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Biomedical subjects

H Nihei

Publications and source records attributed to H Nihei.

At least 127 records · Page 7Linked to original sources

[Nephropathy associated with electrolyte disorders].

It is well known that renal dysfunction is associated with several types of electrolyte disorders. On the other hand, renal manifestations have been attributed to electrolyte disorders. Hypokalemia is the most frequent electrolyte abnormality encountered in clinical practice. The main cause of hypokalemia is due to abuse of laxatives and diuretics or to anorexia nervosa. Hypercalcemia is another major electrolyte abnormality, associated with numerous renal manifestations. Renal tubules damages and chronic interstitial nephritis are characteristic pathological findings in prolonged electrolyte disorders. The mechanism of renal involvement and characteristic clinical manifestations of the electrolyte disorders are reviewed.

Animals↗

Difference of myosin heavy chain expression between mesangial cells and vascular smooth muscles.

Contraction of the pre- and postglomerular arteries play an important role in the regulation of glomerular blood flow. Mesangial cells may also be involved in the mechanism of this regulation, but it has not been clarified yet whether or not mesangial cells and vascular smooth muscles show an identical phenotype, especially in terms of their contractile proteins. In this study, in order to elucidate any difference in the cellular phenotypes between mesangial cells and renal vascular smooth muscles, we investigated the localization of myosin heavy chain isoforms using a monoclonal antibody against SM1 and SM2. Both SM1 and SM2 are specific to smooth muscles. SM1 is specifically expressed in smooth muscles from early development and SM2 appears after birth. In normal renal tissues, SM1 and SM2 were expressed only in the smooth muscle cells of the arterioles and small arteries. However, glomerular cells, including mesangial cells, were not stained with either anti-SM1 antibody or anti-SM2 antibody. Localization of SM1 and SM-2 was similar to that of alpha-smooth muscle actin (SM alpha-actin). Staining for SM-1 was not observed in the mesangial areas of renal tissues with glomerular disease. These results clearly indicate that mesangial cells have a different phenotype from that of vascular smooth muscle cells in terms of their contractile proteins.

Fluorescent Antibody Technique↗

High glucose modulates albumin permeability across glomerular endothelial cells via a protein kinase C-dependent mechanism.

To investigate the mechanism of glomerular endothelial response to high glucose, an in vitro model of the glomerular endothelial barrier was established in which transfer of fluorescein-labeled albumin across confluent monolayers of immortalized bovine glomerular endothelial cells (GEN) grown on polycarbonate membranes was measured. We first examined the effects of increased concentrations of D-glucose on albumin permeability across GEN monolayers and further investigated the role of protein kinase C (PKC) in the regulation of glucose-induced changes in endothelial barrier function. Incubation with 30 mM D-glucose increased albumin permeability more than those with 10 mM D-glucose. Albumin permeability incubated with 10 mM D-glucose plus 20 mM mannitol was not significantly different from those with 10 mM D-glucose, indicating that the increase in albumin permeability induced by 30 mM D-glucose was not due to high osmolar stimuli. A protein kinase C (PKC) inhibitor, H-7 (25 microM) significantly reduced the permeability-increasing effects of D-glucose. Lactate dehydrogenase release from endothelial cells was not significantly increased above baseline after incubation with 10 mM or 30 mM D-glucose. These results suggest that elevated concentrations of glucose activates PKC, resulting in an increase in albumin permeability across GEN.

Animals↗

[Japan coma scale in the prediction of outcome after early surgery for aneurysmal subarachnoid hemorrhage].

The value of the 10-grade Japan Coma Scale (JCS) as a means of evaluating patients undergoing early aneurysm surgery was assessed in terms of its relationship to surgical outcome. The 13-grade Glasgow Coma Scale (GCS) was also assessed, and comparisons were made between the two. A series of 765 patients who underwent aneurysm surgery within 7 days after hemorrhage were evaluated both by JCS and GCS immediately prior to surgery, and outcome was assessed by the Glasgow Outcome Scale (GOS) 6 months postoperatively. Both the JCS and GCS scores were significantly correlated with surgical outcome (JCS vs GOS: rs = 0.586, GCS vs GOS: rs = 0.615, p < 0.001). There was no significant difference between the correlation coefficients for outcome of the JCS and GCS. In general, the better the JCS or GCS score was, the better the surgical outcome was, however, outcome among those with a JCS score of 3 was poorer than among those with a score of 10, 20, or 30. The results of this study indicate that both JCS and GCS are useful in predicting surgical outcome, but the GCS may be better than the JCS because of the problem with the score of 3 in the latter.

Acute Disease↗

Expression of intercellular adhesion molecule-1 on cultured glomerular endothelial cells by pro-inflammatory cytokines and lipopolysaccharide.

Infiltration of leukocytes and mononuclear cells into the glomeruli is an early pathological finding in human and experimental glomerulonephritis. However, the cellular and molecular basis for cell infiltration into the glomeruli is not yet completely understood. In addition, there is little information on the expression of intercellular adhesion molecule-1 (ICAM-1) on glomerular cells. In the present study, we investigated the expression of ICAM-1 on cultured bovine glomerular endothelial cells (GEN) and its regulation by the pro-inflammatory cytokines, interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and lipopolysaccharide (LPS). Immunocytochemical staining showed that ICAM-1 molecules were constitutively expressed on the surface of GEN. In flow cytometric and ELISA analyses, ICAM-1 molecule expression on GEN was significantly upregulated by IL-1 beta, MCP-1 and LPS in a dose-dependent manner, but not by IL-6. LPS was the most potent inducer of ICAM-1 molecule expression on GEN. The effects of IL-1 beta, MCP-1 and LPS were observed as early as 4 h and reached a maximal level by 18 h. These results suggest that ICAM-1 on GEN can participate in the infiltration of mononuclear cells into glomeruli in human and experimental glomerulonephritis.

Animals↗

Analysis of the expression of cell surface antigens and intercellular adhesion molecules on lymphocytes in CAPD patients.

The aim of the present study was to assess immunological aspects in patients on continuous ambulatory peritoneal dialysis (CAPD). The CAPD patients were divided into two groups. Group A consisted of patients in which high-somolar dialysate was used infrequently, and group B consisted of patients in which high-osmolar dialysate was used frequently. We characterized cell populations in the peritoneal effluent (PE) of CAPD patients. Analysis of the nucleated cell composition revealed that one-third of the PE cells were lymphocytes. Flow cytometric analysis of the surface antigen expression on lymphocytes revealed that the proportion of helper/inducer T-cells was lower in PE than in peripheral blood (PB). By contrast, the rates of DR antigen expression on T-cells and CD45RO antigen expression on helper/inducer T-cells (memory T-cells) were higher in PE than in PB. However, there were no statistically significant differences between the rates of expression of any lymphocyte surface antigens in the two groups. Expression of intercellular adhesion molecules, such as ICAM-1 and LFA-1, was higher in PE than in PB. It is of interest that the expression of ICAM-1 and LFA-1 on T-cells in PB was significantly higher in group B than in group A. In summary, there is an increase in memory T-cells in the PE and up-regulation of intercellular adhesion molecules of PE lymphocytes of CAPD patients. The up-regulation of intercellular adhesion molecules is also observed in PB lymphocytes in whom high-osmolar dialysate is used frequently.

Adult↗

Accumulation of phosphatydilcholine-hydroperoxide in dialysis patients with diabetic nephropathy.

Plasma lipid peroxidation in noninsulin dependent diabetes mellitus (DM) patients were evaluated in DM patients undergoing hemodialysis (HD) by means of a chemiluminescence-HPLC for the specific determination of phosphatidylcholine hydroperoxide (PCOOH). Thirty-three uremic patients with DM nephropathy, undergoing 12 hours HD a week using polymethylmethacrylate membrane, were studied. Of them 22 DM patients on HD were divided into 2 age and sex matched groups treated and conventional group in order to clarify therapeutic effect of 500 mg alfa-tocopherol and 600 mg probucol daily. Fifty DM patients without end-stage renal disease (ESRD) who were age-, period of diabetes-, and sex-matched, were selected as positive control of the subjects. Plasma PCOOH levels were significantly elevated in both DM patients, while the plasma PCOOH in normal controls were 227.0 +/- 68.7 pmol/ml. Plasma PCOOH levels of DM patients undergoing HD were significantly higher than that of patients without ESRD (1,330.8 +/- 642.7 pmol/ml vs. 756.6 +/- 431.9 pmol/ml, p < 0.025). Partial correlation coefficient of plasma PCOOH level demonstrated PCOOH and period of HD in DM patients were highly significantly positively correlated (p < 0.01), although single session of HD was not found to produce significantly increased lipid-peroxidation. Plasma PCOOH roughly remained within similar levels as base lines by medication with anti-oxidant compared to that of conventional group. From these results we conclude that HD intensifies lipid peroxidation and such accumulation of hydroperoxide could account for accelerated progress of atherosclerosis in DM patients with renal insufficiency. It is worthwhile to try an administration of free radical scavenger in order to reduce PCOOH and slow down the progression of atherosclerotic vascular disease.

Adult↗

Glomerular endothelial cells in culture express and secrete vascular endothelial growth factor.

Vascular endothelial growth factor (VEGF) is a specific growth factor for endothelial cells, and its abundant expression has been reported in kidney glomeruli. In this study, we focused on glomerular endothelial cells (GEN) as a possible source of VEGF secretion and sought to uncover a potential autocrine role of VEGF for GEN. Ribonuclease protection assay demonstrated VEGF mRNA expression in cultured GEN, and 46-kDa VEGF protein was detected in the conditioned medium by immunoblot analysis using polyclonal antibody raised against the NH2-terminal portion of VEGF. Removal of fetal bovine serum (FBS) from the culture medium for 2 h decreased VEGF mRNA abundance, which was restored by the readdition of FBS (10%) within 2 h. The effect of FBS was completely abolished by protein kinase inhibitor H-7 (10 microM), suggesting that FBS-stimulated VEGF mRNA induction involves activation of protein kinases. The treatment of GEN with 10(-7) M 12-O-tetradecanoylphorbol-13-acetate (TPA) increased the VEGF mRNA abundance fivefold, supporting the idea that VEGF expression is regulated by protein kinase C. [3H]thymidine incorporation into GEN treated with TPA (10(-7) M) was inhibited by neutralizing antibody for VEGF. Thus VEGF was identified as an autocrine growth factor for GEN in vitro. Its physiological role might be the regulation of GEN proliferation, and the induction of VEGF expression by FBS and TPA suggests its involvement in the response of glomerular capillary endothelial cells to injury in certain pathophysiological states.

Animals↗

IGF-I as an early indicator of malnutrition in patients with end-stage renal disease.

The present study was performed to clarify the possibility of IGF-I as an early indicator of malnutrition in patients with end-stage renal disease. Thirty-two patients (19 males, 13 females; mean age 49.6 +/- 10.0 years) undergoing dialysis were enrolled in the study. Body weight, skinfold thickness, and midarm muscle circumferences (MAMCs) were measured for anthropometric nutritional indices. Blood samples were collected to measure the following endocrinological, biochemical and hematological indices: IGF-I, growth hormone, (GH), total protein, prealbumin, albumin, transferrin, hematocrit, and lymphocyte count. Nutritional indices were measured again 1 month later to calculate the percent difference among them. Moreover, 2 patients who showed a decrease in IGF-I and suffered from malnutritional complications, such as hypoproteinemia and emaciation, which could not be successfully treated by conventional therapies were selected in order to confirm the nutritional role of IGF-I mediated by recombinant human GH (r-hGH). The serum IGF-I concentration distribution ranged from 22 to 225 ng/ml. In 15 patients (10 males, 5 females), it fell from 22 to 82 ng/ml below the normal range. Partial correlation coefficient analysis demonstrated that baseline IGF-I and the percent difference of each the body weight, MAMC, prealbumin and albumin were highly significantly correlated (r = 0.431, 0.641, 0.624 and 0.348, respectively; p = 0.014, 0.001, 0.001 and 0.028, respectively). The percent difference of IGF-I did not correlate significantly with that of any other nutritional index during the 1-month observation without administration of r-hGH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[The early lesions of renal amyloidosis].

Two patients with minimal amyloid deposition in association with nephrotic syndrome are reported. Since the amyloid deposits in each renal biopsy specimen were inconspicuous, both were first thought to be minimal glomerular changes. A few widely scattered, silver-positive, epimembranous spicules were found on careful reexamination by light microscopy. Congo red stain and electron microscopy confirmed the presence of small glomerular amyloid deposits and amyloid fibrils. Furthermore, immuno-fluorescence microscopy showed partial IgA deposits in the mesangial area and capillary wall. We therefore urge careful examination to detect amyloid deposits of all kidney biopsy specimens of minor glomerular abnormalities, or glomerulonephritis with IgA deposits from elderly patients with nephrotic syndrome. Light microscopy of Congo-red-stained sections and electron microscopy of the fibrillar structure very useful for the detection of small amyloid deposits.

Adult↗

[Association of cell cycle and protein kinase C with the expression of cytoskeletal protein in cultured rat mesangial cells].

We conducted a study to investigate whether expression of the contractile proteins in cultured rat mesangial cells (MC) was associated with the cell cycle and protein kinase C (PKC). When growth-arrested MC were stimulated with 100 nM phorbol myristate acetate (PMA) for 24 hours, an increased expression of smooth muscle alpha-actin and vimentin was detected by immunocytochemistry. A proportion of the S- and G2/M-phase in MC was increased in accordance with the enhanced expression of contractile proteins on flow cytometry. Immunoblot analysis revealed that 100 nM PMA stimulated expression of alpha-actin and vimentin as a single band. These results indicate that expression of contractile proteins, such as alpha-actin and vimentin, is dependent on the cell cycle and PKC, suggesting a phenotypic change in which MC assume smooth muscle cell characteristics.

Animals↗

A case of primary glomerular fibrosis associated with the accumulation of type I and type III collagen.

A 49-year-old woman suffering from nephrotic syndrome (NS) was admitted for renal biopsy and treatment of NS. Light microscopy demonstrated that the glomerular capillary wall was markedly thickened with diffuse accumulation of periodic acid Schiff- and periodic acid methenamine-positive materials, leading to lobular accentuation of glomerular tufts. By electron microscopy, numerous collagenous fibers were observed in the mesangium and subenodothelial area. The fibers were peculiarly curved and frayed, as reported in nail-patella syndrome. These materials were thought to be type I and type III collagen as a result of immunohistochemical studies. No laboratory data or pathological findings were found to be compatible with previously described glomerulonephritis. The primary glomerular fibrosis in the present patient seemed to be a case of collagenofibrotic glomerulonephropathy.

Collagen↗

Establishment and characterization of an immortalized bovine glomerular endothelial cell line.

Bovine subcultures (second passage) of glomerular endothelial cells (GEN) isolated from one-year-old kidney were successfully transfected by recombinant plasmids containing the simian virus (SV)-40 T antigen (Tag) using a lipofectin-mediated procedure. One cell clone was selected, propagated and characterized. This clone can be grown in RPMI 1640 medium supplemented with 10% fetal calf serum. The advantage of this cell line is the cultivation of bovine GEN without the addition of fibroblast growth factor or a coating of fibronectin or gelatin on the culture plate. More than 80 passages were achieved and the doubling time was 32 h. The Tag was easily identified in transfected-GEN by indirect immunofluorescence. These cells weakly expressed factor VIII-related antigen, slightly took up acetylated-low density lipoprotein and secreted a detectable amount of angiotensin-converting enzyme. Immunocytochemical staining for UAE-1 was also positive. Moreover, oncoproteins, such as Ki-67 and p53, were expressed in these cells. Cell cycle analysis by flow cytometry revealed that the percentages of G1, S, and G2/M stages in cycling transfected-GEN culture in RPMI 1640 medium supplemented with 10% fetal calf serum were 34%, 52.9%, and 13.1%, respectively. The conditioned medium from confluent transfected-GEN stimulated [3H]thymidine incorporation into glomerular mesangial cells. This cell line may provide a useful tool for examining modulators of mesangial cell growth. Thus this cell line is the first immortalized bovine GEN that retain the morphologic, phenotypic, and functional characteristics of bovine GEN.

Animals↗

Identification of GTP-binding proteins in human glomeruli.

The localization of GTP-binding proteins (G-proteins) in human glomeruli was examined using immunohistochemistry and immunoblotting. Immunohistochemical staining for G-protein subunits demonstrated the existence of Gs alpha, Gi alpha and Go alpha proteins in the glomeruli. Moreover, immunoblots further revealed Gs alpha (52 kD), Gi alpha 1/2 (40-41 kD), Gi alpha 3 (40 kD) and Go alpha (39 kD) in the glomerular membranes. The predominant subspecies of Gs was a 52-kD protein, and Go alpha was detectable in the smallest amounts of the G-protein subunits. However, immunoblots failed to demonstrate detectable amounts of G-proteins in cytosolic extracts. This is the first report that characterizes G-protein subunits in human glomeruli. Further study is required to determine the roles of G-proteins in signal transductions in human glomeruli.

GTP-Binding Proteins↗

[Significance of membrane attack complex inhibitory factor expression in cultured human glomerular epithelial cells].

Membrane attack complex (MAC) inhibitory factor (MACIF) is a 20-kD membrane protein that inhibits MAC formation on homologous cells. Until recently, a functional role of MACIF had been demonstrated in erythrocytes. Therefore, we have focused on the fact that glomerular epithelial cells (GECs) are the primary target of MAC-mediated damage in rat Heymann's nephritis model of human membranous nephropathy. Using immunocytochemistry and western blotting we have shown that MACIF is expressed in cultured human GECs. Phosphatidyl-inositol (PI)-phospholipase C (PLC) reduced MACIF expression in these cells, suggesting that MACIF is a PI-linked membrane protein in GECs. In addition, we elucidated that MACIF protects GECs against complement-mediated lysis. These findings suggest that MACIF expressed on GECs plays an important role in the protection of GECs against complement mediated-cellular damage in vivo.

CD59 Antigens↗

[A case of malignant lymphoma in the skull base].

A case of malignant lymphoma located in the clivus, sella and cavernous sinus is reported. A 46-year-old female was hospitalized with a 3-week history of diplopia. Neurological examination showed left oculomotor, trochlear, abducens and hypoglossal nerve palsy. Improvement of cranial nerve palsy was achieved with the administration of prednisolone but it was only transient. Laboratory studies and endocrinological examination showed almost no abnormal findings. Skull x-ray film revealed a widely damaged base. MR studies showed a homogeneously enhanced mass lesion in the clivus, sella and bilateral cavernous sinus. Partial removal of the lesion was performed via the transsphenoidal route. The histopathological diagnosis of the mass was consistent with diffuse, medium sized cell, B-cell type malignant lymphoma. A postoperative systemic evaluation by tumor scan with 67Ga disclosed no abnormal uptake except in the skull base. Postoperatively, the patient was treated with radiation, a total of 50 Gy, followed by chemotherapy every 3 week consistent of cyclophosphamide, vincristine, pirarubicin, bleomycin, procarbazine and prednisolone. The cranial nerve symptoms disappeared during radiation therapy. The MR studies after three courses of chemotherapy revealed almost complete remission. The patient died of acute progression of pneumonia without any evidence of the recurrence of malignant lymphoma 10 months after the operation. Skull base involvement of malignant lymphoma is unusual. Five cases of malignant lymphoma invading the skull base have been reported since 1987. In most cases, the lesion originated from paranasal sinuses and was usually accompanied with intradural extensions. In the case we have reported there was no intradural invasion of the tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗

Hereditary serum cholinesterase deficiency associated with severe lipid deposition in the kidney.

A 47-year-old woman who was homozygous for a silent cholinesterase gene (hereditary serum cholinesterase deficiency) presented with nephrotic syndrome and hyperlipidemia. Renal biopsy performed in 1986 demonstrated mesangial proliferative glomerulonephritis. Four years later, a second biopsy revealed progression with mesangial interpositions and severe lipid deposition in the glomeruli, tubules and interstitium. This is the first case of hereditary serum cholinesterase deficiency accompanied by renal disease. Serum cholinesterase deficiency may be related to hyperlipidemia and abnormal lipid deposition in the kidney, which promotes the progression of renal disease.

Adolescent↗