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H Koide

Publications and source records attributed to H Koide.

At least 109 records · Page 6Linked to original sources
PubMed1995

Glomerular expression of smooth-muscle myosin heavy-chain isoforms in aminonucleoside nephrosis in rats.

1. We investigated the glomerular expression of three types of myosin heavy-chain isoforms, including S-myosin heavy-chain 40 (SM1), S-myosin heavy-chain 29 (SM2) and FS-myosin heavy-chain 34 (SMemb) in puromycin aminonucleoside nephrosis. 2. There was little change in SM1 and SM2 mRNA levels throughout the experiment. In contrast, glomerular SMemb mRNA increased on days 2 and 4 (before and soon after the onset of proteinuria, respectively), but declined on day 8 (the peak of proteinuria). 3. Histological myosin heavy-chain expression was examined using three antibodies against SM1, SM2 and SMemb. Immunohistochemically, SM1 and SM2 were absent in the glomeruli associated with puromycin aminonucleoside 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 puromycin aminonucleoside nephrosis. In the puromycin aminonucleoside-treated rats, the number of SMemb-positive glomerular cells increased on days 2 and 4. 4. We examined whether levels of alpha-smooth-muscle actin or proliferating cell nuclear antigen correlated with myosin heavy-chain levels in the glomeruli of rats with puromycin aminonucleoside nephrosis. None of the cellular components in the glomeruli was positive for either alpha-smooth-muscle actin or proliferating cell nuclear antigen in puromycin aminonucleoside nephrosis. 5. Administration of methylprednisolone to puromycin aminonucleoside-treated rats resulted in the rapid disappearance of proteinuria. However, methylprednisolone did not affect SMemb mRNA or immunostaining in a glomeruli of rats with puromycin aminonucleoside nephrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Binding capacity of serum IgA to jacalin in patients with IgA nephropathy using jacalin-coated microplates.

Binding capacity of serum IgA to jacalin in 22 patients with IgA nephropathy, 14 patients with diffuse mesangial proliferative glomerulonephritis (non-IgA nephropathy) and 20 age-matched healthy adults was examined by enzyme-linked immunoassay (ELISA) using jacalin-coated microplates. In contrast to previous findings, the binding capacity of serum IgA to jacalin in patients with IgA nephropathy measured by ELISA using jacalin-coated microplates was significantly higher than that in healthy adults. The ratio of serum IgA levels measured by this method to those obtained by single radial immunodiffusion was significantly increased in patients with IgA nephropathy. It appeared that the capacity of serum IgA binding to jacalin was marked in these patients. It is concluded that the binding capacity of serum IgA to jacalin is not ubiquitously impaired in all patients with IgA nephropathy.

Adult↗
PubMed1995

beta-Carbolinium cations, endogenous MPP+ analogs, in the lumbar cerebrospinal fluid of patients with Parkinson's disease.

We measured beta-carbolinium cations (BC+s) endogenous analogs of the N-methyl-4-phenylpyridinium ion (MPP+), in the lumbar CSF of 22 patients with idiopathic Parkinson's disease (PD) and 11 age-matched controls without any symptoms of parkinsonism. Among the BC+s, 2,9-diemethylnorharmanium cation (2,9-Me2NH+), the most potent neurotoxicant that mirrors MPP+ in mitochondria toxicity, was present in 12 patients with PD but not in controls. Although the 2-monomethylated beta-carbolinium cations (2-MeBC+s), which were present in almost all subjects, registered a slightly higher level in PD patients than in controls, the difference was not significant. The total BC+ content, sum of 2-MeBC+ and 2,9-Me2NH+ levels, was significantly higher in PD patients than in controls. The 2-MeBC+ contents significantly increased with the progression of the PD, but 2,9-Me2NH+ decreased as the disease exacerbated, although levels varied within a wide range. The present results strongly support the hypothesis that "bioactivated" BC+s, especially 2,9-Me2NH+s, may be the endogenous causative factors underlying PD.

1-Methyl-4-phenylpyridinium↗
PubMed1995

Enalapril attenuates increased gene expression of extracellular matrix components in diabetic rats.

This study was designed to assess whether the glomerular expression of mRNA for extracellular matrix (ECM) components including alpha 1 (I), alpha 1 (III), and alpha 1 (IV) collagen chains, laminin B1 and B2 chains, metalloproteinases (MMP), and tissue inhibitor of metalloproteinases (TIMP) is affected by enalapril in 12- and 24-wk-old rat after streptozotocin injection. Animals were divided into three groups; untreated diabetic rats, enalapril-treated diabetic rats, and control rats. Enalapril treatment was continued for 24 wk. Enalapril reduced both creatinine clearance (P < 0.01) and urinary protein excretion (P < 0.01) in diabetic rats. In diabetic rats, mRNA levels for alpha 1 (IV) collagen chain, laminin B1 and B2 chains, and alpha 1(I) and alpha 1(III) collagen chains increased significantly at 24 wk compared with those in controls [alpha 1(IV): 3.8-fold (P < 0.01); laminin B1: 6.2-fold (P < 0.01); laminin B2:5.4-fold (P < 0.01), alpha 1(i): 4.8-fold (P < 0.01) and alpha 1(III): 3.8-fold (P < 0.01)]. At 24 wk, 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 compared with levels in controls. In contrast, mRNA levels for TIMP-1 and TIMP-2 increased significantly at 24 wk after streptozotocin injection (TIMP-1: 8.0-fold (P < 0.01) and TIMP-2: 6.4-fold (P < 0.01)).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Modulation of glomerular endothelin and endothelin receptor gene expression in aminonucleoside-induced nephrosis.

This study assessed glomerular endothelin (ET)-1, ET-3, and ET-receptor A and B mRNA levels in puromycin aminonucleoside (PAN)-induced nephrosis. During the nephrotic stage, 8 days after PAN injection, ET-1 and ETB receptor mRNA were elevated by 2.8 +/- 0.8-fold (P < 0.01) and 2.4 +/- 0.9-fold (P < 0.01), respectively, as compared with controls. These mRNA levels decreased to control levels by Day 20, when the nephrosis was in remission. In contrast, glomerular ETA receptor mRNA levels did not change in PAN nephrosis or control rats during the experimental period. ET-3 mRNA was not detected in the glomeruli of PAN nephrosis or control rats. Additionally, plasma ET concentration and glomerular ET production were measured in PAN nephrosis and control rats by radio-immunoassay. Eight days after PAN injection, ET-1 levels in plasma and glomeruli were not significantly altered in rats with PAN-induced nephrosis (glomeruli, 104.68 +/- 16.46 pg/mg of protein versus 98.24 +/- 13.68 pg/mg of protein; plasma, 2.68 +/- 1.10 versus 2.52 +/- 0.98 pg/mL). The administration of methylprednisolone to PAN rats resulted in the rapid disappearance of proteinuria and partially attenuated the increased ET-1 and ETB receptor gene expression in the glomeruli. These data indicate that glomerular ET-1 and ETB receptor expression in PAN nephrosis in increased at the mRNA level and that methylprednisolone treatment results in an attenuated increase.

Animals↗
PubMed1995

Effect of a specific endothelin receptor A antagonist on mRNA levels for extracellular matrix components and growth factors in diabetic glomeruli.

We have previously reported that the mRNA levels of extracellular matrix (ECM) components including alpha 1(I), alpha 1(III), and alpha 1(IV) collagen chains, laminin B1 and B2 chains, and growth factors including tumor necrosis factor (TNF)-alpha, platelet-derived growth factor (PDGF)-B chain, transforming growth factor (TGF)-beta, and basic fibroblast growth factor (FGF) all increase with age in diabetic glomeruli. The present study was designed to assess whether glomerular expression of these mRNAs in rat diabetic glomeruli is affected by a specific endothelin receptor A antagonist, FR139317. Diabetes was produced by streptozotocin injection, and animals were divided into four groups: untreated diabetic rats, FR139317-treated diabetic rats, control nondiabetic rats, and FR139317-treated control rats. FR139317 treatment was continued for 24 weeks. FR139317 attenuated the rise in creatinine clearance (P < 0.01) and reduced urinary protein excretion (P < 0.01) in diabetic rats, but did not affect blood pressure. FR139317 attenuated the increases in glomerular mRNA levels of alpha 1(I) (P < 0.01), alpha 1(III) (P < 0.01), and alpha 1(IV) (P < 0.01) collagen chains, laminin B1 (P < 0.01) and B2 (P < 0.01) chains, TNF-alpha (P < 0.01), PDGF-B (P < 0.01), TGF-beta (P < 0.001) and basic FGF (P < 0.01) in diabetic rats. However, FR139317 did not affect these mRNA levels in glomeruli of control rats. These findings suggest that FR139317 may be useful in the treatment of diabetic glomerulopathy by reducing mRNA levels of ECM components and growth factors.

Aging↗
PubMed1995

[Fall in the elderly and periventricular hyperintensity].

To investigate the relationship between brain white-matter changes and incidences of falling in the elderly, we studied periventricular hyperintensity (PVH) on brain MRI and history of falling in 73 neurologically normal elderly people. They were divided into 3 groups: group I; 9 prone to falling (mean ages 79 years), group II; 16 who felt mild gait disturbance without falling (75), group III; 48 asymptomatic controls (76). We evaluated white-matter changes as the sum of the length of PVH at 4 and 8 measuring points. Cognitive function and body sway were also evaluated. The frontal PVH was significantly larger in the group I than in the other two groups. Group I showed significantly lower Kohs' IQ than those in the other two groups. There was no difference in body sway among the groups. These results suggests that the propensity to falling in the elderly may be an initial symptom of frontal white-matter changes.

Accidental Falls↗
PubMed1995

Clinical effect of the anti-platelet drug, dilazep dihydrochloride, in patients at the microalbuminuric stage of diabetic nephropathy--a multi-center study.

Clinical effects of an anti-platelet drug (dilazep dihydrochloride) in the microalbuminuric stage of diabetic nephropathy were investigated in a multi-center study. Thirty-seven patients with at the microalbuminuric stage of diabetic nephropathy were examined in the present study. They were administered 300 mg/day of dilazep dihydrochloride (Comelian-Kowa) orally for 6 months. Mean values of albuminuria after the administration of dilazep dihydrochloride were significantly decreased compared with the pre-administration values. Urinary NAG activity was improved after this treatment in the microalbuminuric stage of diabetic nephropathy. Furthermore, impairment of renal function was not observed at that stage. It appears that administration of dilazep dihydrochloride from the early stage of diabetic nephropathy may be useful for the improvement of albuminuria and prevention of renal dysfunction.

Adult↗
PubMed1994

Receptor-binding affinities of human epidermal growth factor variants having unnatural amino acid residues in position 23.

Ile-23 of human epidermal growth factor (hEGF) has been indicated, by mutagenesis and NMR studies, to be directly recognized by the receptor. In the present study, an unnatural phenylalanine analog, either 2-azaphenylalanine (2aF), 3-azaphenylalanine (3aF), 4-azaphenylalanine (4aF), or 4-fluorophenylalanine (4fF), was incorporated by an in vivo protein synthesis system into position 23 of [Phe23]hEGF, which retains appreciable receptor-binding affinity (about 20% of the wild type). We compared the receptor-binding affinities of the variants with that of [Phe23]hEGF and found that substitution of Phe-23 with 2aF or 3aF raised the affinity, while substitution with 4aF or 4fF remarkably reduced the affinity. The tertiary structure of [Phe23]hEGF was not significantly affected by the substitution of Phe-23 with 2aF, as shown by the two-dimensional nuclear magnetic resonance analysis. In addition, the substitution of residue 23 with His or Tyr produced an hEGF variant with a slightly higher receptor-binding affinity than that of [Phe23]hEGF. Our results suggest that the receptor has an asymmetric hydrophobic pocket for recognition of the side chain in position 23 of hEGF. Furthermore, on the receptor surface, this pocket seems to be adjacent to a less hydrophobic region with a hydrogen-bond acceptor and donor. Thus, the use of unnatural amino acids in addition to the 20 natural ones allows analyses of the structure-function relationship of a protein at a higher resolution than conventional site-directed substitution by only natural amino acid residues.

Amino Acids↗
PubMed1994

Site-directed mutagenesis, fluorescence, and two-dimensional NMR studies on microenvironments of effector region aromatic residues of human c-Ha-Ras protein.

The Tyr residues in positions 32 and 40 of human c-Ha-Ras protein were replaced by site-directed mutagenesis (Y32F, Y32W, Y40K, and Y40W) to examine their roles in the signal-transducing activity and the sensitivity to the GTPase activating protein (GAP). The signal-transducing activity of the oncogenic Ras protein in PC12 cells was lost upon mutations Y32F and Y40K, but retained upon mutations Y32W and Y40W. These results suggest that residues 32 and 40 are both required to have aromatic groups and residue 32 is further required to have a hydrogen donor. On the other hand, three mutations (Y32F, Y32W, and Y40W) caused no appreciable reduction in either GAP-binding affinity or GAP sensitivity. By the Y40K mutation, GAP-binding affinity was slightly lowered, while GAP sensitivity was drastically impaired. Therefore, for residues 32 and 40 of Ras, interactions with GAP appear to be different from those with the target of signal transduction in the PC12 cell. As for the Y32W-Ras protein bound with an unhydrolyzable GTP analogue (GMPPNP), the Trp32 fluorescence is appreciably red-shifted, weaker, and more susceptible to KI quenching as compared to that of the GDP-bound form. Two-dimensional NMR spectroscopy with selectively deuterated Ras proteins revealed fewer and weaker nuclear Overhauser effects on the aromatic protons of Trp32 in the GMPPNP-bound form than in the GDP-bound form. This indicates that the side chain of Trp32 is more exposed to the solvent in the GMPPNP-bound form than in the GDP-bound form.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Detection of glycosylated protein in glomeruli of STZ-induced diabetic rats using the nitroblue tetrazolium (NBT) reaction.

Detection of glycosylated protein in renal tissues was determined in streptozotocin (STZ)-induced diabetic rats using the nitroblue tetrazolium (NBT) reaction. The glycosylation of extra-cellular matrix (ECM) components such as laminin and fibronectin was examined in vitro using the same method. Immunofluorescence staining of laminin or type IV collagen was also performed in renal tissues of STZ-induced diabetic rats. There was no significant difference in the intensity of NBT in renal tissues between 4 week STZ-induced diabetic rats and control rats of the same age. The intensity of NBT staining in the glomerular mesangial areas and capillary walls was marked in 12 week diabetic rats. The mean values of fructosamine measured by the NBT reaction in the glycosylated-laminin and fibronectin were increased dose dependently. In immunofluorescence, laminin and type IV collagen were observed significantly in the glomerular mesangial areas and capillary walls of 12 week diabetic rats. However, there was no significant change in renal histopathology in 4 and 12 weeks diabetic rats. It appears that the non-enzymatic glycosylation and expression of ECM components in glomeruli increased in the early stage of diabetic nephropathy prior to the appearance of marked histologic alterations. In conclusion, non-enzymatic glycosylation of glomerular structural components may play an important role in the initiation of the early stage of renal injuries in diabetes.

Animals↗
PubMed1994

Low protein diet blunts the rise in glomerular gene expression in focal glomerulosclerosis.

The present study was designed to assess whether expression of mRNA for extracellular matrix (ECM) components, metalloproteinases (MMP) and tissue inhibitor of metalloproteinases (TIMP) in glomeruli is affected by a low protein diet during the course of focal glomerulosclerosis (FGS). Puromycin aminonucleoside (PAN) was injected intraperitoneally in rats and the right kidney was removed on day 22. Nephrotic rats received successive intraperitoneal injections of PAN on days 27, 34, and 41. Control rats were subjected to a nephrectomy or a sham operation on day 22. Animals were divided into six groups. In group 1, the PAN-injected rats were fed a standard diet containing 22% protein. In group 2, the PAN-injected rats were fed a low protein diet containing 6% protein, starting on the same day as the first PAN injection. In group 3, the nephrectomized rats without PAN were fed a standard diet. In group 4, the nephrectomized rats without PAN were fed a low protein diet for the same period. In group 5, the sham operated rats were fed a standard diet. In group 6, the sham operated rats were fed a low protein diet for the same period. Rats were sacrificed on days 0, 60 or 80 after the initial PAN or saline injection. The percentage of sclerotic glomeruli in group 1 rats increased markedly with time, reaching 77% on day 80. The mRNA levels encoding for alpha 1(I), alpha 1(III), alpha 1(IV) collagen chains, laminin B1 and B2 chains, heparan sulfate proteoglycan (HSPG), MMP-2, TIMP-1 and TIMP-2 increased significantly as glomerulosclerosis progressed, whereas MMP-1 and MMP-3 mRNA levels were unchanged, and no MMP-9 mRNA was detected throughout the experiments. In group 2, the low protein diet reduced the prevalence of glomerulosclerosis and attenuated the increased mRNA expression for ECM components, MMP-2, TIMP-1 and TIMP-2 in FGS glomeruli. In groups 3 through 6, mRNA levels for ECM components decreased with age, whereas those for MMPs and TIMPs changed little throughout the experiments. Immunofluorescence studies revealed the accumulation of types I, III and IV collagens, laminin, and HSPG in the sclerotic area and low protein diet attenuated the accumulation of these proteins. These data suggest that glomerulosclerosis may result from an imbalance among ECM components, MMPs and TIMPs and that a low protein diet attenuates the otherwise increased levels of mRNA for ECM components, MMP-2, TIMP-1 and TIMP-2 in glomerulosclerosis.

Animals↗
PubMed1994

Effect of monoclonal antibody CD4 on expression of intercellular adhesion molecule 1 in renal tissues of ddY mice: a spontaneous animal model of IgA nephropathy.

Immunofluorescence studies were performed to determine whether the expression of intercellular adhesion molecule 1 (ICAM-1) in ddY mice, a model for IgA nephropathy (Berger's disease), is influenced by treatment with a rat monoclonal antibody to murine CD4 molecules. The ddY mice were initially treated with intravenous injections, followed by weekly intraperitoneal injections of monoclonal antibody CD4. Using immunofluorescence, the mean intensity of IgA deposits in renal glomerular mesangial areas and capillary walls of the treated ddY mice was significantly lower than that in saline-treated control ddY mice of comparable ages. Marked expression of ICAM-1 was observed in glomerular capillary walls and mesangial areas in both control and treated ddY mice aged 40 and 70 weeks. The glomerular mesangial expansion in the treated ddY mice was milder than that found in the control ddY mice. No significant difference in glomerular cell proliferation between the treated and control ddY mice was observed. Although the infiltration of CD4+ T cells in glomeruli was slightly decreased after the treatment, that of CD8+ T cells and macrophages/monocytes was marked in both control and treated ddY mice aged 40 and 70 weeks. Thus, it appears that CD4+ T cells modulate the amount of IgA deposits in glomeruli, and other factors may be involved in the expression of ICAM-1 in glomeruli of IgA nephropathy in ddY mice.

Animals↗
PubMed1994

IgA deposits might not influence the production of extracellular matrix in glomeruli of ddY mice, a spontaneous animal model for IgA nephropathy.

Immunofluorescence studies were carried out to determine whether the expression of extracellular matrix (ECM) in glomeruli of ddY mice, a model for IgA nephropathy (Berger's disease), is influenced by treatment with a rat monoclonal antibody to murine CD4 molecules (mAb CD4). This mAb CD4 showed a selective decrease in the number of CD4+ T cells in the peripheral blood of ddY mice as described previously. The ddY mice were initially treated with intravenous injections, followed by weekly intraperitoneal injections of mAb CD4. In immunofluorescence, the mean intensity of IgA deposits in the renal glomerular mesangial areas and capillary walls of the treated ddY mice was significantly lower than that in saline-treated control mice at comparable ages. There was no significant difference in the distribution or intensity of ECM components, i.e. type IV collagen, fibronectin and heparan sulfate proteoglycan, in glomeruli between the mAB CD4-treated and the control ddY mice. In light microscopy, mesangial expansion in the treated ddY mice was milder than that found in the saline control mice. No significant differences in the average number of intraglomerular cells, levels of serum IgA and urinary protein between the treated and control ddY mice were observed. Thus, it appears that although CD4+ T cells modulate the amounts of glomerular IgA deposits, other factors may be involved in the expression of ECM in glomeruli of IgA nephropathy in ddY mice.

Animals↗
PubMed1994

Expression of intercellular adhesion molecule-1 and infiltration of lymphocytes in glomeruli of patients with IgA nephropathy.

Using immunofluorescence, we studied 19 patients with IgA nephropathy to determine whether the expression of intercellular adhesion molecule (ICAM)-1 in glomeruli might reflect the disease activity. The relationship between the expression of ICAM-1 and the infiltration of lymphocytes, monocytes and polymorphonuclear leukocytes (PMN) in glomeruli of IgA nephropathy cases was examined. The expression of ICAM-1 in patients in the advanced stage was significantly higher than that in patients in the mild stage. In double immunofluorescence, the distribution of ICAM-1 expression in glomeruli was different from that of IgA deposition in patients in both stages. Glomeruli which showed increases of ICAM-1 expression had marked infiltration of lymphocytes (OKT4+, OKT8+ T cells), and monocytes (OKM1+ cells). Increase of urinary protein and decreases in renal function were observed in patients in the advanced stage. It appears that the expression of ICAM-1 is closely linked to glomerular cell proliferation, and infiltration of lymphocytes and monocytes in patients with IgA nephropathy. However, the expression of ICAM-1 in glomeruli might not be correlated with IgA-dominant immune complexes in this disease.

Antibodies, Monoclonal↗
PubMed1994

Detection of glycosylated protein in renal tissues and dermal vascular vessels in the microalbuminuric stage of diabetic nephropathy using the nitro blue tetrazolium reaction.

Detection of glycosylated protein in renal and dermal tissues was performed in patients in the microalbuminuric stage of diabetic nephropathy using the nitro blue tetrazolium (NBT) reaction. The intensity of NBT staining in glomeruli and dermal vascular vessels was marked in the microalbuminuric stage as well as in the overtly proteinuric stage. The NBT staining in the renal and dermal vascular walls in both stages was significantly stronger than in the samples of control autopsy patients. It appeared that nonenzymatic glycosylation in various tissues, i.e. kidneys and dermal vascular vessels, had already progressed in the microalbuminuric stage in patients with diabetic nephropathy.

Adult↗