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S Osada

Publications and source records attributed to S Osada.

115 records · Page 7Linked to original sources
PubMedDate not supplied

Expression of vascular endothelial growth factor in hepatocellular carcinoma and the surrounding liver: correlation with MR imaging and angiographically assisted CT.

We summarize and discuss our previous research results on the correlation between findings on magnetic resonance (MR) imaging and angiographically assisted computed tomography (CT) and the intensity of vascular endothelial growth factor (VEGF) expression in hepatocellular carcinoma (HCC) and in the surrounding nontumorous liver. MR images (n = 22), CT during arterial portography (n = 20), and CT hepatic arteriography (n = 17) were retrospectively correlated quantitatively and qualitatively with VEGF expression in HCCs and in the surrounding liver assessed by western blotting. HCC-to-liver contrast-to-noise ratio correlated with VEGF expression index (VEGF(IND)) values of HCCs inversely on opposed-phase, T1-weighted, spoiled gradient recalled-echo (GRE) images, directly on T2-weighted, fast spin-echo images, and marginally and inversely on gadolinium-enhanced hepatic arterial-phase GRE images. On T2-weighted fast spin-echo images, standard deviation ratio of HCCs correlated directly with VEGF(IND) values of HCCs. By CT hepatic arteriography, the contrast-enhancement index of HCCs showed a moderate inverse correlation with VEGF(IND) values of HCCs, and the contrast-enhancement index of the liver showed marginal, moderate direct correlation with VEGF(IND) values in the liver. Heterogeneities of HCCs on images correlated directly with VEGF(IND) values of HCCs on opposed-phase T1-weighted GRE images, T2-weighted fast spin-echo images, hepatic arterial-phase GRE images, equilibrium-phase GRE images, and CT hepatic arteriogram. Our results may reflect that MR signal intensity, hepatic arterial vascularity, and heterogeneity of HCCs on CT or MR images are closely related to the intensity of VEGF expression in HCC as upregulated by hyper- or hypoxia in HCCs. Although the real effects of our results on radiologic practice are debatable at this moment, we believe that our results may help future radiologic practice in conjunction with biomolecular or genetic treatment for HCCs.

Carcinoma, Hepatocellular↗
PubMedDate not supplied

Effect of cerivastatin on urinary albumin excretion and plasma endothelin-1 concentrations in type 2 diabetes patients with microalbuminuria and dyslipidemia.

BACKGROUND/AIMS: To determine whether cerivastatin, a newly developed novel synthetic potent statin, exerts a renoprotective effect, we assessed urinary albumin excretion (UAE) and plasma and urinary endothelin (ET)-1 concentrations in normotensive microalbuminuric type 2 diabetes patients with dyslipidemia. METHODS: Sixty normotensive type 2 diabetic patients (38 men and 22 women; mean age 56.5 years) with microalbuminuria (20-200 microg/min) and dyslipidemia (total cholesterol >200 mg/dl, LDL cholesterol >160 mg/dl, HDL cholesterol <35 mg/dl, and triglyceride >150 mg/dl) were enrolled in a double-blind study for 6 months, receiving either cerivastatin (0.15 mg/day) or placebo. Plasma and urinary ET-1 concentrations were measured by radioimmunoassay. RESULTS: Cerivastatin did not affect serum creatinine and HbA(1c) levels, and reduced systolic blood pressure slightly, but not significantly. Plasma levels of total cholesterol and LDL cholesterol were significantly reduced (p < 0.01), and plasma triglyceride levels were also reduced significantly (p < 0.05) after 6 months of cerivastatin treatment. A concomitant significant decrease in UAE (p < 0.01), and urinary and plasma ET-1 concentrations (p < 0.01) were found during this period. CONCLUSION: The use of cerivastatin is associated with decreased microalbuminuria and plasma and urinary ET-1 levels in microalbuminuric patients with type 2 diabetic mellitus and speculate that this may represent an amelioration of renal injury.

Albuminuria↗
PubMedDate not supplied

Effect of methylprednisolone on transforming growth factor-beta, insulin-like growth factor-I, and basic fibroblast growth factor gene expression in the kidneys of NZB/W F1 mice.

The present study was carried out to determine whether transforming growth factor-beta, insulin-like growth factor-I and basic fibroblast growth factor mRNA levels were correlated with disease activity in NZB/W F1 mice, an animal model of systemic lupus erythematosus. Levels of mRNA for these three growth factors increased significantly as nephritis progressed in these mice. At 48 weeks of age, transforming growth factor-beta, insulin-like growth factor-I, and basic fibroblast growth factor mRNA levels showed a 11- (p < 0.001), 10- (p < 0.001), and 8-fold (p < 0.001) increase, respectively, in the renal cortex of NZB/W F1 mice when compared with NZW control mice. In NZW kidneys, these mRNA levels showed little change throughout the study period. At 24 weeks of age, NZB/W F1 mice were divided in 2 groups that received either methylprednisolone or saline injections for 24 weeks. The development of histological lesions and the increase in these growth factor mRNA levels in the kidneys of NZB/W F1 mice were both suppressed by methylprednisolone. These results indicate that the transforming growth factor-beta, insulin-like growth factor and basic fibroblast growth factor may play a role in the progression of murine lupus nephritis and that methylprednisolone may be an effective treatment at the transcription level of these growth factor genes for this type of nephritis.

Animals↗
PubMedDate not supplied

Renal expression of mRNAs for endothelin-1, endothelin-3 and endothelin receptors in NZB/W F1 mice.

Endothelin (ET)-1, ET-3, and ET receptors are widely distributed in the vascular system and the kidney. The present study was designed to measure the renal concentrations of ET-1, ET-3, and ET receptor mRNAs in NZB/W F1 mice at 8, 24, and 48 weeks of age. The renal concentration of ET-1 mRNA increased significantly in NZB/W F1 mice as their nephritis progressed, reaching, by 48 weeks, a 10-fold higher concentration than in control NZW mice. Renal ET-3 mRNA concentrations, however, remained unchanged. The renal concentrations of ET receptor A and B mRNAs in NZB/W F1 mice increased gradually with the progression of nephritis, reaching 5- and 3-fold higher concentrations, respectively, at 48 weeks of age than found in control mice. Transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha) have been shown to stimulate ET-1 mRNA expression in cultured mesangial cells. We therefore also examined the concentrations of TGF-beta and TNF-alpha mRNAs in the renal tissues of NZB/W F1 mice, and found that, at 48 weeks of age, they were 10- and 8-fold higher, respectively, than in control NZW mice. At 24 weeks, NZB/W F1 mice were divided into two groups receiving either methylprednisolone (MPSL) or saline injections for the following 24 weeks. The development of the histologic lesions characteristic of lupus nephritis and the increased renal concentrations of ET-1, ET receptors, TGF-beta and TNF-alpha mRNAs were suppressed by MPSL treatment. These data suggest that ET and ET receptor gene transcription is upregulated in the renal tissues of NZB/W F1 mice and that the beneficial treatment of lupus nephritis with MPSL is accompanied by a reduction in the elevated concentrations of ET-1, ET receptors, TGF-beta and TNF-alpha mRNAs.

Aging↗
PubMedDate not supplied

Abnormal gene expression of matrix metalloproteinases and their inhibitor in glomeruli from diabetic rats.

The steady state levels of mRNA encoding for metalloproteinase (MMP)-1, -2, -3, and -9 and tissue inhibitor of metalloproteinase (TIMP)-1 were examined in glomeruli at 4, 12, and 24 weeks after the injection of streptozocin (STZ) in rats. The mRNA levels for MMP-1 and MMP-3 decreased with age in STZ-induced diabetes. At 24 weeks after STZ injection, 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 when compared with control rats. In contrast, mRNA levels for TIMP-1 increased significantly with age in the diabetic glomeruli and reached an 8-fold (p < 0.01) increased at 24 weeks after STZ injection. mRNA levels for MMP-2 were not altered in glomeruli from diabetic and control rats throughout the experimental period, whereas those for MMP-9 were not detected in glomeruli from either group of rats. Insulin treatment partially ameliorated the decrease in mRNA levels for MMP-1 and MMP-3 and the increase in those for TIMP-1 in the glomeruli of diabetic rats. These data indicate that abnormal gene regulation of MMPs and TIMP-1 in the glomeruli of diabetic rats may contribute to the progression of glomerular lesions and that hyperglycemia or insulin deficiency may be associated with abnormal MMPs and TIMP-1 gene regulation.

Animals↗
PubMedDate not supplied

In situ hybridization of type I collagen mRNA in puromycin aminonucleoside-induced glomerulosclerosis.

In puromycin aminonucleoside (PAN)-induced focal glomerulosclerosis (FGS), the accumulation of type I collagen has been reported to be observed immunohistochemically in the sclerotic area. The present study was designed to identify the cell type involved in the synthesis of type I collagen in glomerulosclerosis. Tissue sections obtained from rat kidneys with PAN-induced FGS were hybridized with digoxigenin-labeled alpha 1(I) collagen anti-sense and sense cRNA probes. Hybridization signals of alpha 1(I) collagen mRNA were mainly detected in adhesive lesions on the glomerular capillary loop, suggesting that alpha 1(I) collagen mRNA-positive cells were visceral or parietal epithelial cells and did not have a mesangial distribution. Signals were also detected in interstitial cells. The alpha 1(I) collagen mRNA expression, however, was not observed in ED-1-positive cells. It is likely that intrinsic glomerular cells and interstitial cells, but not macrophages, synthesize type I collagen in sclerotic glomeruli.

Animals↗