
50. The mechanisms of intramesangial coagulation in IgA nephropathy, and the relationship to factor V expression
- Author
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Fumiaki Nogaki, Shigetake Sasayama, Hitoshi Kusano, Ning Liu, Eri Muso, Takahiko Ono, and Katsuo Suyama
- Subjects
medicine.medical_specialty ,Mesangial cell ,biology ,business.industry ,Factor V ,General Medicine ,Factor XIII ,medicine.disease ,Tissue factor ,Endocrinology ,Thrombin ,Coagulation ,Nephrology ,Prothrombinase ,Internal medicine ,medicine ,biology.protein ,Mesangial proliferative glomerulonephritis ,business ,medicine.drug - Abstract
Fibrin deposition is often noted in mesangial areas in active types of human mesangioproliferative glomerulonephritis; IgA nephropathy or Henoch-Schonlein purpura nephritis.1,2In vivo, mesangial cells are provided with various coagulation factors from blood circulation through fenestration of glomerular capillary endothelium. Factor V in its active form (Va) officiates as a membrane-bound cofactor to factor Xa, forming prothrombinase complex Xa/Va, which converts prothrombin to thrombin. In the present study, to clarify the contribution of factor V in intramesangial coagulation, mesangial factor V expression and its relationship to mesangial proliferation was investigated. Cross-linked fibrin (XFb) was detected in renal biopsy specimens from the patients of IgA nephropathy using anti-d-dimer antibody combined with plasmin exposure,1 and factor V was detected with rabbit antibody against human factor V. The expression of factor V mRNA was assessed by in situ hybridization in relation to the simultaneous antigen staining of alpha-smooth muscle actin (α-SMA). For in vitro study, cultured human mesangial cells (MCs) were stimulated with TNF-α (100 U/mL), and immunocytochemically stained the factor V protein, or evaluated by Western blot analysis. In another experiment, starved MCs were further incubated in combination with factor Xa, prothrombin, fibrinogen and factor XIII, and fibrin production on MCs was assessed. In a blocking test using an antibody against factor V, suppression of fibrin production was evaluated. XFb deposition and factor V expression were markedly correlated with disease activity (Table 1). By in situ hybridization, factor V mRNA was detected mainly in the mesangial cells which were positive for α-SMA, and partly in endothelial cells. In vitro study revealed that factor V expression was elevated time-dependently after TNF-α stimulation (P < 0.01), and that fibrin production on TNF-α-stimulated MCs was increased (P < 0.0001), and inhibited by the addition of antifactor V antibody (P < 0.01). Table 1. Relationship of XFb deposition and factor V expression to histological and immunohistochemical findings P value vs XFb P value vs factor V Mesangial cell proliferation 0.02 0.04 Necrotizing lesion 0.02 0.03 Cellular crescent 0.02 0.03 Interstitial mononuclear infiltrate 0.04 0.07 Activity index 0.005 0.008 In conclusion, factor V is expressed in mesangial cells after stimulation by inflammation, and may exert procoagulant activity in cooperation with exogenous factor Xa, leading to intramesangial coagulation in IgA nephropathy.
- Published
- 2001
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