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Biomedical subjects

Z Ota

Publications and source records attributed to Z Ota.

At least 91 records · Page 5Linked to original sources

Alteration of renal receptors for atrial natriuretic peptide and vasopressin in spontaneously hypertensive rats treated with antihypertensive diuretics.

To investigate the alteration of the renal atrial natriuretic peptide (ANP) and arginine vasopressin (AVP) receptors in the controlled hypertensive state of spontaneously hypertensive rat (SHR) treated with antihypertensive diuretics, 12 weeks old SHRs were administered an antihypertensive diuretic, furosemide, trichloromethiazide, or indapamide, daily for 10 days and investigated by radiolabeled receptor assay (RRA) of ANP and AVP. The urine volume was significantly increased in all groups treated with antihypertensive diuretics as compared with the untreated control group on day 3. Systolic blood pressure was significantly decreased in groups treated with both trichloromethiazide and indapamide. The number of renal ANP receptors decreased; affinity was increased only in the SHR administered indapamide. The affinity of the renal AVP receptor was also decreased in that group. Alteration of ANP and AVP receptors was observed only in the group treated with indapamide. This indicates that the ANP and AVP receptor in the kidney of SHR was changed not only by diuresis or reduction of blood pressure, but by the pharmacological action of indapamide.

Animals↗

Effect of chronic ceruletide treatment on dopaminergic neurotransmitters, receptors and their mRNAs in the striatum of rats with dyskinesia induced by iminodipropionitrile.

To clarify the mechanism of long-lasting ceruletide action, an analogue of cholecystokinin, in relieving the dyskinesia induced by the iminodipropionitrile (IDPN), we investigated the changes in dopaminergic neuronal system in the striatum. In the control rats, ceruletide had no significant effect on the concentrations of dopamine (DA), DOPAC or HVA or on the turnover of DA in the striatum. The concentration of DA was decreased and the turnover of DA [(DOPAC + HVA)/DA] was increased in the striatum of IDPN-treated rats. Chronic administration of ceruletide (160 micrograms.kg-1.day-1 x 10 days) increased DA concentration and decreased DA turnover only transiently. Both D1 and D2 receptors and their mRNAs were decreased in the striatum of rats given IDPN. After chronic ceruletide treatment, D1 receptor rose to the control level for 3 days, while the D2 receptor rose to a level 1.5 times the control level for 3 days. Even at the 7 days after chronic ceruletide treatment, D2-R rose significantly as compared with the IDPN-treated rats. Both D1 and D2 receptor mRNAs were significantly increased for 3 days in the IDPN-treated rats. These observations indicate that the synthesis of DA receptors is increased by ceruletide treatment in the striatum of IDPN-treated rats. These changes in DA receptors and their mRNAs closely paralleled the changes in dyskinetic movement of the IDPN-treated rats after repeated daily administration of ceruletide, as previously reported. The parallel changes between the DA receptors and dyskinetic movement suggest that an up-regulation of DA receptors in the striatum corresponds with an improvement of dyskinesia in the IDPN-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

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↗

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↗

The effects of thyroid-stimulating hormone and thyroid microsomal antibody on thyroid peroxidase activity in human follicular cells: a mini organ culture study.

Thyroid peroxidase (TPO) is an essential enzyme involved in thyroid hormone synthesis and is closely related to the microsomal antigen which is the target of thyroid microsomal antibody. There have been several reports on direct inhibition of peroxidase activity by thyroid microsomal antibody. We prepared a mini organ culture of thyroid glands obtained at operation, and investigated the localization of thyroid peroxidase activity in follicular cells proliferated around the thyroid tissue blocks by electron microscopy. The development of microvilli containing TPO activity on the cell surface facing the culture medium was observed when normal thyroid tissue or Graves' thyroid tissue was incubated with TSH but in the TSH-free group the development of microvilli was poor and TPO activity was very much decreased. After the addition of serum positive for thyroid microsomal antibody, the TPO activity of the microvilli was retained in 4/6 tissue samples, but it disappeared in 2 cases. Our findings suggested that thyroid peroxidase activity is regulated by thyroid stimulating substances such as TSH and by TPO in tissue.

Adolescent↗

A study on cross-reactivity of anti-DNA antibody with glycosaminoglycans.

To study the pathogenesis of lupus nephritis, the cross reactivity between anti-DNA antibody and glycosaminoglycans (GAGs) was investigated. Monoclonal anti-DNA antibodies were obtained from hybridomas by the fusion of MRL/lpr/lpr splenocytes with murine myeloma cells. Some of these monoclonal anti-DNA antibodies showed cross reactivity with GAGs, such as hyaluronic acid, chondroitin sulfate and heparan sulfate. To elucidate the mechanism of cross reactivity, inhibition assays with propanol and polyethylenimine (PEI), a cationic agent, were carried out. Increase of the concentration of PEI (0.6-2.0% vol/vol) resulted in a dose dependent decrease in the binding ability of anti-DNA antibody to GAGs. Propanol, an organic reagent which disrupts the van der Waals bonds between epitopes and paratopes, showed little inhibitory effect on the binding activity of monoclonal anti-DNA antibody to GAGs. These results indicate that the binding of anti-DNA antibody to GAGs is due to a charge interaction rather than van der Waals forces. Anti-DNA antibody which can react with GAGs in the glomerular basement membrane seems to play an important role in the pathogenesis of lupus nephritis.

Animals↗

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↗

Stimulation by interleukin-7 of mononuclear cells in peripheral blood, synovial fluid and synovial tissue from patients with rheumatoid arthritis.

To determine how interleukin-7 (IL-7) affects the proliferation of T cells in patients with rheumatoid arthritis (RA), we evaluated the response of mononuclear cells (MNC) obtained from their peripheral blood (PB), synovial fluid (SF) and synovial tissue (ST) to stimulation by recombinant IL-7 and interleukin-2 (IL-2). Each cytokine was administered alone or combined with phytohemagglutinin (PHA). Cellular DNA synthesis was assayed by the [3H]-thymidine incorporation method. The stimulatory effect of 500 u/ml IL-7 on PBMNC obtained from 19 patients with RA was significantly lower than on PBMNC from 19 healthy controls. However, the same degree of stimulatory activity of 500 u/ml IL-2 was observed on the PBMNC from both RA patients and control subjects. The response of PBMNC to a suboptimal dose of PHA (0.2 micrograms/ml) was enhanced by adding either IL-7 or IL-2 (100 or 500 u/ml) to the cultures. The enhanced synthesis of DNA by both RA and control PBMNC on exposure to IL-7 following stimulation by a suboptimal dose of PHA was higher than that of IL-2. The effect of IL-7 on RA PBMNC was significantly greater than that of IL-2 at the concentration of 100 u/ml on PBMNC from the same RA patients. The stimulatory activity of IL-2 at the concentrations of 100 and 500 u/ml on SF MNC and ST MNC exceeded that of IL-7. In particular, an IL-2 dose of 500 u/ml had a marked effect on SF MNC. The PHA response of SF MNC was the lowest seen among the MNC from three different compartments.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

What factors are involved in the knowledge necessary for the self-management of diabetic patients?

The aim of this study is to obtain data for improving a training program for patients with diabetes mellitus. One hundred eighty-seven patients with non-insulin dependent diabetes mellitus were tested with 20 questions about their knowledge for self-management of diabetes mellitus. Then to draw out factors in their personal backgrounds relating to their correct answers, multiple regression analyses were conducted. As a result, four factors showed significant differences in the following order: Educational careers > ages > duration of disease > socioeconomic strata. The results of the present study have shown for the first time, that these four factors closely concern patients to acquire the necessary knowledge for their self-management of the disease. In addition, this study has raised some fundamental problems regarding the training program for patients: how education should be given to patients.

Adolescent↗

Immune complex glomerulonephritis in a pregnant woman with congenital C9 deficiency.

A 27-year-old woman developed proteinuria, hypertension, and peripheral edema during the ninth month of her first pregnancy. The clinical and serological features were compatible with a diagnosis of toxemia of pregnancy, except for the presence of hypocomplementemia. The patient had glomerulonephritis characterized by large electron-dense deposits, predominantly in the mesangium. Immunofluorescence studies revealed striking accumulations of Clq and C3, and the presence of small amounts of IgG and IgM in the mesangium. Serum and plasma levels of complement components were normal, except for the C9 component. Family studies demonstrated that the C9 deficiency was inherited.

Adult↗

Studies on the glomerular permeability with human liver ferritin.

To clarify the roles of the glomerular basement membrane (GBM) in filtration mechanisms, human liver ferritin was used for the first time as a tracer. Urinary excretion of human liver ferritin was measured and the injected ferritin was tracked under electron microscopy. Puromycin aminonucleoside (PAN) nephrosis was induced in Sprague Dawley rats and normal saline was injected into control rats. Monomeric and polymeric human ferritin were isolated from post mortem samples. Both kinds of human liver ferritin were injected into the experimental and control rats and urine samples were examined for human ferritin by radioimmunoassay. Rats with PAN nephrosis excreted approximately 33 times more monomeric ferritin than the controls. Appreciably more monomeric ferritin was excreted than polymeric ferritin. In control rats, monomeric ferritin particles were restricted in the lamina rara interna and inner aspect of the glomerular basement membrane 30 min after injection. On the other hand, in rats with PAN nephrosis, monomeric ferritin particles were seen throughout the width of the GBM and in the epithelial cells. With human liver ferritin, we were able to demonstrate the escape of the ferritin into the urine in addition to conducting the conventional electron microscopic tracer study of the glomerular capillary wall. Human liver ferritin shows potential as a useful tracer in the study of glomerular permselectivity.

Animals↗

[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↗

Ultrastructural localization of three major basement membrane components--type IV collagen, heparan sulfate proteoglycan and laminin in the normal human GBM.

Human glomerular basement membrane (GBM) is known to contain type IV collagen, heparan sulfate proteoglycan (HS-PG) and laminin in the extracellular matrix. In this study, ultrastructural distribution of these antigens was investigated in normal human glomeruli using the immunogold technique. Type IV collagen was present throughout the GBM, mainly on the lamina densa, and all over the mesangial region. HS-PG was present on the laminae rarae, predominantly on the lamina rara externa, and periphery of the mesangial region. Laminin was present throughout the GBM and peripheral region of the mesangial matrix. Our study demonstrated the preferential localization of each component in the GBM.

Basement Membrane↗

Alterations in glomerular extracellular matrix components in glomerulonephritis.

We investigated alterations in the main components of glomerular extracellular matrices, including heparansulfate proteoglycan (HS-PG), laminin, type IV collagen and fibronectin in the renal tissues of 61 patients with various types of glomerulonephritis. Indirect immunofluorescence stainings with polyclonal antibodies of these extracellular matrix components were performed. In minimal change nephrotic syndrome, no remarkable changes were observed. In membranous glomerulonephritis, non-collagenous components, such as HS-PG and laminin altered in distribution, forming spikes in stage II and circles between or around the immune deposits in stage III. These changes were observed more clearly in HS-PG and laminin than in type IV collagen. These results suggested that non-collagenous components played an important role in repairing the GBM. In membranoproliferative glomerulonephritis and IgA nephropathy, type IV collagen and fibronectin expanded in the proliferated mesangial area. These findings showed that there was a close relationship between these extracellular matrix and the progression of glomerulosclerosis. In dense deposit disease, double contour of staining of HS-PG, laminin and type IV collagen was observed along the capillary wall. These findings suggested that there were no main extracellular matrix components within the dense materials.

Collagen↗

[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↗

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↗