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K Shikata

Publications and source records attributed to K Shikata.

At least 73 records · Page 4Linked to original sources
PubMed1996

Roles of advanced glycation end-products in the progression of diabetic nephropathy.

Available data indicate that the development of diabetic nephropathy is linked to hyperglycaemia. Glucose reacts nonenzymatically with proteins to form Schiff base and Amadori products. Further incubation of these early products leads to the formation of advanced glycation end-products (AGEs). AGEs seem to play a central role in the progression of diabetic nephropathy. Immunohistochemically, AGEs were also detected in an expanded mesangial matrix, especially in nodular lesions from patients with diabetic nephropathy. AGEs staining was noted in the Bowman's capsule, periglomerular fibrosis in sclerosing glomeruli. In our ultrastructural study of mesangial matrix from patients with diabetic nephropathy by high-resolution scanning electron microscopy after cellular removal, the meshwork structure was evident at higher magnification. In nodular lesions, the loose meshwork structure appeared to be composed of various sized strands, ranging from 6 to 24 nm (mean +/- SD: 11.4 +/- 3.8 nm). The pore sizes were variable, ranging from 4 to 70 nm (mean +/- SD: 23.6 +/- 12.3 nm), and were statistically larger than those of normal controls. As the AGEs are localized most notably in nodular lesions, advanced glycations play a role in the progression of diabetic nephropathy through impairment of the assembly of matrix proteins in vivo. Because type V and type VI collagens are the major components of nodular lesions, increases in these interstitial and fibril or microfibril collagens may contribute to the formation of wider strands in the mesangial matrix of a nodular lesion. As no metalloprotease that is specific for type VI collagen has been identified thus far, AGEs formation might occur preferentially in type VI collagen-rich nodular lesions, which are sites of slow turnover.

Diabetic Nephropathies↗
PubMed1996

Increased gene expression of insulin-like growth factor-i receptor in experimental diabetic rat glomeruli.

Renal hypertrophy is a characteristic and early manifestation of diabetes in humans and experimental animals. We examined the precise distribution of insulin-like growth factor-I (IGF-I) mRNA and IGF-I receptor mRNA in the experimental diabetic rat kidney using a nonradioactive in situ hybridization technique. No significant difference in the distribution of IGF-I mRNA was found between the diabetic and control rats. IGF-I mRNA-positive cells were found in the collecting ducts and in scattered single cells in the distal tubules. The number of IGF-I mRNA-positive cells was very low in the glomeruli. 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, peaking at 4 weeks as compared with the control rats. Overexpression of IGF-I receptor in glomerular cells, especially mesangial and visceral epithelial cells, may contribute to glomerular hypertrophy in diabetic nephropathy.

Animals↗
PubMed1996

The critical role of intercellular adhesion molecule-1 in Masugi nephritis in rats.

Intercellular adhesion molecule-1 (ICAM-1, CD54), an adhesion molecule of the immunoglobulin superfamily, is an endothelial cell surface ligand for such leukocyte integrins as lymphocyte-function-associated molecule 1 (LFA-1, CD11a/CD18), Mac-1 (CD11b/CD18) and CD43. These molecules mediate adhesive interactions between leukocytes and endothelial cells and are critically involved in infiltration of leukocytes into inflammatory lesions. We examined the expression of ICAM-1 in renal tissues of Masugi nephritis rats and directly examined the role of ICAM-1 by administration of neutralizing monoclonal antibodies (MAbs) to rat ICAM-1, LFA-1 alpha-subunit (LFA-1 alpha), beta-subunit (LFA-1 beta) and Mac-1 alpha-subunit (Mac-1 alpha). Within 3 h after injection of nephrotoxic serum, increased expression of ICAM-1 was detected in the glomeruli by in situ hybridization and an immunofluorescence study. Proteinuria was significantly suppressed by the MAbs against ICAM-1, Mac-1 alpha and LFA-1 beta. Neutrophil infiltration into the glomeruli was significantly prevented by injection of the MAbs against ICAM-1, LFA-1 alpha and LFA-1 beta. These results indicate that both ICAM-1/LFA-1 and ICAM-1/Mac-1 pathways are involved in neutrophil infiltration into the glomeruli. On the other hand, monocytic infiltration was prevented by the MAbs against ICAM-1, LFA-1 alpha and LFA-1 beta but not by anti-Mac-1 alpha MAb. Due to these results, ICAM-1 is considered to be a critical molecule involved in the pathogenesis of the leukocyte infiltration into the glomeruli in the heterologous phase of Masugi nephritis. Anti-ICAM-1 antibody may be beneficial in the treatment of leukocyte-mediated glomerular diseases.

Animals↗
PubMed1996

The changes of Mac-1 and L-selectin expression on granulocytes and soluble L-selectin level during hemodialysis.

L-selectin and Mac-1 expressed on leukocytes are critical for leukocyte adhesion to inflamed endothelium. L-selectin is known to be rapidly shed from the cell surface of granulocytes after activation. In the present study the change of expressions of these adhesion molecules on granulocytes were analyzed by flow cytometry, and the serum concentration of shed L-selectin (soluble L-selectin; sL-selectin) was measured by enzyme-linked immunosorbent assay (ELISA) during hemodialysis in patients treated with regenerated cellulose membranes (RC group) versus polysulfone membranes (PS group). In the RC group, Mac-1 expression on granulocytes increased significantly at 30 min after the initiation of hemodialysis (p < 0.05) compared with predialysis values, coinciding with the nadir of dialysis-induced granulocytopenia. Granulocyte L-selectin expression decreased significantly at 15 min after the initiation of hemodialysis (p < 0.05) and remained decreased through the course of dialysis session, compared with predialysis values. Serum sL-selectin level significantly increased at 15 min after the initiation of hemodialysis (p < 0.05), compared with predialysis values. In the PS group, no significant variation in Mac-1 and L-selectin expression on granulocytes and serum sL-selectin level were detected. This reciprocal change of Mac-1 and L-selectin on granulocyte cell surface was attributed to development of granulocytopenia and subsequent reversal during dialysis with cellulose membranes. In this study, we confirmed the shedding of L-selectin during cellulosic dialysis by ELISA. The increase in sL-selectin, which has potential activity of inhibiting L-selectin-dependent adhesion of granulocyte to endothelium, might be involved in rebound granulocytosis during dialysis with cellulose membranes and impairment of the granulocyte function in patients on chronic hemodialysis.

Aged↗
PubMed1996

Two new genes, PHO86 and PHO87, involved in inorganic phosphate uptake in Saccharomyces cerevisiae.

The PHO84 gene in Saccharomyces cerevisiae encodes a Pi transporter, mutation of which confers constitutive synthesis of repressible acid phosphatase (rAPase), in medium containing repressible amounts of Pi, and an arsenate-resistant phenotype. We selected an arsenate-resistant mutant showing the constitutive synthesis of rAPase on nutrient plates containing 4.5 mM arsenate. This mutant has double mutations designated as pho86 and pho87. The mutant transcribes PHO84 even in the repressible condition but has a severe defect in Pi uptake. The constitutive rAPase+ phenotype of the pho86 pho87 mutant was partially suppressed by an increased dosage of the PHO84 gene. The PHO87 gene was found to be identical with YCR524, according to the published nucleotide sequence of chromosome III, which encodes a protein of 923 amino-acid residues with a highly charged N-terminal half followed by a C-terminal half consisting of 12 membrane-spanning segments as in Pho84p. These and the other findings suggest that the Pho86p and Pho87p proteins collaborate with Pho84p in Pi uptake.

Acid Phosphatase↗
PubMed1996

What is the best index of glycemic control in patients with diabetes mellitus on hemodialysis?

Since red blood cell survival time is shortened in patients with diabetes mellitus (DM) on hemodialysis (HD), it is unlikely that indices of glycemic control accurately reflect the glycemic state of these individuals. In this study, in order to determine the best index of glycemic control in diabetic patients on HD, we measured HbAlc, 1,5-anhydroglucitol (1,5-AG), fructosamine (Fr) and glycated albumin (GA) in 31 diabetic patients on HD (20 males and 11 females, mean age: 66.9 years), and examined the correlation between each index and predialysis plasma glucose level. Since the mean values of predialysis plasma glucose during the final 2 and 4 weeks before the study were best correlated with HbAlc, this parameter was considered to be the most reliable index of glycemic control in diabetic patients on HD. GA was more closely correlated with mean values of predialysis plasma glucose during the final 2 and 4 weeks, than any other index of glycemic control, followed by HbAlc. In conclusion, HbAlc is considered to be the most reliable index of glycemic control in diabetic patients on HD.

Aged↗
PubMed1996

Glomerular expression of macrophage colony-stimulating factor and granulocyte-macrophage colony-stimulating factor in patients with various forms of glomerulonephritis.

Macrophage colony-stimulating factor (M-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are major mediators for the differentiation, proliferation, and activation of the macrophage. Recently, M-CSF was documented to play a pivotal role in the development of nephritis via macrophage activation in MRL-lpr mice. The macrophage is also considered to be an important component in the development of human glomerulonephritis. The expression and function of colony-stimulating factors (CSF) in the human kidney have not yet been defined. This study was undertaken to elucidate the various roles of CSF in the development of glomerulonephritis in humans. We examined the glomerular expression of M-CSF and GM-CSF in patients with various forms of glomerulonephritis and in normal subjects using immunohistochemical methods and nonradioisotopic in situ hybridization. The expression of CSF at both the protein and mRNA level in the glomeruli was compared with the degree of mesangial proliferation; the number of macrophages, Ki67-positive cells, and HLA-DR-positive cells; and the degree of alpha-smooth muscle actin-positive area in the glomerulus and clinical data. M-CSF and GM-CSF were expressed mainly on the mesangial cells in the glomerulus. Intraglomerular expressions of CSF at the protein level were increased in cases of IgA nephropathy and lupus nephritis. There was a positive correlation among the M-CSF protein expression and glomerular proliferation, macrophage infiltration, and the degree of proteinuria. M-CSF mRNA expression also was increased in the cases of IgA nephropathy and lupus nephritis. The number of Ki67-positive cells and HLA-DR-positive cells and alpha-smooth muscle actin-positive area in the glomerulus were increased in the cases with enhanced M-CSF expression. These results suggest that the glomerular secretion of M-CSF promotes macrophage infiltration into the glomerulus and activates resident and extraneous macrophages in the mesangial proliferative glomerulonephritis. M-CSF is considered to be a major mediator in the development of mesangial proliferative glomerulonephritis in humans.

Adult↗
PubMed1995

Oligomannose-coated liposomes as an adjuvant for the induction of cell-mediated immunity.

The effect of the coating of ovalbumin-reconstituted liposomes with various oligosaccharides on their immunogenicity was investigated in mice. The coating of liposomes with oligomannose or yeast mannan drastically enhanced their ability to induce an ovalbumin-specific delayed-type footpad swelling response with a peak at 24 to 48 h post-challenge. Among various oligosaccharides tested, only those with mannose residue at the nonreducing termini manifested the activity when applied to liposomes. Since such oligosaccharides are ubiquitously found in the body, these results suggested the usefulness of oligomannose-coated liposomes as a safe adjuvant for the induction of cell-mediated immunity.

Adjuvants, Immunologic↗
PubMed1995

Immunohistological localization of the novel epitope related to type IV collagen in normal and diseased renal tissues.

Type IV collagen is a major component of the renal glomerular extracellular matrix. A recently characterized monoclonal antibody, JK132, which was originally produced by immunization with human placental type IV collagen, recognizes a new epitope which is different from alpha 1-alpha 6 chains of type IV collagen. Using immunofluorescence and immunogold electron microscopy, the distribution of the epitope of JK132 has been compared with the distribution of alpha 1, alpha 2, alpha 3 and alpha 4 chains of type IV collagen in normal human kidney and in the renal tissues of patients with various types of glomerulonephritis. In normal human kidney, JK132 reacted with mesangial matrix, Bowman's capsular basement membrane (BCBM), tubular basement membrane, and vessel walls, but did not react with glomerular basement membrane (GBM). This distribution is different from the distribution of alpha 1-alpha 4(IV) chains. In IgA nephropathy and membranoproliferative glomerulonephritis, the staining intensity for JK132 was increased in expanded mesangial matrix. In glomeruli with severe mesangial proliferation, the epitope of JK132 extended to the endothelial side of the GBM. In membranous nephropathy, staining for JK132 was virtually unchanged from normal. This study suggests that the epitope of JK132 increases in amount during the process of mesangial proliferation and could serve as a marker for mesangial matrix expansion in glomerulonephritis.

Collagen↗
PubMed1995

Massive eosinophilic infiltration in a patient with the nephrotic syndrome and drug-induced interstitial nephritis.

The pathologic feature of acute interstitial nephritis is the infiltration of mononuclear cells, predominantly lymphocytes and monocytes, into the interstitium. We present an unusual case of a 49-year-old man with drug-induced acute interstitial nephritis whose renal biopsy specimen showed a massive infiltration of eosinophils into the interstitium and eosinophils infiltrating into the glomerulus through a gap in Bowman's capsule and the juxtaglomerular zone. The patient initially was referred to us with a recurrence of the nephrotic syndrome. Deterioration of renal function and an increase in proteinuria was noted at that time. Triazolam, a sleep inducer, was the suspected cause of the acute interstitial nephritis. Renal biopsy revealed sclerotic glomeruli containing eosinophils among massive infiltrated eosinophils and a loss of endothelial cells and mesangial cells in contrast to a preservation of epithelial cells. Infiltrating eosinophils were directly attached to the glomerular basement membrane, and free granules from the eosinophils were observed in the capillary lumen. In addition to chronic sclerotic change, eosinophils may have further damaged the glomerular capillary wall, leading to an increased severity of proteinuria in this case.

Eosinophilia↗
PubMed1995

Distribution of extracellular matrix receptors in various forms of glomerulonephritis.

Integrins are heterodimeric transmembrane receptor glycoproteins consisting of alpha and beta subunits that mediate adhesion and interactions between cells and extracellular matrix. Such interactions may be perturbed in various pathologic states, resulting in the altered phenotypic expressions of the integrins in affected tissues. To ascertain the alterations in integrins in various renal diseases, their distribution was investigated in different forms of glomerulonephritis by indirect immunofluorescence and immunoelectron microscopy using specific antibodies directed against beta 1 integrins and integrin alpha v beta 3 (vitronectin receptor). In addition, the distribution of certain extracellular matrix components (ie, fibronectin, vitronectin, and type IV collagen) was examined. Integrin beta 1 and alpha v beta 3 were highly expressed in proliferating mesangial cells in immunoglobulin A nephropathy, membranoproliferative glomerulonephritis type I and diffuse proliferative lupus nephritis. Their putative ligands (ie, fibronectin, vitronectin, and type IV collagen) also were increased in the expanded mesangial regions. In immunoglobulin A nephropathy, integrin beta 1 and alpha v beta 3 were seen by immunoelectron microscopy to be localized to the mesangial cell membranes in close proximity to the immune complex deposits; however, fibronectin and vitronectin immunoreactivities were observed in the mesangial immune complex deposits. Similarly, vitronectin also was detected in the immune complex deposits of other forms of proliferative nephritis, ie, membranoproliferative glomerulonephritis type I and diffuse proliferative lupus nephritis. In diffuse proliferative lupus nephritis, the cellular crescents displayed immunoreactivity toward integrin alpha v beta 3 and vitronectin. In nonimmune complex glomerular disease associated with nephrotic syndrome (ie, minimal change nephrotic syndrome), integrin alpha 3 beta 1, which normally has a linear capillary distribution, was decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Collagen↗
PubMed1995

Ultrastructure of nonenzymatically glycated mesangial matrix in diabetic nephropathy.

Advanced protein glycation has been proposed as a major factor in the development of diabetic nephropathy. Advanced glycation end products (AGEs) have altered the structure of extracellular matrix component and impaired self association in vitro. To elucidate the role of AGEs in the progression of diabetic nephropathy, the present study was undertaken to localize glomerular AGEs immunohistochemically. Ultrastructural changes of the mesangial matrix were analyzed with high resolution scanning electron microscopy. No glomerular AGEs staining was noted in normal control kidney specimens, or in tissue from glomerulonephritis patients without diabetes mellitus. The mesangium showed a positive AGEs staining in advanced stages of diabetic nephropathy, and the most characteristic finding was the strong AGEs staining in nodular lesions. By high resolution scanning electron microscopy, control and diabetic mesangial matrices revealed a meshwork structure composed of fine fibrils (10 nm in width) and numerous pores (12 to 13 nm in diameter). In the nodular lesions, however, loosening of the meshwork was significant, and the diameter of the pores was enlarged (approximately 24 nm). This study provides the first immunohistochemical evidence that AGEs are localized in diabetic glomeruli, most notably to nodular lesions. Advanced glycation might play a role in the progression of diabetic nephropathy through impairment of the assembly of matrix proteins in vivo.

Adult↗
PubMed1995

Escape of red blood cells through gaps in glomerular basement membrane in a patient with mixed connective tissue disease.

Hematuria in patients with glomerulonephritis seems to result from the passage of red blood cells through anatomical gaps in the glomerular basement membrane. However, such morphological evidence has rarely been demonstrated. A patient with mixed connective tissue disease associated with membranous glomerulonephritis is described in whom the renal biopsy specimen showed an escape of red blood cells through a gap in the basement membrane. These findings support the morphological basis of hematuria in glomerulonephritis.

Adult↗
PubMed1995

Minimal-change nephrotic syndrome associated with systemic lupus erythematosus.

A case of systemic lupus erythematosus (SLE) associated with minimal-change nephrotic syndrome (MCNS) is described. A 41-year-old woman with SLE presented with symptoms of nephrotic syndrome. Renal biopsy revealed minor glomerular abnormalities without the deposition of immune complexes. The initial heavy proteinuria promptly decreased after the prednisolone dosage was increased and disappeared 4 weeks later. The patient had a relapse of nephrotic syndrome without exacerbation of immunoserological reactions when the prednisolone dose was subsequently decreased. Remission was achieved 5 days after methylprednisolone pulse therapy. T cell dysfunction, which is present both in SLE and MCNS, might have triggered MCNS during the course of SLE.

Adult↗
PubMed1995

Transition of morphologic features in lupus nephritis: does steroid therapy accelerate glomerulosclerosis?

We retrospectively evaluated the morphologic change of 28 follow up biopsies from 24 cases of lupus nephritis according to the classification of the World Health Organization and determined the activity index (AI) and the chronicity index (CI). In the cases with biopsies repeated within 6 months, the AI decreased significantly from 6.7 +/- 1.3 to 3.5 +/- 0.8, while the CI showed no significant change. In cases which were rebiopsied after longer intervals, AI increased significantly from 3.2 +/- 0.7 to 7.5 +/- 1.2; the CI did not change significantly. When AI and CI changes in the cases biopsied again beyond 6 months were compared with respect to therapy, AI showed no significant difference in the methylprednisolone pulse therapy group but was significantly increased in the oral steroid therapy group. The CI tended to be increased in both groups, but not significantly. Steroid pulse therapy was effective in improving active lesions with a high AI. Steroid therapy for lupus nephritis prevented short-term progression of glomerulosclerosis and did not accelerate glomerulosclerosis.

Biopsy↗
PubMed1995

[Activation of complement during hemodialysis].

In hemodialysis using 3 types of dialysis membrane materials [regenerated cellulose (RC), cellulose triacetate (CTA), and polysulfone (PS)], activation of the complement, reduction of white blood cells, and variation of vitronectin (VN) were observed. RC membrane caused a significant reduction of white blood cells and elevations of Bb and soluble membrane attack complex (S-MAC), indicating a strong activation of the alternative complement pathway. Especially, the increase of S-MAC persisted for a long time during hemodialysis. Because reduction of VN was transient, it was assumed that the S-MAC escaping removal by VN receptors might have persisted in the circulation. These findings suggested that S-MAC would become useful as an index for evaluating biocompatibility of various artificial organs including dialysis membranes.

Aged↗
PubMed1995

Urinary detection of type IV collagen and its increase in glomerulonephritis.

Type IV collagen is the major component of the glomerular extracellular matrix. The nature of type IV collagen antigens in the urine from various forms of glomerulonephritis was studied using enzyme-linked immunosorbent assay for monoclonal antibodies to the 7S domain and some of the non-7S and non-NC1 domains. The size distribution of antigenic material in urinary samples from a patient with IgA nephropathy was analyzed by gel filtration chromatography. The results demonstrated a single peak at 340 kDa, suggesting the measurement of almost intact type IV collagen molecules. The urinary concentration of type IV collagen in patients with membranous nephropathy and chronic renal failure was significantly increased compared with that of normal controls. Measurement of the urinary concentrations of type IV collagen is useful in the diagnosis of glomerular disease, particularly in cases where invasive methods are contraindicated and clinically membranous nephropathy is suspected.

Adolescent↗