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  • 1
    Electronic Resource
    Electronic Resource
    Activation of mRNA expression of collagen, collagenase and its inhibitor on renal biopsy specimens in patients with IgA nephropathy (1997)
    Oxford, UK : Blackwell Publishing Ltd
    Nephrology 3 (1997), S. 0 
    Details
    ISSN: 1440-1797
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary: In situ hybridization of mRNA for collagen IV, collagen VI, stromelysin (MMP-3) and TIMP1 was examined in renal biopsy specimens from patients with IgA nephropathy (IgAN) or diabetic nephropathy with various degrees of tissue damage. The majority of cells in the glomeruli expressed these mRNA almost simultaneously, but a few cells demonstrated positive expression for only one of these probes. There was a parallel relationship between the degree of tissue damage and that of mRNA expressions of these probes in patients with IgAN, while patients with diabetic nephropathy showed a reverse relationship between these two parameters. It is concluded that patients with mesangial proliferative glomerulonephritis expressed mRNA for collagen collagenase and its inhibitor in the glomeruli in parallel with the progress of tissue damage. In contrast, glomerular samples from patients with diabetic nephropathy showed that there was an inverse relationship between tissue damage and expression of mRNA. It is concluded that expression of collagen, collagenase and its inhibitor parallels the progression of glomerular changes in IgAN, but such parallel expression was not observed in patients with diabetic nephropathy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1797.1997.tb00196.x
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  • 2
    Electronic Resource
    Electronic Resource
    Intrarenal synthesis of IL-6 in IgA nephropathy (1997)
    Oxford, UK : Blackwell Publishing Ltd
    Nephrology 3 (1997), S. 0 
    Details
    ISSN: 1440-1797
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary: Recent in vitro studies have shown the synthesis of interleukin-6 (IL-6) in glomerular mesangial and epithelial cells, and suggested the involvement of IL-6 in mesangial proliferative glomerulonephritis. However, the expression site of IL-6 mRNA in renal tissue of IgA nephropathy (IgAN), the most common chronic mesangial proliferative glomerulonephritis, remains obscure. to localize IL-6 mRNA in renal biopsy specimens of IgAN, we used nonradioactive in situ hybridization (ISH) developed in our laboratory, sensitive in detecting individual cells positive for a specific mRNA. In some sections, periodic acid-Schiff staining was performed after ISH in order to identify the topographical relation between IL-6 mRNA positive cells and glomerular basement membrane and mesangial area. In situ hybridization for IL-6 mRNA and immunohistochemistry for CD3 and CD68, markers for lymphocytes and monocytes, respectively, were also performed on serial sections to examine the contribution of infiltrated mononuclear cells to cells positive for IL-6 mRNA in glomeruli. Glomerular resident cells, including glomerular mesangial and epithelial cells and cells of Bowman's capsule, as well as tubular epithelial cells and infiltrated mononuclear cells expressed IL-6 mRNA. We also compared the localization of IL-6 mRNA and protein and showed different distribution between the gene product and protein. the expression of IL-6 mRNA correlated with the degree of mesangial cell proliferation and tubulointerstitial changes. Our results indicate that IL-6 is synthesized in renal tissues of IgAN and suggest that the increased IL-6 expression may be important in the pathogenesis of IgAN.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1797.1997.tb00265.x
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  • 3
    Electronic Resource
    Electronic Resource
    Immunohistochemical staining of renal biopsy samples in patients with diabetic nephropathy in non-insulin dependent diabetes mellitus using monoclonal antibody to advanced glycation end products (1995)
    Oxford, UK : Blackwell Publishing Ltd
    Nephrology 1 (1995), S. 0 
    Details
    ISSN: 1440-1797
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary: Immunohistochemical staining of glomeruli in patients with diabetic nephropathy (DN) in non-insulin dependent diabetes mellitus (NIDDM) using the monoclonal anti-advanced glycation end products (AGE) antibody is described. In order to detect the localization of AGE in human renal tissues, we performed immunohistochemical staining using the monoclonal anti-AGE antibody in the glomeruli of 11 patients with DN and 11 age-matched patients with diffuse mesangial proliferative glomerulonephritis without IgA deposition (DPGN) as controls.Emergence of AGE in the mesangial area was more marked in the glomeruli of patients with severe mesangial expansion than in those with mild expansion. AGE in the extraglomerular arteriolar walls was also observed. In contrast, there was no positive staining using the same antibody in renal tissue obtained from DPGN.These data support the concept that deposition and/or formation of AGE in the mesangial area might be associated with the progression of diabetic nephropathy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1797.1995.tb00028.x
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  • 4
    Electronic Resource
    Electronic Resource
    Glomerular expression of connective tissue growth factor mRNA in various renal diseases (2003)
    Melbourne, Australia : Blackwell Science Pty
    Nephrology 8 (2003), S. 0 
    Details
    ISSN: 1440-1797
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: SUMMARY:  Connective tissue growth factor (CTGF) is a cysteine-rich member of a new family of growth regulators. It is an important factor in the pathogenesis of mesangial matrix accumulation and progressive glomerulosclerosis. The present study was designed to elucidate the role of CTGF in diabetic nephropathy (DN), immunoglobulin A nephropathy (IgA-N), membranous nephropathy (MN), and minimal change nephrotic syndrome (MCNS). We evaluated the expression and localization of CTGF mRNA in surgically excised renal tissue samples from 10 patients with DN, 10 with IgA-N, 10 with MN, 10 with MCNS, and 10 normal human kidney (NHK) tissue samples, by using high-resolution in situ hybridization with digoxigenin-labelled oligonucleotide. To quantify CTGF mRNA expression, we counted all nuclei, and nuclei surrounded by CTGF-positive cytoplasm, in at least 10 randomly selected cross-sections of non-sclerotic glomeruli, and expressed the results as a percentage of total glomerular cells. In all glomeruli, CTGF mRNA was expressed mainly in glomerular intrinsic cells, including glomerular mesangial and epithelial cells and some cells of Bowman's capsule. The percentage of cells positive for CTGF mRNA was significantly higher in DN and IgA-N than in MN, MCNS and NHK. However, there was no significant difference in the percentage of CTGF mRNA-positive cells between DN and IgA-N. Our study indicates that CTGF may play an important role in the development and progression of glomerulosclerosis in DN and IgA-N, which are both accompanied by mesangial matrix expansion and comprise two major causes of end-stage renal failure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1440-1797.2003.00142.x
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  • 5
    Electronic Resource
    Electronic Resource
    Significance of alpha-smooth muscle actin expression in IgA nephropathy: Revisited (2004)
    Melbourne, Australia : Blackwell Science Pty
    Nephrology 9 (2004), S. 0 
    Details
    ISSN: 1440-1797
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1797.2004.00280.x
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  • 6
    Electronic Resource
    Electronic Resource
    Platelet derived growth factor-D may be a possible therapeutic target for advanced IgA nephropathy (2005)
    Melbourne, Australia : Blackwell Science Pty
    Nephrology 10 (2005), S. 0 
    Details
    ISSN: 1440-1797
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1797.2005.00510.x
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  • 7
    Electronic Resource
    Electronic Resource
    Molecular approaches to the study of renal disease (1996)
    Oxford, UK : Blackwell Publishing Ltd
    Nephrology 2 (1996), S. 0 
    Details
    ISSN: 1440-1797
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary: Recent developments in cell biology and molecular biology have provided new techniques for molecular studies on renal diseases. the in situ hybridization technique demonstrates the site and the degree of gene expression of various cytokines and regulating proteins associated with the altered function of the glomeruli. It is not known, however, if the expression of these genes is different among various glomerular diseases. the aim of this study was to elucidate the disease specific phenomena in glomerular gene expression. Renal biopsy specimens were obtained from patients with diabetic nephropathy, and IgA nephropathy. the degree of tissue damage as well as the levels of various clinical parameters were matched between these two groups. In situ hybridization of mRNA in renal tissues for transforming growth factor (TGF)-β, storomelysin (MMP-3) and tissue inhibitor of metalloproteinase (TIMP-1) were performed using nonradioactive digoxigenin (DIG)-labelled oligonucleotide probes. In parallel studies, renal biopsy specimens were stained with monoclonal antibody against advanced glycated end-products (AGE). the results demonstrated that the distribution of mRNA expression of TGF-β was similar between these two diseases, but the expression of MMP-3 and TIMP-1 was parallel with the degree of tissue damage in patients with IgA nephropathy while it was diminished in patients with an advanced degree of tissue damage due to diabetic nephropathy. Positive staining of renal tissues with anti-AGE antibody was only observed in patients with diabetic nephropathy. It is concluded that glycation of renal structural proteins might interfere with their metabolism by enzymes and their inhibitors, while a cytokine responsible for mesangial expansion was similarly expressed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1797.1996.tb00152.x
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  • 8
    Electronic Resource
    Electronic Resource
    Value of pathological grading in prediction of renal survival in IgA nephropathy (1996)
    Oxford, UK : Blackwell Publishing Ltd
    Nephrology 2 (1996), S. 0 
    Details
    ISSN: 1440-1797
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary: In order to clarify the most reliable risk factor to predict renal outcome, 206 patients with IgA nephropathy were studied for mean period of 9.2 years. the histopathological changes of this disease using light microscopy were divided into four grades (grade 1–4). These grades included glomerular, interstitial and vascular lesions. the cumulative rate of kidney survival progressing to end stage renal failure (ESRF) in all patients was 94% at 5 years, 87% at 10 years and 80% at 15 years after renal biopsy. None of the patients in grade 1 reached ESRF. the cumulative rate of kidney survival in grade 2 was 99% at 5 years, 98% at 10 years and 89% at 15 years after renal biopsy. In grade 3, it was 94% at 5 years, 79% at 10 years and 75% at 15 years. In grade 4 it was 53% at 5 years, 33% at 10 years and 22% at 15 years after renal biopsy. Forward stepwise multivariate regression analysis revealed that, in addition to the histopathological findings, three more risk factors were found to influence actuarial renal survival rate. These factors were: (i) the levels of serum creatinine; (ii) the level of serum albumin; and (iii) the amount of proteinuria at the time of renal biopsy. In parallel studies, forward stepwise multivariate regression analysis isolated three risk factors that influenced the progression of the reciprocal of serum creatinine. These factors were: (i) the levels of total protein; (ii) the degree of our pathological grading; and (iii) the amount of proteinuria. It was concluded that our pathological grading was useful as a prognostic parameter because of its simplicity and availability in routine clinical activities.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1797.1996.tb00073.x
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  • 9
    Electronic Resource
    Electronic Resource
    Laminin in the interstitium indicates prognosis in patients with IgA nephropathy (2000)
    Melbourne, Australia : Blackwell Science Pty
    Nephrology 5 (2000), S. 0 
    Details
    ISSN: 1440-1797
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Laminin is implicated in cell migration, remodelling of the extracellular matrix and basement membrane. Therefore, laminin deposition could be of concern in the progression of some renal diseases. In the present study, immunohistochemical and in situ hybridization studies were performed for laminin in IgA nephropathy (IgAN) specimens in order to reveal the importance of laminin deposition for their prognosis. Fifteen patients were used as the stable group who maintained stable renal function for more than 10 years after biopsy. Thirteen patients formed the progressive group who reached end-stage renal failure within 10 years after biopsy. Immunohistochemically, laminin was specifically deposited in damaged glomeruli and strong immunoreactivity was particularly shown in the expanded interstitial area containing infiltrating mononuclear cells. Although the staining score in glomeruli was not significantly different between these two groups (P = 0.181), deposition in the expanded interstitium was extensive and significantly greater in the progressive group (P 〈 0.01). In situ hybridization revealed that most of the interstitial cells and some of the tubular cells expressed laminin messenger ribonucleic acid. In conclusion, the extent of interstitial laminin deposition was an important prediction of adverse renal outcome. This laminin could be produced by interstitial cells and/or tubular cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1440-1797.2000.00502.x
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  • 10
    Electronic Resource
    Electronic Resource
    In situ hybridization studies of stromelysin and tissue inhibitor of metalloproteinase 1 in IgA nephropathy (1995)
    Oxford, UK : Blackwell Publishing Ltd
    Nephrology 1 (1995), S. 0 
    Details
    ISSN: 1440-1797
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary: Accumulation of the extracellular matrix (ECM) in IgA nephropathy (IgAN) is thought to cause deterioration of glomerular function. Stromelysin and tissue inhibitor of matrix proteinase 1 (TIMP1) may play an important role in the turnover of the glomerular ECM. However, the expression of these enzymes in human renal tissues remains undefined. In the present study, non-radioactive in situ mRNA hybridization, which permitted the analysis at a cellular level, was performed to localize stromelysin and TIMP1 in renal tissue of IgAN. We also determined the percentage of cells positive for stromelysin or TIMP1 mRNA among intraglomerular cells. A total of 16 patients with IgAN were examined, including eight patients with severe histopathological changes and eight with mild changes. Three patients without glomerular disease were also studied. Stromelysin and TIMP1 mRNA were weakly expressed in the mesangium of normal kidneys and IgAN renal tissues with mild damage. However, the expression of both mRNA was significantly increased in the area of mesangial proliferation, in glomerular epithelial cells and in Bowman's capsule of advanced lesions. Several cells in the area of mesangial proliferation were double positive for stromelysin and TIMP1 mRNA, while certain cells positive for stromelysin mRNA did not express TIMP1 mRNA. In the interstitium, epithelial cells of certain tubules and some mononuclear cells were positively stained for these mRNA, especially in advanced lesions. Our results indicated that stromelysin and TIMP1 genes were expressed in glomerular resident cells, tubular epithelial cells and infiltrated mononuclear cells in IgAN, and their expression was enhanced in advanced tissue damage. the demonstration of a co-expression and discordant expression of the genes indicates that each gene expression may be regulated in a cell type-specific manner and that it could also be altered by cellular environmental factors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1797.1995.tb00017.x
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