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Biomedical subjects

I Shirato

Publications and source records attributed to I Shirato.

At least 55 records · Page 3Linked to original sources
PubMed1996

The development of focal segmental glomerulosclerosis in masugi nephritis is based on progressive podocyte damage.

We analysed the sequence of structural changes leading to focal segmental glomerulosclerosis (FSGS) in chronic Masugi nephritis. The protocol resulted in an immediate onset of the disease and the development of segmental sclerosis in a considerable proportion of glomeruli within 28 days of serum injection. Throughout the study, the degree of structural damage was significantly correlated with protein excretion. Even 1 day after injection of the serum, the whole spectrum of early lesions was encountered involving all three cell types. Endothelial detachments, mesangiolysis and podocyte foot process effacement were most prominent. There was focal persistence of capillary microthrombosis but, generally, mesangial and endothelial injuries recovered. The development of podocyte lesions was different: on one hand recovery was seen leading to the re-establishment of an interdigitating foot process pattern, and on the other persistent podocyte detachments from peripheral capillaries allowed the attachment of parietal epithelial cells to "naked" portions of the glomerular basement membrane (GBM), and thus to the formation of a tuft adhesion to Bowman's capsule. Progressive podocyte degeneration at the flanks of an adhesion permitted expansion of the adhesion by encroachment of parietal cells onto the tuft along the denuded GBM. Inside an adhesion, capillaries and mesangial areas either collapse or become obstructed by hyalinosis or thrombosis. Resident cells disappear progressively from inside an adhesion; macrophages may invade. Segmental sclerosis in this model consists of collapsed tuft structures adhering broadly to the cortical interstitium. Proliferation of mesangial cells did not contribute to this development. Recovery of endothelial and mesangial lesions was associated with cell proliferation in early stages of the disease; podocyte proliferation was not encountered at any stage. We conclude that the inability to replace an outmatched podocyte crucially underlies the development of sclerosis. Severe podocyte damage cannot be repaired but leads to tuft adhesions to Bowman's capsule followed by progressive collapse of tuft structures inside an adhesion, resulting in segmental glomerulosclerosis.

Animals↗
PubMed1996

Stability and leakiness: opposing challenges to the glomerulus.

The complex architecture of the glomerular tuft is stabilized by several mechanisms. The basic system consists of the GBM and the mesangium maintaining the branching pattern of the capillary network. Superimposed are the podocytes, which appear to take effect by two mechanisms. First, podocytes contribute to the stabilization of the capillary folding pattern by supporting the angles between neighboring capillaries. Second, podocyte foot processes fixed to the outer aspect of the GBM probably function as contractile patches counteracting the elastic distension of the GBM. Simultaneously, the pattern of foot process interdigitation underlies the elaboration of a filtration slit and is thus pivotal for the high hydraulic permeability and the specificity of the glomerular filter. The loss of this pattern-commonly termed "foot process effacement" or "foot process fusion"-is frequently found in pathological situations and results in a decrease in permeability and impairment in specificity. On the other hand, foot process effacement is associated with prominent hypertrophy of the contractile apparatus of podocytes, suggesting an increased ability to generate forces counteracting capillary expansion. Thus, foot process effacement appears as an adaptive change in podocyte phenotype giving priority to the support function of podocytes for the prize of reducing the specific permeability.

Animals↗
PubMed1996

Three-dimensional analysis of the whole mesangium in the rat.

The three-dimensional structure of the mesangium was analyzed by means of reconstruction from serial semithin and ultrathin sections of the rat glomerulus. The mesangial domains traced on light micrographs of semithin sections were transferred to styrene models, which were stacked up to reconstruct the whole mesangium. The reconstructed mesangium was tree-like in shape and was divided into three lobes that were connected to the vascular pole by a slender neck. The glomerulus contained no islets of mesangium which were not connected to the vascular pole. The mesangium contained 64 mesangial loops that were penetrated by capillaries. Reliability of the findings on the mesangial loops was ascertained by various methods including reconstruction of part of the mesangium from ultrathin sections. Electron microscopic observations revealed that the arms of the mesangial loops were frequently very slender and consisted of mesangial cell processes containing prominent bundles of actin filaments. The mesangial loops were distributed evenly within the mesangium. Considering previous reports showing about 400 capillary branches in the rat glomerulus as well as the present findings, we concluded that the mesangial loops may change the distribution of intraglomerular blood flow by dynamic contraction of the mesangial cells, or serve as an additional safety device to prevent the expansion of glomerular capillaries.

Animals↗
PubMed1996

Re-evaluation of foot process effacement in acute puromycin aminonucleoside nephrosis.

The sequence of morphological changes during foot process effacement in acute puromycin aminonucleoside (PAN) nephrosis was examined by means of NaOH maceration and freeze cracking for scanning electron microscopy (SEM). The micrographs of SEM and those of transmission electron microscopy (TEM) were quantitatively analyzed by computerized morphometry, and were correlated with renal function. On day 2 after PAN injection, the slit length was moderately decreased by both shortening and degradation of the foot processes. On day 4, membrane-bounded vesicles were scattered in the lamina rara externa. During foot process effacement, the basal surface of podocytes developed palm-like domains that represented the cytoplasmic areas between interdigitation. The decrease in the length of podocyte cell borders paralleled the decrease of 24-hour creatinine clearance. The development of the palm-like domains on the basal aspects of podocytes estimated by distance class analysis was closely correlated with the sudden onset of proteinuria. We conclude that foot process effacement in PAN nephrosis caused by the retraction and degradation of foot processes leads to the development of palm-like domains, which is correlated with podocyte detachment as well as massive proteinuria.

Animals↗
PubMed1996

Case report: late relapse in a case of mesangioproliferative glomerulonephritis.

A case of atypical proliferative glomerulonephritis (PGN) without mesangial immunoglobulin (Ig) A deposition (so-called non-IgA PGN) showing exacerbation of heavy proteinuria under long-term observation is reported. Examinations of first renal biopsy specimens revealed membranoproliferative glomerulonephritis (MPGN)-like findings. Urinary protein excretion completely disappeared after treatment with prednisolone (PSL) and an antiplatelet drug, i.e., dipyridamole. Negative reaction for urinary protein continued for more than 10 years. Fourteen and a half years after the first biopsy, the patient had heavy proteinuria again. Results of the second renal biopsy showed marked proliferation of glomerular mesangial cells. Under electron microscopy, lobulation and double contours of the glomerular capillary walls were also observed segmentally. Depositions of IgG, IgM, IgA, and C3 were observed mainly in the glomerular capillary walls, but not in the mesangial areas; however, these findings were not compatible with IgA nephropathy or MPGN. No hypocomplementemia was observed during the clinical course. The patient was treated with 30 mg of PSL and 75 mg of dipyridamole daily and showed a good response to such treatment. It appears that this patient had a rare case of atypical non-IgA PGN.

Adult↗
PubMed1996

A frequent pathway to glomerulosclerosis: deterioration of tuft architecture-podocyte damage-segmental sclerosis.

Lesions in glomerular architecture include mesangial expansion, capillary ballooning, capillary unfolding and microaneurysm formation. Such lesions appear to develop in response to mechanical overextension. A frequent pathway to segmental glomerulosclerosis starts from capillary ballooning and unfolding. Podocytes supporting those deranged capillaries are exposed to increased mechanical stress. This may lead to podocyte injury terminating in detachments from the GBM. Naked GBM areas at peripheral capillary loops allow the attachment of parietal cells to the GBM, i.e. the formation of a tuft adhesion to Bowman's capsule. An adhesion has a strong tendency to progress to segmental sclerosis.

Animals↗
PubMed1996

Cytoskeletal changes in podocytes associated with foot process effacement in Masugi nephritis.

Foot process effacement represents the most characteristic change in podocyte phenotype under a great variety of experimental as well as human glomerulopathies. It consists in simplification up to a total disappearance of an interdigitating foot process pattern. Finally, podocytes affix to the glomerular basement membrane by outspread epithelial sheets. Structural and immunocytochemical techniques were applied to analyze the cytoskeletal changes associated with foot process effacement in Masugi nephritis. Three days after injection of the anti-glomerular-basement-membrane serum an interdigitating foot process pattern was almost fully lost; more than 90 percent of the outer glomerular capillary surface were covered by expanded sheets of podocyte epithelium that contain a highly organized cytoskeleton adhering to the basal cell membrane. Structurally, this cytoskeleton consists of an interwoven network of microfilaments with regularly distributed dense bodies, which obviously serve as cross-linkers within this network. Immunocytochemically, the expression of actin, alpha-actinin, and pp44 (a specific podocyte protein normally associated with the cytoskeleton of foot processes) were increased in this structure; alpha-actinin was especially prominent in the dense bodies. The results are consistent with the view that foot process effacement represents an adaptive change in cell shape including hypertrophy of the contractile apparatus, reinforcing the supportive role of podocytes. Several factors associated with increased distending forces to podocytes may underlie this phenotype change including loss of mesangial support, elevated glomerular pressures, and impairment of GBM substructure as well as of podocyte-GBM-contacts. Twenty-eight days after serum injection a remodeling of the foot process pattern was seen. It appears that this restitution depends on a preceding repair of mesangial support function to glomerular capillaries.

Animals↗
PubMed1996

A case of reflex anuria and uremia related to a unilateral ureteral stone.

A 63-year-old man had anuria associated with a unilateral ureteral stone for 24 hours. Laboratory data indicated marked azotemia with the serum creatinine concentration of 7.2 mg/dL and urea nitrogen of 48 mg/dL. The radiological findings revealed contralateral hydronephrosis. Spontaneous discharge of the ureteral stone reversed the anuria and uremia. Both ureteral and vascular spasms were attributed to the anuria in this patient.

Anuria↗
PubMed1995

Diversity and variability of smooth muscle phenotypes of renal arterioles as revealed by myosin isoform expression.

The contractility and distensibility of renal arterioles are important in the regulation of glomerular filtration. However, little is known regarding the characteristics of contractile proteins in these arterioles. Recently it was demonstrated that vascular smooth muscles contain two types of myosin heavy chain (MHC) isoforms, SM1 and SM2, which are unique molecular markers of smooth muscle cell phenotypes. SM1 is constitutively expressed in all types of smooth muscles, whereas SM2 exists only in mature smooth muscles. We characterized the expression of MHC isoforms as well as the ultrastructural myofilament assembly of renal arteriolar smooth muscles in human, rat and rabbit by immunohistochemical techniques. SM1 and alpha-smooth muscle actin were localized in both the preglomerular vessels (including the afferent arterioles) and efferent arterioles, whereas SM2 was present only in the preglomerular vessels. Renin-producing cells in the afferent arterioles (juxtaglomerular granular cells, JG cells) were positive for alpha-smooth muscle actin but negative for SM2. When renin synthesis was stimulated, the more proximal afferent arteriolar smooth muscles turned renin-positive and SM2 disappeared. Glomerular mesangial cells did not show immunoreactivities for SM1, SM2 or alpha-smooth muscle actin. The difference in MHC isoform expression in these arterioles was also reflected by ultrastructures; the afferent arteriolar smooth muscles contained abundant myofilaments including thick filaments, whereas the efferent arteriolar smooth muscles had a few myofilaments composed only of thin microfilaments. The JG cells displayed a myofilament assembly similar to that in the efferent arteriolar smooth muscles. We conclude from these observations that smooth muscles in pre-and postglomerular arterioles, the glomerular mesangial cells and JG cells differ in phenotypes, suggesting that they may have different contractile properties which may be critically involved in the regulation of glomerular filtration.

Actin Cytoskeleton↗
PubMed1995

Binding capacity of serum IgA to jacalin in patients with IgA nephropathy using jacalin-coated microplates.

Binding capacity of serum IgA to jacalin in 22 patients with IgA nephropathy, 14 patients with diffuse mesangial proliferative glomerulonephritis (non-IgA nephropathy) and 20 age-matched healthy adults was examined by enzyme-linked immunoassay (ELISA) using jacalin-coated microplates. In contrast to previous findings, the binding capacity of serum IgA to jacalin in patients with IgA nephropathy measured by ELISA using jacalin-coated microplates was significantly higher than that in healthy adults. The ratio of serum IgA levels measured by this method to those obtained by single radial immunodiffusion was significantly increased in patients with IgA nephropathy. It appeared that the capacity of serum IgA binding to jacalin was marked in these patients. It is concluded that the binding capacity of serum IgA to jacalin is not ubiquitously impaired in all patients with IgA nephropathy.

Adult↗
PubMed1995

Establishment of vasopressin-responsive early proximal tubular cell lines derived from transgenic mice harboring temperature-sensitive simian virus 40 large T-antigen gene.

A little is known about vasopressin receptor in early proximal tubule (S1). The purpose of this study is to establish the vasopressin-responsive S1 cell line derived from transgenic mice harboring temperature-sensitive(ts) simian virus (SV) 40 large T-antigen gene. The cells showed a temperature-sensitive cell growth characteristic of encoding tsSV40. The S1 cells retained a unique morphology specific to proximal tubule. The cells showed the vasopressin-induced increase in intracellular calcium concentration ([Ca2+]i) mediated by both V1a and the putative Vp receptor. Of nineteen clonal cell lines established from the parental cells, three expressed only V1a receptor, and five retained both V1a and Vp receptor. In conclusion, these immortalized S1 cell lines may be useful for studying vasopressin receptor subtypes in S1.

Animals↗
PubMed1994

Detection of glycosylated protein in glomeruli of STZ-induced diabetic rats using the nitroblue tetrazolium (NBT) reaction.

Detection of glycosylated protein in renal tissues was determined in streptozotocin (STZ)-induced diabetic rats using the nitroblue tetrazolium (NBT) reaction. The glycosylation of extra-cellular matrix (ECM) components such as laminin and fibronectin was examined in vitro using the same method. Immunofluorescence staining of laminin or type IV collagen was also performed in renal tissues of STZ-induced diabetic rats. There was no significant difference in the intensity of NBT in renal tissues between 4 week STZ-induced diabetic rats and control rats of the same age. The intensity of NBT staining in the glomerular mesangial areas and capillary walls was marked in 12 week diabetic rats. The mean values of fructosamine measured by the NBT reaction in the glycosylated-laminin and fibronectin were increased dose dependently. In immunofluorescence, laminin and type IV collagen were observed significantly in the glomerular mesangial areas and capillary walls of 12 week diabetic rats. However, there was no significant change in renal histopathology in 4 and 12 weeks diabetic rats. It appears that the non-enzymatic glycosylation and expression of ECM components in glomeruli increased in the early stage of diabetic nephropathy prior to the appearance of marked histologic alterations. In conclusion, non-enzymatic glycosylation of glomerular structural components may play an important role in the initiation of the early stage of renal injuries in diabetes.

Animals↗
PubMed1994

IgA deposits might not influence the production of extracellular matrix in glomeruli of ddY mice, a spontaneous animal model for IgA nephropathy.

Immunofluorescence studies were carried out to determine whether the expression of extracellular matrix (ECM) in glomeruli of ddY mice, a model for IgA nephropathy (Berger's disease), is influenced by treatment with a rat monoclonal antibody to murine CD4 molecules (mAb CD4). This mAb CD4 showed a selective decrease in the number of CD4+ T cells in the peripheral blood of ddY mice as described previously. The ddY mice were initially treated with intravenous injections, followed by weekly intraperitoneal injections of mAb CD4. In immunofluorescence, the mean intensity of IgA deposits in the renal glomerular mesangial areas and capillary walls of the treated ddY mice was significantly lower than that in saline-treated control mice at comparable ages. There was no significant difference in the distribution or intensity of ECM components, i.e. type IV collagen, fibronectin and heparan sulfate proteoglycan, in glomeruli between the mAB CD4-treated and the control ddY mice. In light microscopy, mesangial expansion in the treated ddY mice was milder than that found in the saline control mice. No significant differences in the average number of intraglomerular cells, levels of serum IgA and urinary protein between the treated and control ddY mice were observed. Thus, it appears that although CD4+ T cells modulate the amounts of glomerular IgA deposits, other factors may be involved in the expression of ECM in glomeruli of IgA nephropathy in ddY mice.

Animals↗
PubMed1994

Expression of intercellular adhesion molecule-1 and infiltration of lymphocytes in glomeruli of patients with IgA nephropathy.

Using immunofluorescence, we studied 19 patients with IgA nephropathy to determine whether the expression of intercellular adhesion molecule (ICAM)-1 in glomeruli might reflect the disease activity. The relationship between the expression of ICAM-1 and the infiltration of lymphocytes, monocytes and polymorphonuclear leukocytes (PMN) in glomeruli of IgA nephropathy cases was examined. The expression of ICAM-1 in patients in the advanced stage was significantly higher than that in patients in the mild stage. In double immunofluorescence, the distribution of ICAM-1 expression in glomeruli was different from that of IgA deposition in patients in both stages. Glomeruli which showed increases of ICAM-1 expression had marked infiltration of lymphocytes (OKT4+, OKT8+ T cells), and monocytes (OKM1+ cells). Increase of urinary protein and decreases in renal function were observed in patients in the advanced stage. It appears that the expression of ICAM-1 is closely linked to glomerular cell proliferation, and infiltration of lymphocytes and monocytes in patients with IgA nephropathy. However, the expression of ICAM-1 in glomeruli might not be correlated with IgA-dominant immune complexes in this disease.

Antibodies, Monoclonal↗
PubMed1994

Detection of glycosylated protein in renal tissues and dermal vascular vessels in the microalbuminuric stage of diabetic nephropathy using the nitro blue tetrazolium reaction.

Detection of glycosylated protein in renal and dermal tissues was performed in patients in the microalbuminuric stage of diabetic nephropathy using the nitro blue tetrazolium (NBT) reaction. The intensity of NBT staining in glomeruli and dermal vascular vessels was marked in the microalbuminuric stage as well as in the overtly proteinuric stage. The NBT staining in the renal and dermal vascular walls in both stages was significantly stronger than in the samples of control autopsy patients. It appeared that nonenzymatic glycosylation in various tissues, i.e. kidneys and dermal vascular vessels, had already progressed in the microalbuminuric stage in patients with diabetic nephropathy.

Adult↗