Biomedical subjects

K Shikata

Publications and source records attributed to K Shikata.

At least 91 records · Page 5Linked to original sources

PubMed1995

[A case of systemic lupus erythematosus associated with severe fibrinoid necrosis located mainly in the glomerular afferent arteriole].

We report here, a patient of systemic lupus erythematosus (SLE) with severe fibrinoid necrosis in the afferent arteriole of the glomerulus, in whom antiphospholipid antibody might have contributed to the pathogenesis. A 24-year-old female who was suffering from severe anemia with fragmented red blood cells, acute renal failure and thrombocytopenia, was admitted to our hospital. Further examinations revealed findings compatible with active lupus nephritis. Moreover, she was found to be positive for antiphospholipid antibody, and anticardiolipin antibody, as well as for lupus anticoagulant and syphilis test. Intensive treatment by methylprednisolone pulse therapy, hemodialysis, and double filtration plasmapheresis were performed. However, 13 days after admission she died suddenly because of intracranial hemorrhage. Pathological investigation of renal tissue revealed severe fibrinoid necrosis of the arterioles mainly in the glomerular afferent arteriole associated with diffuse proliferative lupus nephritis. In this case, hemolytic uremic syndrome (HUS) was associated with SLE. Antiphospholipid antibody was considered to be not only an accelerator in the arterial lesions of HUS, but also an initiator of HUS itself.

Adult↗

PubMed1995

Changes in soluble ICAM-1 level during hemodialysis.

Intercellular adhesion molecule-1 (ICAM-1) is expressed on the surface of various types of cells, including lymphocytes, monocytes and vascular endothelial cells. Recently, ICAM-1 was reported to be shed from the cell membranes and released into circulation. The soluble ICAM-1 (sICAM-1) level has been reported to be increased in patients with certain inflammatory diseases. It is well known that the functions of leukocytes including neutrophils, lymphocytes and monocytes are impaired in patients with chronic hemodialysis. In this study, we evaluated the effect of hemodialysis (HD) on the lymphocytes and monocytes by periodically measuring the serum concentration of sICAM-1 during HD. Pre-HD sICAM-1 levels in chronic hemodialysis patients were significantly increased as compared with healthy subjects. Two hundred and forty minutes after the start of HD, sICAM-1 levels were significantly higher than the pre-HD levels. The sICAM-1 levels at the venous side of the dialyzer were significantly increased compared with the levels at the arterial side. There was no significant difference between the sICAM-1 levels of the patients under hemodialysis with the regenerated cellulose membrane and those with the polymethylmethacrylate membrane. These results suggest that ICAM-1 is shed from the surface of mononuclear cells (lymphocytes and monocytes) and released into circulation stimulated by hemodialysis membranes. Chronic hemodialysis may impair the function of mononuclear cells by inducing the shedding of ICAM-1.

Aged↗

PubMed1995

A comparative study of myocardial troponin T levels in patients undergoing hemodialysis.

This study included 25 patients receiving hemodialysis (HD) but in whom diabetes mellitus was not the primary disease (HD-non DM group), 25 patients receiving hemodialysis with diabetes mellitus as the primary disease (HD-DM group), and 50 patients with diabetes mellitus who had not yet been treated with hemodialysis (DM group). The following markers of myocardial injury were measured in these patients: troponin T (TnT), creatine kinase (CK), myoglobin (Mb), and myosin light chain-1 (MLC-1). No significant correlation was found between myocardial TnT and Cr in any study group. The Mb and MLC-1 values in patients receiving HD were markedly higher than normal regardless of the primary disease involvement, while myocardial TnT was found to be only slightly abnormal. These results suggest that myocardial TnT may be a more useful marker of myocardial injury in HD patients than the markers in current use. In the present investigation, myocardial TnT was the only marker that was higher in the HD-DM group than in the HD-non DM group. This suggests the possibility that the HD-DM group included more patients with arteriosclerotic lesions, such as myocardial injury.

Aged↗

PubMed1994

Immunoreactivity of the JK-132 monoclonal antibody directed against basement membrane collagen in normal and diabetic glomeruli.

The possible involvement of basement membrane-associated collagen (recognized by the monoclonal antibody JK-132) in the evolution of diabetic nephropathy was studied in kidney specimens from seven patients with noninsulin-dependent diabetes mellitus, and its distribution was compared with those of antibodies against alpha 1 to alpha 4 chains of type IV collagen. JK-132, a monoclonal antibody against basement membrane-associated collagen, reacted immunohistochemically exclusively with the mesangial matrix of the glomerular capillary. In contrast, antibodies to the alpha 1 and alpha 2 chains (IV) reacted strongly with mesangial matrix, and less strongly with the glomerular basement membrane (GBM). Antibodies to the alpha 3 and alpha 4 chains (IV) reacted mainly with GBM. In diabetes, JK-132 reacted most extensively with the expanded mesangial matrix, its staining intensity increasing with progression of the diabetic glomerulosclerosis. Antibodies to the alpha 1 and alpha 2 chains (IV) reacted prominently with the expanded mesangial matrix but less strongly with the GBM. Antibodies to the alpha 3 and alpha 4 chains reacted intensely with the thickened GBM. These results suggest that basement membrane-associated collagen differs from alpha 1 to alpha 4 chains of type IV collagen and that basement membrane-associated collagen is a good marker of mesangial expansion in diabetic nephropathy.

Aged↗

PubMed1994

Localization of fibril/microfibril and basement membrane collagens in diabetic glomerulosclerosis in type 2 diabetes.

Collagen is one of the major components of the extracellular matrices of the kidney. Basement membrane collagen, type IV collagen, is the major component in normal glomeruli. Fibril and interstitial collagen such as type III collagen, type V collagen, and type VI collagen are minor components of glomerular extracellular matrices and are localized mainly in the interstitium. Diabetic glomerulosclerosis is characterized by the expansion of the glomerular mesangial matrix as well as by thickening of the glomerular basement membrane. In order to clarify the roles of these various types of collagen in the development of diabetic glomerulosclerosis, immunohistochemical studies were performed in kidney specimens from patients with Type 2 diabetes. Early glomerulosclerosis is characterized by expansion of mesangial matrix with basement membrane collagen. However, in later stages glomerulosclerosis is characterized by an increase in the minor collagen components, such as type V and type VI collagen or collagens not normally present, such as type III collagen. Mesangial cells are known to synthesize all these types of collagen. In diabetes, phenotypic change in mesangial cells might produce excess amounts of fibril and interstitial collagen such as type III, type V, and type VI collagen, thus, leading to glomerulosclerosis.

Aged↗

PubMed1994

Mesangial matrices act as mesangial channels to the juxtaglomerular zone. Tracer and high-resolution scanning electron-microscopic study.

The mesangium is centrally located in the glomerulus and plays an important role in the microcirculation within the glomerulus. In order to reveal the role of the mesangial matrix in the microcirculation, the movement of native anionic ferritin into the juxtaglomerular region was tracked following the intravenous injection of ferritin into rats. The three-dimensional ultrastructures of the mesangial matrix and juxtaglomerular apparatus were studied by conventional scanning and high-resolution scanning electron microscopy after removal of the cellular components. Many ferritin particles were observed from the glomerular capillary to the mesangial matrix, in the mesangial matrix of the juxtaglomerular apparatus and in the tubular lumen of the macula densa after the injection of ferritin. Secretion of macromolecules from the distal tubules seems to be one of the exits from the juxtaglomerular zone. The mesangial matrix was continuous from the vascular pole to the periphery like a branching tree. The intraglomerular mesangial matrix was continuous to the extraglomerular mesangial matrix in the juxtaglomerular region. The mesangial matrix appeared to consist of a polygonal meshwork structure of thin fibrils and pores with high-resolution scanning electron microscopy. The thinnest fiber was approximately 6-nm wide, and the pore size was averaged 20 nm in diameter. We were able to demonstrate the meshwork structure of the mesangial matrix, thus giving the morphological basis of the mesangial matrix to serve as mesangial pathway from the intraglomerular to the extraglomerular mesangial matrix.

Animals↗

PubMed1994

Nephrotic tunnels in glomerular basement membrane as revealed by a new electron microscopic method.

To clarify the ultrastructure in situ of the normal human glomerular basement membrane and ultrastructural changes of the glomerular basement membrane in patients with nephrotic syndrome, specimens of normal renal tissue and specimens from patients with membranous nephropathy, lupus nephritis, minimal change nephrotic syndrome, diabetic nephropathy, and Alport's syndrome were obtained. Specimens were examined by transmission electron microscopy by the newly devised "tissue negative staining method." Normal glomerular basement membrane showed a three-dimensional lattice-like meshwork of fibrils measuring 1.9 +/- 0.4 nm in diameter that formed numerous uniform, round, oval, or polygonal pores 2.5 +/- 0.4 nm in short diameter and 2.8 +/- 0.5 nm in long dimension. The nephrotic glomerular basement membrane revealed varying degrees of ultrastructural defects, the most prominent being tunnels and cavities. Tortuous tunnels measuring approximately 15 to 50 nm in diameter penetrated the entire glomerular basement membrane. Cavities of various shapes measuring 15 to 200 nm in diameter were diffusely scattered in the glomerular basement membrane and occasionally aggregated to form a honeycomb structure that occupied the whole thickness of the glomerular basement membrane. These defects appeared to be the pathway for protein leakage.

Diabetic Nephropathies↗

PubMed1994

Changes in plasma concentrations of vitronectin in patients with diabetic nephropathy.

To investigate the role of vitronectin in the progression of diabetic nephropathy, plasma concentrations of vitronectin were measured by enzyme-linked immunosorbent assay in patients with diabetes mellitus and compared with normal control subjects. In diabetic patients with normoalbuminuria and microalbuminuria, plasma concentrations of vitronectin were significantly higher than those of control subjects. Plasma concentrations of vitronectin in diabetic patients with chronic renal failure were significantly lower than those with normal renal function. There was a significant positive correlation between plasma concentration of vitronectin and blood platelet counts. In the early stage of diabetic nephropathy, vitronectin may be increased caused by synthesis from activated platelets. With progression of diabetic nephropathy, plasma vitronectin may be decreased because of accumulation in sclerotic glomeruli and arteriosclerotic lesions. In conclusion, the plasma concentration of vitronectin appears to be an important marker for the progression of diabetic nephropathy.

Aged↗

PubMed1994

Clinical significance of necrosis in lupus nephritis.

The significance of necrosis (karyorrhexis), among the most characteristic findings in lupus nephritis, was evaluated by studying the correlation between the existence of necrosis in renal biopsy specimens and laboratory findings. The subjects were 54 patients with diffuse proliferative lupus nephritis and 6 patients with focal proliferative lupus nephritis selected from 143 patients with lupus nephritis. We also compared the clinical course of oral prednisolone and intravenous methylprednisolone pulse therapies after steroid administration. Compared with the non-necrosis group, the necrosis group had significantly lower CH50 levels and more proteinuria. Patients with necrosis were effectively treated with repeated pulse therapy judging by immunological activity and the decrease in proteinuria at an early stage, but responded poorly to oral steroid therapy. As the presence of necrosis in cases of lupus nephritis means high immunological activity of the lesion and there is responsiveness to a large dose of steroids, extensive immunosuppressive therapy including methylprednisolone pulse therapy should be applied to these patients.

Administration, Oral↗

PubMed1994

[Effect of heparin and low-molecular-weight heparin on proliferative glomerulonephritis].

Effect of heparin and low-molecular-weight heparin (LMWH) were evaluated on 15 patients with proliferative glomerulonephritis with various degrees of sclerosing legion. Five cases were subcutaneously administered with 7000 to 11000 units of heparin for 4 weeks. Ten cases were administered with 60 unit/kg of LMWH by drip infusion for 4 weeks. Eleven cases were treated with prednisolone and all cases were treated with anti-platelet agent as well. Urinary protein excretion reduced from 3.0 +/- 1.8 to 1.8 +/- 0.6 g/day in the heparin-treated group and from 2.4 +/- 1.9 to 1.8 +/- 1.4 g/day in the LMWH-treated group, respectively. There were no remarkable changes in the renal functions of both groups. In one case, both heparin and LMWH brought about reduction of proteinuria. Therefore, LMWH reduced urinary protein excretion by the same mechanism as heparin. The LMWH has an advantage over heparin in that the former has less risk of causing bleeding. We conclude that heparin and LMWH reduce proteinuria in some patients with proliferative glomerulonephritis. The LMWH is beneficial in the treatment of proliferative glomerulonephritis with a sclerosing lesion.

Adolescent↗

PubMed1993

Ultrastructural changes of the glomerular basement membrane in diabetic nephropathy revealed by newly devised tissue negative staining method.

In order to clarify the mechanism of proteinuria in diabetic nephropathy, ultrastructural changes of the glomerular basement membrane (GBM) in patients with diabetic nephropathy were examined by electron microscopy using our newly devised "tissue negative staining method". The normal human GBM showed a fine meshwork structure consisting of fibrils forming the small pores. 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, hitherto unknown cavities and tunnel structures, which were not seen in normal controls, were observed in the thickened GBM. In some portions, these cavities presented a honeycomb-like appearance. The diameters of the cavities and tunnels were far larger than the dimensions of albumin molecules. These enlarged structures are believed to allow serum protein molecules to pass through the GBM from the capillary lumen to the urinary space. These results suggest that the cause of massive proteinuria in diabetic nephropathy is the disruption of the size barrier of the GBM.

Basement Membrane↗

PubMed1993

[A case of non-IgA mesangioproliferative glomerulonephritis with huge paramesangial hemispherical deposits].

A 16-year-old female was admitted to our hospital because of chance proteinuria. On admission, mild proteinuria (0.6g/day) was observed, but microhematuria was not detected during the observation period. All the values of the renal function tests were within the normal range. Her renal biopsy demonstrated a prominent increase in the mesangial area by light microscopy and showed marked paramesangial hemispherical deposits by electron microscopy. Though IgM, IgG, Clq, C3, and fibrinogen were localized in the mesangial region, IgA was not detected by immunofluorescence study. It has been reported that paramesangial hemispherical deposits are strongly indicative of IgA glomerulonephritis. We conclude that this patient is a rare case of non-IgA glomerulonephritis with huge paramesangial hemispherical deposits.

Adolescent↗

PubMed1993

[Two cases of hypercalcemic nephropathy associated with primary hyperparathyroidism].

We present two cases of hypercalcemic nephropathy associated with primary hyperparathyroidism. Case 1 is a 37-year-old man who had repeated bone fractures and recurrent ureteral stones, which led to the diagnosis of primary hyperparathyroidism. Case 2 is a 35-year-old man in whom parathyroid carcinoma was discovered because of secondary nephrogenic diabetes insipidus, resulting from severe hypercalcemia. Both patients developed mild renal dysfunction during the course of hyperparathyroidism. In the renal biopsy materials obtained from case 1, the renal interstitium showed chronic inflammatory changes. The tubules were partly damaged (focal necrosis). Deposition of calcium was sometimes noted within the mitochondria of the tubular epithelial cells. Some glomeruli showed glomerular sclerosis. In biopsy materials obtained from case 2 after resection of the carcinoma, similar histological features were observed, but tubular atrophy and necrosis were advanced. Polyuria and hypercalcemia were ameliorated after resection. These findings indicate that severe hypercalcemia might induce tubular dysfunction as well as organized changes.

Adult↗

PubMed1993

Expression of the VLA family of integrins in the renal glomerulus.

The expression of glomerular extracellular matrix receptors of the very late antigen (VLA) family was examined in the human renal glomerulus by indirect immunofluorescence studies. Beta 1 subunits of integrin were localized in glomerular epithelial, endothelial and mesangial cells and Bowman's capsule. Alpha 3 integrin was localized dominantly in the glomerular capillary wall and less in the mesangium and Bowman's capsule. Alpha 2, alpha 4 and alpha 5 integrins were barely stained in the glomerulus. Our findings indicate that the VLA family of integrins plays an important role in the attachment of glomerular cells to the extracellular matrices.

Extracellular Matrix Proteins↗

PubMed1993

[A clinicopathological study of patients with immune complex type and pauci immune type rapidly progressive glomerulonephritis].

We made clinicopathological studies of twelve patients with rapidly progressive glomerulonephritis (RPGN) treated at our department of Okayama University Medical School Hospital for the last eight years. By immunofluorescence microscopy, seven cases were immune complex (IC) type and five were pauci immune type. By light microscopy, the mean percentage of glomeruli with crescents was seventy five, and cellular and fibro-cellular crescents were dominant in eleven cases. Combined therapy including methylprednisolone pulse or oral steroid was effective in eleven. Hemodialysis was performed in four patients with severe uremia and three of them recovered from hemodialysis. Two cases of RPGN associated with systemic lupus erythematosus died of cerebral hemorrhage. We conclude that IC type and pauci immune type RPGN have good prognosis when treated at their active stage with intensive combined therapy and with hemodialysis if necessary.

Adult↗

PubMed1993

Ultrastructural changes of extracellular matrices in diabetic nephropathy revealed by high resolution scanning and immunoelectron microscopy.

BACKGROUND: Diabetic nephropathy is invariably associated with proteinuria. EXPERIMENTAL DESIGN: To delineate the mechanism(s) of proteinuria in diabetic nephropathy, ultrastructural changes of the glomerular basement membranes (GBMs) were studied by high resolution scanning and immunoelectron microscopy. Acellular glomeruli from diabetic and age-matched control human subjects were prepared by detergent method and subjected to conductive staining, the technique in which the tissues are impregnated with metals rather than surface-coated with metallic alloys for visualization by electron microscopy. Subsequent to conductive staining, the tissues were examined by in-lens field emission scanning electron microscopy. RESULTS: Thirty glomeruli, each from the control and diabetic groups, were examined by scanning microscopy. In diabetic GBMs, a loose meshwork structure consisting of numerous pores of approximately 8 nm in diameter and distinct strands was observed. In contrast, meshwork structure was not readily discernible in controls and a few pores were observed. Five glomerular capillary loops, each from control and diabetic groups, were examined by immunoelectron microscopy. In controls, heparan sulfate-proteoglycan was localized in the lamina rara interna and externa, and type-IV collagen was distributed throughout the whole width of the GBM. In diabetic GBMs, a relative loss of staining of heparan sulfate-proteoglycan, both in the lamina rara interna and externa of the GBM, was observed. Type IV collagen was distributed in all layers of the thickened GBM, and the absolute number of the immunogold particles was increased. However, immunogold particle density of type IV collagen per unit area was decreased as compared with the control. CONCLUSIONS: These ultrastructural and immunoelectron microscopic changes in the GBM may explain the loss of charge as well as size selectivities of the glomerulus, as observed in diabetic nephropathy associated with proteinuria.

Aged↗

PubMed1992

A case of nephrotic syndrome and renal dysfunction in a pregnant woman with diabetes mellitus.

A 29-year-old diabetic woman who developed severe anaemia, nephrotic syndrome, and hypertension before the 28th week of gestation, had residual evidence of toxaemia and renal dysfunction more than 1 month following delivery. The histopathological findings of renal biopsy specimens were considered most consistent with toxaemia of pregnancy complicated by diabetic glomerulosclerosis. We consider that rapid acceleration of renal dysfunction may have been induced by: (1) poor control of diabetes before pregnancy; (2) glomerular hyperfiltration of the remnant nephrons throughout pregnancy; (3) hypercoagulopathy associated with pregnancy; (4) appearance of hypertension following these three conditions.

Adult↗

PubMed1992

Mechanism of proteinuria in nephrotic syndrome.

We developed a "tissue negative staining method" to observe the molecular-level ultrastructure in situ in any portion of the ultrathin sections routinely prepared for electron microscopy. This method was used in electron microscopy of the glomerular basement membranes (GBM). The GBM in patients with nephrotic syndrome was discovered to possess a tunnel structure, designated as "nephrotic tunnel", with lumen large enough to allow free passage of protein molecules. This tunnel seemed to be involved in the etiology of nephrotic syndrome. This new method appears to be applicable to a variety of purposes in biological studies.

Animals↗