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Biomedical subjects

H Koide

Publications and source records attributed to H Koide.

At least 91 records · Page 5Linked to original sources
PubMed1997

[Isolation rate of Enterococcus spp. from surgical infections and their susceptibilities].

Enterococcus spp. isolated from surgical infections during the period from July 1982 to June 1995 were investigated in a multicenter study involving 19 hospitals in Japan, and the following results were obtained. 1. Though the isolation rate of Enterococcus faecalis and other Enterococcus spp. were not high from primary infections, and from postoperative infections the isolation rate of other Enterococcus spp. was also low, the isolation rate of E. faecalis was highest from postoperative infections after 1993. 2. Vancomycin (VCM) showed strongest activity against E. faecalis, and followed by those of ampicillin (ABPC), imipenem. levofloxacin (LVFX) and meropenem in this order. Against other Enterococcus spp., VCM showed strongest activity, and followed by those of ABPC and LVFX. There were no resistant strains against VCM.

Ampicillin↗
PubMed1996

Unfarnesylated transforming Ras mutant inhibits the Ras-signaling pathway by forming a stable Ras.Raf complex in the cytosol.

Farnesyltransferase inhibitors cause the growth arrest of ras-transformed cells, but not that of normal cells. To elucidate the mechanism of this differential effect, we examined the effect of accumulation of unfarnesylated Ras in the cytosol by using RasG12V,C186S and RasC186S, which mimic unfarnesylated form of the oncogenic and the normal Ras, respectively. We found that RasG12,C186S inhibited activation and membrane translocation of Raf by forming a stable complex with Raf in the cytosol. In contrast, RasC186S showed inhibitory effect on neither Raf activation nor Raf translocation. These results indicate that unfarnesylated oncogenic Ras interacts with Raf in the cytosol and inhibits its membrane translocation, a crucial step for the Raf activation, while unfarnesylated normal Ras does not.

Cell Line↗
PubMed1996

Molecular detection and differentiation of enteroviruses in endomyocardial biopsies and pericardial effusions from dilated cardiomyopathy and myocarditis.

Enteroviruses (EVs), especially group B coxsackieviruses, have been implicated in the pathogenesis of myocarditis and dilated cardiomyopathy (DCM). To determine whether a specific type of EV is present in DCM hearts, we examined the genotypes of EVs detected in endomyocardial biopsies and pericardial effusions by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis. Positive PCR results were obtained from biopsies in 6 (19 percent) of 31 patients with DCM, 5 (18 percent) of 28 with myocarditis, 5 (22 percent) of 23 with other cardiac diseases, and from pericardial effusions in 4 (57 percent) of 7 patients with pericarditis. SSCP profiles of most of the clinical samples were different and were not identical to any of the standard group B coxsackie viruses. Our findings suggest that EV genomes are involved in the myocardium of patients with various cardiac conditions and that a particular type of EV is not present in DCM hearts.

Adolescent↗
PubMed1996

Increased mRNA expression of metalloproteinase-9 in peripheral blood monocytes from patients with immunoglobulin A nephropathy.

We examined metalloproteinase (MMP)-1, -2, -3, and -9 mRNA expression by peripheral blood monocytes from 50 patients with immunoglobulin A (IgA) nephropathy, 20 with membranous nephropathy, 10 with minimal-change nephrotic syndrome, five with focal glomerulosclerosis, 30 with non-IgA proliferative glomerulonephritis, and 40 healthy normal controls who were comparable with regard to age and sex. Monocytes from patients with IgA nephropathy expressed a higher level of MMP-9 mRNA than those from patients with other forms of glomerulonephritis or from healthy controls (MMP-9 to glyceraldehyde-3-phosphate dehydrogenase ratio: IgA nephropathy, 1.68 +/- 0.24; membranous nephropathy, 0.22 +/- 0.08; minimal-change nephrotic syndrome, 0.24 +/- 0.06; focal glomerulosclerosis, 0.32 +/- 0.08; non-IgA proliferative glomerulonephritis, 0.30 +/- 0.12; and healthy controls, 0.16 +/- 0.04). When the biopsy specimens were classified into four grades according to the severity of glomerular and interstitial pathology, highly significant differences were observed among MMP-9 mRNA levels in monocytes from all four groups of patients with IgA nephropathy (grade I, 0.44 +/- 0.09; grade II, 1.06 +/- 0.26; grade III, 2.22 +/- 0.68; grade IV, 2.86 +/- 0.88). In addition, MMP-9 mRNA levels from patients with IgA nephropathy correlated with urinary protein excretion (P < 0.001). However, we detected minimal mRNA expression of MMP-1, -2, and -3 by peripheral blood monocytes from patients with IgA nephropathy or other forms of glomerulonephritis and from normal healthy controls. Our results suggest that increased MMP-9 mRNA expression in circulating monocytes may contribute to the progression of IgA nephropathy.

Adult↗
PubMed1996

Re-evaluation of foot process effacement in acute puromycin aminonucleoside nephrosis.

The sequence of morphological changes during foot process effacement in acute puromycin aminonucleoside (PAN) nephrosis was examined by means of NaOH maceration and freeze cracking for scanning electron microscopy (SEM). The micrographs of SEM and those of transmission electron microscopy (TEM) were quantitatively analyzed by computerized morphometry, and were correlated with renal function. On day 2 after PAN injection, the slit length was moderately decreased by both shortening and degradation of the foot processes. On day 4, membrane-bounded vesicles were scattered in the lamina rara externa. During foot process effacement, the basal surface of podocytes developed palm-like domains that represented the cytoplasmic areas between interdigitation. The decrease in the length of podocyte cell borders paralleled the decrease of 24-hour creatinine clearance. The development of the palm-like domains on the basal aspects of podocytes estimated by distance class analysis was closely correlated with the sudden onset of proteinuria. We conclude that foot process effacement in PAN nephrosis caused by the retraction and degradation of foot processes leads to the development of palm-like domains, which is correlated with podocyte detachment as well as massive proteinuria.

Animals↗
PubMed1996

Effect of a specific endothelin receptor A antagonist on glomerulonephritis of ddY mice with IgA nephropathy.

The present study assessed renal endothelin (ET)-1, ET-3, and ET receptor A and B mRNA levels in ddY mice at 8, 40, and 60 weeks of age. The renal mRNA levels of ET-1 increased significantly in ddY mice as their nephritis progressed, reaching a 6.6-fold (p < 0.01) higher level by 60 weeks than in control ICR mice. Renal ET-3 mRNA levels, however, remained unchanged. The renal mRNA levels of ET receptor A and B in ddY mice increased gradually with the progression of nephritis, reaching 4.8- (p < 0.01) and 3.6-fold (p < 0.01) higher levels, respectively, at 60 weeks of age than found in control ICR mice. A positive correlation was noted between ET-1 and ET receptor mRNA levels and histopathological changes in renal tissues. In addition, we assessed whether a specific ET receptor A antagonist, FR 139317, affects the progression of glomerulonephritis in ddY mice. At 24 weeks of age (before glomerulonephritis developed), ddY mice were divided into two groups that received intraperitoneally either FR139317 or its vehicle (saline) daily for 36 weeks. The development of histopathological lesions and urinary protein excretion were suppressed by FR139317 treatment. These data suggest that ET families play a role in the progression of glomerulonephritis and that FR139317 treatment can be used therapeutically in ddY mice with IgA nephropathy.

Age Factors↗
PubMed1996

Modulation of endothelin family gene expression in renal hypertrophy.

The present study was designed to assess how the renal expression of mRNA for endothelin (ET) families is regulated during compensatory renal hypertrophy in rats. ET family gene expression was studied in the contralateral kidney of uninephrectomized and sham-operated rats. Rats were sacrificed at 0, 1, 3, 6, 12, adn 24 h after unilateral nephrectomy of the sham operation. Three hours after the left nephrectomy, ET-1 and ET receptor B mRNA levels in the renal cortex increased significantly (ET-1, 10.6-fold compared to those in sham-operated rats, p < 0.001, and ET receptor B, 6.8-fold, p < 0.001), and then decreased gradually to the control level after 24 h; in contrast, ET-3 and ET receptor A mRNA levels demonstrated little change throughout the experiment. We additionally measured the plasma ET concentration and renal ET-1 production following unilateral nephrectomy. ET-1 levels in the renal cortex increased gradually, with a peak 6 h after nephrectomy (3.6-fold compared to those in sham-operated rats, p < 0.01), and then decreased to the control level after 24 h. However, plasma ET-1 levels demonstrated little change until after 24 h. The glomerular expression of ET-1 and ET receptors A and B mRNA demonstrated minimal change throughout the experimental period. Glomerular ET-3 mRNA expression were detected in neither the unilateral nephrectomy nor the sham-operated rats. Our results indicate that the time course of the mRNA expression of ET-1 and ET receptor B differs from that of ET-3 and ET receptor A in the renal cortex, and that glomerular mRNA levels for ET families are not associated with renal hypertrophy in the early stages following unilateral nephrectomy.

Animals↗
PubMed1996

Cigarette smoking and silent brain infarction in normal adults.

We investigated the relationship between cigarette smoking and silent brain infarction in 365 neurologically normal male Japanese subjects (smokers: 119, nonsmokers: 246). Silent brain infarction was identified in 32 (26.9%) of 119 smokers and in 54 (22.8%) of 246 nonsmokers. Mild or moderate periventricular hyperintensity was presented in 27 smokers (22.7%) and 54 nonsmokers (22.8%). There was no significant difference in the regional cerebral blood flow or the average systolic, diastolic, and mean arterial blood pressures between groups. The HDL-cholesterol level was significantly lower in smokers than in nonsmokers (p < 0.01). Cigarette smoking was not related to the incidence of silent brain infarction or leuko-araiosis in healthy adults in Japan.

Cerebral Infarction↗
PubMed1996

[Influence of social environments on brain aging].

To investigate influence of social activity on normal brain aging, we studied the social activity score, cognitive functions, self-rating depression scale, cerebral blood flow (CBF), MRI and motor function in the normal elderly people living in different social environments. There was no difference in risk factors for stroke, MRI findings and CBF between the two groups. However, the subjects living in a home for elderly showed significantly lower social activities than those living with families. Cognitive functions and motor function were lower, and SDS was higher in subjects living in retirement house than those living with families. The social environment including social activities closely related to life style may significantly influence brain aging with regard to silent brain infarctions or risk factors for stroke.

Aged↗
PubMed1996

Alteration of growth-related proto-oncogene expression in diabetic glomeruli by a specific endothelin receptor A antagonist.

BACKGROUND: The early phase of glomerular growth in diabetic rats is accompanied by increased c-fos and c-jun expression. The renal endothelin (ET)-1 mRNA levels increased with the progression of diabetic nephropathy. This study was designed to assess whether glomerular mRNA expression of growth-related proto-oncogenes in diabetic rat glomeruli is affected by a specific ET receptor A antagonist, FR139317. METHODS: Diabetes was produced by streptozotocin (STZ) injection. Animals were divided into four groups: (1) untreated diabetic rats (n = 25); (2) FR139317-treated diabetic rats (n = 20); (3) control non-diabetic rats (n = 20); and (4) FR139317-treated controls (n = 20). FR139317 treatment was continued for 24 weeks. c-myc, c-fos, c-jun and proliferating cell nuclear antigen (PCNA) mRNA expression in rat glomeruli from each group (n = 7) at 4, 12 and 24 weeks after STZ or saline injection was evaluated. RESULTS: Glomerular mRNA levels for c-myc, c-fos, c-jun and PCNA in group 1 increased with the progression of diabetic nephropathy (24 weeks: c-myc, 4.6-fold; c-fos, 3.8-fold; c-jun, 4.2-fold; and PCNA, 4.4-fold). FR139317 treatment attenuated increases in glomerular mRNA levels of these genes (24 weeks, c-myc, 0.4-fold; c-fos, 0.4-fold; c-jun, 0.5-fold; and PCNA, 0.4-fold) in group 2. However, FR139317 did not affect mRNA levels in control glomeruli. CONCLUSIONS: These data suggest that FR139317 may protect against glomerular injury of diabetes in rats by reducing mRNA levels of growth-related genes.

Animals↗
PubMed1996

Effect of a low-protein diet on expression of non-muscle type myosin heavy-chain isoforms in glomeruli of rats with puromycin aminonucleoside nephrosis.

BACKGROUND: We reported that an embryonic type of non-muscle-type myosin heavy-chain isoform (SMemb) may be a molecular marker for phenotypic alteration in initial glomerular injury and that methyl-prednisolone has no effect on SMemb expression in glomeruli of rats with puromycin aminonucleoside (PAN) nephrosis. The present study was designed to assess whether SMemb mRNA and protein expression in glomeruli are affected by a low-protein diet in rats with PAN-induced nephrosis and in control rats. METHODS: Rats were divided into four groups: group 1, PAN-injected rats fed a standard diet containing 22% protein; group 2, PAN-injected rats fed a low-protein diet containing 6% protein, starting on the day of PAN injection; group 3, control rats fed a standard diet; group 4, control rats fed a low-protein diet for the same period. We prepared glomerular RNA and performed Northern blot analysis and immunohistochemistry in all groups. RESULTS: Glomerular SMemb mRNA increased on days 2 and 4 (prior to and soon after the onset of proteinuria), but declined on day 8 (the peak of proteinuria). Myosin heavy-chain protein expression was evaluated immunohistochemically by use of three antibodies against SM1, SM2, and SMemb. SM1 and SM2 were absent from the glomeruli of rats with PAN 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 PAN nephrosis. In the latter condition, the number of SMemb-positive glomerular epithelial cells increased on days 3 and 4, then decreased in subsequent days. Moreover, some mesangial cells became SMemb-positive transiently, returning to barely detectable levels on day 20. In addition, alpha-smooth-muscle actin, type I and III collagens were absent from the glomeruli of rats with PAN nephrosis until day 20. Urinary protein excretion was markedly suppressed by the 6% protein diet in PAN nephrosis. The low-protein diet reduced the increased mRNA expression of SMemb as well as the increased number of SMemb-positive cells in the glomeruli of rats with PAN nephrosis. However, the low-protein diet did not affect SMemb mRNA and protein levels in the glomeruli of control rats. CONCLUSIONS: In rats with PAN nephrosis, findings suggest that restriction of dietary protein leads to a reduction in glomerular SMemb expression.

Animals↗
PubMed1996

Effect of probucol on mRNA expression of glomerular antioxidant enzymes in rat with subtotal nephrectomy.

OBJECTIVE: To investigate 1) the glomerular mRNA expression and protein activity of antioxidant enzymes (AOEs) including superoxide dismutase (SOD) and glutathine peroxidase (GSH-Px) and the glomerular content of lipid peroxide-malondiadehyde (MDA), 2) the effects of probucol (P), a potent antioxidant agent on these AOEs and MDA levels, in the chronic phase of subtotal nephrectomized rats. METHODS: The adult male Spregue-Dawley rats were randomly divided into three groups at the first week after subtotal renal ablation. Group 1 was sham rats (sham n = 8), group 2 underwent 5/6 nephrectomy without special therapy (5/6 Nx n = 8), and group 3 with 5/6 nephrectomy received probucol (5/6 Nxs+P n = 8) at a dose of 1% in the rat chow. At the 12th week after P was administrated, all of the rats were sacrificed to remove left kidney for the determination of glomerular level of MDA, activity of SOD, and GSH-Px, glomerular mRNA expression of AOEs by Northern blot analysis as well as a histological examination. RESULTS: In 5/6 Nx, serum cholesterol, proteinuria increased and creatinine clearance decreased progressively with age as compared with that in sham. Those abnormalities as well as glomerulosclerosis index (GI) ameliorated with the administration of probucol at the 12th week after subtotal nephrectomy [GI: sham 3.12 +/- 1.20, P < 0.01 vs 5/6 Nx 5/6 Nx 188.6 +/- 25.1; 5/6 Nx +/- P, 106.9 +/- 17.6, P < 0.05 vs 5/6 Nx]. The probucol therapy also significantly improved the decrease of glomerular Mn-SOD and GSH-Px both at mRNA level and protein activity and the increase of glomerular MDA content. CONCLUSIONS: We demonstrated a deficiency of glomerular AOEs in the chronic phase of remnant kidney, which may contribute to the progression of renal injury. The protective effects of probucol on both renal functional impairment and the development of glomerulosclerosis may be partially associated with improving surviving glomerular AOEs.

Animals↗
PubMed1995

Inhibition of Ras/Raf interaction by anti-oncogenic mutants of neurofibromin, the neurofibromatosis type 1 (NF1) gene product, in cell-free systems.

The neurofibromatosis type 1 (NF1) gene encodes a protein, neurofibromin, containing GTPase-activating protein-related domain (GRD) that stimulates intrinsic GTPase activity of Ras protein. By screening a randomly mutagenized NF1-GRD library in Saccharomyces cerevisiae, we isolated two NF1-GRD mutants (NF201 and NF204) with single amino acid substitutions, which suppress the heat shock-sensitive phenotype of the RAS2(G19V) mutant. The NF1-GRD mutants also suppress the oncogenic Ras-induced transformation of NIH 3T3 mouse fibroblasts (Nakafuku, M., Nagamine, M., Ohtoshi, A., Tanaka, K., Toh-e, A., and Kaziro, Y. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 6706-6710). In this paper, we investigated the molecular mechanism of inhibition of the transforming Ras-specific function by the NF1-GRD mutants in mammalian cells. In human embryonic kidney (HEK) 293 cells, the mutant NF1-GRDs attenuated the stimulation of mitogen-activated protein kinase by Ras(G12V), but not by platelet-derived growth factor. In cell-free systems, purified recombinant NF1-GRD mutants showed an inhibitory effect on the association of Ras.guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) with Raf at several times lower concentrations than the wild type. Furthermore, it was revealed that the binding affinity of the mutant NF1-GRDs toward Ras.GTP gamma S is approximately 5-10 times higher than the wild type. These results suggest that the mutant NF1-GRDs tightly bind to an oncogenic Ras in its GTP-bound active conformation and block the interaction between Ras and its effector, Raf.

3T3 Cells↗
PubMed1995

Guanidinoacetic acid (GAA) synthesis in rat tubular suspension as a system for evaluating gentamicin (GM) nephrotoxicity.

Since guanidinoacetic acid (GAA), a precursor of creatine, is synthesized mainly in the proximal tubule of the kidney where gentamicin (GM) nephrotoxicity often occurs, GM-induced renal cell damage was investigated using GAA synthesis in tubular suspension as an indicator. Results obtained were as follows: (1) GAA synthesis was significantly suppressed with 1 mM GM; (2) GM-induced decrease in GAA synthesis was recognized during incubation longer than 15 min; (3) furosemide significantly enhanced the suppression of GAA synthesis by GM. The results obtained parallel with those in the whole animal thus making GAA synthesis in tubular suspension a valid system for evaluating the GM-induced proximal tubular damage.

Animals↗
PubMed1995

Analysis of enterovirus genotypes using single-strand conformation polymorphisms of polymerase chain reaction products.

Enterovirus genotypes were identified rapidly by reverse (RT-PCR) followed by single-strand conformation polymorphism (SSCP) analysis. The primer pair was chosen from the highly conserved sequence at the 5' non-coding region of enterovirus genomes. RT-PCR amplified a 154 bp sequence in all samples from 14 serotypes of enteroviruses, including group A and B Coxsackie viruses, echoviruses and polioviruses. SSCP analysis of these products revealed different electrophoretic profiles. Thus, SSCP analysis will be useful for differentiating the genotypes of enteroviruses, and may be applicable for rapid diagnosis of enteroviral infection.

Base Sequence↗
PubMed1995

Effect of a specific endothelin A receptor antagonist on murine lupus nephritis.

The present study was designed to assess whether a specific endothelin A (ETA) receptor antagonist, FR139317, affects the progression of lupus nephritis and affects transcription of mRNA for extracellular matrix (ECM) components, metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP)-1, and accumulation of ECM proteins in the renal cortex of NZB/W F1 mice. mRNA levels for alpha 1(I), alpha 1(III), alpha 1(IV) collagen chains, laminin B1 and B2 chains, heparan sulfate proteoglycan (HSPG), MMP-1, -2, -3, and TIMP-1 increased significantly as nephritis progressed in NZB/W F1 mice. At 48 weeks of age, the levels of mRNA for alpha 1(I), alpha 1(III), alpha 1(IV) collagen chains, laminin B1 and B2 chains, HSPG, MMP-1, -2, -3, and TIMP-1 were increased by 5.6- (P < 0.001), 3.6- (P < 0.01), 6.8- (P < 0.001), 5.2- (P < 0.001), 5.0- (P < 0.001), 6.0- (P < 0.001), 7.6- (P < 0.001), 4.2- (P < 0.01), 8.2- (P < 0.001), and 15.2-fold (P < 0.001), respectively, in the renal cortex of NZB/W F1 mice compared to NZW mice. Immunofluorescence microscopy showed that the accumulation of collagens I, III, and IV, laminin, and HSPG in the renal cortex of NZB/W F1 mice increased markedly with the progression of nephritis. At 20 weeks of age, NZB/W F1 and NZW mice were divided into two groups that received either FR139317 or its vehicle (saline) intraperitoneally, daily, for 28 weeks. The development of histological lesions, proteinuria, hypertension, accumulation of collagens I, III, and IV, laminin, and HSPG in the renal cortex of NZB/W F1 mice were suppressed by FR139317 treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Effects of a low-protein diet on glomerular endothelin family gene expression in experimental focal glomerular sclerosis.

1. The present study was designed to assess whether glomerular expression of mRNAs for endothelin-1 and endothelin-3, as well as endothelin receptors A and B is affected by a low-protein diet during the course of focal glomerular sclerosis. 2. Focal glomerular sclerosis was induced in rats by injection of puromycin aminonucleoside on days 0, 27, 34 and 41 in conjunction with unilateral nephrectomy on day 22. Control rats were subjected to nephrectomy or sham operation on day 22. 3. Animals were divided into six groups. In group 1, the puromycin aminonucleoside-injected rats were fed a standard diet containing 22% protein. In group 2, the puromycin aminonucleoside-injected rats were fed a low-protein diet containing 6% protein, which was initiated on the day of the first puromycin aminonucleoside injection. In group 3, the nephrectomized rats without puromycin aminonucleoside were fed a standard diet. In group 4, the nephrectomized rats without puromycin aminonucleoside were fed a low-protein diet. 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. 4. The percentage of sclerotic glomeruli in group 1 rats increased markedly with time, reaching 77% on day 80. 5. The glomerular mRNA levels for endothelin-1 and endothelin receptors A and B increased significantly as glomerular sclerosis progressed, whereas no endothelin-3 mRNA was detected in the glomeruli of any group. The endothelin-1 production in isolated glomeruli from group 1 increased significantly as glomerular sclerosis progressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗