Biomedical subjects

H Koide

Publications and source records attributed to H Koide.

339 records · Page 19Linked to original sources

PubMedDate not supplied

Effects of angiotensin-converting enzyme inhibitor, angiotensin II receptor antagonist and calcium antagonist on urinary podocytes in patients with IgA nephropathy.

The urinary podocyte is postulated to be a marker for estimation of the severity of active glomerular injury and a predictor of disease progression in children with glomerulonephritis. Non-dihydropyridine calcium antagonist, including verapamil, reduce proteinuria to an extent similar to that of the angiotensin-converting enzyme inhibitor (ACEI), including trandolapril, but to a greater extent than other antihypertensives. Angiotensin (Ang) II receptor antagonists, including candesartan cilexetil, show potent and long-term preventive effects against the progression of renal injury. The aim of the present study is to assess whether verapamil, trandolapril and candesartan cilexetil affect proteinuria and urinary podocytes in patients with IgA nephropathy. Thirty-two normotensive patients aged 18-54 years with biopsy-proven IgA nephropathy, nonnephrotic proteinuria (1-3 g/day), and normal renal function (creatinine clearance >80 ml/min) were studied. Twenty patients with diffuse mesangial proliferative glomerulonephritis (non-IgA PGN) and 20 healthy controls were also included in this study. The number of urinary podocytes in patients with advanced IgA nephropathy (n = 16) was significantly higher than that in patients with the disease in the mild stage (n = 16) (p < 0.01) or in patients with non-IgA PGN (p < 0.01). Urinary podocytes were not detected in healthy controls. The 32 patients with IgA nephropathy were randomly divided into four treatment groups: those treated with verapamil (120 mg/day, n = 8); those treated with trandolapril (2 mg/day, n = 8); those treated with candesartan cilexetil (8 mg/day, n = 8), and those given a placebo (n = 8). Treatment continued for 3 months. Antiproteinuric response in the trandolapril group was similar to that in the candesartan cilexetil group (-38 vs. -40%). The action of trandolapril or candesartan cilexetil was greater than that of verapamil (p < 0.01). Reduction in the number of urinary podocytes from baseline was significantly greater in patients treated with trandolapril or candesartan cilexetil than in patients treated with verapamil (p < 0.01). However, there was no difference between patients treated with trandolapril and those treated with candesartan cilexetil. Proteinuria and urinary podocytes were unaffected in the placebo group. These data suggest that urinary podocytes may be a marker of disease activity in adult patients with IgA nephropathy and that trandolapril and candesartan cilexetil are more effective than verapamil in reducing the number of podocytes.

Adult↗

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

Intranephron distribution of glycine-amidinotransferase activity in rats.

Guanidinoacetic acid (GAA), a precursor of creatine, is an essential substrate for muscle energy metabolism, and synthesized by glycine-amidinotransferase (transamidinase) mainly in the kidney. Since the intranephron distribution of transamidinase activity has never been quantified yet, the purpose of this study is to provide evidence about the localization of transamidinase activity using microdissected individual nephron segments. Synthesized GAA was separated by HPLC and detected fluorometrically after reacting with 9,10-phenanthrenequinone. Results obtained were as follows. (1) Transamidinase activity was distributed only in the first (S1) and the second (S2) portion of the proximal tubule, S1 being significantly higher than S2. (2) In S2, arginine and glycine were better substrates for GAA synthesis than canavanine and glycine. These results clearly indicate that GAA is synthesized in definite portions of the proximal tubule, and would be transported to the liver for further creatine production.

Amidinotransferases↗

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

Altered extracellular matrix component gene expression in murine polycystic kidney.

The DBA/2FG-pcy mouse has a form of slowly progressive kidney disease that appears similar in many respects to that seen in the autosomal dominant form of human polycystic kidney disease. This study was designed to assess how the expression of extracellular matrix component genes is regulated in a model of murine polycystic kidney disease and control DBA/2 mice at 8, 16, and 30 weeks of age. The mRNA levels encoding for collagen IV, the B1 and B2 chains of laminin, heparan sulfate proteoglycan, fibronectin, and collagens I and III increased with the progression of cystic lesions in the kidney of DBA/2FG-pcy mice. At 30 weeks of age, mRNA levels for collagen IV, laminin B1 and B2, heparan sulfate proteoglycan, fibronectin, and collagens I and III were increased 8.1-fold, 7.0-fold, 7.0-fold, 9.8-fold, 7.0-fold, 5.5-fold, and 5.4-fold, respectively, compared to those of control DBA/2 mice. An immunofluorescence study revealed the irregular staining for collagen IV, laminin, heparan sulfate proteoglycan, and collagens I and III around the cysts. These data suggest that changes in the expression of basement membrane components and interstitial collagens are associated with the development of polycystic kidney disease.

Animals↗

PubMedDate not supplied

Effects of enalapril treatment on gene expression of smooth muscle myosin heavy chain isoforms in glomeruli of diabetic rats.

We have previously shown that smooth muscle contains three types of myosin heavy chains: SM1, SM2, and SMemb. The present study was designed to assess how glomerular expression of mRNA for these isoforms is regulated and whether their expression is affected by enalapril treatment in diabetic rats. Animals were divided into 4 groups: (1) untreated diabetic rats; (2) enalapril-treated diabetic rats; (3) untreated control rats, and (4) enalapril-treated control rats. Enalapril treatment was continued for 24 weeks. The glomerular mRNA levels for SM1 and SM2 showed little change in all groups throughout the experimental period. In contrast, SMemb mRNA in group 1 increased significantly with age compared to levels found in untreated controls (4.6-fold higher at 4 weeks, p < 0.01; 6.8-fold higher at 12 weeks, p < 0.01, and 10.6-fold higher at 24 weeks, p < 0.001). Enalapril reduced both creatinine clearance (p < 0.01) and urinary protein excretion (p < 0.01) in diabetic rats. Moreover, enalapril significantly attenuated the increase in the glomerular SMemb mRNA level in diabetic rats (the difference between treated and untreated rats was significant at p < 0.01 from week 4 to 24). However, enalapril had no effect on SMemb mRNA levels in controls. These data suggest that SMemb is a molecular marker for phenotypic alteration and that the beneficial effect of enalapril on proteinuria and renal function may be, at least in part, associated with reducing SMemb mRNA expression in diabetic glomeruli.

Angiotensin-Converting Enzyme Inhibitors↗

PubMedDate not supplied

A case of massive ascites due to lupus peritonitis with a dramatic response to steroid pulse therapy.

A 52-year-old female patient with massive ascites due to lupus peritonitis is described. Skin biopsy specimens revealed typical features of systemic lupus erythematosus (SLE) in light microscopic and immunofluorescent examinations. Immune-complexes, antinuclear antibody and hypo-complementemia were detected in the peritoneal fluid. The massive ascites responded dramatically to steroid pulse therapy. The levels of circulating immune-complexes, anti-nuclear antibody and complement in sera were also improved after such therapy. It was suggested that steroid pulse therapy may be useful for massive ascites due to lupus peritonitis.

Antibodies, Antinuclear↗

PubMedDate not supplied

A case of neuroleptic malignant syndrome with acute renal failure after the discontinuation of sulpiride and maprotiline.

A 46-year-old man developed neuroleptic malignant syndrome with acute myoglobinuric renal failure after the discontinuation of sulpiride and maprotiline treatment. He showed the characteristic features of hyperpyrexia, altered consciousness, muscle rigidity, and autonomic dysfunction. Laboratory data showed lysis of skeletal muscle cells and renal impairment. Muscle biopsy revealed necrosis and regenerative changes in muscle fibers. Renal biopsy showed focal tubulitis and interstitial infiltration of small inflammatory cells. The combination of sulpiride and maprotiline has not previously been reported to be the cause of neuroleptic malignant syndrome and acute myoglobinuric renal failure.

Acute Kidney Injury↗

PubMedDate not supplied

A case of IgM-associated mesangial proliferative glomerulonephritis with a giant paramesangial spherical deposit.

We report a case of IgM-associated mesangial proliferative glomerulonephritis with microscopic hematuria and renal tubular dysfunction. On electron microscopy, a giant spherical deposit was observed in the glomerular paramesangial area. Deposition of C3 in the glomerular mesangial areas was not observed by immunofluorescence. IgM-associated mesangial proliferative glomerulonephritis is clinically characterized by nephrotic syndrome, mild proteinuria and/or hematuria, tubular dysfunction or renal failure, suggesting that it is considered to be a heterogeneous disorder.

Female↗

PubMedDate not supplied

Assessment of external dose to inhabitants evacuated from the 30-km zone soon after the Chernobyl accident.

According to reports by the former USSR government, IAEA and WHO, no case of acute radiation effects was recognized among inhabitants who were evacuated from the 30-km zone around the Chernobyl site soon after the accident on April 26, 1986. Along with the collapse of the USSR, however, several documents appeared that report the occurrence of acute radiation effects among inhabitants. In order to check the possibility of acute radiation effects among evacuees, we evaluated the external dose of evacuees until their evacuation based on the data about the radiation situation soon after the accident. Our estimates indicate that a substantial number of inhabitants in some villages could have received more than 0.5 Sv that is recognized by ICRP and UNSCEAR as a threshold dose for a clinically significant depression of the blood-forming function of bone marrow. Some of them could have received more than 1 Sv.

Disaster Planning↗

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↗

PubMedDate not supplied

Transcriptional activation of matrix genes by transforming growth factor beta 1 in mesangial cells.

The accumulation of mesangial matrix is a common histologic abnormality observed over the course of various glomerular diseases. To examine the role of transforming growth factor beta 1 (TGF-beta 1), a well-known regulator of extracellular matrix metabolism, in such processes, we studied the effects of this peptide on the gene expression of extracellular matrix components in cultured rat mesangial cells. TGF-beta 1 increased the mRNA levels for alpha 1 (I) and alpha 1 (IV) collagens and fibronectin. The increase in these mRNA levels was detectable 6 h after stimulation by TGF-beta 1. At 24 h, the mRNA levels for alpha 1 (I) and alpha 1 (IV) collagens and fibronectin increased 1.9-, 2.8- and 2.6-fold, respectively, above their basal levels. Concomitant treatment with cycloheximide did not prevent the stimulation by TGF-beta 1 and resulted in exceptional superinduction for the fibronectin gene. Concomitant treatment with actinomycin D completely inhibited the increase in the mRNA levels induced by TGF-beta 1. Furthermore, TGF-beta 1 showed no stabilizing effect on the transcripts. These results suggest that TGF-beta 1, which is released in glomerular injury, induces an increase in the transcription of the alpha 1 (I) and alpha 1 (IV) collagen and fibronectin genes in mesangial cells and may mediate the accumulation of the extracellular matrix in the mesangium.

Animals↗

PubMedDate not supplied

Increased endothelin-1 mRNA expression in peripheral blood monocytes of dialysis patients.

OBJECTIVE: To compare plasma endothelin (ET)-1 level and ET-1 mRNA level in peripheral blood monocytes of patients undergoing hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Endothelin-1 mRNA level in peripheral blood monocytes and plasma ET-1 level were studied in 30 HD patients, 15 CAPD patients, 20 chronic renal failure patients not being dialyzed, and 20 normal healthy controls. Hemodialysis patients were dialyzed three times per week with a bicarbonate dialysate. Different types of dialyzer membrane, viz., cellulose triacetate, cuprophane, polysulfone, polyacrylonitrile, and ethylenevinylalcohol were used in 8, 6, 6, 5, and 5 patients, respectively. Continuous ambulatory peritoneal dialysis patients were dialyzed with four daily exchanges of a 2-L dialysate containing glucose at a concentration of 1.5% to 2.5%. RESULTS: Higher levels of ET-1 mRNA in monocytes were observed in HD patients than in CAPD patients (p < 0.01), chronic renal failure patients (p < 0.01), or normal healthy controls (p < 0.001). The level of ET-1 mRNA in monocytes at the end of HD was not significantly higher than that at the start of HD. In addition, these mRNA levels in HD patients showed little difference with different types of dialysis membrane. Plasma ET-1 level in HD patients (10.2 +/- 2.4 pg/mL) was also higher than that in CAPD patients (7.8 +/- 1.6 pg/mL, p < 0.01), in chronic renal failure patients (4.8 +/- 1.2 pg/mL, p < 0.01), or in normal controls (2.6 +/- 0.8 pg/mL, p < 0.001). CONCLUSION: Dialysis itself did not significantly affect ET-1 mRNA levels in monocytes. Chronic stimulation of peripheral blood monocytes may be associated with higher levels of ET-1 mRNA and plasma ET-1 in HD patients than in CAPD patients.

Adult↗