Toshiyuki Imasawa - Academia.edu (original) (raw)
Papers by Toshiyuki Imasawa
Clinical and Experimental Nephrology, 2000
ABSTRACT Background. Interleukin-1 (IL-1) has been reported to play a major role in the initiatio... more ABSTRACT Background. Interleukin-1 (IL-1) has been reported to play a major role in the initiation and progression of several glomerulonephritis, and inhibition of IL-1 by the blockade of IL-1β-converting enzyme (ICE) has been suggested to be an ideal therapeutic strategy. Methods. To examine the effect of ICE inhibition on glomerulonephritis, we examined the susceptibility of ICE-deficient mice (ICE−/−) to anti-glomerular base-ment membrane antibody-induced glomerulonephritis (antiGBMGN), which has been previously reported to be mediated by IL-1β. Results. After the injection of antiGBM antibody to ICE−/− and wild type mice, albuminuria rose progressively and both groups of mice died within 7–9 days. Laboratory analysis of proteinuria, serum creatinine, and glomerular histology revealed no significant difference between the two groups. To pursue the mechanism of this result, bone marrow-derived monocyte/macrophage lineage cells (Mo/Mq cells) were established from both groups and the potency of IL-1β production in response to lipopolysaccharide was examined. An enzyme-linked immunosorbent assay (ELISA) of IL-1β revealed that, Mo/Mq cells from ICE−/− mice secreted IL-1β in response to lipopolysaccharide, although to a lesser extent than the Mo/Mq cells from ICE+/+ mice, suggesting that other protease(s) may process proIL-1β to generate the mature form. In fact, as was seen in the wild type mice, serum from antiGBM-injected ICE−/− mice contained IL-1β. Conclusions. These data suggest a limited effectiveness of ICE inhibition as a therapeutic strategy for glomerulonephritis.
Nihon Toseki Igakkai Zasshi, 1996
Nihon Toseki Igakkai Zasshi
Journal of the American Society of Nephrology
Bone marrow stem cells (BMC) develop into hematopoietic and mesenchymal lineages but have not bee... more Bone marrow stem cells (BMC) develop into hematopoietic and mesenchymal lineages but have not been known to differentiate into glomerular cells. To investigate whether such differentiation is possible, a search was made for donor glomerular cells in lethally irradiated C57BL/6j (B6) mice given transplants of BMC from syngeneic mice transgenic for green fluorescence protein (GFP) ([GFP-->B6] mice). After the recipients of donor BMC manifested GFP-positive cells in their glomeruli, the numbers of such cells increased markedly, in a time-dependent manner, from 2 wk to 24 wk after bone marrow transplantation. Immunohistochemical analyses revealed that most GFP-positive cells in the glomeruli were neither macrophages nor T cells. With the use of a laser-scanning confocal microscope, GFP-positive cells were observed within the mesangium of [GFP-->B6] mice. Furthermore, indirect immunofluorescence assays demonstrated that desmin-positive cells in the glomeruli of these chimeric mice ...
Nippon Jinzo Gakkai shi
We have investigated the clinical characteristics of renal damage and associated complications of... more We have investigated the clinical characteristics of renal damage and associated complications of 79 patients with accidental hypothermia whom we encountered over the last 5 years. All patients were male, with an average age of 58.9 +/- 9.2 years. Most of these patients were homeless. Body temperature on admission was 29.3 +/- 3.0 degrees C. The most common clinical manifestations on admission were consciousness disturbance and severe hypotension. Complications, including increase in serum transaminase, alcoholism, pneumonia, liver cirrhosis, sepsis, diabetes mellitus, hypoglycemia, acidosis, and an increased level of serum CPK and amylase were found frequently on admission. Death within 48 hours after admission occurred in 23 cases (the death rate; 23/79 = 29%). Renal damage was found in 36 cases (36/79 = 46%), consisting of acute renal failure (ARF) in 27, and acute on chronic in 6. Urinary diagnostic indices suggested that the etiological factor for ARF was pre-renal, which respo...
Nephrology Dialysis Transplantation
Nephrology Dialysis Transplantation
We identified a novel gene, termed megsin, predominantly expressed in mesangial cells utilizing a... more We identified a novel gene, termed megsin, predominantly expressed in mesangial cells utilizing a 3'-directed regional cDNA library from cultured human mesangial cells. Megsin is a novel serine protease inhibitor (serpin), and the level of megsin RNA/protein expression is up-regulated in patients with IgA nephropathy or diabetic nephropathy, suggesting a link between megsin expression and the pathogenesis of mesangial expansion and/or proliferation. To assess the pathophysiological significance of megsin, we produced human megsin transgenic mice. Genetic manipulation of megsin engenders two elementary mesangial lesions, mesangial expansion and an increase in the number of mesangial cells.
Journal of Infection and Chemotherapy, 2015
Chronic kidney disease (CKD) is an increased risk for the development of active tuberculosis, but... more Chronic kidney disease (CKD) is an increased risk for the development of active tuberculosis, but few studies have analyzed the treatment outcome of pulmonary tuberculosis among CKD patients. A retrospective cohort study was conducted at Chiba-East Hospital in Chiba, Japan. Our study estimated the treatment outcomes in smear-positive pulmonary tuberculosis in relation to CKD and its stages. Total subjects were 759 patients (12-99 years) hospitalized between 2007 and 2012. Patients suffering from multi-drug-resistant tuberculosis were excluded. Patients with CKD were 19.3% aged <65 years (n = 384), and 49.6% aged ≥ 65 years, respectively (P < 0.001). Successful treatment was 52.7% in CKD (n = 260) and 67.3% in non-CKD (n = 499) (P < 0.001). Death was 25.4% in CKD and 12.4% in non-CKD (P < 0.001). Treatment outcome was especially poor in patients with low estimated glomerular filtration rate (eGFR) of <30 ml/min/1.73 m(2), as successful treatment was 20.0%, and death was 50.0%, significantly lower than in other CKD and non-CKD patients. After multivariate logistic regression analysis, eGFR<30 ml/min/1.73 m(2) was an independent factor affecting successful treatment and death, and its adjusted odds ratios (aOR) were 0.20 (95% confidence interval (CI) 0.07-0.50) and 2.99 (95%CI 1.20-7.51), respectively. Other factors affecting successful treatment were serum albumin <3.0 mg/dl, steroid therapy for underlying disease and cardiovascular disease, with aOR (95%CI) of 0.28 (0.20-0.39), 0.32 (0.16-0.63) and 0.49 (0.28-0.86), respectively. Several factors were associated with poor treatment outcome of smear-positive pulmonary tuberculosis. Advanced stage of CKD with eGFR of <30 ml/min/1.73 m(2) was a risk factor for poor treatment outcome.
Nihon Jinzo Gakkai shi, 2010
To improve chronic kidney disease (CKD) outcomes, board-certified nephrologists of the Japanese S... more To improve chronic kidney disease (CKD) outcomes, board-certified nephrologists of the Japanese Society of Nephrology (certified nephrologists) are anticipated to play an important role in community medicine and establish an effective cooperative relationship with primary care physicians. We analyzed the present status of certified nephrologists in each prefecture of Japan based on national data. As a result, in 2008, the maximum number of certified nephrologists per population among the 47 prefectures was 5.3 times higher than the minimum number. The rate of increase was not high in prefectures with a small number of certified nephrologists per population, which indicates that the disparities among the prefectures will persist in the future. To analyze how certified nephrologists participate in the community medicine of the 47 prefectures of Japan, we performed an ecological regression study. At first, it was shown that the number of certified nephrologists per resident population ...
Diagnostic pathology, 2014
Individuals born with a low birth weight (LBW) have a higher risk of developing kidney dysfunctio... more Individuals born with a low birth weight (LBW) have a higher risk of developing kidney dysfunction during their lifetime and sometimes exhibit focal segmental glomerulosclerosis (FSGS) lesions in their glomeruli. We herein try to obtain other pathological characteristics of LBW-related nephropathy. We retrospectively evaluated the renal pathology of four patients demonstrating FSGS with a history of LBW. Two mitochondrial cytopathy patients were also analyzed. DNA mutations were surveyed using a PCR-Luminex assay. In all four FSGS patients with a history of LBW, focal segmental glomerulosclerosis were detected. Interestingly, granular swollen epithelial cells (GSECs), which have previously been reported exclusively in patients with mitochondrial cytopathy, were also observed in the distal tubules and/or collecting ducts of all four patients with a history of low birth weight in this study. Electron microscopy revealed that these granular swollen epithelial cells included an increase...
Renal failure, 2014
The presence of granular swollen epithelial cells (GSECs) in tubular cells was recently reported ... more The presence of granular swollen epithelial cells (GSECs) in tubular cells was recently reported to be a specific change associated with mitochondrial cytopathy. However, at present, GSEC is not routinely evaluated. We, in this study, present a case of glomerulosclerosis, in which the presence of GSECs should provide us one clue to understand the pathogenesis of its progressive decline of renal function. A 54-year-old Japanese female, who had been diagnosed with Graves' disease, was referred for the examination and treatment of her proteinuria (5.4 g/gCre at the first visit to our hospital). A kidney biopsy showed 28.6% of the glomeruli to be globally sclerosed and 10.7% of the glomeruli to have completely collapsed. However, according to a light microscopic analysis, all other glomeruli showed an almost normal appearance, except for some slight enlargement. Almost 30% of the interstitium was damaged by fibrosis. Characteristically, GSECs were observed in the medulla collecting ...
Clinical and experimental nephrology, 2012
An ecological study is a useful epidemiologic tool for public health surveillance and establishme... more An ecological study is a useful epidemiologic tool for public health surveillance and establishment of a new hypothesis. Here, we used an ecological study to analyze the association between birth weight and end-stage renal disease (ESRD). We performed ecological regression analysis by using data obtained from the national database of Japan. The data include regional incidence of ESRD beginning maintenance dialysis therapy, regional rate of low-birth weight (LBW) newborn babies of all newborn babies, the average birth weight of newborns, the body mass index (BMI) score, the prevalence of diabetes mellitus, and the amount of payment for drugs, in the 47 prefectures of Japan. The mean regional rates of LBW newborn babies from 1999 to 2008 statistically correlated with the mean incidences of ESRD during the same time periods in each prefecture. The correlation coefficients between the yearly rate of LBW newborns and the yearly incidence of ESRD in each prefecture became higher after sta...
Clinical and Experimental Nephrology, 1997
Background The purpose of this study was to examine the effects of bacterial suporantigens, whic... more Background The purpose of this study was to examine the effects of bacterial suporantigens, which can derange the immune response and contribute to the renal lesions of immunoglobulin A (lgA) nephropathy. Methods Twenty-five micrograms of a bacterial superantigen, staphylococcal enterotoxin B (SEB), was injected into IgA nephropathy-prone ddY mice intrathymically when they reached 6 weeks of age. Evaluation included measurement of albumin
Clinical journal of the American Society of Nephrology : CJASN, Jan 7, 2014
X-linked Alport syndrome is caused by mutations in the COL4A5 gene. Although many COL4A5 mutation... more X-linked Alport syndrome is caused by mutations in the COL4A5 gene. Although many COL4A5 mutations have been detected, the mutation detection rate has been unsatisfactory. Some men with X-linked Alport syndrome show a relatively mild phenotype, but molecular basis investigations have rarely been conducted to clarify the underlying mechanism. In total, 152 patients with X-linked Alport syndrome who were suspected of having Alport syndrome through clinical and pathologic investigations and referred to the hospital for mutational analysis between January of 2006 and January of 2013 were genetically diagnosed. Among those patients, 22 patients had suspected splice site mutations. Transcripts are routinely examined when suspected splice site mutations for abnormal transcripts are detected; 11 of them showed expected exon skipping, but others showed aberrant splicing patterns. The mutation detection strategy had two steps: (1) genomic DNA analysis using PCR and direct sequencing and (2) m...
Nephron Experimental Nephrology, 2002
The pathogenesis of IgA nephropathy (IgAN) is still obscure. In this study, we investigated wheth... more The pathogenesis of IgA nephropathy (IgAN) is still obscure. In this study, we investigated whether the fundamental pathogenesis of IgAN lies in bone marrow stem cells (BMCs) and whether bone marrow transplantation from normal C57BL/6j (B6) mice can attenuate glomerular lesions in a murine IgAN model (high serum level IgA ddY mouse; HIGA mouse). Mesangial deposits of IgA and C3 and glomerular sclerosis in HIGA recipients of BMCs from B6 mice (B6-->HIGA) were decreased as compared with those in HIGA recipients of BMCs from HIGA mice (HIGA-->HIGA). Furthermore, the serum levels of IgA and macromolecular IgA were notably lower in B6-->HIGA mice than in HIGA-->HIGA mice. Of note, bone marrow derived H-2(b)-positive cells from B6 donors were observed in the glomeruli of H-2(b)-negative HIGA recipients. Our data suggest that qualitative and quantitative changes of serum IgA are determined at the level of stem cells and that bone marrow transplantation from normal mice may not only replace recipients' immune cells with donors' BMCs, but also regenerate glomerular cells in HIGA mice. This approach offers a promising strategy for the treatment of IgAN.
Nephron, 2000
... Exp Nephrol 1996;4:1925. 8 Kohzumi M, Yasujima M, Kanagawa M, Yo-shida K, Fu LP, Obara K, Sa... more ... Exp Nephrol 1996;4:1925. 8 Kohzumi M, Yasujima M, Kanagawa M, Yo-shida K, Fu LP, Obara K, Saito T, Abe K: Anti-hypertensive and renal-protective effects of lo-sartan in streptozotocin diabetic rats. J Hyper-tens 1995;13:97100. ... Kid-ney Int 1996(suppl 50):132136. ...
Nephrology Dialysis Transplantation, 2014
Background. The study aim was, for the first time, to conduct a multicenter randomized controlled... more Background. The study aim was, for the first time, to conduct a multicenter randomized controlled trial to evaluate the effect of tonsillectomy in patients with IgA nephropathy (IgAN). Methods. Patients with biopsy-proven IgAN, proteinuria and low serum creatinine were randomly allocated to receive tonsillectomy combined with steroid pulses (Group A; n = 33) or steroid pulses alone (Group B; n = 39). The primary end points were urinary protein excretion and the disappearance of proteinuria and/or hematuria. Results. During 12 months from baseline, the percentage decrease in urinary protein excretion was significantly larger in Group A than that in Group B (P < 0.05). However, the frequency of the disappearance of proteinuria, hematuria, or both (clinical remission) at 12 months was not statistically different between the groups. Logistic regression analyses revealed the assigned treatment was a significant, independent
Clinical and Experimental Nephrology, 2000
ABSTRACT Background. Interleukin-1 (IL-1) has been reported to play a major role in the initiatio... more ABSTRACT Background. Interleukin-1 (IL-1) has been reported to play a major role in the initiation and progression of several glomerulonephritis, and inhibition of IL-1 by the blockade of IL-1β-converting enzyme (ICE) has been suggested to be an ideal therapeutic strategy. Methods. To examine the effect of ICE inhibition on glomerulonephritis, we examined the susceptibility of ICE-deficient mice (ICE−/−) to anti-glomerular base-ment membrane antibody-induced glomerulonephritis (antiGBMGN), which has been previously reported to be mediated by IL-1β. Results. After the injection of antiGBM antibody to ICE−/− and wild type mice, albuminuria rose progressively and both groups of mice died within 7–9 days. Laboratory analysis of proteinuria, serum creatinine, and glomerular histology revealed no significant difference between the two groups. To pursue the mechanism of this result, bone marrow-derived monocyte/macrophage lineage cells (Mo/Mq cells) were established from both groups and the potency of IL-1β production in response to lipopolysaccharide was examined. An enzyme-linked immunosorbent assay (ELISA) of IL-1β revealed that, Mo/Mq cells from ICE−/− mice secreted IL-1β in response to lipopolysaccharide, although to a lesser extent than the Mo/Mq cells from ICE+/+ mice, suggesting that other protease(s) may process proIL-1β to generate the mature form. In fact, as was seen in the wild type mice, serum from antiGBM-injected ICE−/− mice contained IL-1β. Conclusions. These data suggest a limited effectiveness of ICE inhibition as a therapeutic strategy for glomerulonephritis.
Nihon Toseki Igakkai Zasshi, 1996
Nihon Toseki Igakkai Zasshi
Journal of the American Society of Nephrology
Bone marrow stem cells (BMC) develop into hematopoietic and mesenchymal lineages but have not bee... more Bone marrow stem cells (BMC) develop into hematopoietic and mesenchymal lineages but have not been known to differentiate into glomerular cells. To investigate whether such differentiation is possible, a search was made for donor glomerular cells in lethally irradiated C57BL/6j (B6) mice given transplants of BMC from syngeneic mice transgenic for green fluorescence protein (GFP) ([GFP-->B6] mice). After the recipients of donor BMC manifested GFP-positive cells in their glomeruli, the numbers of such cells increased markedly, in a time-dependent manner, from 2 wk to 24 wk after bone marrow transplantation. Immunohistochemical analyses revealed that most GFP-positive cells in the glomeruli were neither macrophages nor T cells. With the use of a laser-scanning confocal microscope, GFP-positive cells were observed within the mesangium of [GFP-->B6] mice. Furthermore, indirect immunofluorescence assays demonstrated that desmin-positive cells in the glomeruli of these chimeric mice ...
Nippon Jinzo Gakkai shi
We have investigated the clinical characteristics of renal damage and associated complications of... more We have investigated the clinical characteristics of renal damage and associated complications of 79 patients with accidental hypothermia whom we encountered over the last 5 years. All patients were male, with an average age of 58.9 +/- 9.2 years. Most of these patients were homeless. Body temperature on admission was 29.3 +/- 3.0 degrees C. The most common clinical manifestations on admission were consciousness disturbance and severe hypotension. Complications, including increase in serum transaminase, alcoholism, pneumonia, liver cirrhosis, sepsis, diabetes mellitus, hypoglycemia, acidosis, and an increased level of serum CPK and amylase were found frequently on admission. Death within 48 hours after admission occurred in 23 cases (the death rate; 23/79 = 29%). Renal damage was found in 36 cases (36/79 = 46%), consisting of acute renal failure (ARF) in 27, and acute on chronic in 6. Urinary diagnostic indices suggested that the etiological factor for ARF was pre-renal, which respo...
Nephrology Dialysis Transplantation
Nephrology Dialysis Transplantation
We identified a novel gene, termed megsin, predominantly expressed in mesangial cells utilizing a... more We identified a novel gene, termed megsin, predominantly expressed in mesangial cells utilizing a 3'-directed regional cDNA library from cultured human mesangial cells. Megsin is a novel serine protease inhibitor (serpin), and the level of megsin RNA/protein expression is up-regulated in patients with IgA nephropathy or diabetic nephropathy, suggesting a link between megsin expression and the pathogenesis of mesangial expansion and/or proliferation. To assess the pathophysiological significance of megsin, we produced human megsin transgenic mice. Genetic manipulation of megsin engenders two elementary mesangial lesions, mesangial expansion and an increase in the number of mesangial cells.
Journal of Infection and Chemotherapy, 2015
Chronic kidney disease (CKD) is an increased risk for the development of active tuberculosis, but... more Chronic kidney disease (CKD) is an increased risk for the development of active tuberculosis, but few studies have analyzed the treatment outcome of pulmonary tuberculosis among CKD patients. A retrospective cohort study was conducted at Chiba-East Hospital in Chiba, Japan. Our study estimated the treatment outcomes in smear-positive pulmonary tuberculosis in relation to CKD and its stages. Total subjects were 759 patients (12-99 years) hospitalized between 2007 and 2012. Patients suffering from multi-drug-resistant tuberculosis were excluded. Patients with CKD were 19.3% aged &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;65 years (n = 384), and 49.6% aged ≥ 65 years, respectively (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Successful treatment was 52.7% in CKD (n = 260) and 67.3% in non-CKD (n = 499) (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Death was 25.4% in CKD and 12.4% in non-CKD (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Treatment outcome was especially poor in patients with low estimated glomerular filtration rate (eGFR) of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;30 ml/min/1.73 m(2), as successful treatment was 20.0%, and death was 50.0%, significantly lower than in other CKD and non-CKD patients. After multivariate logistic regression analysis, eGFR&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;30 ml/min/1.73 m(2) was an independent factor affecting successful treatment and death, and its adjusted odds ratios (aOR) were 0.20 (95% confidence interval (CI) 0.07-0.50) and 2.99 (95%CI 1.20-7.51), respectively. Other factors affecting successful treatment were serum albumin &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;3.0 mg/dl, steroid therapy for underlying disease and cardiovascular disease, with aOR (95%CI) of 0.28 (0.20-0.39), 0.32 (0.16-0.63) and 0.49 (0.28-0.86), respectively. Several factors were associated with poor treatment outcome of smear-positive pulmonary tuberculosis. Advanced stage of CKD with eGFR of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;30 ml/min/1.73 m(2) was a risk factor for poor treatment outcome.
Nihon Jinzo Gakkai shi, 2010
To improve chronic kidney disease (CKD) outcomes, board-certified nephrologists of the Japanese S... more To improve chronic kidney disease (CKD) outcomes, board-certified nephrologists of the Japanese Society of Nephrology (certified nephrologists) are anticipated to play an important role in community medicine and establish an effective cooperative relationship with primary care physicians. We analyzed the present status of certified nephrologists in each prefecture of Japan based on national data. As a result, in 2008, the maximum number of certified nephrologists per population among the 47 prefectures was 5.3 times higher than the minimum number. The rate of increase was not high in prefectures with a small number of certified nephrologists per population, which indicates that the disparities among the prefectures will persist in the future. To analyze how certified nephrologists participate in the community medicine of the 47 prefectures of Japan, we performed an ecological regression study. At first, it was shown that the number of certified nephrologists per resident population ...
Diagnostic pathology, 2014
Individuals born with a low birth weight (LBW) have a higher risk of developing kidney dysfunctio... more Individuals born with a low birth weight (LBW) have a higher risk of developing kidney dysfunction during their lifetime and sometimes exhibit focal segmental glomerulosclerosis (FSGS) lesions in their glomeruli. We herein try to obtain other pathological characteristics of LBW-related nephropathy. We retrospectively evaluated the renal pathology of four patients demonstrating FSGS with a history of LBW. Two mitochondrial cytopathy patients were also analyzed. DNA mutations were surveyed using a PCR-Luminex assay. In all four FSGS patients with a history of LBW, focal segmental glomerulosclerosis were detected. Interestingly, granular swollen epithelial cells (GSECs), which have previously been reported exclusively in patients with mitochondrial cytopathy, were also observed in the distal tubules and/or collecting ducts of all four patients with a history of low birth weight in this study. Electron microscopy revealed that these granular swollen epithelial cells included an increase...
Renal failure, 2014
The presence of granular swollen epithelial cells (GSECs) in tubular cells was recently reported ... more The presence of granular swollen epithelial cells (GSECs) in tubular cells was recently reported to be a specific change associated with mitochondrial cytopathy. However, at present, GSEC is not routinely evaluated. We, in this study, present a case of glomerulosclerosis, in which the presence of GSECs should provide us one clue to understand the pathogenesis of its progressive decline of renal function. A 54-year-old Japanese female, who had been diagnosed with Graves' disease, was referred for the examination and treatment of her proteinuria (5.4 g/gCre at the first visit to our hospital). A kidney biopsy showed 28.6% of the glomeruli to be globally sclerosed and 10.7% of the glomeruli to have completely collapsed. However, according to a light microscopic analysis, all other glomeruli showed an almost normal appearance, except for some slight enlargement. Almost 30% of the interstitium was damaged by fibrosis. Characteristically, GSECs were observed in the medulla collecting ...
Clinical and experimental nephrology, 2012
An ecological study is a useful epidemiologic tool for public health surveillance and establishme... more An ecological study is a useful epidemiologic tool for public health surveillance and establishment of a new hypothesis. Here, we used an ecological study to analyze the association between birth weight and end-stage renal disease (ESRD). We performed ecological regression analysis by using data obtained from the national database of Japan. The data include regional incidence of ESRD beginning maintenance dialysis therapy, regional rate of low-birth weight (LBW) newborn babies of all newborn babies, the average birth weight of newborns, the body mass index (BMI) score, the prevalence of diabetes mellitus, and the amount of payment for drugs, in the 47 prefectures of Japan. The mean regional rates of LBW newborn babies from 1999 to 2008 statistically correlated with the mean incidences of ESRD during the same time periods in each prefecture. The correlation coefficients between the yearly rate of LBW newborns and the yearly incidence of ESRD in each prefecture became higher after sta...
Clinical and Experimental Nephrology, 1997
Background The purpose of this study was to examine the effects of bacterial suporantigens, whic... more Background The purpose of this study was to examine the effects of bacterial suporantigens, which can derange the immune response and contribute to the renal lesions of immunoglobulin A (lgA) nephropathy. Methods Twenty-five micrograms of a bacterial superantigen, staphylococcal enterotoxin B (SEB), was injected into IgA nephropathy-prone ddY mice intrathymically when they reached 6 weeks of age. Evaluation included measurement of albumin
Clinical journal of the American Society of Nephrology : CJASN, Jan 7, 2014
X-linked Alport syndrome is caused by mutations in the COL4A5 gene. Although many COL4A5 mutation... more X-linked Alport syndrome is caused by mutations in the COL4A5 gene. Although many COL4A5 mutations have been detected, the mutation detection rate has been unsatisfactory. Some men with X-linked Alport syndrome show a relatively mild phenotype, but molecular basis investigations have rarely been conducted to clarify the underlying mechanism. In total, 152 patients with X-linked Alport syndrome who were suspected of having Alport syndrome through clinical and pathologic investigations and referred to the hospital for mutational analysis between January of 2006 and January of 2013 were genetically diagnosed. Among those patients, 22 patients had suspected splice site mutations. Transcripts are routinely examined when suspected splice site mutations for abnormal transcripts are detected; 11 of them showed expected exon skipping, but others showed aberrant splicing patterns. The mutation detection strategy had two steps: (1) genomic DNA analysis using PCR and direct sequencing and (2) m...
Nephron Experimental Nephrology, 2002
The pathogenesis of IgA nephropathy (IgAN) is still obscure. In this study, we investigated wheth... more The pathogenesis of IgA nephropathy (IgAN) is still obscure. In this study, we investigated whether the fundamental pathogenesis of IgAN lies in bone marrow stem cells (BMCs) and whether bone marrow transplantation from normal C57BL/6j (B6) mice can attenuate glomerular lesions in a murine IgAN model (high serum level IgA ddY mouse; HIGA mouse). Mesangial deposits of IgA and C3 and glomerular sclerosis in HIGA recipients of BMCs from B6 mice (B6--&amp;amp;amp;gt;HIGA) were decreased as compared with those in HIGA recipients of BMCs from HIGA mice (HIGA--&amp;amp;amp;gt;HIGA). Furthermore, the serum levels of IgA and macromolecular IgA were notably lower in B6--&amp;amp;amp;gt;HIGA mice than in HIGA--&amp;amp;amp;gt;HIGA mice. Of note, bone marrow derived H-2(b)-positive cells from B6 donors were observed in the glomeruli of H-2(b)-negative HIGA recipients. Our data suggest that qualitative and quantitative changes of serum IgA are determined at the level of stem cells and that bone marrow transplantation from normal mice may not only replace recipients&amp;amp;amp;#39; immune cells with donors&amp;amp;amp;#39; BMCs, but also regenerate glomerular cells in HIGA mice. This approach offers a promising strategy for the treatment of IgAN.
Nephron, 2000
... Exp Nephrol 1996;4:1925. 8 Kohzumi M, Yasujima M, Kanagawa M, Yo-shida K, Fu LP, Obara K, Sa... more ... Exp Nephrol 1996;4:1925. 8 Kohzumi M, Yasujima M, Kanagawa M, Yo-shida K, Fu LP, Obara K, Saito T, Abe K: Anti-hypertensive and renal-protective effects of lo-sartan in streptozotocin diabetic rats. J Hyper-tens 1995;13:97100. ... Kid-ney Int 1996(suppl 50):132136. ...
Nephrology Dialysis Transplantation, 2014
Background. The study aim was, for the first time, to conduct a multicenter randomized controlled... more Background. The study aim was, for the first time, to conduct a multicenter randomized controlled trial to evaluate the effect of tonsillectomy in patients with IgA nephropathy (IgAN). Methods. Patients with biopsy-proven IgAN, proteinuria and low serum creatinine were randomly allocated to receive tonsillectomy combined with steroid pulses (Group A; n = 33) or steroid pulses alone (Group B; n = 39). The primary end points were urinary protein excretion and the disappearance of proteinuria and/or hematuria. Results. During 12 months from baseline, the percentage decrease in urinary protein excretion was significantly larger in Group A than that in Group B (P < 0.05). However, the frequency of the disappearance of proteinuria, hematuria, or both (clinical remission) at 12 months was not statistically different between the groups. Logistic regression analyses revealed the assigned treatment was a significant, independent