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Biomedical subjects

I Ebihara

Publications and source records attributed to I Ebihara.

At least 55 records · Page 3Linked to original sources
PubMed1998

Increased plasma metalloproteinase-9 concentrations precede development of microalbuminuria in non-insulin-dependent diabetes mellitus.

We determined plasma metalloproteinase-9 (MMP-9) concentrations in 30 patients with non-insulin-dependent diabetes mellitus (NIDDM) at an initial examination (baseline) and on three separate occasions during a 48-month follow-up period. All patients had normal urinary albumin excretion (<20 microg/min) at the first three examinations. At the fourth examination (48 months after the first examination), 22 patients had normal urinary albumin excretion and eight had microalbuminuria (median, 36.4 microg/min; range, 20.2 to 46.6 microg/min). Compared with patients with normal urinary albumin excretion, patients with microalbuminuria had significantly higher plasma levels of MMP-9 at the second (56+/-14 microg/L v36+/-12 microg/L; P < 0.05), third (88+/-23 microg/L v 39+/-14 microg/L; P < 0.01), and fourth (117+/-30 microg/L v 44+/-16 microg/L; P < 0.01) examinations, but not at the first examination (34+/-12 microg/L v 33+/-14 microg/L; P=NS). An increase in plasma MMP-9 concentrations preceded the occurrence of microalbuminuria within 4 years. The groups did not differ with regard to age, sex, duration of NIDDM, blood pressure, or mean glycated hemoglobin. In addition, the eight patients with microalbuminuria were treated with an angiotensin-converting enzyme inhibitor (cilazapril; 0.5 mg once daily) for 6 months. Microalbuminuria was reduced to within the normal range, and plasma MMP-9 concentrations were significantly decreased with the cilazapril treatment (52+/-18 microg/L; P < 0.01). However, serum MMP-1 and tissue inhibitor of MMP-1 showed no change during the study period. These data suggest that plasma MMP-9 concentrations preceded and may predict the development of microalbuminuria in NIDDM.

Adult↗
PubMed1998

Effect of hemoperfusion with polymyxin B-immobilized fiber on plasma endothelin-1 and endothelin-1 mRNA in monocytes from patients with sepsis.

Hemoperfusion using polymyxin B-immobilized fiber (PMX-F) is reported to be an effective treatment for sepsis. The aim of the present study is to assess whether plasma endothelin-1 (ET-1) and ET-1 messenger RNA (mRNA) levels in peripheral-blood monocytes are altered in patients with sepsis and whether PMX-F treatment affects plasma ET-1 and monocyte ET-1 mRNA levels. Sixteen patients with sepsis and 20 healthy volunteers were included in this study. Plasma ET-1 concentration was measured by radioimmunoassay (RIA), and plasma levels of transforming growth factor-beta (TGF-beta), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta) were measured by enzyme-linked immunosorbent assay (ELISA). Sixteen patients with sepsis were treated with direct hemoperfusion using PMX-F columns. Blood endotoxin levels decreased significantly from 35 to 10 pg/mL after two treatments of direct hemoperfusion, each for 2 hours. Patients with sepsis showed significantly increased levels of plasma ET-1 (P < 0.001) and monocyte ET-1 mRNA (P < 0.001) compared with healthy volunteers. However, no differences in plasma levels of TGF-beta, TNF-alpha, and IL-1beta existed between patients with sepsis and healthy volunteers. Increased plasma ET-1 levels and monocyte ET-1 mRNA levels in patients with sepsis decreased significantly after PMX-F treatment (P < 0.01). These data suggest that the secretion of ET-1 from peripheral-blood monocytes may be stimulated by endotoxin, and PMX-F treatment may be effective in reducing ET-1 secretion in patients with sepsis.

APACHE↗
PubMed1998

Elevated levels of erythropoietin in cerebrospinal fluid of depressed patients.

To investigate the role of erythropoietin (EPO) in the central nervous systems, we assayed EPO concentrations in the cerebrospinal fluid (CSF) of patients with depression or old cerebrovascular injuries and controls. Concentrations of EPO in the CSF were significantly higher in 13 patients with depression (3.21+/-0.46 mU/mL) than in 10 patients with old cerebrovascular diseases (1.80+/-0.32 mU/mL, P < 0.01), and in 10 healthy controls (0.98+/-0.26 mU/mL, P < 0.01). Serum EPO concentrations did not differ among these three groups. In the patients with depression, 5 months of treatment with imipramine and/or nortriptyline significantly reduced EPO concentrations in the CSF (1.56+/-0.34 mU/ mL, P < 0.01). Results suggest that the brain of patients with depression may be in an hypoxic state, and that the increased EPO in the CSF may act to limit hypoxia-induced damage to neurons in these patients.

Antidepressive Agents, Tricyclic↗
PubMed1998

Modulation of plasma metalloproteinase-9 concentrations and peripheral blood monocyte mRNA levels in patients with septic shock: effect of fiber-immobilized polymyxin B treatment.

The authors measured plasma metalloproteinase (MMP)-9 and corresponding monocyte mRNA in 20 patients with septic shock. Plasma MMP-9 concentrations and monocyte MMP-9 mRNA levels were significantly higher in the 10 nonsurviving patients with septic shock than in 10 surviving patients and 25 normal controls. Hemoperfusion using polymyxin B immobilized on fibers (PMX-F), a reportedly effective treatment for septic shock, was studied for effects on MMP-9 in the patients. Increases in plasma MMP-9 concentrations and corresponding monocyte mRNA levels were attenuated significantly by PMX-F treatment in both nonsurviving and surviving patients. These data suggest that plasma MMP-9 concentrations and monocyte MMP-9 mRNA levels may be useful prognostic markers in septic shock, and that PMX-F treatment affects MMP-9.

Adult↗
PubMed1998

Metalloproteinase-9 mRNA expression in monocytes from patients with chronic renal failure.

Long-term dialysis patients suffer from various complications including atherosclerosis. It has been suggested that metalloproteinases (MMPs) contribute to vascular remodeling during the development and progression of human atherosclerosis. Activated human monocytes have been demonstrated to secrete MMPs. In the present study, we measured levels of MMP mRNA in peripheral blood monocytes obtained from patients on continuous ambulatory peritoneal dialysis (CAPD) or hemodialysis (HD) and chronic-renal-failure patients not undergoing dialysis. Twenty patients with chronic renal failure were not undergoing dialysis, 20 patients were on CAPD, 40 patients were on chronic HD and 20 healthy volunteers served as controls. We used cDNA probes encoding for MMP-1, MMP-2, MMP-3 and MMP-9 and glyceraldehyde phosphate dehydrogenase. Higher levels of MMP-9 mRNA in the peripheral blood monocytes were observed in HD patients than in CAPD patients, undialyzed chronic renal failure patients or healthy controls. MMP-9 mRNA levels at the end of HD were not significantly higher than those at the start of HD. MMP-9 mRNA levels from HD patients did not differ among the types of membranes. We could detect minimal MMP-1, MMP-2 and MMP-3 mRNA expression in monocytes from all groups. Serum gelatinase activity was detectable in all samples; however, no significant differences existed among the groups. In summary, MMP-9 mRNA expression is enhanced in monocytes from HD and CAPD patients, and the enhancement may be, in part, associated with cardiovascular complications, including atherosclerosis, in dialysis patients. This increase in monocyte MMP-9 mRNA levels is lower in CAPD patients that it is in HD patients.

Adult↗
PubMed1998

Hemoperfusion with polymyxin B-immobilized fiber attenuates the increased plasma levels of thrombomodulin and von Willebrand factor from patients with septic shock.

AIMS: The present study assessed whether plasma levels of thrombomodulin and von Willebrand factor (vWF) are altered in patients with septic shock and whether treatment with polymyxin B-immobilized fiber (PMX-F) affects these levels. METHODS: Twenty-four patients with septic shock and 20 normal healthy controls were included in this study. Plasma levels of thrombomodulin and vWF were measured by enzyme immunoassay (EIA). The treatments with direct hemoperfusion using PMX-F column on patients with septic shock were repeated twice for 2 h each. Healthy controls were not subjected to hemoperfusion. RESULTS: 13 of 24 patients with septic shock survived (survival rate was 54.2%). Levels of blood endotoxin decreased significantly from 41.2 +/- 4.8 pg/ml at baseline to 13.2 +/- 3.6 pg/ml after direct hemoperfusion. Systolic blood pressure increased significantly from 82 +/- 6 mm Hg at baseline to 118 +/- 12 mm Hg after treatment. The patients with septic shock demonstrated significantly increased plasma levels of thrombomodulin (p < 0.001) and vWF (p < 0.001) compared with those in healthy controls. These increased levels of plasma thrombomodulin and vWF in patients with septic shock decreased significantly after treatment with PMX-F (p < 0.01). CONCLUSION: These data suggest that plasma thrombomodulin and vWF may be related to septic shock and that PMX-F is effective in reducing these factors in patients with septic shock.

Adult↗
PubMed1998

Glomerular nonmuscle-type myosin heavy-chain isoform gene expression in glomerulosclerosis.

This study was designed to assess how the glomerular expression of the nonmuscle-type myosin heavy-chain isoform, SMemb, is regulated in rats with focal glomerulosclerosis induced by puromycin aminonucleoside. SMemb was barely detectable in control glomeruli. On day 48 of focal glomerulosclerosis, SMemb was expressed in mesangial area and glomerular epithelial cells. When glomerulosclerosis became prominent on day 80, SMemb stained immunohistochemically in a focal segmental pattern in the sclerotic glomeruli. SMemb-expressing cells did not always express alpha-smooth muscle actin. In Northern blot analysis, SMemb mRNA was not detected in control glomeruli, whereas it was transiently upregulated in glomeruli on day 48 in rats with focal glomerulosclerosis. The mRNA levels of SMemb were thereafter gradually downregulated by day 80; however, they remained higher than those of control glomeruli. These data suggest that glomerular embryonic nonmuscle-type myosin heavy chain is abnormally regulated in glomerulosclerosis and that glomerulosclerosis may be associated with dedifferentiation of not only the mesangial cells, but also the other resident glomerular cells.

Animals↗
PubMed1997

Effect of a specific endothelin receptor A antagonist and an angiotensin-converting enzyme inhibitor on glomerular mRNA levels for extracellular matrix components, metalloproteinases (MMP) and a tissue inhibitor of MMP in aminonucleoside nephrosis.

BACKGROUND: We previously reported that mRNA levels for extracellular matrix (ECM) components and endothelin (ET)-1 are upregulated in glomeruli of puromycin aminonucleoside (PAN) nephrosis. Angiotensin-converting enzyme (ACE) inhibitors are effective in experimental models of renal injury, including PAN nephrosis. This study was designed to assess whether the glomerular expression of mRNA for ECM components, ET-1, metalloproteinases (MMP), and a tissue inhibitor of metalloproteinases (TIMP) is modulated by a specific endothelin receptor A antagonist (FR139317) or angiotensin-converting enzyme inhibitor (enalapril) in PAN-injected rats. METHODS: Animals were divided into six groups. Group 1 consisted of PAN-injected rats given no treatment. In group 2, PAN-injected rats were given enalapril 35 mg/l. In group 3, PAN-injected rats were given an intraperitoneal injection of FR139317. Group 4 consisted of saline-injected rats given no treatment. In group 5, saline-injected rats were given enalapril. In group 6, saline-injected rats were given FR139317. We prepared glomerular RNA and performed Northern blot analysis in all groups. RESULTS: In PAN nephrosis, glomerular mRNA levels for alpha 1 (IV) collagen chain, laminin B1 and B2 chains, ET-1, MMP-2 and TIMP-1 increased at the peak of proteinuria on day 8 and then decreased to the control level by day 20, whereas those for alpha 1 (I) and alpha 1 (III) collagen chains, MMP-1, MMP-3 and GAPDH showed little change in PAN nephrosis throughout the experimental periods. In contrast, mRNA levels for heparan sulphate proteoglycan (HSPG) decreased on day 8 and then increased to the control level by day 20. Both enalapril and FR139317 attenuated the increases in mRNA levels for alpha 1 (IV) collagen chain (P < 0.01), laminin chains (P < 0.01), and ET-1 (P < 0.01), and attenuated the decreases in mRNA levels for HSPG (P < 0.01) in glomeruli of PAN-injected rats. Enalapril had little effect on increased glomerular mRNA levels for MMP-2 and TIMP-1 in PAN nephrosis, whereas FR139317 attenuated the increases in glomerular mRNA levels for MMP-2 (P < 0.01) and TIMP-1 (P < 0.01). CONCLUSIONS: These data suggest that the beneficial effects of enalapril and FR139317 may be related to modulation of glomerular mRNA expression of ECM components and ET-1 and that these agents may follow a different mechanism in regulating the glomerular mRNA expression for MMP-2 and TIMP-1 in PAN nephrosis.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Effect of unilateral nephrectomy on gene expression of metalloproteinases and their inhibitors.

Levels of mRNA encoding for metalloproteinase (MMP) 1, 2, 3 and 9 and tissue inhibitor of metalloproteinase (TIMP) 1 were measured in both the renal cortex and glomeruli following unilateral nephrectomy or a sham operation. The expression of MMP-1 and MMP-3 increased 3-fold (p < 0.001) within the renal cortex 24 h following nephrectomy, and then gradually decreased to the control level after 7 days. In contrast, expression of MMP-2 and MMP-9 remained unchanged following nephrectomy. TIMP-1 mRNA levels also significantly increased 4-fold (p < 0.001) within the renal cortex 12 h following nephrectomy, followed by a decrease to the control level after 3 days. In contrast, the glomerular expression of MMP-1, -2, -3 and TIMP-1 remained stable while minimal MMP-9 mRNA was detectable. MMPs and TIMP-1 may be associated with the early stages of renal hypertrophy following unilateral nephrectomy.

Animals↗
PubMed1996

Increased mRNA expression of metalloproteinase-9 in peripheral blood monocytes from patients with immunoglobulin A nephropathy.

We examined metalloproteinase (MMP)-1, -2, -3, and -9 mRNA expression by peripheral blood monocytes from 50 patients with immunoglobulin A (IgA) nephropathy, 20 with membranous nephropathy, 10 with minimal-change nephrotic syndrome, five with focal glomerulosclerosis, 30 with non-IgA proliferative glomerulonephritis, and 40 healthy normal controls who were comparable with regard to age and sex. Monocytes from patients with IgA nephropathy expressed a higher level of MMP-9 mRNA than those from patients with other forms of glomerulonephritis or from healthy controls (MMP-9 to glyceraldehyde-3-phosphate dehydrogenase ratio: IgA nephropathy, 1.68 +/- 0.24; membranous nephropathy, 0.22 +/- 0.08; minimal-change nephrotic syndrome, 0.24 +/- 0.06; focal glomerulosclerosis, 0.32 +/- 0.08; non-IgA proliferative glomerulonephritis, 0.30 +/- 0.12; and healthy controls, 0.16 +/- 0.04). When the biopsy specimens were classified into four grades according to the severity of glomerular and interstitial pathology, highly significant differences were observed among MMP-9 mRNA levels in monocytes from all four groups of patients with IgA nephropathy (grade I, 0.44 +/- 0.09; grade II, 1.06 +/- 0.26; grade III, 2.22 +/- 0.68; grade IV, 2.86 +/- 0.88). In addition, MMP-9 mRNA levels from patients with IgA nephropathy correlated with urinary protein excretion (P < 0.001). However, we detected minimal mRNA expression of MMP-1, -2, and -3 by peripheral blood monocytes from patients with IgA nephropathy or other forms of glomerulonephritis and from normal healthy controls. Our results suggest that increased MMP-9 mRNA expression in circulating monocytes may contribute to the progression of IgA nephropathy.

Adult↗
PubMed1996

Effect of a specific endothelin receptor A antagonist on glomerulonephritis of ddY mice with IgA nephropathy.

The present study assessed renal endothelin (ET)-1, ET-3, and ET receptor A and B mRNA levels in ddY mice at 8, 40, and 60 weeks of age. The renal mRNA levels of ET-1 increased significantly in ddY mice as their nephritis progressed, reaching a 6.6-fold (p < 0.01) higher level by 60 weeks than in control ICR mice. Renal ET-3 mRNA levels, however, remained unchanged. The renal mRNA levels of ET receptor A and B in ddY mice increased gradually with the progression of nephritis, reaching 4.8- (p < 0.01) and 3.6-fold (p < 0.01) higher levels, respectively, at 60 weeks of age than found in control ICR mice. A positive correlation was noted between ET-1 and ET receptor mRNA levels and histopathological changes in renal tissues. In addition, we assessed whether a specific ET receptor A antagonist, FR 139317, affects the progression of glomerulonephritis in ddY mice. At 24 weeks of age (before glomerulonephritis developed), ddY mice were divided into two groups that received intraperitoneally either FR139317 or its vehicle (saline) daily for 36 weeks. The development of histopathological lesions and urinary protein excretion were suppressed by FR139317 treatment. These data suggest that ET families play a role in the progression of glomerulonephritis and that FR139317 treatment can be used therapeutically in ddY mice with IgA nephropathy.

Age Factors↗
PubMed1996

Modulation of endothelin family gene expression in renal hypertrophy.

The present study was designed to assess how the renal expression of mRNA for endothelin (ET) families is regulated during compensatory renal hypertrophy in rats. ET family gene expression was studied in the contralateral kidney of uninephrectomized and sham-operated rats. Rats were sacrificed at 0, 1, 3, 6, 12, adn 24 h after unilateral nephrectomy of the sham operation. Three hours after the left nephrectomy, ET-1 and ET receptor B mRNA levels in the renal cortex increased significantly (ET-1, 10.6-fold compared to those in sham-operated rats, p < 0.001, and ET receptor B, 6.8-fold, p < 0.001), and then decreased gradually to the control level after 24 h; in contrast, ET-3 and ET receptor A mRNA levels demonstrated little change throughout the experiment. We additionally measured the plasma ET concentration and renal ET-1 production following unilateral nephrectomy. ET-1 levels in the renal cortex increased gradually, with a peak 6 h after nephrectomy (3.6-fold compared to those in sham-operated rats, p < 0.01), and then decreased to the control level after 24 h. However, plasma ET-1 levels demonstrated little change until after 24 h. The glomerular expression of ET-1 and ET receptors A and B mRNA demonstrated minimal change throughout the experimental period. Glomerular ET-3 mRNA expression were detected in neither the unilateral nephrectomy nor the sham-operated rats. Our results indicate that the time course of the mRNA expression of ET-1 and ET receptor B differs from that of ET-3 and ET receptor A in the renal cortex, and that glomerular mRNA levels for ET families are not associated with renal hypertrophy in the early stages following unilateral nephrectomy.

Animals↗
PubMed1996

Alteration of growth-related proto-oncogene expression in diabetic glomeruli by a specific endothelin receptor A antagonist.

BACKGROUND: The early phase of glomerular growth in diabetic rats is accompanied by increased c-fos and c-jun expression. The renal endothelin (ET)-1 mRNA levels increased with the progression of diabetic nephropathy. This study was designed to assess whether glomerular mRNA expression of growth-related proto-oncogenes in diabetic rat glomeruli is affected by a specific ET receptor A antagonist, FR139317. METHODS: Diabetes was produced by streptozotocin (STZ) injection. Animals were divided into four groups: (1) untreated diabetic rats (n = 25); (2) FR139317-treated diabetic rats (n = 20); (3) control non-diabetic rats (n = 20); and (4) FR139317-treated controls (n = 20). FR139317 treatment was continued for 24 weeks. c-myc, c-fos, c-jun and proliferating cell nuclear antigen (PCNA) mRNA expression in rat glomeruli from each group (n = 7) at 4, 12 and 24 weeks after STZ or saline injection was evaluated. RESULTS: Glomerular mRNA levels for c-myc, c-fos, c-jun and PCNA in group 1 increased with the progression of diabetic nephropathy (24 weeks: c-myc, 4.6-fold; c-fos, 3.8-fold; c-jun, 4.2-fold; and PCNA, 4.4-fold). FR139317 treatment attenuated increases in glomerular mRNA levels of these genes (24 weeks, c-myc, 0.4-fold; c-fos, 0.4-fold; c-jun, 0.5-fold; and PCNA, 0.4-fold) in group 2. However, FR139317 did not affect mRNA levels in control glomeruli. CONCLUSIONS: These data suggest that FR139317 may protect against glomerular injury of diabetes in rats by reducing mRNA levels of growth-related genes.

Animals↗
PubMed1996

Effect of a low-protein diet on expression of non-muscle type myosin heavy-chain isoforms in glomeruli of rats with puromycin aminonucleoside nephrosis.

BACKGROUND: We reported that an embryonic type of non-muscle-type myosin heavy-chain isoform (SMemb) may be a molecular marker for phenotypic alteration in initial glomerular injury and that methyl-prednisolone has no effect on SMemb expression in glomeruli of rats with puromycin aminonucleoside (PAN) nephrosis. The present study was designed to assess whether SMemb mRNA and protein expression in glomeruli are affected by a low-protein diet in rats with PAN-induced nephrosis and in control rats. METHODS: Rats were divided into four groups: group 1, PAN-injected rats fed a standard diet containing 22% protein; group 2, PAN-injected rats fed a low-protein diet containing 6% protein, starting on the day of PAN injection; group 3, control rats fed a standard diet; group 4, control rats fed a low-protein diet for the same period. We prepared glomerular RNA and performed Northern blot analysis and immunohistochemistry in all groups. RESULTS: Glomerular SMemb mRNA increased on days 2 and 4 (prior to and soon after the onset of proteinuria), but declined on day 8 (the peak of proteinuria). Myosin heavy-chain protein expression was evaluated immunohistochemically by use of three antibodies against SM1, SM2, and SMemb. SM1 and SM2 were absent from the glomeruli of rats with PAN 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 PAN nephrosis. In the latter condition, the number of SMemb-positive glomerular epithelial cells increased on days 3 and 4, then decreased in subsequent days. Moreover, some mesangial cells became SMemb-positive transiently, returning to barely detectable levels on day 20. In addition, alpha-smooth-muscle actin, type I and III collagens were absent from the glomeruli of rats with PAN nephrosis until day 20. Urinary protein excretion was markedly suppressed by the 6% protein diet in PAN nephrosis. The low-protein diet reduced the increased mRNA expression of SMemb as well as the increased number of SMemb-positive cells in the glomeruli of rats with PAN nephrosis. However, the low-protein diet did not affect SMemb mRNA and protein levels in the glomeruli of control rats. CONCLUSIONS: In rats with PAN nephrosis, findings suggest that restriction of dietary protein leads to a reduction in glomerular SMemb expression.

Animals↗
PubMed1995

Effect of a specific endothelin A receptor antagonist on murine lupus nephritis.

The present study was designed to assess whether a specific endothelin A (ETA) receptor antagonist, FR139317, affects the progression of lupus nephritis and affects transcription of mRNA for extracellular matrix (ECM) components, metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP)-1, and accumulation of ECM proteins in the renal cortex of NZB/W F1 mice. mRNA levels for alpha 1(I), alpha 1(III), alpha 1(IV) collagen chains, laminin B1 and B2 chains, heparan sulfate proteoglycan (HSPG), MMP-1, -2, -3, and TIMP-1 increased significantly as nephritis progressed in NZB/W F1 mice. At 48 weeks of age, the levels of mRNA for alpha 1(I), alpha 1(III), alpha 1(IV) collagen chains, laminin B1 and B2 chains, HSPG, MMP-1, -2, -3, and TIMP-1 were increased by 5.6- (P < 0.001), 3.6- (P < 0.01), 6.8- (P < 0.001), 5.2- (P < 0.001), 5.0- (P < 0.001), 6.0- (P < 0.001), 7.6- (P < 0.001), 4.2- (P < 0.01), 8.2- (P < 0.001), and 15.2-fold (P < 0.001), respectively, in the renal cortex of NZB/W F1 mice compared to NZW mice. Immunofluorescence microscopy showed that the accumulation of collagens I, III, and IV, laminin, and HSPG in the renal cortex of NZB/W F1 mice increased markedly with the progression of nephritis. At 20 weeks of age, NZB/W F1 and NZW mice were divided into two groups that received either FR139317 or its vehicle (saline) intraperitoneally, daily, for 28 weeks. The development of histological lesions, proteinuria, hypertension, accumulation of collagens I, III, and IV, laminin, and HSPG in the renal cortex of NZB/W F1 mice were suppressed by FR139317 treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗