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K Hironaka

Publications and source records attributed to K Hironaka.

At least 37 records · Page 2Linked to original sources
PubMed1997

[Amyloidosis].

Explore the source record for details and available documents.

Amyloidosis↗
PubMed1996

Ultrastructural change of the glomerular basement membrane in rats with Heymann nephritis revealed by ultrahigh resolution scanning electron microscopy.

To assess the relationship between the glomerular injury induced by immune complex deposition and proteinuria, ultrastructural changes of the glomerular basement membrane (GBM) were investigated in Heymann nephritis. Active Heymann nephritis was induced in rats by injecting them with tubular brush border antigen, known as Fx1A, emulsified in complete Freund's adjuvant (CFA). Measurement of urinary protein excretion and histological examinations were carried out for up to 15 weeks after immunization. Proteinuria developed in rats within 10 weeks of immunization and coincided with the development of subepithelial deposits with minimal spike-like basement membrane protrusion. Acellular glomeruli were prepared by detergent treatment and were subjected to tannic acid-osmium conductive staining prior to examination with an ultrahigh resolution scanning electron microscope (HSEM). HSEM of the acellular GBM prepared from control rats injected with CFA alone revealed a meshwork structure, with pores of about 9 nm in diameter. Proteinuric rats immunized with Fx1A showed a loosened meshwork structure, with pores of about 15 nm in the acellular GBM adjacent to the deposits. The newly formed GBM overlying the deposit consisted of a meshwork structure associated with unorganized thin fibrils. Ultrastructural changes were never seen in GBM devoid of deposits. These findings indicate that subepithelial deposits are closely involved in the development of proteinuria by injuring the size selectivity of the GBM.

Animals↗
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

A patient with sarcoidosis associated with recurrent urolithiasis and tubular injury caused by calcium deposition.

A 38-year-old woman was hospitalized in January 1994 with renal dysfunction and hypercalcemia. Before admission, she was diagnosed as having urolithiasis, and had been treated twice with extracorporeal shock wave lithotripsy (ESWL). Ophthalmologically, she exhibited iritis and secondary glaucoma. Hypercalcemia, an extremely low titer of parathyroid hormone (PTH), and elevation of angiotensin-converting enzyme (ACE) and lysozyme activity were noted. These findings suggested sarcoidosis, although the chest X-ray showed only fibrotic changes. Hypercalcemia was suspected of having been caused secondarily by sarcoidosis. Since her laboratory data also showed renal dysfunction and abnormal urinalysis, a renal biopsy was performed. The histological findings indicated a tubular and interstitial disorder without glomerular abnormality; calcium deposition, which was detected by X-ray energy dispersive analysis, was observed in the tubular cytoplasm. Administration of prednisolone alleviated the renal dysfunction and decreased the elevation of ACE activity and lysozyme level of the blood. Sarcoidosis is sometimes associated with hypercalcemia, but rarely with renal dysfunction. These findings suggested that sarcoidosis may be associated with renal dysfunction due to tubular injury caused by calcium deposition in the tubules, and that glucocorticoid therapy was effective for these disorders.

Adult↗
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

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

Calpain is implicated in rat myocardial injury after ischemia or reperfusion.

Calpain activity was measured in the various subfractions of rat myocardia after global ischemia for 60 min or after ischemia followed by 30 min of reperfusion after the chromatographic separation of mu- and m-calpains. The activity of m-calpain after ischemia and that of mu-calpain after reperfusion were both higher than that in the control. The activity of the endogenous calpain inhibitor calpastatin in 10,000 x g supernatant was decreased after both ischemia and ischemia-reperfusion. The increase in m- and mu-calpain activities was suppressed by pre-ischemic perfusion with a synthetic calpain inhibitor, transepoxysuccinyl-L-leucylamido (4-guanidino) butane (E64d, 100 micrograms/ml). After reperfusion, the calpain activity in the 10,000 x g pellet was also increased, which was inhibited by pre-ischemic perfusion with E64d or dimethylsulfoxide (a solvent for E64d) or by reperfusion with 1 mmol/L ethyleneglycol bis (beta-aminoethylether)-N, N, N', N'-tetraacetic acid. SDS-polyacrylamide gel electrophoresis revealed the proteolysis of several proteins, including fodrin, in the 10,000 x g and 100,000 x g pellet fractions after ischemia and reperfusion, some of which were confirmed to be in vitro substrates of calpain. The creatine kinase release during the reperfusion was also partially inhibited by E64d or dimethylsulfoxide. Thus, calpain activity in the soluble or particulate fractions was altered during ischemia or reperfusion, and appeared to be implicated in the proteolysis of the membrane proteins, which may contribute to myocardial injury.

Animals↗
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

Olfactory bulbectomy leads to learning/memory impairments in 3-panel runway and 3-lever operant tasks.

The effects of olfactory bulbectomy on the learning and memory of rats were examined, using several memory tasks. In reference memory and working memory tasks using a 3-panel runway apparatus, acquisition was delayed markedly by bilateral ablation of the olfactory bulb (OB). OB lesion performed after acquisition markedly impaired both reference and working memories. Even when the tasks were repeated for several sessions, the impairment of memory in OB-lesioned rats did not recover to the control level of the sham operation group. The delayed matching-to-lever location (DMLL) performance, which was examined using a 3-lever operant apparatus, was markedly impaired by OB lesions. This impairment was mild immediately after surgery, but tended to increase with time. Rats with OB-olfactory tubercule lesions show more severe impairment of memory in the DMLL performance. Reversal learning, using a 2-lever operant apparatus, was markedly impaired by OB lesions. The impairment of working and reference memories in OB lesioned rats, which was assessed using a 3-panel-runway apparatus, was reduced by cholinesterase inhibitor physostigmine and NIK-247. These findings suggest that the OB plays a very important role in the learning and memory processes necessary for both a working memory task and a reference memory task and that, at least in part, the memory impairment in OB lesioned rats is mediated by lowering of cholinergic function.

Animals↗
PubMed1994

In vitro micro-autoradiography of atrial natriuretic peptide in biopsy specimens from patients with renal diseases.

We investigated the localization and density of atrial natriuretic peptide (ANP) receptors in human renal biopsy specimens by using in vitro micro-autoradiography (ARG) of [125I]-alpha-human (1-28) ANP. In a preliminary study, we measured the effect of storing tissue samples on ANP binding, using in vitro micro-ARG of Wistar rat kidney under optimal conditions. Duration of the preservation period did not affect ANP binding to renal tissue until samples had been stored at -30 degrees C for two years. A total of 11 human renal tissues were used to assay binding of ANP-ARG, including normal tissue obtained after nephrectomy because of renal cancer. ANP binding occurred predominantly within the glomerulus and, to a lesser extent, in the tubular region both in rat kidney sections and in human renal biopsy specimens. The density of ANP binding, calculated by counting grains in fixed areas, was compared with normal and pathological tissues. The density of grains tended to decrease in patients with renal dysfunction and hypertension except for one case of IgA nephropathy with normal renal function and blood pressure. The density of grains increased in a patient with nephrogenic diabetes insipidus. In the present study, we have established a method that uses in vitro micro-ARG for assessing ANP binding in human biopsy specimens.

Animals↗
PubMed1993

Renal basement membranes by ultrahigh resolution scanning electron microscopy.

Three-dimensional ultrastructures of basement membranes of the rat kidney were investigated with an ultrahigh resolution scanning electron microscope (HSEM) equipped with a resolving power of 0.5 nm. All cellular components were extracted from renal cortical tissues by sequential-detergent treatment. Four types of acellular basement membranes were observed after tannin-osmium conductive staining: the glomerular basement membrane (GBM) associated with the mesangial matrix, the tubular basement membrane (TBM), the Bowman's capsule basement membrane (BCBM), and the peritubular capillary basement membrane (PTCBM). We could demonstrate the polygonal meshwork structures composed of strands in the respective basement membranes. The strands averaged 6 to 7 nm wide, whereas the pore sizes within the meshworks were variable and differed according to the basement membrane type. Moreover, we confirmed the presence of the heterogeneity of the GBM suggested by several approaches. Present data support the proposition that a polygonal meshwork structure may represent the basic structure of basement membrane. Some of the observed architectural dissimilarities in basement membrane types may reflect their different functional properties, which in turn may reflect the heterogeneous distribution of major basement membrane components as demonstrated by immunohistochemical and biochemical studies.

Animals↗
PubMed1993

Study of glomerular permselectivity for proteins of the glomerular basement membrane using a dialyzer model.

The glomerular basement membrane (GBM) is considered to regulate glomerular permselectivity for proteins by acting as both size barrier and charge barrier. Since heparan sulfate-proteoglycan (HS-PG), which forms the charge barrier of GBM, contains a sulfonic acid, we made membranes with various degrees of negative charge models of GBM by addition of sulfonic acid to ethylene vinyl alcohol (EVAL) membranes. A high-resolution scanning electron-microscopic study revealed no ultrastructural alterations after adding sulfonic acid to EVAL membranes. Both neutrally and negatively charged membranes had porous structures in the inner surface of the membranes. The interrelation between the two actions of size and charge of GBM was studied using special dialyzers with various degrees of negative charge and different pore sizes. The negatively charged membranes adsorbed proteins with positive charge and repulsed proteins with negative charge. The degrees of adsorption and repulsion were weaker in membranes with larger pores and were stronger for proteins with larger molecular weights. The permselectivity for proteins of a charged membrane depends largely upon the interrelation between the pore size of the membrane and the size of the proteins. It is, therefore, suggested that the presence of a size barrier in GBM is necessary for the charge barrier to effectively exert glomerular permselectivity for proteins. Our study may lead to the development of a dialyzer with higher permselectivity by adding sulfonic acid rather than conventional dialyzers.

Basement Membrane↗