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Biomedical subjects

I Shirato

Publications and source records attributed to I Shirato.

At least 19 recordsLinked to original sources
PubMed2002

An (CA)n dinucleotide repeat polymorphism of the interleukin-6 (IL-6) gene is associated with metacarpal bone mineral density in hemodialysis patients.

Genetic factors may play an important role in the pathogenesis of reduced bone mineral density (BMD). IL-6 is a multifunctional cytokine and a candidate gene for regulation of bone mineral density (BMD). The relationship between a microsatellite polymorphism of the IL-6 gene and metacarpal BMD in Japanese hemodialysis patients was examined. We selected 165 patients (96 males and 69 females) with a mean age of 62.0 +/- 13.7 years (mean +/- standard deviation (SD) in this study. They were dialyzed for an average of 75.8 +/- 60.8 months (mean +/- SD). The microsatellite polymorphism in the IL-6 gene was examined. According to the number of cytosine-adenine repeats, varying from 13 to 18, 6 alleles could be distinguished. Patients were categorized based on the presence or absence of the allele with 126 bp (i.e. 14 CA repeats) (allele A, all others allele O). The frequencies of IL-6 gene genotypes in hemodialysis patients were 16.4% for OO, 52.1% for AO and 31.5% for AA. The BMD score adjusted for age and body weight (Z score) in the AA genotype group (-0.93 +/- 1.17) was significantly lower than that in the OO (-0.09 +/- 1.42, mean +/- SD, p < 0.005) or AO group (-0.48 +/- 1.15, mean +/- SD, p < 0.01). Serum intact PTH in the OO genotype group (79.3 +/- 84.6) was lower than that in the AA (120.8 +/- 113.6, mean +/- SD, p 0.10) or AO group (132.1 +/- 106.5, mean +/- SD, p < 0.05). These results suggest that polymorphism of the IL-6 gene may be a useful marker for reduced BMD.

Aged↗
PubMed2001

Blockade of TGF-beta signaling in T cells prevents the development of experimental glomerulonephritis.

Anti-glomerular basement membrane (GBM) Ab-induced glomerulonephritis (GN) at late stage is thought to be mediated by T cells. However, signaling pathways of T cells that are involved in the development of anti-GBM Ab-induced GN are unclear. We have recently established transgenic mice expressing Smad7, an inhibitor of TGF-beta signaling, in mature T cells, where signaling by TGF-beta was blocked specifically in T cells. In this study, we showed that anti-GBM Ab-induced GN was suppressed in several measures in the transgenic mice including the severity of glomerular changes, proteinuria, renal function, and CD4 T cell infiltration into the glomeruli without down-regulation of CD62 ligand (CD62L) (L-selectin) expression on CD4 T cells. Furthermore, treatment with the soluble fusion protein of CD62L and IgG enhanced anti-GBM Ab-induced GN. These findings indicated that blockade of TGF-beta signaling in T cells prevented the development of anti-GBM Ab-induced GN. Because CD62L on T cells appears to be inhibitory for the development of anti-GBM Ab-induced GN, persistent expression of CD62L on CD4 T cells may explain, at least in part, the suppression of anti-GBM Ab-induced GN in the transgenic mice. Our findings suggest that the development of anti-GBM Ab-induced GN requires TGF-beta/Smad signaling in T cells.

Animals↗
PubMed2001

Urinary levels of interleukin-8 (IL-8) and disease activity in patients with IgA nephropathy.

Using quantitative sandwich ELISA, we studied 27 patients with IgA nephropathy to determine whether the levels of urinary IL-8 might reflect the disease activity. The levels of urinary IL-8 in patients with advanced stage IgA nephropathy were significantly higher than those in the patients with the mild stage of this disease, or in the healthy controls. The results showed a positive significant correlation between the levels of IL-8 and disease activity, i.e., between levels of urinary protein and urinary casts. A significant correlation between levels of urinary IL-8 and tubular function damage was also found. It was thus suggested that measurement of urinary IL-8 might be useful in evaluating the degree of renal injuries and/or prognosis in patients with IgA nephropathy.

Adult↗
PubMed2001

Identification of cellular origin of type I collagen in glomeruli of rats with crescentic glomerulonephritis induced by anti-glomerular basement membrane antibody.

BACKGROUND: Type I collagen is an interstitial collagen, which is not present in normal glomeruli. As type I collagen was observed in advanced glomerular lesions, it appears to be associated with deterioration of renal function. However, the origins of cells expressing type I collagen mRNA in glomeruli of diseased kidneys remains controversial. METHODS: We examined the expression of type I collagen in glomeruli at protein and mRNA levels in rat crescentic glomerulonephritis induced by anti-glomerular basement membrane (GBM) antibody. In addition, in situ hybridization and immunohistochemical staining of serial sections were performed to identify the cellular origin of type I collagen in glomeruli. RESULTS: Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) in isolated glomeruli showed that mRNA expression of type I collagen was remarkably increased on days 7, 14, and 28 after anti-GBM antibody injection (12.2+/-1.4, 20.2+/-2.1 and 14.6+/-1.0-fold over day 0, respectively). Immunofluorescence for type I collagen demonstrated marked staining in the fibrocellular and fibrous crescents, and weak staining within glomerular mesangial areas. In close association with mRNA levels analysed by RT-PCR, in situ hybridization revealed predominant presence of alpha1(I) collagen mRNA in cells within crescentic areas and Bowman's capsules. Serial section analysis for immunostaining and in situ hybridization showed that some alpha1(I) collagen mRNA-positive cells were also positive for cytokeratin. In contrast, no alpha1(I) collagen mRNA-positive cells were stained by ED-1 and podocalyxin. CONCLUSIONS: It appears that increased expression of type I collagen at the protein and mRNA levels in glomeruli is involved in the progression of glomerulonephritis. At least in this crescentic model, parietal epithelial cells (PECs) may partially contribute to the dysregulated production of type I collagen, which leads to glomerulosclerosis.

Animals↗
PubMed2001

Relationship between mast cells in the tubulointerstitium and prognosis of patients with IgA nephropathy.

There have been a few reports suggesting that mast cells may play an important role in the development of fibrosis and/or the degradation of extracellular matrix. We examined the relationship between the number of distribution of mast cells in tubulointerstitium and prognosis of patients with IgA nephropathy. Renal biopsy specimens were stained with mouse monoclonal antihuman mast cell tryptase antibody and then with aniline blue. Specimens from 45 patients with IgA nephropathy and from 5 patients with minimal-change nephrotic syndrome were used. There was a significant correlation between the number of mast cells per unit area of the whole tubulointerstitium and the degree of tubulointerstitial fibrosis or renal function. Patients with IgA nephropathy were divided into two groups (group 1: 'minimal' and 'slight'; group 2: 'moderate' and 'advanced') according to the classification by a previously reported method. Mast cells were mainly observed in the fibrotic areas in group 1. In group 2, many mast cells were detected not only in the fibrotic but also in the nonfibrotic areas. It appears that the number of mast cells in the nonfibrotic areas may be one of the predictive factors for the prognosis of patients with IgA nephropathy.

Adolescent↗
PubMed2001

Protein localization and mRNA expression of epimorphin in mouse and human kidneys.

Epimorphin is a mesenchymal cell surface protein which induces epithelial branching morphogenesis. However, the role of epimorphin in the kidney has not been addressed. In the present study, the localization of epimorphin protein and the expression of its mRNA were investigated in the developing mouse and adult human kidneys using immunohistochemistry and semiquantitative RT-PCR. The in vitro expression of epimorphin protein and its mRNA was also explored in cultured mouse and human mesangial cells. Epimorphin protein was expressed in the renal interstitium and the circumference of the comma-shaped body at day 16 of gestation. The intensity and distribution of epimorphin were gradually increased during kidney differentiation and maturation. Epimorphin was first observed in glomeruli at 1 week of age. The localization of epimorphin in glomerular mesangial cells and interstitial fibroblasts was confirmed by immunoelectron microscopy of 2-week-old mouse kidneys. The highest mRNA expression of epimorphin was observed at day 16 of gestation, thereafter it diminished with the maturation of the kidney. A similar localization of epimorphin was observed in a normal adult human kidney. Cultured human mesangial cells expressed epimorphin mRNA 150-kD protein. These results suggest that epimorphin may play a role in the development of the kidney and in the differentiation of fibroblast and mesangial cells.

Animals↗
PubMed2001

Dilazep hydrochloride, an antiplatelet drug, inhibits lipopolysaccharide-induced mouse mesangial cell IL-6 secretion and proliferation.

BACKGROUND: Antiplatelet agents have been widely used to reduce proteinuria and to prevent the progression of chronic glomerulonephritis or diabetic nephropathy to end-stage renal failure. Dipyridamole, one type of antiplatelet drug, inhibits the proliferation of glomerular mesangial cells (MCs). The effect of dilazep hydrochloride (dilazep) on these cells is still obscure. The effects of dilazep on cultured MC IL-6 secretion and proliferation were investigated in the present study. METHODS: IL-6 secretion from MC induced by bacterial lipopolysaccharide (LPS) were assessed using sandwich ELISA. LPS-induced MC proliferation was detected by 3H-thymidine incorporation and WST-1 assay (similar to MTT assay). RESULTS: Incubation of MCs with various dosages of LPS (0, 1, 10, 50 and 100 ng/ml) induced IL-6 secretion in a dose-dependent manner. However, dilazep significantly inhibited this LPS-induced IL-6 secretion from MCs in a dose- and time-dependent manner. Dilazep also significantly inhibited MC proliferation in a dose-dependent manner. CONCLUSION: It appears that these effects of dilazep may prevent progression of mesangial proliferative glomerulonephritis.

Animals↗
PubMed2001

Podocyte injury predicts prognosis in patients with iga nephropathy using a small amount of renal biopsy tissue.

To predict the progression in patients with IgA nephropathy, we analyzed glomerular lesions except for sclerosis, adhesion and/or crescents in 34 patients with this disease by morphometric analysis. Levels of urinary protein excretion (UP), creatinine clearance (Ccr), serum creatinine (sCr) and mean blood pressure (MBP) at the time of renal biopsy were used as the clinical parameters. The slope of 1/sCr was also used as a prognostic parameter. Renal specimens were obtained by echo-guided biopsy. In PAS-stained light microscopic renal sections, three mid sections of open glomeruli were selected and photographed. Stereologic estimation was performed as follows: absolute values of glomerular volume (V(G)), glomerular surface area (S(G)), podocyte and nonpodocyte cell number per glomerulus (N(G(pod)) and N(G(Non-pod))), glomerular surface area covered by one podocyte S(G)/N(G(pod))) and glomerular volume occupied by one nonpodocyte cell (V(G)/N(G(Non-pod))). There was a significant correlation between the levels of UP and the change of podocyte injury parameters (N(G(pod)) and S(G)/N(G(pod))) or N(G(Non-pod)). N(G(pod)) was negatively but S(G)/N(G(pod)) and N(G(Non-pod)) were positively correlated with UP. S(G)/N(G(pod)) or N(G(Non-pod)) was correlated with MBP. N(G(pod)), S(G)/N(G(pod)), N(G(Non-pod)), UP or MBP was significantly correlated with the slope of 1/sCr. High specificity was observed for N(G(pod)), S(G)/N(G(pod)) and MBP. High sensitivity was also observed for N(G(Non-pod)) and UP. It appears that podocyte injury might provide additional prognostic information in patients with IgA nephropathy.

Adolescent↗
PubMed2001

[Immunohistochemical analysis of protein gene product 9.5, a new marker for parietal epithelial cells of Bowman's capsules, in anti-glomerular basement membrane(GBM) antibody induced glomerulonephritis of WKY rats].

Protein gene product 9.5(PGP 9.5) is expressed specifically in neuroendocrine cells and considered to be one of the neuroendocrine markers. Recently, we reported that PGP 9.5 is localized in the parietal epithelial cells(PECs) of Bowman's capsules as well as in neural tissues. In the present study, immunohistochemical analysis of PGP 9.5 as a specific marker of the PECs of Bowman's capsules, synaptopodin as a podocyte-specific marker, and ED-1 as a specific marker of monocytes/macrophages was performed in the cellular crescents in anti-GBM antibody induced glomerulonephritis of WKY rats using serial renal sections. In the acute phase of anti-GBM antibody induced glomerulonephritis, and the expression of PGP 9.5 and ED-1 was observed diffusely in proliferating cells of cellular crescents. However, in most part of cellular crescents, PGP 9.5 positive areas did not overlap with the ED-1 positive areas. Synaptopodin was constantly detected along the glomerular tufts compressed by the crescents. In the chronic phase of this disease, PGP 9.5 was observed in the cells covering the surface of fibrous crescents or scattered within fibrocellular crescents. Synaptopodin was partially detected in such cells. It appears that cellular crescents are composed mainly of proliferating PECs and macrophages in rat anti-GBM antibody-induced glomerulonephritis.

Animals↗
PubMed2001

[A case of gastric antral vascular ectasia (GAVE) with chronic renal failure].

A 76-year-old woman was admitted to our hospital complaining of tarry stool, general fatigue and marked anemia(Hb 5.2 g/dl). Gastric endoscopic findings showed longitudinal red stripes and diffuse erythematous spots, indicating dilated vascular vessels. They resembled the stripes of a watermelon at the gastric antrum. The marked anemia was caused by chronic blood loss from the abnormally dilated mucosal and submucosal capillary veins in the gastric antrum. She was diagnosed as having gastric antral vascular ectasia(GAVE) with chronic renal failure(CRF). The association of GAVE and CRF is considered to be rare according to previous reports in Japan. Endoscopic argon plasma coagulation therapy was performed three times. After therapy, capillary dilatation disappeared, and the marked anemia was greatly improved. Argon plasma coagulation therapy was found to be a safe and effective procedure for this disease. Although GAVE is essentially a benign gastric disease, endoscopic therapy should be the treatment of first choice for this disease.

Aged↗
PubMed2000

Macrophage-derived MT1-MMP and increased MMP-2 activity are associated with glomerular damage in crescentic glomerulonephritis.

Membrane-type matrix metalloproteinases (MT-MMPs) have been shown to activate pro-MMP-2 on the cell surface and are suggested to be key enzymes in tissue remodelling under various physiological and pathological conditions. To investigate the role of MT-MMP in progressive renal injury, the gene expression and enzymatic activity of MT-MMP were examined in crescentic glomerulonephritis induced by anti-glomerular basement membrane (GBM) antibody in WKY rats. Isolated glomeruli were subjected to RNA and protein extraction 0, 1, 3, 7, 14, and 28 days after intravenous injection of rabbit anti-GBM antibody. Semiquantitative RT-PCR analysis revealed that among the three members of the MT-MMP family, mRNA expression of MT2-MMP remained unchanged and that of MT3-MMP was not observed in glomeruli during the development of nephritis. However, MT1-MMP gene expression increased from day 3 and reached maximum levels at day 7 (5.5+/-0.7-fold increase over day 0), closely associated with macrophage accumulation, crescent formation, and increased proteinuria. Gelatin zymography showed that the active from of MMP-2 emerged from day 7 and remained during the experimental period accompanied by increased proMMP-2, while no active form of MMP-2 was found in control rats. Using an antisense cRNA probe, intense signals of MT1-MMP mRNA were observed mostly in cells within the crescent and in some cells in the mesangial areas. Most of these cells were ED-1-positive macrophages, based on immunostaining of sequential sections. These results suggested that in the MT-MMP family, MT1-MMP was induced in infiltrating macrophages during the development of crescentic glomerulonephritis and possibly contributed to pathological degradation of glomerular extracellular matrices through the activation of proMMP-2.

Animals↗
PubMed2000

Effects of the new hydroxy-3-methylglutaryl coenzyme a reductase inhibitor fluvastatin on anti-oxidant enzyme activities and renal function in streptozotocin-induced diabetic rats.

1. The effects of 11 week treatments with the new hydroxy3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor fluvastatin on renal intrinsic anti-oxidant enzyme (AOE) activities and renal function were evaluated in streptozotocin (STZ)-induced diabetic rats. 2. Renal intrinsic AOE activities, creatinine clearance and urinary albumin excretion were examined in STZ-induced diabetic rats. The levels of total cholesterol (TC), triglyceride (TG) and phospholipid (PL) were also examined. 3. In general, renal AOE activities and function were lower in diabetic rats than in non-diabetic Sprague-Dawley rats. 4. Decreases in TC, TG and PL levels and urinary albumin excretion by the HMG-CoA reductase inhibitor fluvastatin improved renal function and produced a non-uniform alteration in renal AOE; only glutathione peroxidase (GSH-Px) activity increased significantly with fluvastatin treatment. 5. It appears that the improvement in renal function and albuminuria may be related to increases in GSH-Px activity, but there was no correlation between changes in renal function and changes in the activity of Mn-superoxide dismutase or catalase.

Animals↗
PubMed2000

Effect of calcium channel blockers, nifedipine and benidipine, on death of cultured mouse mesangi al cells.

We examined the effects of the short-acting calcium channel blocker (CCB) nifedipine and the long-acting CCB benidipine on the death of mouse cultured mesangial cells induced by tumor necrosis factor alpha (TNF-alpha) and/or cycloheximide (CHX). Cell death was evaluated by a morphological study using semithin sections. The dead cells were divided into three types, i.e., apoptotic cells (type 1), necrotic cells (type 3) and other types of dead cells, the so-called 'secondary necrotic cells' or 'postapoptotic necrotic cells' (type 2). In the morphological study with semithin sections, cells in the presence of TNF-alpha or CHX and nifedipine or benidipine showed low percentages of all dead cell types with 24 h incubation. Both nifedipine and benidipine have protective effects against TNF-alpha or CHX. It is postulated that CCB might inhibit the apoptotic or necrotic processes by TNF-alpha or CHX with 24 h incubation. With 36 h incubation, CCB increased the percentages of all types of dead cells except for treatment with 1x10(-5) M benidipine and CHX. It appears that these cell-protective effects might be decreased after treatment with TNF-alpha or CHX and CCB for 36 h. In conclusion, the short-acting CCB nifedipine and the long-acting CCB benidipine have protective effects on mouse cultured mesangial cells against TNF-alpha or CHX. However, nifedipine and benidipine did not inhibit specific types of cell death using semithin sections in this study.

Animals↗
PubMed2000

Effect of dilazep hydrochlorideon the Im munohistopathology of IgA nephropathy in ddY mice.

We determined the clinical and immunopathological effects of dilazep hydrochloride (dilazep) on IgA nephropathy of ddY mice. Group I (early-treatment group, n = 10) was orally treated with 300 mg/kg body weight of this drug from 12 weeks of age until 60 weeks of age, and group II (late-treatment group, n = 10) was also treated with the same dosage of this drug from 20 weeks of age until 60 weeks of age. Group III (control group, n = 10) received drinking water. On immunofluorescence, distribution and intensity of IgA and C3 depositions in glomeruli of group I and group II animals were significantly decreased as compared with those in group III. The expression of fibronectin, laminin, or type IV collagen in glomeruli was basically similar in the three groups treated with or without dilazep. On light microscopy, the expansion of glomerular mesangial areas and the average number of intraglomerular cells were markedly decreased as compared with those in group III. The levels of urinary protein excretion in groups I and II were significantly lower than those in group III (p < 0.01 and p < 0.05). These findings suggest that treatment with dilazep might improve the clinical and immunopathological findings in IgA nephropathy of ddY mice.

Animals↗