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Biomedical subjects

H Nihei

Publications and source records attributed to H Nihei.

At least 91 records · Page 5Linked to original sources
PubMed1997

Anti-mitogenic effects of sarpogrelate in cultured rat mesangial cells.

We investigated the effects of the new 5-HT2A receptor antagonist, sarpogrelate, on DNA synthesis in renal mesangial cells stimulated with 5-HT in the presence and absence of platelet-derived growth factor (PDGF)-BB. Both 5-HT and PDGF-BB demonstrated a mitogenic effect on these cells. When mesangial cells were incubated in the absence of PDGF-BB, sarpogrelate inhibited DNA synthesis in these cells in a dose-dependent manner. In the presence of PDGF-BB, sarpogrelate had a weaker anti-mitogenic effect in mesangial cells stimulated with 5-HT. Sarpogrelate was cytotoxic at concentrations over 10(-5) M according to the results of LDH release assays, and it reduced the S1 phase in mesangial cells stimulated with 5-HT by a flow cytometry. These findings suggest that sarpogrelate may be effective in the treatment of some glomerulonephritis associated with mesangial cell proliferation.

Animals↗
PubMed1997

Thrombotic microangiopathy associated with alpha-interferon therapy for chronic myelocytic leukemia.

A 31-year-old man diagnosed as having chronic myelocytic leukemia (CML) developed renal insufficiency with nephrotic-range proteinuria during alpha-interferon (IFN) therapy for CML. A renal biopsy specimen showed remarkable thrombotic microangiopathic lesions resembling those of hemolytic-uremic syndrome. The patient had papules on both lower legs, and a cutaneous biopsy showed similar microangiopathic lesions in dermal and subcutaneous vessels. Although discontinuation of IFN and initiation of prednisolone therapy resulted in resolution of proteinuria, renal insufficiency persisted. These findings suggest that long-term IFN therapy can induce late-onset thrombotic microangiopathy in systemic microvessels.

Adult↗
PubMed1997

Molecular cloning of rat p38 mitogen-activated protein kinase and it's osmotic regulation in rat kidney.

Rat p38 mitogen-activated protein (MAP) kinase cDNA was isolated from rat kidney cDNA library using a PCR cloning strategy. The deduced amino acid sequence consists of 360 amino acids and shares 95.3% similarity with human p38 MAP kinase. The message for rat p38 MAP kinase was about 3.4 kilobases and was highly expressed in the kidney. In water-deprived rat kidneys, the steady-state levels of p38 MAP kinase mRNA increased about 2.7-fold as compared with those of control rats. This result suggests that p38 MAP kinase may play an important role in the osmoregulation in the kidney.

Amino Acid Sequence↗
PubMed1997

Therapeutic effect of a newly developed antioxidative agent (OPC-15161) on experimental immune complex nephritis.

The effect of a newly developed free radical scavenger (OPC-15161) on the progression of nephrotoxic serum (NTS) nephritis was evaluated. NTS nephritis rats were sacrificed immediately before and 1, 2, 3, 6, and 24 h and 13 and 19 days after intravenous injection of NTS. The tissue content of phosphatidylcholine hydroperoxide, the activity of superoxide, the activity of superoxide dismutase in the renal cortex, and the serum malondialdehyde levels were measured. The phosphatidylcholine hydroperoxide content in the renal cortex of OPC-15161-treated NTS nephritis rats was lower than that in the control rats 24 h after NTS injection. The activity of superoxide dismutase in OPC-15161-treated rats was sustained in contrast to the decrease in this activity in the control rats 6 h after injection of NTS. The effects of OPC-15161, dipyridamole, and prednisolone on NTS nephritis rats were investigated. OPC-15161 (20 mg/kg p.o.) showed a potent inhibitory effect on the urinary protein excretion, whereas dipyridamole (30 and 100 mg/kg p.o.) and prednisolone (2 mg/kg p.o.) had less suppressive effects. In view of these results, we conclude that OPC-15161 notably ameliorated the urinary protein excretion by way of the suppression of lipid peroxidation in the renal tissue of NTS nephritis rats.

Animals↗
PubMed1997

IGF-I/IGFBP-1 as an index for discrimination between responder and nonresponder to recombinant human growth hormone in malnourished uremic patients on hemodialysis.

From a clinical aspect, there are still a number of unsolved problems in patients with end-stage renal disease, for instance intractable malnutrition. The present study was undertaken to establish the therapeutic effect of recombinant human growth hormone (r-hGH) on the nutritional state and clarify the usefulness of the insulin-like growth factor-I (IGF-I) insulin-like growth factor binding protein-1 (IGFBP-1) ratio as nutritional indices for prediction of the clinical response in uremic patients on hemodialysis. Thirty hemodialysis patients (13 females and 17 males, mean age 56.7 +/- 15.2 years) were studied who were suffering from malnutrition and could not be treated by any of the usual nutritional therapies; they were subjected to 0.5 IU/kg/week of r-hGH subcutaneously after hemodialysis for 2 weeks. Blood samples were collected for measurement of the following plasma biochemical and hematological indices: serum IGF-I, IGFBP-1, growth hormone, total protein (TP), prealbumin, transferrin, albumin, serum urea nitrogen (SUN), creatinine, hematocrit, and amino acids. Immediately after r-hGH administration, SUN, essential amino acid and nonessential amino acid changed from 67.7 +/- 12.3 to 56.5 +/- 10.5 mg/dl (p < 0.05), from 798 +/- 84 to 1,115 +/- 208 microM/l (p < 0.05 vs. baseline), and from 2,185 +/- 221 to 2,814 +/- 621 microM/l (p < 0.05), respectively. Serum IGF-I increased markedly from 193 +/- 49 to 321 +/- 81 ng/ml, whereas serum IGFBP-1 decreased from 139 +/- 13 to 81 +/- 19 micrograms/l (p < 0.05). Four weeks after r-hGH administration, serum TP and albumin increased from 5.5 +/- 0.2 to 6.0 +/- 0.3 g/dl (p < 0.05) and from 3.2 +/- 0.2 to 3.6 +/- 0.3 g/dl (p < 0.05), respectively. Serum IGF-I/IGFBP-1 ratio was significantly higher in patients with an increase of 0.5 g/dl or more in serum albumin than in other patients with poor response and the control group before r-hGH administration. Patients with marked improvement in serum albumin showed an IGF-I/IGFBP-1 ratio of 2 or less. On the other hand, patients without favorable improvement in serum albumin had a higher ratio of 4 or more. We conclude that r-hGH and IGF-I improve the malnutritional state by alleviating hypoproteinemia and abnormality of serum amino acid profile in uremic patients on hemodialysis. In addition, the serum IGF-I/IGFBP-1 ratio is useful not only as a nutritional parameter but also as a predicting index of responsiveness to r-hGH.

Amino Acids↗
PubMed1997

Detailed analysis of phenotypes of macrophages infiltrating glomeruli in rat anti-Thy1 nephritis.

A phenotypic analysis of infiltrating macrophages in rat anti-Thy1 glomerulonephritis induced by monoclonal antibody (mAb) 1-22-3 was carried out using recently reported macrophage-specific mAbs. This was combined with a more detailed quantitative analysis, counting positive cells in isolated glomeruli, to obtain more information on the roles played by macrophages in glomerulonephritis. In normal glomeruli a small number of ED1- or OX-3(anti-Ia)-positive cells but almost no ED2-, TRPM-3- or Mar-3-positive cells were observed. ED1-positive cells increased from 2 h and peaked between days 3 and 7 after mAb injection. TRPM-3-positive cells increased from day 3 and peaked on day 7, later than ED1. The numbers of OX-3-positive cells changed in parallel with those of ED1-positive cells. Mar-3, which stained blood monocytes and ED2, which is an indicator oftissue-fixed resident macrophages, did not react with glomerular infiltrating macrophages. In a double staining study, about 40% of ED1- or OX-3-positive cells costained with TRPM-3 on day 3 and the percentage increased on day 7, but hardly any cells were positive for TRPM-3 alone. This results in two different phenotypes (ED1+,ED2-,OX-3+,Mar-3-, TRPM-3- and ED1+,ED2-,OX-3+,Mar-3-,TRPM-3+) of infiltrating macrophages. We conclude that in rat anti-Thy1 glomerulonephritis, monocytes/macrophages may infiltrate the mesangium, rapidly changing their phenotype (Mar-3+ to Mar-3-) and resulting in a gradual shift to TRPM-3-positive, activated macrophages.

Animals↗
PubMed1997

Regulated expression of endothelin converting enzymes in glomerular endothelial cells.

Endothelin converting enzyme (ECE) constitutes a potential regulatory site for the production of active mature endothelins. Two cDNAs (ECE-1 and -2) encoding ECE have recently been cloned, but the regulation of the expression of these ECE has not been clarified. In the study presented here, an attempt was made to determine whether or not glomerular endothelial cells (GEN) express ECE-1 and -2, and to learn how the expression of ECE-1 and -2 is regulated by kinase-mediated signaling systems. Ribonuclease protection assay revealed the expression of ECE-1 and -2 in cultured GEN, and the expression was increased approximately 2.5- and approximately 1.8-fold, respectively, by treatment with 10(-7) M 12-O-tetradecanocyl-phorbol-13-acetate (TPA) for 4 hours. These increases in ECE-1 and -2 expression with TPA were inhibited by cotreatment with calphostin C (10(-7) M). In contrast, 24-h treatment with 10(-7) M TPA significantly decreased the expression of ECE-1 and -2, indicating that the expression was tightly regulated by protein kinase C (PKC)-dependent mechanism(s). Actinomycin D (1 microgram/mL) abolished the TPA-induced increase of ECE-1 and -2 mRNA, whereas TPA treatment did not affect the mRNA stability of ECE-1 and -2, thus suggesting that TPA-induced increases of ECE-1 and -2 mRNA resulted from the transcriptional activation of ECE-1 and -2, gene, rather than from the increase of mRNA stability. In addition to the regulation by PKC, the effects of protein kinase A and G on ECE-1 and -2 expression were also examined. Treatment with chlorophenyl-thio cyclic AMP (200 microM) for 24 h decreased ECE-1 and -2 expression to approximately 50% and approximately 40% of the control value, respectively. 8-bromo-3', 5'-cyclic GMP also decreased ECE-1 and -2 expression to approximately 80% and approximately 25% of the control value, respectively. These results demonstrate that the expression of ECE-1 and -2 is regulated by kinase-mediated signaling systems, with the most prominent regulatory effect shown by protein kinase C.

Animals↗
PubMed1997

Effect of varying amino acid levels on protein metabolism in nephrotic rats during total parenteral nutrition.

In an attempt to determine appropriate diet in nephrotic syndrome, nephrotic rats, induced by puromycin aminonucleoside, were nourished by total parenteral nutrition fluid containing the same energy, but three different levels (1.65, 3.3, and 6.6%) of amino acids for 7 d. The fractional rate of total protein synthesis in the liver was determined by injecting a flooding dose of [3H]phenylalanine. The proportion of newly synthesized proteins retained and exported by the liver was estimated by injecting a tracer dose of [14C]leucine and then measuring the protein radioactivity remaining in the liver and present in the plasma after secretion was completed. Nephrotic animals synthesized more protein than control animals. Although the absolute synthesis rates of total protein in liver were increased with increasing amino acid administration, the absolute rates of synthesis of albumin were higher in the 3.3% group than in the other groups in nephrotic rats. However, kidney protein synthesis in nephrotic rats was higher in the 1.65% group than in the 3.3% group. Interestingly, the 3.3% group revealed the smallest urinary excretion of total protein and albumin. In addition, in the 3.3% group, plasma concentrations of total protein and albumin were higher, and plasma concentrations of total cholesterol and triglyceride were lower than in other groups. It was concluded that the 3.3% group, corresponding to a normal protein diet, has the greatest salutary effect on urinary protein excretion, followed by protein and lipid metabolism, in nephrotic rats. Not only protein intake but also the energy:protein ratio are important for diet therapy in nephrotic animals. The technique of total parenteral nutrition may be useful in defining the factors involved in glomerular permeability or permselectivity and intracellular protein metabolism.

Amino Acids↗
PubMed1997

The effect of glucose on the proliferation of peritoneal fibroblasts.

The purpose of this study was to clarify the pathophysiological role of glucose and glucose transporters (GLUTs) in the proliferation and production of extracellular matrix (ECM) in peritoneal fibroblasts. Peritoneal fibroblasts from rat omentum were cultured in medium M199 with 5% fetal bovine serum (FBS) with (Group B) and without (Group A) 4% glucose. The rate of cell growth at the M stage of the cell cycle in Group B was higher than that in Group A at 12 and 24 hours after culture. However, cell numbers in Group B were less than in Group A at 24, 72, and 120 hours after culture. The GLUT inhibitor suppressed the proliferation of cells 72 and 120 hours after culture. The procollagen III peptide (PIIIP) contents in the supernatant of cells cultured in a high glucose medium were higher than those of control cells at 24, 72, and 120 hours after culture. PIIIP levels of cells cultured with the GLUT inhibitor were also higher than those of cells without the GLUT inhibitor. These results suggest that initially glucose stimulates cell proliferation and thereafter inhibits its proliferation. GLUTs may accelerate the proliferation of peritoneal fibroblasts. We suggest that glucose stimulates the ECM component PIIIP, and GLUT may have an inhibitory effect on the production of the ECM component PIIIP.

Animals↗
PubMed1997

Nitric oxide synthase I immunoreactivity in the macula densa of the kidney is angiotensin II dependent.

The present study was undertaken to clarify the mechanism of the regulation of nitric oxide synthase (NOS)-I in the macula densa of the kidney. We determined the changes in NOS-I immunoreactivity of the macula densa relevant to the changes in systemic blood pressure (BP) and the renin-angiotensin system. Rats received four different types of treatment, and kidney sections were immunohistochemically stained for renin, NOS-I, and NOS-III. Plasma renin activity (PRA) and angiotensin II (Ang II) concentration were determined by radioimmunoassay. In the low-salt group, PRA, plasma Ang II, and the number of renin and NOS-I positively stained areas in the juxtaglomerular apparatus (JGA) were all increased, while BP and NOS-III in the glomerular capillaries did not change. In the desoxycorticosterone acetate (DOCA)-salt group, in contrast to the elevation of BP, PRA, plasma Ang II, and all immunohistochemical parameters were decreased. In the Ang II infusion group, BP, plasma Ang II, and the number of NOS-I positive glomeruli were increased, while PRA and renin staining were decreased. Administration of Ang II type 1 receptor (AT-1) antagonist TCV-116 significantly increased PRA, plasma Ang II, and the number of renin-positive glomeruli. However, BP, and NOS-I and NOS-III staining did not show any difference. These results clearly suggest that NOS-I in the macula densa changes in parallel with plasma Ang II, but not renin or systemic BP.

Angiotensin II↗
PubMed1997

[Effects of recombinant human erythropoietin (rHuEpo) on the interactions between glomerular endothelial cells and mesangial cells: regulation of cell proliferation via endothelin (ET)-1].

To elucidate the effects of recombinant human erythropoietin (rHuEpo) on the interactions between glomerular endothelial cells (GENs) and mesangial cells (GMCs), we investigated whether or not cultured bovine GENs alter endothelin (ET)-1 secretion from bovine MCs and MC proliferate under basal or rHuEpo-stimulated conditions. Incubation for 24 hours with synthetic ET-1 stimulated MC in a dose-dependent manner. In addition, 100 pg/ml of ET-1 significantly stimulated MC proliferation after more than 12 hours incubation. Moreover, rHuEpo stimulated ET-1 secretion from GENs in a dose-dependent manner and showed less stimulation of ET-1 secretion from GMCs than GENs. DNA synthesis in both GENs and GMCs was significantly stimulated with more than 5 U/ml of rHuEpo. ET-1 secretion from GENs co-cultured with GMCs was higher than that from cultured GENs only. Conditioned medium, obtained from co-culture of GENs and GMCs, stimulated the proliferation of GMCs that were significantly inhibited with 10(-6) M approximately 10(-5) M BQ-123, a ETA receptor antagonist. These results suggest that rHuEpo directly stimulates the proliferation of GENs and GMCs, and this stimulatory effect is in part due to ET-1 secreted from these cells, especially GENs.

Animals↗
PubMed1996

Morphological changes in the peritoneal vasculature of patients on CAPD with ultrafiltration failure.

Vascular changes in the peritoneum were histochemically assessed in patients on continuous ambulatory peritoneal dialysis (CAPD) with ultrafiltration failure. Light microscopy showed extensive interstitial fibrosis, mesothelial denudation and vascular changes. Morphological changes in the vasculature were observed at different levels. The specific changes in the vasculature in these patients were characterized by severe fibrosis and hyalinization of the media of venules. Immunofluorescence microscopy revealed extensive deposition of such extracellular matrices as type IV collagen and laminin in the vascular wall. Electron microscopy revealed a significant increase in collagenous fibers and degeneration of smooth muscle cells in the media. However, the endothelial cells at the levels of vasculature affected were relatively well preserved. These pathological alterations in the vasculature in CAPD patients with ultrafiltration failure suggest that certain toxic factors, such as a high osmolar dialysate or low pH of dialysate, had affected the peritoneal vasculature from the adventitial side rather than the endothelial side. These vascular changes in the peritoneum are thought to be irreversible, associated with deterioration of peritoneal function, and to cause ultrafiltration failure in the patients on long-term CAPD therapy.

Adult↗