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Biomedical subjects

M Mune

Publications and source records attributed to M Mune.

At least 19 recordsLinked to original sources
PubMed2001

Significantly rapid relief from steroid-resistant nephrotic syndrome by LDL apheresis compared with steroid monotherapy.

Rapid amelioration of hypercholesterolemia by LDL apheresis (LDL-A) was performed for long-standing nephrotic syndrome (NS) with hyperlipidemia due to focal segmental glomerulosclerosis (FGS) and the clinical data and prognosis were compared between LDL-A-treated and nontreated groups. Seventeen steroid-resistant NS patients treated with LDL-A (LDL-A group) and 10 NS patients treated with steroids only (steroid-monotherapy (SM) group) were compared. Serum cholesterol and phospholipid levels were significantly lowered only in the LDL-A group (p < 0.01, respectively). The LDL-A group showed a significant decrease of urinary protein (UP, p < 0.01) and increase of serum albumin (p < 0.05). Average time needed to achieve a decrease of UP to less than nephrotic range (< 3.5 g/day) was significantly shorter in the LDL-A group than in the SM group (p < 0.01). Although this is not a prospective study, it is highly expected that a rapid improvement of hypercholesterolemia by LDL-A in steroid-resistant NS will provide more rapid relief from NS than steroid therapy alone.

Adolescent↗
PubMed2001

Lipid abnormality.

Explore the source record for details and available documents.

Diabetes Mellitus, Type 1↗
PubMed1999

Vitamin E treatment of experimental glomerular disease in rats.

BACKGROUND: Kidney mesangial cells (MCs) and vascular smooth muscle cells (VSMCs) are closely related in terms of origin, microscopic anatomy, histochemistry, and contractility. This relationship suggests a similarity between kidney glomerular sclerosis and atherosclerosis. Vitamin E appears beneficial in the prevention and treatment of coronary heart disease and it also inhibits the proliferation of VSMCs in vitro. Thus, we investigated the effect of vitamin E on glomerular sclerosis and MC-proliferative glomerulonephritis (GN) in two rat models of glomerular disease. METHODS: A remnant kidney rat model accelerated with hyperlipidemia was used to examine progressive glomerular sclerosis leading to chronic renal failure. A rat model of MC-proliferative GN was induced by the intravenous administration of absorbed rabbit anti-rat thymocyte serum (ATS). RESULTS: In the remnant kidney rat model, dietary supplementation with vitamin E (500 IU dl-alpha-tocopheryl acetate/kg) and cholesterol (2%) significantly inhibited glomerular sclerosis and macrophage infiltration in glomeruli relative to controls receiving basal and cholesterol-supplemented diets. In the ATS-induced GN model, glomerular cell proliferation (principally MCs) was lower in rats fed diets supplemented with vitamin E (1000 IU dl-alpha-tocopheryl acetate/kg) compared with controls fed the basal diet only. Although the degree of glomerular macrophage infiltration was similar in both groups, fewer proliferative cell nuclear antigen (PCNA)-positive cells were observed in the vitamin E group, suggesting that MC proliferation was suppressed via the inhibition of intracellular transduction. CONCLUSIONS: Supplemental dietary vitamin E suppresses MC proliferation and glomerular sclerosis in models of glomerular disease in rats. This action of vitamin E in experimental nephritis suggests the value of clinical trials testing the potential benefit of vitamin E in chronic GN patients.

Animals↗
PubMed1999

Low density lipoprotein apheresis therapy for steroid-resistant nephrotic syndrome. Kansai-FGS-Apheresis Treatment (K-FLAT) Study Group.

BACKGROUND: The pathogenic role of hyperlipidemia in long-standing nephrotic syndrome (NS) is known to be responsible for both the progression of glomerulosclerosis and tubulointerstitial injury, especially in focal segmental glomerulosclerosis (FGS). METHODS: Aggressive lipid lowering treatment by low density lipoprotein (LDL) apheresis (LDL-A) using a dextran sulfate cellulose column to treat patients with steroid-resistant or frequently recurrent severe NS was performed first without fixing the protocol in eight patients with FGS and one with minimal change nephrotic syndrome (MCNS). The period of NS before LDL-A, number and average intervals of LDL-A until the end of the therapy, and the prognosis were investigated. Next, a multicenter study with a fixed protocol of LDL-A treatment was designed in combination with steroid therapy for treatment twice a week for three weeks and weekly for six weeks, and was performed in 17 patients with FGS. The effects on the state of NS in addition to the change of urinary eicosanoid metabolites and remission rates were evaluated. RESULTS: In the preliminary study, along with a rapid improvement of hyperlipidemia, a high incidence of remission was achieved by LDL-A performed at relatively short intervals. In the multicenter study with a fixed protocol, there was a significant decrease of urinary protein (P < 0.001) and increase of serum albumin (P < 0.02) as well as a decrease of thromboxane B2 (TXB2) excretion (P < 0.05) after the treatment. Urinary excretion of TXB2 was significantly reduced after LDL-A (P < 0.05). The rate of entering into complete or incomplete remission was 71% with a relatively short duration of nephrotic-range proteinuria using the LDL-A therapy in comparison with steroid therapy alone. CONCLUSION: The rapid improvement of hypercholesterolemia with LDL-A treatment may provide a new approach for a high rate of improvement in the degree of NS in steroid-resistant NS of FGS and MCNS.

Adolescent↗
PubMed1999

Ongoing clinical trials of lipid reduction therapy in patients with renal disease.

BACKGROUND: Lipid abnormalities in renal disease are associated with both a progressive decline in renal function and cardiovascular complications. Whether or not lipid anomalies are causal is not yet clear. Experimental studies have demonstrated that potentially atherogenic lipoproteins, such as low density lipoproteins (LDL), are associated with renal pathophysiological changes that result in progressive glomerular and interstitial damage and an ultimate reduction in renal function. These findings indicate that hyperlipidemia accelerates glomerular and interstitial damage in renal disease. Clinical studies also show that renal function declines more rapidly among patients with primary renal disease or diabetic nephropathy who have hyperlipidemia. However, few reports have demonstrated the effect of hypolipidemic agents on the progression of renal function among patients with renal disease, and those renal patients who were treated with lipid-lowering agents have not been clinically studied under large-scale controlled conditions. In addition, although cardiovascular complications are the most important factors associated with mortality in dialysis patients, randomized, large-scale trials studying the relationship between therapeutic intervention by lipid-lowering agents and prevention of cardiovascular complications have not been implemented. METHODS: We reviewed controlled and uncontrolled reported studies that examined the effects of lipid-lowering therapy in patients with renal disease. RESULTS: Most studies showed that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors reduce cholesterol-rich apolipoprotein (apo)B-containing lipoproteins with no effects on renal function or proteinuria among patients with progressive renal disease. Small uncontrolled studies show that simvastatin and probucol moderately reduce proteinuria among patients with membranous nephropathy. One small retrospective study showed that long-term vitamin E therapy reduces aortic calcification in dialysis patients. CONCLUSIONS: Prospective, randomized large-scale trials including ongoing clinical trials of lipid reduction therapy and therapeutic interventions such as the use of the combination therapy with hypolipidemic agents and angiotensin converting enzyme (ACE) inhibitors, vitamins, or LDL apheresis are urgently required. Such trials will clarify the effect of treating dyslipidemia on the progression of renal insufficiency and dialysis-related cardiovascular complications.

Blood Component Removal↗
PubMed1999

Evaluation of serum lipid abnormalities in chronic nephritis.

BACKGROUND: In glomerular disease, disorders of lipid metabolism are suspected as factors exacerbating glomerular dysfunction. Although many reports have been published regarding metabolic disorders of lipids in renal disease, including nephrotic syndrome and chronic renal failure, there have been few published reports describing metabolic disorders of lipids in chronic nephritis. Therefore, in patients with IgA nephritis, we evaluated correlations between serum lipid levels and renal function and proteinuria. METHODS: In 191 patients with IgA nephritis, we evaluated the correlations between serum lipid levels and renal function [creatinine clearance (CCr)] and proteinuria (UP). Serum lipids examined included total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoproteins, phospholipids (PL), lipoprotein(a) [Lp(a)], and malondialdehyde (MDA). RESULTS: Significant correlations were observed between serum lipid levels and CCr, UP, and age. There were no abnormalities in the mean values of respective serum lipids examined. Although TC levels increased with age, HDL-C levels were not correlated with age. Hyperlipidemia was observed in 39.8% of subjects. Significant correlations were observed between levels of TC, TG, PL, LDL-C, apoB, apoC-II, and apoC-III and Ccr, UP, and age. Significant correlations were also observed between levels of MDA, apoB/apoA-I, apoE/apoC-III, and Ccr and age, as well as between apoE levels and UP and age. The levels of apoA-I and apoA-I/apoA-II ratio were significantly correlated with UP alone, whereas the apoC-II/apoC-III ratio was significantly correlated with Ccr alone. There were no significant correlations between levels of HDL-C, apoA-II, and Lp(a) and Ccr, UP, and age. CONCLUSIONS: Age, proteinuria, and renal function were related with changes in serum lipid levels in IgA nephritis. There were correlations between proteinuria and levels of apoA, as well as between renal function and apoC levels.

Adult↗
PubMed1999

Lysophosphatidylcholine up-regulates IL-1 beta-induced iNOS expression in rat mesangial cells.

BACKGROUND: Nitric oxide (NO), a simple molecule synthesized from L-arginine by NO synthases (NOS), has been identified to play an important role in cell communication, cell defense and cell injury. Several studies have shown that glomeruli from rats with immune-mediated glomerular inflammation have increased production of NO. Recently, it was also reported that inducible NOS (iNOS) is localized in mesangial cells, glomerular epithelial cells and infiltrating cells in the diseased human glomeruli. On the other hand, while oxidized low density lipoprotein (ox-LDL) has been suggested to be related to progression of glomerular disease, the mechanism remains unknown. We investigated the effect of lysophosphatidylcholine (LPC), a modified phospholipid produced during LDL oxidation, on iNOS expression in rat mesangial cells. METHODS AND RESULTS: Treatment of mesangial cells with interleukin-1 beta (IL-1 beta) induced iNOS activity measured as nitrite levels in cell culture supernatants. Treatment with LPC had no effect. In contrast, coincubation with LPC and IL-1 beta resulted in a markedly higher nitrite content compared to that after incubation with IL-1 beta alone. Western blot analysis revealed that LPC caused a significant increase in the formation of iNOS protein in the presence of IL-1 beta. CONCLUSION: These findings suggest that LPC may contribute to progression of glomerular inflammation by augmenting IL-1 beta-induced iNOS expression.

Animals↗
PubMed1999

Phospholipase A2 activity in ox-LDL-stimulated mesangial cells and modulation by alpha-tocopherol.

BACKGROUND: Oxidized LDL increases the production of both prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) in rat mesangial cells. These increases were suppressed by antioxidants such as alpha-tocopherol (alpha-Toc) or probucol. METHODS: We investigated the mechanism by which oxidized LDL leads to an increase in PGE2 production using rat mesangial cells in culture. We also examined how alpha-Toc supresses this augmentation, by measuring intracellular Ca2- and phospholipase A2 (PLA2) activity. RESULTS: In rat mesangial cells, oxidized LDL increased PLA2 activity by increasing the intracellular calcium ion content, which resulted in the induction of PGE2 production. On the other hand, pretreatment of cells with alpha-Toc, which resulted in a large uptake of alpha-Toc in cell membranes, markedly suppressed the augmentation of PGE2 production and PLA2 activity by oxidized LDL in a dose dependent manner. However, cytosolic PLA2 partially purified from mesangial cells was not inhibited by alpha-Toc despite an increase of alpha-Toc. CONCLUSION: These results suggest that the augmentation of PLA2 activity in mesangial cells by oxidized LDL in a result of oxidative stresses, and that the antioxidant action of alpha-Toc is responsible for the suppression of augmentation of PLA2 activity observed in mesangial cells exposed to oxidized LDL.

Animals↗
PubMed1999

Erythropoietin supplement increases plasma lipoprotein lipase and hepatic triglyceride lipase levels in hemodialysis patients.

BACKGROUND: We reported in previous studies that plasma triglyceride levels, as well as remnant-like particles-cholesterol (RLP-C) and -triglyceride (RLP-TG) levels, were significantly lower in maintenance hemodialysis (HD) patients treated with erythropoietin (EPO) than in HD patients treated without EPO. However, little is known about the mechanisms underlying the improvements in abnormal RLP metabolism in HD patients. This study investigates whether EPO supplement therapy in cases of uremic anemia increases the plasma lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) levels in HD patients. METHODS: Twenty HD patients who had not previously received EPO were divided into two groups according to the stage of HD: 12 at the initial stage, defined as a mean HD duration of 0.35 +/- 0.68 months (range of 0 to 2.47 months), and 8 at the maintenance stage, defined as a mean HD duration of 114.1 +/- 91.9 months (range of 13.0 to 253.9 months). Fasting plasma was collected from the HD patients prior to the start of the EPO supplement therapy and at one month after the therapy. RLP-C levels were determined using a RLP-C JIMRO II kit. Fasting plasma was also collected from the HD patients 10 minutes after an intravenous injection of heparin (30 U/kg body wt). Plasma LPL levels were determined using an enzyme immunoassay, and HTGL levels were determined using a modified version of the Hernell et al method. RESULTS: Plasma RLP-C levels showed a tendency to decrease after the start of the EPO supplement therapy in HD patients at the maintenance stage. Plasma LPL levels were significantly higher in the two groups of HD patients one month after the start of the EPO supplement therapy than in the same patients prior to the start of the EPO supplement therapy. Plasma HTGL levels were significantly higher in HD patients at the maintenance stage one month after the start of the EPO supplement therapy than in HD patients at the maintenance stage prior to the start of the EPO supplement therapy. CONCLUSIONS: The results of this study suggest that the EPO supplement therapy may reduce plasma RLP-C levels by increasing the plasma LPL and HTGL levels in maintenance-stage HD patients.

Adult↗
PubMed1999

Effect of simvastatin on the lipid profile of hemodialysis patients.

BACKGROUND: Simvastatin, a 3-hydroxy 3-methylglutaryl co-enzyme A (HMG-CoA) reductase inhibitor, is used widely for treatment of hypercholesterolemia. Simvastatin may be a suitable treatment for dyslipidemia in hemodialysis (HD) patients. However, investigation of the side-effects and safety of long-term administration of simvastatin to HD patients has been limited. In this study, we investigated the effects and safety of simvastatin and its effects on lipoprotein metabolism in hypercholesterolemic patients on HD. METHODS: Simvastatin was administered at a dosage of 5 mg/day for 24 weeks to 38 HD patients with high serum total cholesterol (TC) levels (200 mg/dl) or low high-density lipoprotein cholesterol (HDL-C) levels (35 mg/dl). Every four weeks, serum lipids, apolipoprotein, lipoprotein (a) [Lp(a)] and malondialdehyde (MDA) levels were measured. In addition, lipid levels were determined in each lipoprotein fraction separated by ultracentrifugation. RESULTS: After 24 weeks of simvastatin administration, TC significantly decreased by 25.7%, and low-density lipoprotein cholesterol (LDL-C) was significantly decreased by 33.6%. Triglyceride (TG) and HDL-C showed no significant changes. Apolipoprotein (apo) B significantly decreased by 24.5% and apo E by 30.0%. No significant changes were observed in the other apolipoproteins. MDA was also significantly decreased, whereas Lp(a) was not significantly altered. In the lipoprotein fractions, very LDL cholesterol (VLDL-C), intermediate-density lipoprotein cholesterol (IDL-C), LDL1 cholesterol (LDL1-C), and LDL2 cholesterol (LDL2-C) showed significant decreases. No particular side-effects were observed during the 12 months of simvastatin administration. CONCLUSIONS: These results suggest that simvastatin appears to be safe and effective in HD patients with hypercholesterolemia.

Aged↗
PubMed1999

Factors associated with calcification of the abdominal aorta in hemodialysis patients.

BACKGROUND: Cardiovascular and cerebrovascular injury caused by arteriosclerosis has been the major cause of the death in hemodialysis (HD) patients. We quantitatively analyzed and evaluated the severity of abdominal aortic calcification in HD patients in comparison to risk factors for arteriosclerosis. METHODS: One hundred thirty-seven HD patients were examined. Using image analysis software, areas of the calcified abdominal aorta were quantitatively analyzed on plain computerized tomography images. Other factors such as blood pressure (BP), lipid levels, and calcium (Ca) x phosphorus (Pi) value were also analyzed. RESULTS: Patients with a higher one-year average of systolic BP showed a higher severity of abdominal aortic calcification. That is, the severity of abdominal aortic calcification in patients with a one-year systolic BP average above 160 mm Hg was 31.5 +/- 13.6%, and this severity was significantly higher than that in patients with a one-year systolic BP average of less than 120 mm Hg (8.0 +/- 7.7%, P < 0.01). The severity of abdominal aortic calcification in patients demonstrating risk values of ectopic calcification, that is serum Ca x Pi > or = 60 (mg/dl), on more than 4 of 24 measurements within one year (25.8 +/- 13.6%) was significantly higher than the severity of aortic calcification in patients demonstrating this value less than four times in one year (P < 0.05). There was no correlation between levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, lipoprotein(a), and severity of abdominal aortic calcification. CONCLUSIONS: Systolic BP levels and the product of serum Ca and Pi were related to the severity of abdominal aortic calcification in HD patients. These observations suggested that BP control, as well as control of serum Ca and Pi levels, was important in preventing the progression of abdominal aortic arteriosclerosis.

Age Factors↗
PubMed1999

Phosphotyrosine of macrophage by low-density lipoproteins from hemodialysis patients.

BACKGROUND: Because of the possible importance of tyrosine phosphorylation in the signal transduction process, we investigated whether an interaction of low-density lipoprotein (LDL) from hemodialysis patients (HD-LDL) and human macrophages induces tyrosine-phosphorylated proteins in the macrophages. METHODS: Human monocyte-derived macrophages were incubated with HD-LDL (100 micrograms/ml) or native LDL (100 micrograms/ml) for 15 minutes at 37 degrees C. Whole cells were lyzed with Tris-HCl buffer containing vanadate and Triton X-100. After centrifugation, lyzed proteins were divided into Triton-soluble and -insoluble fractions. Both fractions (soluble and insoluble) were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and were electroblotted onto a polyvinylidene difluoride (PVDF) membrane. Immunoblotting was performed using an antibody against phosphotyrosine or c-Src. RESULTS: Several proteins in the range 40 to 100 kDa were found to be phosphorylated constitutively in the macrophages and not affected by the addition of HD-LDL. HD-LDL did not induce any tyrosine-phosphorylated proteins either in the soluble or insoluble fractions. Macrophages pretreated with tyrosine kinase inhibitor genestein drastically inhibited tyrosine phosphorylation of these proteins. The nonreceptor tyrosine kinase, c-Src p60, was also strongly tyrosine phosphorylated in the macrophages, and this was not enhanced by the stimulation of HD-LDL. CONCLUSION: These data suggest that tyrosine autophosphorylated proteins may play a role in the early step of signal transduction in the macrophages.

Enzyme Inhibitors↗