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I Ebihara

Publications and source records attributed to I Ebihara.

At least 73 records · Page 4Linked to original sources
PubMed1995

Effects of a low-protein diet on glomerular endothelin family gene expression in experimental focal glomerular sclerosis.

1. The present study was designed to assess whether glomerular expression of mRNAs for endothelin-1 and endothelin-3, as well as endothelin receptors A and B is affected by a low-protein diet during the course of focal glomerular sclerosis. 2. Focal glomerular sclerosis was induced in rats by injection of puromycin aminonucleoside on days 0, 27, 34 and 41 in conjunction with unilateral nephrectomy on day 22. Control rats were subjected to nephrectomy or sham operation on day 22. 3. Animals were divided into six groups. In group 1, the puromycin aminonucleoside-injected rats were fed a standard diet containing 22% protein. In group 2, the puromycin aminonucleoside-injected rats were fed a low-protein diet containing 6% protein, which was initiated on the day of the first puromycin aminonucleoside injection. In group 3, the nephrectomized rats without puromycin aminonucleoside were fed a standard diet. In group 4, the nephrectomized rats without puromycin aminonucleoside were fed a low-protein diet. In group 5, the sham-operated rats were fed a standard diet. In group 6, the sham-operated rats were fed a low-protein diet. 4. The percentage of sclerotic glomeruli in group 1 rats increased markedly with time, reaching 77% on day 80. 5. The glomerular mRNA levels for endothelin-1 and endothelin receptors A and B increased significantly as glomerular sclerosis progressed, whereas no endothelin-3 mRNA was detected in the glomeruli of any group. The endothelin-1 production in isolated glomeruli from group 1 increased significantly as glomerular sclerosis progressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Glomerular expression of smooth-muscle myosin heavy-chain isoforms in aminonucleoside nephrosis in rats.

1. We investigated the glomerular expression of three types of myosin heavy-chain isoforms, including S-myosin heavy-chain 40 (SM1), S-myosin heavy-chain 29 (SM2) and FS-myosin heavy-chain 34 (SMemb) in puromycin aminonucleoside nephrosis. 2. There was little change in SM1 and SM2 mRNA levels throughout the experiment. In contrast, glomerular SMemb mRNA increased on days 2 and 4 (before and soon after the onset of proteinuria, respectively), but declined on day 8 (the peak of proteinuria). 3. Histological myosin heavy-chain expression was examined using three antibodies against SM1, SM2 and SMemb. Immunohistochemically, SM1 and SM2 were absent in the glomeruli associated with puromycin aminonucleoside nephrosis until day 20. The SMemb isoform was barely detectable in normal glomeruli, but substantial amounts of SMemb were demonstrated in the glomeruli of rats with puromycin aminonucleoside nephrosis. In the puromycin aminonucleoside-treated rats, the number of SMemb-positive glomerular cells increased on days 2 and 4. 4. We examined whether levels of alpha-smooth-muscle actin or proliferating cell nuclear antigen correlated with myosin heavy-chain levels in the glomeruli of rats with puromycin aminonucleoside nephrosis. None of the cellular components in the glomeruli was positive for either alpha-smooth-muscle actin or proliferating cell nuclear antigen in puromycin aminonucleoside nephrosis. 5. Administration of methylprednisolone to puromycin aminonucleoside-treated rats resulted in the rapid disappearance of proteinuria. However, methylprednisolone did not affect SMemb mRNA or immunostaining in a glomeruli of rats with puromycin aminonucleoside nephrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Enalapril attenuates increased gene expression of extracellular matrix components in diabetic rats.

This study was designed to assess whether the glomerular expression of mRNA for extracellular matrix (ECM) components including alpha 1 (I), alpha 1 (III), and alpha 1 (IV) collagen chains, laminin B1 and B2 chains, metalloproteinases (MMP), and tissue inhibitor of metalloproteinases (TIMP) is affected by enalapril in 12- and 24-wk-old rat after streptozotocin injection. Animals were divided into three groups; untreated diabetic rats, enalapril-treated diabetic rats, and control rats. Enalapril treatment was continued for 24 wk. Enalapril reduced both creatinine clearance (P < 0.01) and urinary protein excretion (P < 0.01) in diabetic rats. In diabetic rats, mRNA levels for alpha 1 (IV) collagen chain, laminin B1 and B2 chains, and alpha 1(I) and alpha 1(III) collagen chains increased significantly at 24 wk compared with those in controls [alpha 1(IV): 3.8-fold (P < 0.01); laminin B1: 6.2-fold (P < 0.01); laminin B2:5.4-fold (P < 0.01), alpha 1(i): 4.8-fold (P < 0.01) and alpha 1(III): 3.8-fold (P < 0.01)]. At 24 wk, mRNA levels for MMP-1 and MMP-3 fell to 40% (P < 0.01) and 20% (P < 0.01), respectively, in the glomeruli of diabetic rats compared with levels in controls. In contrast, mRNA levels for TIMP-1 and TIMP-2 increased significantly at 24 wk after streptozotocin injection (TIMP-1: 8.0-fold (P < 0.01) and TIMP-2: 6.4-fold (P < 0.01)).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Modulation of glomerular endothelin and endothelin receptor gene expression in aminonucleoside-induced nephrosis.

This study assessed glomerular endothelin (ET)-1, ET-3, and ET-receptor A and B mRNA levels in puromycin aminonucleoside (PAN)-induced nephrosis. During the nephrotic stage, 8 days after PAN injection, ET-1 and ETB receptor mRNA were elevated by 2.8 +/- 0.8-fold (P < 0.01) and 2.4 +/- 0.9-fold (P < 0.01), respectively, as compared with controls. These mRNA levels decreased to control levels by Day 20, when the nephrosis was in remission. In contrast, glomerular ETA receptor mRNA levels did not change in PAN nephrosis or control rats during the experimental period. ET-3 mRNA was not detected in the glomeruli of PAN nephrosis or control rats. Additionally, plasma ET concentration and glomerular ET production were measured in PAN nephrosis and control rats by radio-immunoassay. Eight days after PAN injection, ET-1 levels in plasma and glomeruli were not significantly altered in rats with PAN-induced nephrosis (glomeruli, 104.68 +/- 16.46 pg/mg of protein versus 98.24 +/- 13.68 pg/mg of protein; plasma, 2.68 +/- 1.10 versus 2.52 +/- 0.98 pg/mL). The administration of methylprednisolone to PAN rats resulted in the rapid disappearance of proteinuria and partially attenuated the increased ET-1 and ETB receptor gene expression in the glomeruli. These data indicate that glomerular ET-1 and ETB receptor expression in PAN nephrosis in increased at the mRNA level and that methylprednisolone treatment results in an attenuated increase.

Animals↗
PubMed1995

Effect of a specific endothelin receptor A antagonist on mRNA levels for extracellular matrix components and growth factors in diabetic glomeruli.

We have previously reported that the mRNA levels of extracellular matrix (ECM) components including alpha 1(I), alpha 1(III), and alpha 1(IV) collagen chains, laminin B1 and B2 chains, and growth factors including tumor necrosis factor (TNF)-alpha, platelet-derived growth factor (PDGF)-B chain, transforming growth factor (TGF)-beta, and basic fibroblast growth factor (FGF) all increase with age in diabetic glomeruli. The present study was designed to assess whether glomerular expression of these mRNAs in rat diabetic glomeruli is affected by a specific endothelin receptor A antagonist, FR139317. Diabetes was produced by streptozotocin injection, and animals were divided into four groups: untreated diabetic rats, FR139317-treated diabetic rats, control nondiabetic rats, and FR139317-treated control rats. FR139317 treatment was continued for 24 weeks. FR139317 attenuated the rise in creatinine clearance (P < 0.01) and reduced urinary protein excretion (P < 0.01) in diabetic rats, but did not affect blood pressure. FR139317 attenuated the increases in glomerular mRNA levels of alpha 1(I) (P < 0.01), alpha 1(III) (P < 0.01), and alpha 1(IV) (P < 0.01) collagen chains, laminin B1 (P < 0.01) and B2 (P < 0.01) chains, TNF-alpha (P < 0.01), PDGF-B (P < 0.01), TGF-beta (P < 0.001) and basic FGF (P < 0.01) in diabetic rats. However, FR139317 did not affect these mRNA levels in glomeruli of control rats. These findings suggest that FR139317 may be useful in the treatment of diabetic glomerulopathy by reducing mRNA levels of ECM components and growth factors.

Aging↗
PubMed1995

[Progressive pulmonary fibrosis in a case of Sjögren's syndrome with asbestos exposure].

A 62-year-old man had an occupational history of exposure to asbestos for 27 years (1947-1974). Dry mouth, dry eyes and swollen gums were noted in 1974. Sjögren's syndrome was diagnosed in 1975. The chest radiograph in 1984 showed bilateral pleural thickening and small reticular opacities in the left lower lung field. In 1990, he complained of dyspnea and cough, and diffuse interstitial pneumonia was diagnosed. While being treated for diffuse interstitial pneumonia, pulmonary fibrosis progressed rapidly, and advanced pulmonary fibrosis was obvious in 1992. Laboratory data showed hyper gamma-globulinemia (36.8%) and a high level of IgG (3772 mg/dl) in 1976. These values decreased to within the normal ranges during the subsequent clinical course. The results of lymphocyte subset counts in 1988 were normal. With the progression of diffuse interstitial pneumonia in 1990, the lymphocyte subset counts showed a low percentage of CD4 (19.2%), a low CD4/8 ratio (0.46), and a low percentage of CD20 (26.8%). In 1992, as pulmonary fibrosis progressed despite treatment, the disorder of lymphocyte subsets became worse. The CD4 percentage was very low (5.0%), as was the CD4/8 ratio (0.08), and the percentage of CD20 (1.4%); the CD8 percentage was high (64.7%), as was the percentage of Leu 7 (49.0%). These immunologic and pulmonary changes could be not explained by Sjögren's syndrome. Determining what factor induced these changes is difficult, but asbestos exposure is a likely cause.

Asbestos↗
PubMed1994

Low protein diet blunts the rise in glomerular gene expression in focal glomerulosclerosis.

The present study was designed to assess whether expression of mRNA for extracellular matrix (ECM) components, metalloproteinases (MMP) and tissue inhibitor of metalloproteinases (TIMP) in glomeruli is affected by a low protein diet during the course of focal glomerulosclerosis (FGS). Puromycin aminonucleoside (PAN) was injected intraperitoneally in rats and the right kidney was removed on day 22. Nephrotic rats received successive intraperitoneal injections of PAN on days 27, 34, and 41. Control rats were subjected to a nephrectomy or a sham operation on day 22. Animals were divided into six groups. In group 1, the PAN-injected rats were fed a standard diet containing 22% protein. In group 2, the PAN-injected rats were fed a low protein diet containing 6% protein, starting on the same day as the first PAN injection. In group 3, the nephrectomized rats without PAN were fed a standard diet. In group 4, the nephrectomized rats without PAN were fed a low protein diet for the same period. In group 5, the sham operated rats were fed a standard diet. In group 6, the sham operated rats were fed a low protein diet for the same period. Rats were sacrificed on days 0, 60 or 80 after the initial PAN or saline injection. The percentage of sclerotic glomeruli in group 1 rats increased markedly with time, reaching 77% on day 80. The mRNA levels encoding for alpha 1(I), alpha 1(III), alpha 1(IV) collagen chains, laminin B1 and B2 chains, heparan sulfate proteoglycan (HSPG), MMP-2, TIMP-1 and TIMP-2 increased significantly as glomerulosclerosis progressed, whereas MMP-1 and MMP-3 mRNA levels were unchanged, and no MMP-9 mRNA was detected throughout the experiments. In group 2, the low protein diet reduced the prevalence of glomerulosclerosis and attenuated the increased mRNA expression for ECM components, MMP-2, TIMP-1 and TIMP-2 in FGS glomeruli. In groups 3 through 6, mRNA levels for ECM components decreased with age, whereas those for MMPs and TIMPs changed little throughout the experiments. Immunofluorescence studies revealed the accumulation of types I, III and IV collagens, laminin, and HSPG in the sclerotic area and low protein diet attenuated the accumulation of these proteins. These data suggest that glomerulosclerosis may result from an imbalance among ECM components, MMPs and TIMPs and that a low protein diet attenuates the otherwise increased levels of mRNA for ECM components, MMP-2, TIMP-1 and TIMP-2 in glomerulosclerosis.

Animals↗
PubMed1994

Two adult cases of IgM-associated mesangial proliferative glomerulonephritis.

Two adult patients with mesangial proliferative glomerulonephritis with diffuse IgM deposition in the glomeruli are reported. Case 1 was a 25-year-old female with nephrotic syndrome who showed complete remission after treatment with prednisolone (PSL). Case 2 was a 46-year-old male with asymptomatic proteinuria who showed incomplete remission (0.5-1.0 g/24 hr) of urinary protein without any medication. In light microscopy, these patients revealed minimal or slight proliferation of glomerular mesangial cells without glomerular sclerosis and crescent formation. Deposition of IgM and C3 was observed in the glomerular mesangial areas and capillary walls by immunofluorescence. Electron-dense deposits were observed in the glomerular mesangial areas in these patients. Mesangial proliferative glomerulonephritis associated with diffuse IgM deposition in the glomeruli appears to have a benign clinical course. It has also been suggested that this disease has variant clinical courses since we recently experienced two other patients with mesangial proliferative glomerulonephritis with focal IgM deposits who showed renal tubular dysfunction or chronic renal failure.

Adult↗
PubMed1994

Effects of enalapril on endothelin-1 and growth factor gene expression in diabetic rat glomeruli.

We have previously reported that the mRNA levels of endothelin (ET-1), tumor necrosis factor-alpha), (TNF-alpha), platelet-derived growth factor (PDGF)-B chain, transforming growth factor (TGF-beta), and basic fibroblast growth factor (bFGF) all increased with age in diabetic rat glomeruli. We have now assessed the effect of the angiotensin-converting enzyme inhibitor enalapril on the expression of the ET-1, TNF-alpha, PDGF-B, TGF-beta, and bFGF genes in 24-week-old rat glomeruli after streptozotocin injection. Animals were divided into controls, enalapril-treated diabetic rats, and untreated diabetic rats. Treatment continued for 24 weeks. Enalapril reduced both creatinine clearance (p < 0.001) and urinary protein excretion (p < 0.01) in diabetic rats. Enalapril produced a nonsignificant 15 mm Hg reduction in blood pressure in diabetic rats. Enalapril also attenuated the increases in ET-1 mRNA levels observed in the glomeruli of diabetic rats (0.5-fold compared with untreated diabetic rats at 24 weeks [p < 0.01]) but had no effect on increased mRNA levels of TNF-alpha, PDGF-B, TGF-beta, and bFGF. These findings suggest that enalapril therapy may be effective in reducing ET-1 mRNA expression in the glomeruli of diabetic nephropathy.

Animals↗
PubMed1993

Endothelin-1 mRNA expression by peripheral blood monocytes in IgA nephropathy.

We investigated endothelin-1 mRNA expression in peripheral blood monocytes from 40 patients with IgA nephropathy, 40 with other glomerulonephritides and 10 with essential hypertension without renal diseases, and from 30 healthy age-matched controls. 95% of patients with IgA nephropathy had increased endothelin-1 mRNA expression in monocytes but little was detected from the other groups. Endothelin-1 mRNA was positively correlated with urinary protein excretion (95% CI 0.835-0.952) and histopathological findings (0.796-0.939). In 15 patients with IgA nephropathy endothelin-1 mRNA values and proteinuria decreased gradually after treatment. Endothelin-1 mRNA-expressing activated monocytes may be associated with the progression of IgA nephropathy.

Adolescent↗
PubMed1993

Messenger RNA expression for growth factors in glomeruli from focal glomerular sclerosis.

Focal glomerular sclerosis was induced in rats by chronic injections of puromycin aminonucleoside (PAN) on Days 0, 27, 34, and 41 and by unilateral nephrectomy on Day 22. Rats were sacrificed on Days 0, 8, and 20 (acute phase) and on Days 48, 60, and 80 (sclerotic phase). The percentage of sclerosing glomeruli was 16.6% on Day 48 and increased significantly to 72.8% on Day 80. We examined glomerular mRNA levels for proliferating cell nuclear antigen (PCNA), platelet-derived growth factor (PDGF)-A and B chains, transforming growth factor (TGF)-beta, epidermal growth factor (EGF), insulin-like growth factor (IGF)-I, and basic fibroblast growth factor (bFGF) on Days 0, 8, 20, 48, 60, and 80. Although these growth factor mRNA levels showed little change in glomeruli until Day 20, all growth factor mRNA levels increased in glomeruli during the sclerotic phase of PAN nephrosis as glomerular sclerosis progressed. On Day 80, mRNA levels for PCNA, PDGF-A and B chains, TGF-beta, EGF, IGF-I, and bFGF increased 12-, 10-, 12-, 15-, 2-, 2-, and 8-fold, respectively, in the glomeruli of PAN-treated rats with marked glomerular sclerosis when compared with control rats. Unilateral nephrectomy without PAN administration did not cause glomerular sclerosis up to Day 80 and mRNA levels for PCNA, PDGF-A and -B chains, TGF-beta, EGF, IGF-I, and bFGF in this group were almost the same as those in the normal sham-operated group. These data suggest that changes in growth factor mRNA levels in glomeruli may contribute to the development of PAN-induced glomerular sclerosis.

Animals↗
PubMed1993

Altered glomerular steady-state levels of tumour necrosis factor-alpha mRNA during nephrotic and sclerotic phases of puromycin aminonucleoside nephrosis in rats.

1. We determined glomerular and medullary tumour necrosis factor-alpha mRNA levels in acute puromycin aminonucleoside nephrosis on days 0, 8 and 20. 2. Tumour necrosis factor-alpha mRNA levels were increased fourfold in glomeruli and twofold in the medulla during the nephrotic stage of acute puromycin aminonucleoside nephrosis (day 8). 3. The high tumour necrosis factor-alpha mRNA levels in both glomeruli and the medulla were ameliorated significantly by methylprednisolone administration. 4. Focal glomerular sclerosis was induced in rats by injection of puromycin aminonucleoside on days 0, 27, 34 and 41 and by unilateral nephrectomy on day 22. 5. The percentage of sclerosing glomeruli was 16.6% on day 48 and had increased significantly to 72.8% on day 80. 6. During the sclerotic phase of puromycin amino-nucleoside nephrosis, glomerular tumour necrosis factor-alpha mRNA levels increased as glomerular sclerosis progressed. On day 80, glomerular tumour necrosis factor-alpha mRNA levels were 13-fold higher than levels in control rats. 7. These data suggest that glomerular tumour necrosis factor-alpha mRNA expression is associated with the development of puromycin aminonucleoside-induced glomerular sclerosis.

Acute Disease↗
PubMed1993

Gene expression of metalloproteinases and their inhibitor in renal tissue of New Zealand black/white F1 mice.

1. The present study was carried out to determine how levels of the mRNA of metalloproteinases (metalloproteinase-1, 72 kDa type IV collagenase, metalloproteinase-3 and 92 kDa type IV collagenase) and tissue inhibitor of metalloproteinases are regulated in the renal tissues of New Zealand Black/White F1 mice. 2. mRNA levels for metalloproteinase-1, 72 kDa type IV collagenase, metalloproteinase-3 and tissue inhibitor of metalloproteinases increased significantly with the progression of nephritis in New Zealand Black/White F1 mice. 3. At 48 weeks of age, the levels of mRNA for metalloproteinase-1, 72 kDa type IV collagenase, metalloproteinase-3 and tissue inhibitor of metalloproteinases increased by 8-, 4-, 8- and 15-fold, respectively, in the renal tissues of New Zealand Black/White F1 mice compared with New Zealand White mice. 4. In the kidneys of New Zealand White mice, however, the mRNA levels of these proteins changed little throughout the experimental period. 5. We could not detect expression of mRNA for 9 2 kDa type IV collagenase in the renal tissue of New Zealand Black/White F1 mice at 8 weeks of age or in New Zealand White mice at 8, 24 or 48 weeks of age, whereas we could detect expression of mRNA for this protein in New Zealand Black/White F1 mice at 24 and 48 weeks of age when mononuclear cells had infiltrated the interstitium and surrounding blood vessels. 6. At 24 weeks of age, New Zealand Black/White F1 mice were divided into two groups and received either methylprednisolone or saline injection for 24 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗