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ABSTRACT: BACKGROUND: Matrix Gla protein (MGP) is one of the important proteins inhibiting vascular calcification (VC). Single nucleotide polymorphisms (SNPs) located in the promoter and coding regions of the MGP gene affect the transcriptional activity. In this study, we investigated the relationship between the SNPs and progression of VC in patients undergoing maintenance hemodialysis (MHD). METHODS: This was a retrospective, longitudinal cohort study of 134 MHD patients whose VC could be followed by multi-detector computed tomography (MDCT) examinations. MGP-SNPs (T-138C, rs1800802 and G-7A, rs1800801) were determined. The progression speed of VC was examined by plotting the abdominal aortic calcium volume scores. RESULTS: The progression speed of VC of patients with the CC genotype of T-138C was significantly slower than that of patients with the CT or TT genotype. Multiple regression analysis showed that CT/TT genotype, greater age at the beginning of MHD, male sex, high levels of calcium × phosphate, low levels of high-density lipoprotein cholesterol, high levels of low-density lipoprotein cholesterol, low levels of ferritin and non-use of angiotensin II receptor blockers were significantly associated with progression of VC. CONCLUSIONS: The MGP-138CC genotype may be associated with slower progression of VC in MHD patients. The genotype of the MGP gene will be a genomic biomarker that is predictive of VC progression.
Clinical and Experimental Nephrology 03/2013; · 1.37 Impact Factor
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ABSTRACT: Blood color of dialysis patients can be seen routinely. Darkened blood color is often observed in critically ill patients generally because of decreased oxygen saturation, but little is known about the other factors responsible for the color intensity. In addition, quantitative blood color examination has not been performed yet. Therefore, no one has evaluated the predictive power of blood color. The aim of this study was to evaluate if blood color darkness reflects some medical problems and is associated with survival disadvantage. Study design is a prospective cohort study. One hundred sixty-seven patients were enrolled in this study. Quantification of blood color was done using a reflected light colorimeter. Demographic and clinical data were collected to find out the factors that can be related to blood color. Follow-ups were performed for 2 years to analyze the risk factors for their survival. Regression analysis showed that C-reactive protein and white blood cell count were negatively correlated with blood color. In addition, blood color was positively correlated with mean corpuscular hemoglobin concentration and serum sodium concentration as well as blood oxygen saturation. During a follow-up, 34 (20.4%) patients died. Cox regression analysis revealed that darkened blood color was an independent significant risk factor of mortality in hemodialysis patients as well as low albumin and low Kt/V. These results suggest that inflammation independently affects blood color and quantification of blood color is useful to estimate prognosis in patients undergoing hemodialysis. It is possible that early detection of blood color worsening can improve patients' survival.
Artificial Organs 07/2012; · 2.00 Impact Factor
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Akira Mima,
Takeshi Matsubara,
Hidenori Arai,
Hideharu Abe, Kojiro Nagai,
Hiroshi Kanamori,
Eriko Sumi,
Toshikazu Takahashi,
Noriyuki Iehara,
Atsushi Fukatsu,
Toru Kita,
Toshio Doi
Laboratory Investigation 05/2012; 92(5):797. · 3.64 Impact Factor
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ABSTRACT: Activation of mesangial cells (MCs), which is characterized by induction of smooth muscle α-actin (SMA) expression, contributes to a key event in various renal diseases; however, the mechanisms controlling MC differentiation are still largely undefined. Activated Smad1 induced SMA in a dose-dependent manner in MCs. As a direct regulating molecule for SMA, we identified and characterized scleraxis (Scx) as a new phenotype modulator in advanced glycation end product (AGE)-exposed MCs. Scx physically associated with E12 and bound the E-box in the promoter of SMA and negatively regulated the AGE-induced SMA expression. Scx induced expression and secretion of bone morphogenetic protein 4 (BMP4), thereby controlling the Smad1 activation in AGE-treated MCs. In diabetic mice, Scx was concomitantly expressed with SMA in the glomeruli. Inhibitor of differentiation 1 (Id1) was further induced by extended treatment with AGE, thereby dislodging Scx from the SMA promoter. These data suggest that Scx and Id1 are involved in the BMP4-Smad1-SMA signal transduction pathway besides the TGFβ1-Smad1-SMA signaling pathway and modulate phenotypic changes in MCs in diabetic nephropathy.
Journal of Biological Chemistry 04/2012; 287(24):20430-42. · 4.77 Impact Factor
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Akira Mima,
Hideharu Abe, Kojiro Nagai,
Hidenori Arai,
Takeshi Matsubara,
Makoto Araki,
Kazuo Torikoshi,
Tatsuya Tominaga,
Noriyuki Iehara,
Atsushi Fukatsu,
Toru Kita,
Toshio Doi
PLoS ONE 01/2012; 7(9). · 4.09 Impact Factor
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ABSTRACT: The prevalence of postinfectious glomerulonephritis has decreased in most developed countries. We report the case of a previously healthy, immunocompetent 65-year-old woman who developed acute glomerulonephritis associated with human parvovirus B19 infection. She was referred by her primary care physician for suspected congestive heart failure but she had an elevated creatinine level and an abnormal urinalysis. Renal biopsy showed diffuse endocapillary proliferative glomerulonephritis. After biopsy, we learned that she had been in frequent contact with her grandson who had been diagnosed with erythema infectiosum. Her human parvovirus B19 serum IgM titer was elevated at 3.50, indicating current infection.
Internal Medicine 01/2012; 51(16):2197-201. · 0.94 Impact Factor
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Hiroshi Kanamori, Kojiro Nagai,
Takeshi Matsubara,
Akira Mima,
Motoko Yanagita,
Noriyuki Iehara,
Hajime Takechi,
Keiichi Fujimaki,
Kazumasa Usami,
Atsushi Fukatsu,
Toru Kita,
Kozo Matsubayashi,
Hidenori Arai
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ABSTRACT: The number of hemodialysis (HD) patients is increasing along with their mean age in Japan. The assessment of their psychosocial status and quality of life (QOL) is therefore becoming more and more important along with laboratory data or comorbidities.
We examined the psychosocial status of 211 HD patients (72 elderly and 139 non-elderly) and compared the difference between elderly and non-elderly patients using a visual analogue scale (VAS). We then examined how QOL affected mortality rate in 3-year prospective follow up. We assessed 10 items of QOL: health condition, appetite, sleep, mood, memory, family relationships, friendship, economical status, life satisfaction in daily life, and happiness with qualified self-evaluating questionnaires along with laboratory data and comorbidities. Furthermore, we investigated the correlation between the scores of mood and geriatric depression scale (GDS)-15.
There was no difference in VAS scores between elderly and non-elderly patients. Lower VAS scores for appetite and mood correlated with higher mortality in HD patients, especially in the non-elderly. VAS scores for mood correlated with GDS-15 in HD patients.
More attention should be paid to appetite and the diagnosis and therapy of depressive mood to improve the prognosis of HD patients, especially for the non-elderly.
Geriatrics & Gerontology International 08/2011; 12(1):65-71.
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Seiji Kishi,
Hideharu Abe,
Haruhiko Akiyama,
Tatsuya Tominaga,
Taichi Murakami,
Akira Mima, Kojiro Nagai,
Fumi Kishi,
Motokazu Matsuura,
Takeshi Matsubara,
Noriyuki Iehara,
Otoya Ueda,
Naoshi Fukushima,
Kou-ichi Jishage,
Toshio Doi
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ABSTRACT: Diabetic nephropathy (DN) is the most important chronic kidney disease. We previously reported that Smad1 transcriptionally regulates the expression of extracellular matrix in DN. Phenotypic change in mesangial cells (MCs) is a key pathologic event in the progression of DN. The aim of this study is to investigate a novel mechanism underlying chondrogenic phenotypic change in MCs that results in the development of DN. MCs showed chondrogenic potential in a micromass culture, and BMP4 induced the expression of chondrocyte markers (SRY-related HMG Box 9 (SOX9) and type II collagen (COL2)). Advanced glycation end products induced the expression of chondrocyte marker proteins downstream from the BMP4-Smad1 signaling pathway in MCs. In addition, hypoxia also induced the expression of BMP4, hypoxia-inducible factor-1α (HIF-1α), and chondrocyte markers. Overexpression of SOX9 caused ectopic expression of proteoglycans and COL2 in MCs. Furthermore, forced expression of Smad1 induced chondrocyte markers as well. Dorsomorphin inhibited these inductions. Glomerular expressions of HIF-1α, BMP4, and chondrocyte markers were observed in diabetic nephropathy mice. These positive stainings were observed in mesangial sclerotic lesions. SOX9 was partially colocalized with HIF-1α and BMP4 in diabetic glomeruli. BMP4 knock-in transgenic mice showed not only similar pathological lesions to DN, but also the induction of chondrocyte markers in the sclerotic lesions. Here we demonstrate that HIF-1α and BMP4 induce SOX9 expression and subsequent chondrogenic phenotype change in DN. The results suggested that the transdifferentiation of MCs into chondrocyte-like cells in chronic hypoxic stress may result in irreversible structural change in DN.
Journal of Biological Chemistry 07/2011; 286(37):32162-9. · 4.77 Impact Factor
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Tatsuya Tominaga,
Hideharu Abe,
Otoya Ueda,
Chisato Goto,
Kunihiko Nakahara,
Taichi Murakami,
Takeshi Matsubara,
Akira Mima, Kojiro Nagai,
Toshikazu Araoka,
Seiji Kishi,
Naoshi Fukushima,
Kou-ichi Jishage,
Toshio Doi
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ABSTRACT: Diabetic nephropathy (DN) is the most common cause of chronic kidney disease. We have previously reported that Smad1 transcriptionally regulates the expression of extracellular matrix (ECM) proteins in DN. However, little is known about the regulatory mechanisms that induce and activate Smad1. Here, bone morphogenetic protein 4 (Bmp4) was found to up-regulate the expression of Smad1 in mesangial cells and subsequently to phosphorylate Smad1 downstream of the advanced glycation end product-receptor for advanced glycation end product signaling pathway. Moreover, Bmp4 utilized Alk3 and affected the activation of Smad1 and Col4 expressions in mesangial cells. In the diabetic mouse, Bmp4 was remarkably activated in the glomeruli, and the mesangial area was expanded. To elucidate the direct function of Bmp4 action in the kidneys, we generated transgenic mice inducible for the expression of Bmp4. Tamoxifen treatment dramatically induced the expression of Bmp4, especially in the glomeruli of the mice. Notably, in the nondiabetic condition, the mice exhibited not only an expansion of the mesangial area and thickening of the basement membrane but also remarkable albuminuria, which are consistent with the distinct glomerular injuries in DN. ECM protein overexpression and activation of Smad1 in the glomeruli were also observed in the mice. The mesangial expansion in the mice was significantly correlated with albuminuria. Furthermore, the heterozygous Bmp4 knock-out mice inhibited the glomerular injuries compared with wild type mice in diabetic conditions. Here, we show that BMP4 may act as an upstream regulatory molecule for the process of ECM accumulation in DN and thereby reveals a new aspect of the molecular mechanisms involved in DN.
Journal of Biological Chemistry 04/2011; 286(22):20109-16. · 4.77 Impact Factor
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ABSTRACT: Skin pigmentation is a common problem for dialysis patients, but little is known about the factor responsible for the colour intensity. Middle-molecular-weight (MMW) substances have been suggested to be responsible for the skin colour. Several papers have reported that β(2)-microglobulin (β(2)-MG) correlates with the skin colour, and haemodiafiltration (HDF) is effective to reduce the skin hyperpigmentation. However, a quantitative skin colour follow-up on patients treated with online haemodiafiltration (online HDF) has not been performed.
Sixty-one patients were enrolled in this study. Quantification of skin colour was done using a reflected light colorimeter. Among them, 51 patients were under haemodialysis (HD), and the other 10 patients were under online HDF. Follow-ups to estimate the skin colour change were performed for 6 months. Among 10 patients under online HDF, four patients were also investigated by crossover way between HD and online HDF.
Compared with controls, patients treated with HD had darker skin. The colour value was well correlated with age, haematocrit, sex, diabetes and β(2)-MG but not with Kt/V. The skin colour got worse under HD treatment as well as the values of β(2)-MG, but online HDF improved the hyperpigmentation and the β(2)-MG values.
Our data show the effectiveness of online HDF on skin colour and suggest that HD patients' skin colour can be improved by modality change.
Nephrology Dialysis Transplantation 03/2011; 26(3):988-92. · 3.40 Impact Factor
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Akira Mima,
Fumihiko Shiota,
Takeshi Matsubara,
Noriyuki Iehara,
Taro Akagi,
Hideharu Abe, Kojiro Nagai,
Motokazu Matsuura,
Taichi Murakami,
Seiji Kishi,
Toshikazu Araoka,
Fumi Kishi,
Naoki Kondo,
Reiko Shigeta,
Kazuhiro Yoshikawa,
Toru Kita,
Toshio Doi,
Atsushi Fukatsu
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ABSTRACT: A 50-year-old man who underwent hemodialysis (HD) at local outpatient HD center due to end-stage renal disease (ESRD) was transferred to our hospital because of pneumonia. He had severe emaciation and past history of congestive heart failure. Presenting symptoms almost consistently involved difficulty in hearing and recurrent attacks of migraine-like headaches. He was diagnosed with dilated cardiomyopathy, showing diastolic mechanical dyssynchrony by tissue Doppler echocardiography. On the day of death, he had hematemesis and hemorrhagic shock. Autopsy revealed perforation of duodenum, and genetic analysis using mitochondrial DNA from cardiac muscle and iliopsoas muscle revealed a 3243A > G mutation in the mitochondrial tRNA(Leu(UUR)) gene, which is related to mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Multiple organ failure due to the mutation of mitochondrial DNA with gastrointestinal bleeding is not a common.
Renal Failure 01/2011; 33(6):622-5. · 0.82 Impact Factor
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Taichi Murakami, Kojiro Nagai,
Motokazu Matsuura,
Naoki Kondo,
Seiji Kishi,
Toshikazu Araoka,
Fumi Kishi,
Tsutomu Sakiyama,
Akira Mima,
Yoshimi Bando,
Hideharu Abe,
Toshio Doi
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ABSTRACT: Anti-glomerular basement membrane (GBM) antibody disease is clinically manifested as rapidly progressive glomerulonephritis (RPGN) with crescentic changes. The renal prognosis is poor. We report here the case of a 61-year-old woman with myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-positive anti-GBM antibody disease. This patient was referred to our hospital because of RPGN. Anti-GBM antibody was positive with a titer of 38 EU. The MPO-ANCA titer was 65 EU. Chest imaging examination revealed pulmonary multiple nodules. ANCA-associated vasculitis was suspected. Renal pathology revealed cellular crescents in 13 out of 17 glomeruli. Immunofluorescence with anti-IgG antibody, anti-C3 antibody, and anti-fibrin antibody showed linear staining along the glomerular capillary walls. Based on these findings, the patient was diagnosed with anti-GBM antibody disease. Hemodialysis was started because of uremic syndrome with elevated serum creatinine (6.84 mg/dL). In addition, treatment with plasma exchange using 3.6 L (90 mL/kg) of fresh frozen plasma combined with an oral dose of 40 mg of prednisolone was initiated. Within 3 weeks, both types of autoantibodies became undetectable. Subsequently, this patient achieved dialysis independence and remission of glomerulonephritis. No adverse effects were observed. In patients with MPO-ANCA-positive anti-GBM antibody disease, intensive therapy predominantly with plasma exchange might be operative, even though renal function is less likely to recover.
Renal Failure 01/2011; 33(6):626-31. · 0.82 Impact Factor
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Akira Mima,
Hideharu Abe, Kojiro Nagai,
Hidenori Arai,
Takeshi Matsubara,
Makoto Araki,
Kazuo Torikoshi,
Tatsuya Tominaga,
Noriyuki Iehara,
Atsushi Fukatsu,
Toru Kita,
Toshio Doi
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ABSTRACT: Platelet-derived growth factor (PDGF) plays critical roles in mesangial cell (MC) proliferation in mesangial proliferative glomerulonephritis. We showed previously that Smad1 contributes to PDGF-dependent proliferation of MCs, but the mechanism by which Smad1 is activated by PDGF is not precisely known. Here we examined the role of c-Src tyrosine kinase in the proliferative change of MCs. Experimental mesangial proliferative glomerulonephritis (Thy1 GN) was induced by a single intravenous injection of anti-rat Thy-1.1 monoclonal antibody. In Thy1 GN, MC proliferation and type IV collagen (Col4) expression peaked on day 6. Immunohistochemical staining for the expression of phospho-Src (pSrc), phospho-Smad1 (pSmad1), Col4, and smooth muscle α-actin (SMA) revealed that the activation of c-Src and Smad1 signals in glomeruli peaked on day 6, consistent with the peak of mesangial proliferation. When treated with PP2, a Src inhibitor, both mesangial proliferation and sclerosis were significantly reduced. PP2 administration also significantly reduced pSmad1, Col4, and SMA expression. PDGF induced Col4 synthesis in association with increased expression of pSrc and pSmad1 in cultured MCs. In addition, PP2 reduced Col4 synthesis along with decreased pSrc and pSmad1 protein expression in vitro. Moreover, the addition of siRNA against c-Src significantly reduced the phosphorylation of Smad1 and the overproduction of Col4. These results provide new evidence that the activation of Src/Smad1 signaling pathway plays a key role in the development of glomerulosclerosis in experimental glomerulonephritis.
PLoS ONE 01/2011; 6(3):e17929. · 4.09 Impact Factor
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Kojiro Nagai,
Kenya Kusunose,
Susumu Nishio,
Yoshio Taketani,
Hirotsugu Yamada,
Masataka Sata,
Naoki Kondo,
Fumi Kishi,
Seiji Kishi,
Toshikazu Araoka,
Motokazu Matsuura,
Akira Mima,
Hideharu Abe,
Taichi Murakami,
Masayuki Nakamura,
Toshio Doi
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ABSTRACT: Arteriosclerotic renal artery stenosis is one of the increasingly common diseases that affects many aged patients. There are various non-invasive methods to diagnose renal artery stenosis, such as contrast enhanced CT or MRI. However, these methods are not appropriate for patients with renal dysfunction. Ultrasound sonography is becoming one of the promising methods to diagnose artery stenosis because of photographic improvements. In this case, a 72-year-old woman was hospitalized 7 months after nephrectomy because of severe hypertension, heart failure and kidney dysfunction. The heart failure was quite uncontrollable in spite of massive administration of diuretics, and finally, hemodialysis was started to control her volume status. In consideration of her past history and abdominal bruit, we evaluated the renal artery stenosis by ultrasound sonography and confirmed the diagnosis by renal angiography. To improve hypertension control, we performed renal artery stenting, which resulted in an impressive improvement of her blood pressure and renal function. We recognized the importance of careful causal evaluation of renal dysfunction, even though it is difficult to apply invasive therapy to patients after nephrectomy.
Nippon Jinzo Gakkai shi 01/2011; 53(1):68-74.
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Taichi Murakami,
Hideharu Abe, Kojiro Nagai,
Tatsuya Tominaga,
Norimichi Takamatsu,
Toshikazu Araoka,
Seiji Kishi,
Toshikazu Takahashi,
Akira Mima,
Yoshimi Takai,
Jeffrey B Kopp,
Toshio Doi
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ABSTRACT: trophoblast glycoprotein (Tpbg), a 72-kDa transmembrane glycoprotein, is known to regulate the phenotypes of epithelial cells by modifying actin organization and cell motility. Recently, a microarray study showed that Tpbg is upregulated in Thy1 glomerulonephritis (Thy1 GN). We hypothesized that Tpbg regulates cytoskeletal rearrangement and modulates phenotypic alteration in podocytes under pathological conditions.
we examined Tpbg expression in Thy1 GN and Tpbg function in mouse podocytes.
we demonstrated that Tpbg is upregulated in the injured podocytes of Thy1 GN. In vitro, immunofluorescence studies revealed that Tpbg colocalized with the focal adhesion protein, vinculin, in parallel with stress fiber formation. This colocalization was observed even when actin filaments were depolymerized with cytochalasin D. Tpbg localization at focal adhesions was induced by dominant-active RhoA and suppressed by the ROCK1 inhibitor Y-26732. In addition, transforming growth factor-β increased Tpbg expression at focal adhesions concurrently with rearrangement of stress fibers. Stress fiber formation was suppressed in differentiated podocytes transfected with full-length Tpbg. Furthermore, knockdown of Tpbg using small interfering RNA decreased podocyte motility.
our findings suggest a novel role of Tpbg in the phenotypic alteration of injured podocytes, and we accordingly propose a new mechanism of glomerular injury in glomerulonephritis.
American Journal of Nephrology 10/2010; 32(6):505-21. · 2.54 Impact Factor
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Toshikazu Araoka,
Hiroya Takeoka,
Keisuke Nishioka,
Masaki Ikeda,
Makiko Kondo,
Azusa Hoshina,
Seiji Kishi,
Makoto Araki,
Rokuro Mimura,
Taichi Murakami,
Akira Mima, Kojiro Nagai,
Hideharu Abe,
Toshio Doi
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ABSTRACT: Refractory pleural effusion in systemic immunoglobulin light chain amyloidosis without cardiac decompensation is rarely reported and has a poor prognosis in general (a median survival of 1.6 months). Moreover, the optimum treatment for this condition is still undecided. This is the first report on the successful use of vincristine, adriamycin and dexamethasone chemotherapy for refractory pleural effusion due to systemic immunoglobulin light chain amyloidosis without cardiac decompensation.
We report the case of a 68-year old Japanese male with systemic immunoglobulin light chain amyloidosis presenting with bilateral pleural effusion (more severe on the right side) in the absence of cardiac decompensation that was refractory to diuretic therapy. The patient was admitted for fatigue, exertional dyspnea, and bilateral lower extremity edema. He had been receiving intermittent melphalan and prednisone chemotherapy for seven years. One month before admission, his dyspnea had got worse, and his chest radiograph showed bilateral pleural effusion; the pleural effusion was ascertained to be a transudate. The conventionally used therapeutic measures, including diuretics and thoracocentesis, failed to control pleural effusion. Administration of vincristine, adriamycin, and dexamethasone chemotherapy led to successful resolution of the effusion.
Treatment with vincristine, adriamycin, and dexamethasone chemotherapy was effective for the refractory pleural effusion in systemic immunoglobulin light chain amyloidosis without cardiac decompensation and appears to be associated with improvement in our patient's prognosis.
Journal of Medical Case Reports 10/2010; 4:322.
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ABSTRACT: Smad1 has previously been shown to play a key role in the development of diabetic nephropathy (DN), by increasing synthesis of extracellular matrix. However, the regulatory mechanism of Smad1 in DN is still unclear. This study aims to elucidate molecular interactions between activin receptor-like kinase 1 (ALK1)/Smad1 signaling pathway and transcription factor 7-like 2 (TCF7L2) in the progression of DN in vitro and in vivo. The expressions of TCF7L2 and ALK1 were induced by advanced glycation end products (AGEs) in parallel with Smad1, phosphorylated Smad1 (pSmad1), and alpha-smooth muscle actin (α-SMA) through TGF-β1 in cultured mesangial cells. Constitutively active ALK1 increased pSmad1 and α-SMA expressions. The binding of TCF7L2 to ALK1 promoter was confirmed by chromatin immunoprecipitation assay. Furthermore, TCF7L2 induced promoter activity of ALK1. AGEs and TGF-β1 induced a marked increase in TCF7L2 expression in parallel with ALK1. Overexpression of TCF7L2 increased the expressions of ALK1 and Smad1. Inversely, TCF7L2 knockdown by siRNA suppressed α-SMA expression as well as ALK1 and Smad1. The iNOS transgenic mice (iNOS-Tgm), which developed diabetic glomerulosclerosis resembling human diabetic nephropathy, exhibited markedly increased expressions of ALK1, TCF7L2, Smad1, pSmad1, and α-SMA in glomeruli in association with mesangial matrix expansion. These results provide a new evidence that the TCF7L2/ALK1/Smad1 pathway plays a key role in the development of DN.
Molecules and Cells 09/2010; 30(3):209-18. · 2.18 Impact Factor
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Toshikazu Araoka,
Hiroya Takeoka,
Hideharu Abe,
Seiji Kishi,
Makoto Araki,
Keisuke Nishioka,
Masaki Ikeda,
Tetsuro Mazaki,
Shiori Ikemura,
Makiko Kondo,
Azusa Hoshina, Kojiro Nagai,
Akira Mima,
Taichi Murakami,
Rokuro Mimura,
Kazumasa Oka,
Takao Saito,
Toshio Doi
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ABSTRACT: Type Iota(a) glycogen storage disease (GSD Iota(a)) is caused by the deficiency of glucose-6-phosphatase activity, which results in metabolic disorder and organ failure, including renal failure. GSD Iota(a) patients are generally diagnosed at a median age of 6 months. However, we report a 20-year-old Japanese female with newly diagnosed GSD Iota(a) . The renal disorder of GSD Iota(a) is considered to be produced by glomerular hyperfiltration, TGF-beta expression which is induced by renin-angiotensin-aldosterone system (RAS) and uric acid, and the increase in both small dense LDL and modified LDL which is characteristic of GSD Iota(a) as well as hypertriglyceridemia. With the administration of intensive therapies, including angiotensin type 1-receptor blocker and some lipid lowering drugs, along with traditional dietary therapy, daily proteinuria of the patient improved from 2.1 g to 0.78 g. Although the patients of GSD Iota(a) should receive an early and accurate diagnosis and effective therapies before the age of 1 year, the combination of traditional dietary therapies and intensive therapies may have therapeutic potential for the complications of adult patients. In this report, we describe the management of renal disease and the characteristic features of this metabolic disorder.
Internal Medicine 01/2010; 49(16):1787-92. · 0.94 Impact Factor
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Akira Mima,
Masanao Toma,
Takeshi Matsubara,
Fumihiko Shiota,
Noriyuki Iehara,
Hideharu Abe, Kojiro Nagai,
Toshikazu Takahashi,
Motokazu Matsuura,
Taichi Murakami,
Seiji Kishi,
Toshikazu Araoka,
Fumi Kishi,
Naoki Kondo,
Reiko Shigeta,
Kazuhiro Yoshikawa,
Takeshi Kimura,
Toru Kita,
Toshio Doi,
Atsushi Fukatsu
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ABSTRACT: Renal artery pseudoaneurysm is a rare clinical entity that has been reported after renal biopsy, percutaneous renal surgery, penetrating trauma, and rarely blunt renal trauma. We present the case of a 37-year-old man with ruptured renal artery pseudoaneurysm accompanied by massive gross hematuria, urinary clot retention, and bladder tamponade, which were the presenting signs seven hours after renal biopsy. Abdominal CT scan showed a large perinephric, intracapsular hematoma of left kidney. His angiogram revealed a left renal segmental artery pseudoaneurysm that measured 1 cm x 1 cm. He was successfully treated by selective embolization of the arterial branch supplying the pseudoaneurysm.
Renal Failure 01/2009; 31(8):753-5. · 0.82 Impact Factor
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Akira Mima,
Hidenori Arai,
Takeshi Matsubara,
Hideharu Abe, Kojiro Nagai,
Yukinori Tamura,
Kazuo Torikoshi,
Makoto Araki,
Hiroshi Kanamori,
Toshikazu Takahashi,
Tatsuya Tominaga,
Motokazu Matsuura,
Noriyuki Iehara,
Atsushi Fukatsu,
Toru Kita,
Toshio Doi
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ABSTRACT: We reported that Smad1 is a key transcriptional factor for mesangial matrix expansion in diabetic nephropathy. In this study, we examined whether urinary Smad1 in an early phase of diabetes can predict later development of glomerulosclerosis in diabetic nephropathy and how an angiotensin II type 1 receptor blocker (ARB) can modulate structural changes and urinary markers.
Smad1 and albumin in the urine were examined 4 weeks after injection of streptozotocin in 48 rats or 6 weeks of diabetes in db/db mice. Their renal pathology was analyzed after 20 weeks in rats or 12 weeks in mice. Among 48 diabetic rats 7 rats were treated with olmesartan for 20 weeks.
Urinary Smad1 of diabetic rats at 4 weeks was nicely correlated with mesangial matrix expansion at 24 weeks (r = 0.70, P < 0.001), while albuminuria showed a weaker association (r = 0.31, P = 0.043). Olmesartan treatment significantly ameliorated glomerulosclerosis and dramatically decreased urinary Smad1 (from 3.9 +/- 2.9 to 0.3 +/- 0.3 ng/mg creatinine, P < 0.05). In db/db mice, urinary Smad1 at 6 weeks was also significantly correlated with mesangial expansion at 18 weeks. In contrast, there was no change in urinary Smad1 in control diabetic rats or mice.
The increase of urinary Smad1 in the early stages of diabetes is correlated with later development of glomerulosclerosis in two rodent models. These data indicate that urinary Smad1 could be a novel predictor for later onset of morphological changes and can be used to monitor the effect of ARBs in diabetic nephropathy.
Diabetes 07/2008; 57(6):1712-22. · 8.29 Impact Factor
