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Biomedical subjects

M Mune

Publications and source records attributed to M Mune.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1999

Successful pregnancy and delivery in a case of systemic lupus erythematosus treated with immunoadsorption therapy and cyclosporin A.

A 32-year-old woman diagnosed as systemic lupus erythematosus (SLE) became pregnant. During pregnancy she was treated with a daily dosage of prednisolone 15 mg. However, because the exanthema became worse, she was hospitalized on January 14, 1997 in order to receive immunoadsorption therapy. Before delivery we implemented the immunoadsorption therapy twice and cyclosporin A (CsA) was administered simultaneously. She gave birth in her 37th week. The baby weighed 2260 g at the time of delivery and had no deformities. The mother also had no side effects. The success of pregnancy and childbirth in our case, without any side effects, shows the possibility that the combination of CsA and immunoadsorption therapy may be considered safe to control a pregnancy complicated by SLE.

Adult↗
PubMed1999

Effect of vitamin E on lipid metabolism and atherosclerosis in ESRD patients.

BACKGROUND: Oxidative stress is enhanced in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD). Bioincompatibility represents an important source of reactive oxygen species. HD patients exhibit altered anti-oxidative defences and anti-oxidative vitamins such as vitamin E and C are altered in uremia. Frequently, HD patients also suffer from atherosclerotic cardiac disease. We have previously reported that low density lipoprotein (LDL) of HD patients is rich in malondialdehyde (MDA), an end product of lipid peroxidation. MDA rich LDL is thought to be an atherogenic lipoprotein due to its enhancement of macrophage foam cell formation. METHODS: We conducted a controlled study for two years comparing the effects of a vitamin E coated cellulose membrane dialyzer and an ordinary cellulose membrane dialyzer on lipid metabolism and the progress of atherosclerosis. LDL-MDA and oxidized LDL (ox-LDL) were measured in HD patients using these two types of dialyzers. Plasma vitamin E and lipid concentrations were also evaluated. The aortic calcification index (ACI) was evaluated by CT scan to assess the progress of atherosclerosis before and for every year after treatment. RESULTS: Use of a vitamin E coated cellulose membrane dialyzer for six months, one year and two years resulted in a significant reduction in LDL-MDA and ox-LDL compared to the ordinary cellulose membrane dialyzer. Treatment with a vitamin E-coated dialyzer significantly reduced the percentage increase in ACI after 24 months compared to the control. There were no significant changes in plasma vitamin E and lipid concentrations between the two groups. CONCLUSIONS: These results suggest that the oxidative stress could be one of the stimulating factors of abnormal lipid metabolism and atherosclerosis in ESRD patients.

Aged↗
PubMed1999

Involvement of MCP-1 and M-CSF in glomerular foam cell formation in ExHC rats.

BACKGROUND: An increase in glomerular macrophages (MO) is considered a potential effector mechanism by which hypercholesterolemia exacerbates glomerular injury. To investigate the mechanism underlying recruitment of MO into glomeruli, the expression of glomerular monocyte chemoattractant protein-1 (MCP-1) and macrophage colony-stimulating factor (M-CSF) mRNA were examined using a lipid-induced glomerular injury rat model. METHODS: Eight-week-old male ExHC rats, a strain susceptible to hyperlipidemia, were divided into the following 4 groups: a control group (C), a high cholesterol diet group (HH), a high cholesterol diet/standard diet group (HN), which were fed a high cholesterol diet for the first 4 weeks and a standard diet for the following 4 weeks, and a probucol-treatment group (PT). Both MCP-1 and M-CSF mRNA expression in glomeruli were analyzed using the RT-PCR method. An additional experimental group (M) fed a high cholesterol diet was administered M-CSF daily for 4 weeks. RESULTS: The expression of MCP-1 mRNA in glomeruli increased accompanied by an increased total serum cholesterol level in HH and HN. However, M-CSF mRNA expression was significantly suppressed at 1 or 2 weeks and gradually increased to almost basal levels. In the PT group, MCP-1 mRNA expression was suppressed. The early suppression of M-CSF mRNA expression was inhibited in PT. Renal histology showed a significant increase in foam cells in glomeruli in HH and HN rats at 4 weeks. HH rats showed increased and expanded foam cells at 8 weeks. In HN rats, however, foam cells decreased significantly after the transfer to a standard diet from a high cholesterol diet. The MCP-1 mRNA expression was suppressed after the transfer. In the PT group, foam cell formation was also suppressed. Foam cells were identified as MO. M-CSF-treatment significantly suppressed foam cell formation in glomeruli when compared with the untreated group levels. CONCLUSION: These findings suggest that hypercholesterolemia stimulated the expression of MCP-1 in glomeruli and attracted the MO into glomeruli. They also suggest that the reduction of hypercholesterolemia after the change in diet or treatment with probucol suppressed glomerular injury by suppressing the glomerular MCP-1 expression. M-CSF may suppress the recruitment of MO into glomeruli and foam cell formation at an early stage of hypercholesterolemia-induced glomerular injury.

Animals↗
PubMed1999

[Plasma nicotinic acid levels in hemodialysis patients after the administration of niceritrol].

Lp(a) has recently begun to attract attention as a risk factor of atherosclerotic disease, especially of ischemic heart disease. The Lp(a) concentration in the serum was shown to be important for chronic hemodialysis patients who have high mortality due to cardiovascular disease. Nicotinic acid derivatives, which are recognized for their capacity to lower the serum Lp(a) concentration, are effective against a high Lp(a) concentration in hemodialysis patients. In this study, niceritrol which is a nicotinic acid derivative was tested on hemodialysis patients and healthy controls by investigating the serum nicotinic acid level. Serum nicotinic acid concentration was also measured by the severity of renal dysfunction of patients untreated by niceritrol. The blood nicotinic acid concentration in healthy controls (n = 4) was changed after 2 hrs by the administration of niceritrol from 9.8 +/- 1.4 ng/ml to 192.7 +/- 23.1 ng/ml then slowly decreased. Chronic hemodialysis patients who take niceritrol every day showed the highest nicotinic acid serum concentration (500-1,000 ng/ml) on the day without hemodialysis and the serum level decreased with dialysis for 4 hrs to 25-80%. There was no significant difference in the nicotinic acid level in the serum between healthy controls (n = 10), chronic glomerulonephritis patients (n = 7), chronic renal failure patients (n = 8) and chronic hemodialysis patients (n = 17). Lp(a) concentration in the serum, however, was increased with greater severity of renal dysfunction, The side effect was not observed in any cases administered niceritrol. These data suggest nicotinate derivatives are effective for hemodialysis patients. High nicotinic acid level in the serum after treatment with niceritrol was lowered by dialysis. It is plausible that the nicotinate level in patients without niceritrol treatment did not influence the Lp(a) concentration, because there was no increase in the nicotinate level of the serum even if the patients had renal dysfunction.

Arteriosclerosis↗
PubMed1999

[Vitamin E disturbances in chronic renal failure].

Plasma levels of alpha-tocopherol (vitamin E) in chronic renal insufficiency (CRI) patients may be decreased, normal or elevated. However, an abnormal distribution of vitamin E in each lipoprotein has been reported. In comparison to control subject low-density lipoprotein (LDL), patient LDL contained less vitamin E. On the contrary, malondialdehyde (MDA) in patient LDL was enhanced. According to the evaluation of the susceptibility of LDL to in vitro oxidation and the rate of lipid peroxidation by fluorescence development during copper exposure, the susceptibility of patient LDL was enhanced, suggesting a possible relationship between excessive LDL peroxidation and accelerated atherosclerosis. In a clinical small uncontrolled trial, the increments of an aortic calcification index estimated by CT scan in patients treated with vitamin E were suppressed compared to those treated without vitamin E, suggesting that vitamin E might prevent the progress of atherosclerosis in CRI patients.

Humans↗
PubMed1996

Increased expression of a brain/embryo-type myosin heavy chain isoform (MIIB2) in mesangial proliferative glomerulonephritis.

Proliferation of mesangial cells is frequently found in glomerulonephritis, such as IgA glomerulonephritis. Recent reports suggest that a brain/embryo-type myosin isoform (MIIB2) is involved in cell proliferation. We have studied the expression of MIIB2 in renal biopsy samples from patients with various renal diseases and in the renal tissues from the rat model of mesangial proliferative glomerulonephritis induced with anti-Thy 1.1 antibody. Immunohistochemical analysis of the biopsy samples using an anti-brain-type myosin heavy chain-specific monoclonal antibody (HBM1) indicated that 92% of the samples from patients with IgA glomerulonephritis contained a significant population of mesangial cells that reacted with the antibody. Most of the samples from patients with other types of proliferative glomerular diseases also contained HBM1-reactive mesangial cells, while none of the samples from patients with non-proliferative glomerular diseases contained a significant population of HBM1-reactive mesangial cells. The expression of a brain/embryo-type myosin heavy chain isoform (MIIB2) in the mesangial cells began at five days after injection of anti-Thy 1.1 antibody and peaked at the tenth day. On the other hand, the expression of the proliferating cell nuclear antigen in the mesangial cells was induced at two days after injection of anti-Thy 1.1 antibody and was maximal at the fourth day. These results indicate that the expression of the MIIB2 isoform by mesangial cells is accelerated in proliferative glomerulonephritis and suggest that the myosin isoform is involved in the phenotypic transformations of the glomerular tissues rather than in the cell proliferation.

Adolescent↗
PubMed1996

[Subjective happiness and psychological condition in SLE].

We reported the relationship between subjective happiness and psychological condition to investigate which factor effects the quality of life (QOL) in 18 patients with systemic lupus erythematosus (SLE) and compared them with age, sex and dose of steroid matched 18 patients with chronic glomerular nephritis (CGN). The patients were evaluated in morale scale-revised (Japanese version) which is a standard method of evaluating subjective happiness in relation to QOL. State-trait anxiety inventory (STAI) of Spielberger was used for evaluation of anxiety condition with self rating depression scale (SDS) of Zung in evaluation of depressive state. We examined the relationship between morale scale and SDS and morale scale and STAI. The relationship between morale scale and age; period of the disease, dose of steroid and activity were also investigated. There were no significant differences between the groups on morale scale, SDS and STAI and there were no significant correlations between morale scale and age; period of the disease and the dose of steroid in the both groups. There were correlations between morale scale and state and trait anxiety in the group with SLE and morale scale and trait anxiety in the group with CGN. We concluded that anxiety decreased the QOL in patients with SLE and CGN.

Adolescent↗
PubMed1995

Effect of alpha-tocopherol on in vitro and in vivo metabolism of low-density lipoproteins in haemodialysis patients.

It has been reported that some modified low-density lipoproteins (LDLs) such as glycated LDL and malondialdehyde-rich LDL (MDA-LDL) probably exist in the circulation. The present study was undertaken to investigate the in vitro and in vivo metabolism of MDA-LDL occurring in chronic haemodialysis patients and the effects of alpha-tocopherol on these abnormalities. MDA-LDL from haemodialysis patients was degraded more rapidly by human monocyte-derived macrophages and disappeared more slowly from the circulation when compared with LDL from healthy controls. Treatment with alpha-tocopherol at doses of 600 mg/day for 2 weeks resulted in improvement of these metabolic abnormalities depending upon the degree of return to normal MDA concentrations in LDL.

Humans↗
PubMed1993

Analysis of viral infection in patients with IgA nephropathy.

We investigated viral infections in the tonsils, pharynx and renal tissues of patients with IgA nephropathy using cell culture, polymerase chain reaction (PCR) and immuno-fluorescent techniques, and measured antibody titers against numerous types of viruses. Neutralization tests found no significant inhibition of growth of adenovirus-1, 2, 3, 4, 5, 6, 7, 11 or 19, Coxsackie virus-A7, A9, A16, B1, B2, B3, B4, B5 or B6, or RS virus. Swabs of the oral cavity of patients with IgA nephropathy were cultured with Hel cells, MDCK cells, FL cells, BHK-21 cells and RD-18S cells. No cytopathic effect was detected in any of these cell cultures. We failed to detect the presence of herpes simplex virus-1 and -2, varicella-zoster virus, cytomegalovirus and Epstein-Barr virus (EBV)-1 and -2 in tonsils, renal tissues and mouthwashings from patients with IgA nephropathy. On the other hand, EBV alone was detected with the PCR technique, in mouthwashings from 6 out of 14 patients with IgA nephropathy (42%). Immunohistological and serological analyses were done to examine the relationship between EBV and IgA nephropathy. No evidence was obtained that EBV-infected B lymphocytes were producing IgA. It seems unlikely that the viral infections examined in this study play a significant role in the pathogenesis of IgA nephropathy.

Adult↗
PubMed1992

Prevention of aortic calcification in patients on hemodialysis by long-term administration of vitamin E.

The effects of vitamin E on the progress of atherosclerosis in patients on hemodialysis was investigated clinically using ACI. There was a significant suppression of the increase in ACI in group A, compared to group B, at the time of observation in each year. On the other hand, no significant changes were noted in BWD, CTR, BP and blood chemical examination, except that the level of MDA was significantly decreased in group A as compared with that in group B 4 years later. Since ACI is an index representing atherosclerosis, the results of this study seemed to suggest that the progress of atherosclerosis was suppressed by long-term administration of vitamin E in patients on hemodialysis.

Aortic Diseases↗
PubMed1992

Study on the inhibitory effect of uremic plasma on lipoprotein lipase.

An investigation was undertaken to determine which plasma factors from normal controls and patients with chronic renal failure (CRF) exert have inhibitory effects on the activity of lipoprotein lipase (LPL) purified from heparinized human plasma by using an accurate LPL assay system. Inhibitors of LPL were found to be present in the plasma. The inhibition of the LPL activity was significantly greater in CRF patients than in normal controls. Following hemodialysis (HD), the same concentration of uremic plasma led to less inhibition. The inhibitors existed only in lipoprotein deficient plasma (LPDS), which demonstrated an LPL-inhibitory activity at extremely high concentrations with a significant difference between the patients and normal controls. There was no difference between the two groups at low concentrations. A specific inhibitory effect on LPL in LPDS was noted in the 7S and 4S fractions separated by gel filtration employing Sephacryl S-200 column chromatography. The inhibitory effect of the 7S fraction was found to be dependent on the concentration, and the difference between the two groups was similar to that for LPDS. The results obtained in the present study suggest that the plasma from CRF patients exhibited a strong inhibitory action on the LPL activity as compared to the plasma from normal controls, and the inhibitory action was due primarily due to poor excretion of dialyzable inhibitors.

Adult↗
PubMed1991

Effect of platelet-activating factor on lipoprotein lipase and blood lipids.

We investigated the effect of platelet-activating factor (PAF) and of the PAF specific antagonist CV-6209 on plasma lipid metabolism, and particularly on post-heparin plasma lipolytic activity in male Wistar rats. Lipoprotein lipase (LPL) activity was enhanced by intravenous injection of PAF before intravenous injection of heparin when the PAF dose was low (0.2 micrograms/kg). PAF activated hepatic triacylglycerol lipase (HTGL) activity dose-dependently. Plasma triacylglycerols (TG) significantly decreased with the activation of LPL and/or HTGL. Plasma total cholesterol (TC) and phospholipid (PL) levels decreased at a low dose of PAF (0.2 micrograms/kg), but increased when higher doses were used. The PAF antagonist CV-6209 partially reversed the PAF induced effects on HTGL, TC and PL.

Animals↗
PubMed1990

[Glomerular apolipoprotein B deposition in glomerular diseases].

In an attempt to elucidate the relationship between the progress of glomerular injury and abnormalities of lipid metabolism, we investigated glomerular deposition of apolipoprotein B (apo B) in renal biopsy specimens from 60 patients with glomerular diseases by indirect immunofluorescence using antihuman apo B-100 monoclonal antibody in comparison with clinical and histopathological findings. The patients were divided into 2 groups according to the intensity in staining of apo B in glomerulus (group A: negative or weakly positive; and group B: definitely positive). Staining of apo B in glomerulus was found in 37 patients (62%). The levels of serum total cholesterol, phospholipids, low density lipoprotein cholesterol and apo B in group B were significantly higher than in group A. The urinary protein excretion in group B was greater than that in group A. Group B was also shown to have a significantly decrease in renal function. Light microscopy revealed severe mesangial proliferation in patients with IgA nephropathy of group B. These findings suggested that glomerular apo B containing-lipoprotein deposition may play an important role in the progression of glomerular injury.

Adolescent↗