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K Shikata

Publications and source records attributed to K Shikata.

105 records · Page 6Linked to original sources
PubMed1992

High resolution three-dimensional meshwork structure of the glomerular basement membrane.

To investigate the ultrastructure of the glomerular basement membrane (GBM), rat GBM was treated with sodium dodecyl sulfate and 2-mercaptoethanol and observed under an electron microscope employing ultrathin sectioning and rotary shadowing methods. Further, thick sections of the treated GBM were examined by high voltage transmission electron microscopy. A fine three-dimensional meshwork structure was clearly observed through the entire thickness of the GBM treated with sodium dodecyl sulfate and 2-mercaptoethanol by conventional transmission electron microscopy and high voltage transmission electron microscopy. The diameter of the fibrils forming the meshwork structure was about 3 nm and the dimensions of the pores present in the meshwork were 3 to 4 nm. The rotary shadowing technique revealed fine fibrils disentangled from the GBM that were bound together, and corresponded morphologically type IV collagen molecules. The present findings suggested that the GBM has a fine three-dimensional meshwork structure through its entire thickness which is composed mainly of type IV collagen and may function as a size barrier in the renal glomerulus.

Animals↗
PubMed1991

A membranous nephropathy associated with adult polycystic kidney disease.

A 53-year-old woman with adult polycystic kidney disease (PKD) developed a nephrotic syndrome. Evaluation of the renal biopsy specimens showed typical findings of membranous nephropathy (MN). There are few reports of nephrotic syndrome associated with PKD and only one proved to be MN. The possible mechanism of the association of PKD with MN was evaluated. Autoantibodies against the brush border were not detected in this patient's serum by indirect immunofluorescence. Three monoclonal antibodies against the tubular brush border and epithelial cell of distal tubulus did not react with subepithelial deposits in the biopsy specimen. Therefore tubular brush border antigen which was reported to induce membranous nephropathy was not detected in the immune complexes deposited in the glomeruli. So we could not determine any direct relationship between PKD and MN. The reaction of antibodies against basement membrane components (type IV collagen, laminin, fibronectin, heparansulfate proteoglycan) with the basement membranes of the cysts was evaluated by indirect immunofluorescence. The reaction with anti-heparansulfate proteoglycan antibody was decreased compared with normal tubular basement membrane. The reactivity to anti-fibronectin antibody was remarkably increased in the cystic walls, tubules, and interstitium. Changes of tubular basement membrane antigens was observed in PKD.

Antigen-Antibody Complex↗
PubMed1990

Three-dimensional architecture of rat glomerular basement membrane by ultra-high resolution scanning electron microscopy.

We demonstrated the ultrastructure of rat glomerular basement membrane (GBM) by ultra-high resolution scanning electron microscopy. GBM prepared by sonication methods and conductive-staining could be observed without metal coating at magnifications as high as 400,000 times. The GBM showed an irregular meshwork structure composed of various strands and pores. The width of the strands ranged from 6 to 15 nm, and the diameter of pores ranged from 6 to 50 nm. The present study confirmed our molecular sieve theory of the basement membrane.

Animals↗
PubMed1990

Three-dimensional meshwork structure of glomerular basement membrane revealed by chemical treatment.

In order to study the three-dimensional ultrastructure of the glomerular basement membrane (GBM), isolated GBM was treated with elastase, sodium dodecyl sulfate, and 2-mercaptoethanol and examined by transmission electron microscopy using ultrathin sectioning method and stereoscopic view. This treatment revealed clearly three-dimensional meshwork structure of GBM mainly composed of type IV collagen. Numerous regular polygonal small pores were present in the meshwork structure. The average short dimension of the small pores was 4.1 +/- 1.8 nm and the average long dimension was 4.8 +/- 2.2 nm. Our present results further support the molecular sieve theory of the basement membrane.

Animals↗
PubMed1990

[Effect of methylprednisolone pulse therapy in patients with lupus nephritis assessed by WHO morphologic classification].

To determine indications for treatment with high-dose intravenous methylprednisolone pulse therapy in lupus nephritis, we retrospectively assessed the response to pulse therapy over oral prednisolone administration in 120 biopsy proven lupus nephritis patients according to WHO morphologic classification. In the pulse group, 1 g of methylprednisolone was administered on three consecutive days and oral steroid therapy (40-30 mg) was started. In many occasions in treating class III and IV-b, repeated pulse therapy was performed. In control oral prednisolone group, middle-dose steroid therapy (50-30 mg) was started. In patients with minor glomerular abnormalities and mesangial lupus nephritis, rapid improvement of serological activities was observed in pulse group assessed by serum complement level, anti-DNA antibodies, and anti-nuclear antibodies. In patients with focal lupus nephritis, rapid rise in serum complement level and fall in proteinuria was observed in the pulse group. In patients with diffuse proliferative lupus nephritis with active necrotizing lesions, faster rise in serum complement level and proteinuria were observed in the pulse group. In patients with membranous lupus nephritis there was no significant difference between two groups. In comparison with the effect of pulse therapy among each morphologic class, the rise of serum complement level was slowest in class IV-b. Both group of IV-b and V manifested nephrotic syndrome and by pulse therapy the decrease in urinary protein was faster and more significant in class IV-b compared with class V. No significant adverse effect of methylprednisolone was observed during about 150 times of pulse therapy. Bacterial, viral infections such as herpes zoster and fungal infections were observed in pulse group as often as control group.

Administration, Oral↗
PubMed1989

Human liver ferritin as a new tracer for studying glomerular permeability.

Sprague-Dawley rats, 6 with aminonucleoside nephrosis and 6 controls, were intravenously injected with human liver ferritin isolated from post mortem liver, and their 24-h urine samples were examined for human ferritin by immunoradiometric assay. In rats with aminonucleoside nephrosis, the amount of excreted ferritin in urine was forty times greater than in control rats. Much more monomeric ferritin was excreted than that of polymeric ferritin. We are the first to have utilized human liver ferritin as a tracer to measure a minor amount of ferritin by a commercially available kit. Our present study seems to indicate a critical role for glomerular basement membrane as a size barrier.

Animals↗
PubMedDate not supplied

Changes in glomerular extracellular matrices components in diabetic nephropathy.

The changes in glomerular extracellular matrices components in diabetic nephropathy were investigated. Indirect immunofluorescence staining, using polyclonal antibodies to heparan sulfate proteoglycan (HS-PG), laminin, type IV collagen, and fibronectin was carried out on renal specimens obtained by needle biopsy. Immunofluorescence intensity and distribution were observed. HS-PG and laminin decreased in the capillary walls; on the other hand, type IV collagen and fibronectin tended to increase in the mesangial area. HS-PG and laminin decreased in inverse proportion to sclerosis grades and proteinuria. These changes seemed to play an important role in progression of diabetic glomerulosclerosis.

Biopsy, Needle↗
PubMedDate not supplied

Increased concentrations of the basement membrane component type IV collagen in sera and urine of diabetics.

We measured serum and urinary concentrations of type IV collagen by radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) in diabetics. Serum and urinary concentrations of type IV collagen measured by RIA and ELISA were increased compared to those of control subjects. In diabetics with macroproteinuria or with renal insufficiency, serum and urinary concentrations of type IV collagen were higher than in diabetics without nephropathy or with early renal damage as determined by the presence of microproteinuria. These results suggest that serum and urinary concentrations of type IV collagen are increased in patients with advanced diabetic nephropathy. These increases may indicate that alteration of basement membrane metabolism has occurred in diabetics.

Antibodies, Monoclonal↗
PubMedDate not supplied

Upregulation of insulin-like growth factor receptor gene in experimental diabetic rat glomeruli.

Renal hypertrophy is a characteristic and early manifestation of diabetes in human and experimental animals. We examined the precise distribution of insulin-like growth factor-I (IGF-I) receptor mRNA in the experimental diabetic rat kidney using a nonradioactive in situ hybridization technique. Expression of IGF-I receptor mRNA was rarely seen in the glomeruli of control rats. IGF-I receptor mRNA was detected after induction of diabetes in glomerular mesangial, visceral epithelial, and parietal epithelial cells. The number of IGF-I receptor mRNA-positive cells in a glomerulus increased significantly at 4 weeks as compared with the control rats. Overexpression of IGF-I receptor in glomerular cells may contribute to the glomerular hypertrophy in diabetic nephropathy.

Animals↗
PubMedDate not supplied

Localization of advanced glycation endproducts in the kidney of experimental diabetic rats.

Advanced glycation endproducts (AGE) have been proposed as a major mediator in the development of various diabetic complications. In order to evaluate the involvement of AGE in the development of diabetic nephropathy, we examined the localization of AGE in the kidney of the streptozotocin-induced diabetic rats immunohistochemically using a monoclonal antibody directed to AGE. In the diabetic rats, glomerular hypertrophy, thickening of the glomerular basement membrane, and expansion of mesangial matrix were observed. AGE was detected in expanded mesangial area and glomerular basement membrane in the kidneys of diabetic rats. The present results suggest that AGE may participate in the development of diabetic nephropathy.

Animals↗
PubMedDate not supplied

Phenotypic changes of the mesangium in diabetic nephropathy.

In diabetic nephropathy there is accumulation of matrix proteins. Overproduction of these matrix proteins considered to be due to the phenotypic change of mesangial cell. In order to detect the phenotypic change of the mesangial cell, renal biopsy specimens from patients with diabetic nephropathy were stained with antibodies against various types of collagens and contractile-associated protein, caldesmon. Type III collagen was not stained in the glomerulus and type VI collagen showed mesangial pattern from normal controls. In diabetes, mesangial staining of type III collagen and increases in type VI collagen were observed in the mesangium. Increased mesangial staining of caldesmon was noted in the glomerulus from diabetic nephropathy in contrast to only vessel staining from normal controls. These results indicate that phenotypic changes are noted in the mesangium in diabetes. Expression of contractile-associated protein such as caldesmon, would serve as a useful marker to predict glomerulosclerosis.

Antibodies↗
PubMedDate not supplied

The ultrastructural disruption of the glomerular basement membrane in diabetic nephropathy revealed by "tissue negative staining method".

To clarify the ultrastructural changes of the glomerular basement membrane (GBM) in diabetic nephropathy, the renal tissues of the patients with diabetic nephropathy were examined by electron microscopy using our newly devised "tissue negative staining method." A fine meshwork structure consisting of fibrils forming the small pores are observed in the normal human GBM. The diameter of these pores was slightly smaller than that of human albumin molecules. The GBM in patients with diabetic nephropathy showed irregular thickening. At higher magnification, cavities and tunnel structures, which were not seen in normal controls, were observed in the thickened GBM. As the diameters of the cavities and tunnels were far larger than the dimensions of albumin molecules, these enlarged structures are considered to allow serum protein molecules to pass through the GBM from the capillary lumen to the urinary space. The present results suggest that the cause of massive proteinuria in diabetic nephropathy is the disruption of the size barrier of the GBM.

Basement Membrane↗
PubMedDate not supplied

Ultrastructure of glomerular basement membrane in active heymann nephritis rats revealed by tissue-negative staining method.

Recently, we have developed a tissue-negative staining method, and successfully visualized fine meshwork structure of the glomerular basement membrane (GBM). To clarify the mechanism of proteinuria in active Heymann nephritis, we performed tissue-negative staining and investigated the ultrastructural alterations of the GBM. Active Heymann nephritis, the animal model of human membranous nephropathy, was induced in Lewis rats by the injection of proximal tubular brush border antigen, i.e. Fx1A. Urinary protein excretion was measured and histological studies were performed over 15 weeks following the Fx1A injection. Proteinuria developed at 10 weeks after injection (38.2 +/- 7.4 mg/day) and progressively increased (160.2 +/- 20.6 mg/day at 15 weeks). Capillary fine deposits of IgG and C3 were seen by immunofluorescence, and subepithelial electron dense deposits (EDD) by transmission electron microscopy (TEM). Using the tissue-negative staining method, regular meshwork structure consisted of fine fibrils and pores (2.5 +/- 0.7 nm in short dimension) was observed in the GBM of control rats. At 10 and 15 weeks after injection, the GBM, directly facing the endothelial side of EDD, contained enlarged pores and nephrotic tunnels. Mean values of the short dimension of enlarged pores were 2.9 +/- 0.5 nm at 10 weeks and 3.1 +/- 0.4 nm at 15 weeks, which were significantly larger than that of control rats (p < 0.01). The rest area of the GBM, including newly produced GBM covering the epithelial side of EDD, had no significant difference in size of the pores from control GBM and no tunnels. Although there was no significant difference in the size of enlarged pores between 10 and 15 weeks, the percentage area of GBM with impaired size barrier increased at 15 weeks (51.4 +/- 8.1%) compared with 10 weeks (24.0 +/- 8.3%) and related to severity of proteinuria. The density of the tunnels also increased at 15 weeks. In conclusion, immune deposits may affect the GBM biosynthesis and induce the defect of size barrier of the GBM, which is responsible for proteinuria in active Heymann nephritis.

Animals↗