Search PubMed⌕ Search

Biomedical subjects

S Okuda

Publications and source records attributed to S Okuda.

At least 163 records · Page 9Linked to original sources
PubMed1992

[Proposal for the nosocomial infection control of methicillin-resistant Staphylococcus aureus (MRSA)].

To determine the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in hospital environments, quantitative isolation of MRSA from environmental and human specimens was performed. It was found that as many as 6 x 10(4) colony forming units (CFU)/100cm2 of MRSA and also methicillin-resistant coagulase-negative Staphylococcus (MRCNS) were isolated from 1) 25-100% of the bed-mattresses tested in 10 out of 11 (90%) hospitals, and also 2) bed sheets for patients, floors of patient wards, laundry, bath-room, toilet and laundry storage-room. And seven and eight palms of 20 patients were contaminated with MRCNS and MRSA, respectively, and MRCNS contamination was revealed in six of medical staffs. These results indicate that hospital environments, especially the mattresses and hospital floors are highly contaminated with MRCNS and MRSA, and sanitation and cleanliness of mattresses and floors are necessary to prevent the dissemination of both MRCNS and MRSA in hospital.

Cross Infection↗
PubMed1992

Inhibition of acyl-CoA: cholesterol acyltransferase activity by cyclodepsipeptide antibiotics.

The effect was studied of the fungal cyclodepsipeptide antibiotics beauvericin and seven distinct enniatins on acyl-CoA: cholesterol acyltransferase (ACAT) activity. In an enzyme assay using rat liver microsomes, all the compounds were found to inhibit ACAT activity. The drug concentration that caused 50% inhibition (IC50 value) of the enzyme activity was determined to be 3.0 microM for beauvericin, indicating that the compound is one of the most potent ACAT inhibitors of microbial origin. Enniatins exhibited much higher IC50 values of 22 to 110 microM. More hydrophobic enniatins showed more potent inhibitory activity. Furthermore, the ACAT inhibitory activity was evaluated as inhibition of cholesteryl ester formation in a cell assay using J774 macrophages. Calculation of the ratio, CD50 value (the drug concentration causing 50% cell damage)/IC50 value of cholesteryl ester formation, indicated that beauvericin shows the highest specificity. These data indicate that beauvericin is one of the most potent and specific ACAT inhibitors of microbial origin.

Animals↗
PubMed1992

[Evaluation of chromo-endoscopy for diagnosis of histological repair of gastric ulcer].

The chromoendoscopic features of healed gastric ulcers were investigated by the methylene blue test. Histological repair of healed ulcers was graded as either Ul3 (incompletely healed) or Ul4 (completely healed). Endoscopically, the Ul4 scar was observed as a flat granular area without any depression, and sometimes associated with redness, the Ul3 scar was observed as a distinct depression in the surrounding normal mucosal surface, and usually associated with homogenous redness. Follow-up studies of patients with Ul4 and Ul3 lesions showed that recurrence was significantly rare in patients with the Ul4 lesion than in patients with the Ul3 lesions. These findings indicate that healing of gastric ulcers should be defined endoscopically as crater disappearance. At 8 weeks after treatment with omepral, most of the ulcers were healed, but judged a as Ul3 scar.

Adenosine Triphosphatases↗
PubMed1992

Effects of a new calcium antagonist, manidipine, on the renal hemodynamics and the vasoactive humoral factors in patients with diabetes mellitus.

The effects of manidipine (10 mg/day for 7 days) on the renal hemodynamics and vasoactive humoral factors were examined in 6 adults with diabetes mellitus (DM). Mean duration of DM was 9 +/- 2 years; serum creatinine concentration was 0.9 +/- 0.04 mg/dL. Plasma endothelin-1 (ET-1) concentration was 5.4 +/- 0.7 pg/mL before manidipine, compared with 1.9 +/- 0.2 pg/mL in 14 controls (p = 0.03%). Systolic and mean blood pressure decreased significantly during treatment without changes in glomerular filtration rate, renal plasma flow, or filtration fraction. Renal vascular resistance tended to decrease and fractional excretion of sodium significantly increased from 1.35 +/- 0.27% to 2.06 +/- 0.47 (p = 2.96%). ET-1 significantly decreased from 5.4 +/- 0.7 pg/mL to 3.5 +/- 0.6 (p = 2.95%), while plasma angiotensin II, atrial natriuretic factor, urinary excretion rate of ET-1, and albumin excretion rate did not change. Manidipine lowers blood pressure without adversely affecting renal function in diabetic patients. Manidipine, which lowers ET-1, may protect from progressive renal injury in diabetics.

Adult↗
PubMed1992

Albuminuria is not an aggravating factor in experimental focal glomerulosclerosis and hyalinosis.

It is widely known that the severity of glomerular sclerosis is proportional to the degree and chronicity of proteinuria and that the degenerative changes of glomerular epithelial cells that are associated with overflow albuminuria can be experimentally induced by the injection of large quantities of heterologous albumin. Such evidence suggests that autologous albuminuria per se may have a harmful effect on the kidneys. To examine the cause and effect relationship between renal lesions and albuminuria, we produced Adriamycin-induced experimental focal glomerular sclerosis in Nagase analbuminemic (NA) rats and control Sprague-Dawley (SD) rats and observed both the renal functional and histologic changes for 20 weeks. At week 4 after injection of Adriamycin glomerular epithelial lesions including foot process fusion were similarly revealed by an electron microscopic study in both groups in spite of the presence of a large difference in the amount of proteinuria (SD rats: 491 +/- 84 mg/day, NA rats: 43 +/- 30 mg/day) and albuminuria (SD rats: 383 +/- 73 mg/day, NA rats: 2 +/- 1 mg/day). At week 20, a light microscopic study showed the same degree of glomerular sclerosis and hyalinosis and tubulointerstitial changes associated with a decrease in inulin clearance in both groups. The increased glomerular accumulation of immunoglobulin M or complement 3 and glomerular trapping of aggregated human immunoglobulin G were also similar between the SD and NA groups. In summary, renal destruction of Adriamycin-nephropathy was not dependent on the degree of albuminuria. These results suggest that albuminuria is not an aggravating factor in focal glomerulosclerosis.

Albumins↗
PubMed1992

[Role of TGF-beta in glomerular diseases].

Accumulation of extracellular matrix (ECM) is a major histological change in glomerular diseases that progress to chronic renal failure. Such accumulation can be mediated by increased production of molecular signal such as cytokines. Transforming growth factor beta 1 (TGF-beta 1) has a combined effect of enhancing the synthesis of ECM, while inhibiting the proteolytic degradation of newly formed matrix proteins. TG1-F beta 1 has stimulative effects on the production of ECM by cultured rat mesangial cells. In an experimental glomerulonephritis, there was a close association between elevated expression of the TGF-beta 1 mRNA and development of glomerulonephritis. Treatment of glomerulonephritic rats with antiserum directed to a synthetic peptide from mature TGF-beta 1 prevented the histological accumulation of ECM in glomeruli. These results suggest that TGF-beta 1 may participate in glomerular matrix expansion.

Animals↗
PubMed1991

Inhibition by the dopamine antagonist haloperidol of experimental carcinogenesis induced by azoxymethane in rat colon.

The effects of the dopamine agonist bromocriptine and antagonist haloperidol on the incidence and histology of colon tumors induced by azoxymethane and on the labeling index of colon mucosa were investigated in Wistar rats. Rats received weekly s.c. injections of 7.4 mg/kg of body weight azoxymethane for 10 weeks and s.c. injections of 2 mg/kg of body weight bromocriptine or 2 mg/kg of body weight haloperidol, in depot form, every other day until the end of the experiment in week 30. Administration of haloperidol resulted in a significant decrease in the incidence of colon tumors. It also caused a significant decrease in the incidence of adenocarcinomas, with 75% of the tumors being adenomas, and in the labeling index of the colon epithelial cells. In contrast, bromocriptine had no influence on the incidence or histology of colon tumors or the labeling index of the colon mucosa. These findings indicate that the dopamine antagonist haloperidol inhibits colon carcinogenesis and that this effect may be related to its effect in decreasing the proliferation of colon epithelial cells.

Adenocarcinoma↗
PubMed1991

Dietary protein restriction rapidly reduces transforming growth factor beta 1 expression in experimental glomerulonephritis.

Dietary protein restriction has been shown to slow the rate of loss of kidney function in humans with progressive glomerulosclerosis due to glomerulonephritis or diabetes mellitus. A central feature of glomerulosclerosis is the pathological accumulation of extracellular matrix within the diseased glomeruli. Transforming growth factor beta 1 (TGF-beta 1) is known to have widespread regulatory effects on extracellular matrix and has been implicated as a major cause of increased extracellular matrix synthesis and buildup of pathological matrix within glomeruli in experimental glomerulonephritis. In the present study, it is shown that administration of a low protein diet to rats rapidly reduces the elevated expression of TGF-beta 1 mRNA and TGF-beta 1 protein that is known to occur within glomeruli after induction of glomerulonephritis. Compared to a normal protein diet, glomerulonephritic rats receiving the low protein diet did not develop an increase in glomerular extracellular matrix and showed significantly less proteinuria. Glomeruli isolated from glomerulonephritic rats fed the normal protein diet showed a marked increase in proteoglycan synthesis on day 7 of disease and were demonstrated to be secreting increased amounts of TGF-beta 1 into the medium, whereas glomeruli at the same point in time isolated from rats on a low protein diet showed no increase in proteoglycan production or TGF-beta 1 secretion. These results suggest that a mechanism of the rapid therapeutic effect of a low protein diet on experimental glomerulonephritis is through suppression of TGF-beta 1 expression and prevention of the induction of extracellular matrix synthesis within the injured glomeruli.

Animals↗
PubMed1991

Enhancement by methionine enkephalin of colon carcinogenesis induced by azoxymethane.

The effect of the opioid receptor agonist methionine enkephalin (Met-enkephalin) and the opioid receptor antagonist naloxone on colonic carcinogenesis induced by azoxymethane was investigated in Wistar rats. Rats received ten weekly injections of 7.4 mg/kg of body weight of azoxymethane and injections of Met-enkephalin (50 micrograms/kg of body weight), naloxone (2 mg/kg of body weight), or Met-enkephalin (50 micrograms/kg of body weight) plus naloxone (2 mg/kg of body weight) once every 2 days. In wk 40, the group treated with Met-enkephalin had a significantly increased incidence of colonic tumors. A combination of Met-enkephalin and naloxone attenuated the enhancing effect by Met-enkephalin on the development of colonic tumors. Administration of naloxone alone had no influence on colonic tumorigenesis. During and after administration of the carcinogen, the bromodeoxyuridine-labeling indices of the colon mucosa and/or cancers were significantly increased in rats treated with Met-enkephalin. However, a combination of Met-enkephalin and naloxone significantly decreased the labeling indices of the colon mucosa and/or cancers. These findings indicate that Met-enkephalin enhanced colon carcinogenesis and that naloxone attenuated this enhancement. Because naloxone is an opioid receptor antagonist, these findings also indicate that the enhancing effect of Met-enkephalin on colon carcinogenesis may be mediated through opioid receptors.

Adenocarcinoma↗
PubMed1991

Chronic tubulointerstitial changes induced by germanium dioxide in comparison with carboxyethylgermanium sesquioxide.

Chronic nephrotoxicity was investigated in rats orally administered germanium dioxide (GeO2) and carboxyethylgermanium sesquioxide (Ge-132) for 24 weeks. Increased BUN and serum phosphate as well as decreased creatinine clearance, weight loss, anemia and liver dysfunction were apparent at week 24 only in the GeO2 treated group. Vacuolar degeneration and granular depositions were observed by light microscope in the degenerated renal distal tubules in the rats of this group, with the semiquantitative scores of tubular degeneration being 95 +/- 9% in the GeO2 group, 3 +/- 1% in the Ge-132 group and 1 +/- 1% in the control group, respectively. Electron microscopy revealed electron-dense inclusions in the swollen mitochondrial matrix of the distal tubular epithelium in the GeO2 group. Although systemic toxicities were reduced after GeO2 was discontinued at week 24, renal tubulointerstitial fibrosis became prominent even at week 40 (16 weeks after discontinuation). A Ge.K alpha X-ray spectrum was clearly demonstrated in the mitochondrial matrix of the distal tubular epithelium in the GeO2 group with the help of electron probe X-ray microanalysis. On the other hand, neither toxic effects nor renal histological abnormalities were manifested in either the Ge-132 or the control group. The renal tissue content of germanium was high at weeks 24 and 40 in the GeO2 group. From these results, it is concluded that GeO2 causes characteristic nephropathy while Ge-132 does not. In addition, it appears that residual GeO2 remains for a considerably long time even after the cessation of GeO2 intake.

Animals↗
PubMed1991

Advantage of early initiation of aluminum hydroxide administration for the prevention of experimental progressive renal disease.

Aluminium hydroxide, a phosphate binder, is regarded as a strong candidate to halt the progression of chronic renal disease. In order to determine the most effective time to start treatment, aluminium hydroxide was administered either immediately (ADR-0w), or at 8 weeks (ADR-8w) or 16 weeks (ADR-16w) after repeated injection of Adriamycin (ADR) inducing glomerular sclerosis. In the aluminium hydroxide-untreated group the survival rate at the end of the experiment was 50%, while the early initiation of aluminium hydroxide (ADR-0w) resulted in a greater survival rate of 90%. Serum phosphate concentration and serum calcium-phosphate product were significantly less in the aluminium hydroxide groups (ADR-0w, 8w, 16w) than in the untreated group after week 20. Urinary protein excretion was significantly less in the ADR-0w and ADR-8w groups at week 12 or 16 compared to the aluminium hydroxide-untreated group. Blood urea nitrogen in the aluminium hydroxide groups was significantly less than that in the untreated group at week 34. Histological examination revealed that glomerular sclerosis was less severe in the ADR-0w and ADR-8w groups than in the aluminium hydroxide-untreated group, and glomerular hypertrophy was significantly decreased in the ADR-0w group. We conclude that early treatment with aluminium hydroxide was effective in preventing renal deterioration in focal glomerular sclerosis induced by Adriamycin.

Aluminum Hydroxide↗
PubMed1991

Dose dependency of germanium-dioxide-induced nephrotoxicity in rats.

The dose dependency of germanium dioxide(GeO2)-induced nephrotoxicity was investigated experimentally in rat groups orally treated with high (150 mg/kg/day), moderate (75 mg/kg/day), or low (37.5 mg/kg/day) doses of GeO2, and in an untreated group. Renal dysfunction, indicated by the increase of blood urea nitrogen and the decrease of creatinine clearance, and systemic toxicity by weight loss, anemia, and hypoproteinemia were more apparent in rats treated with higher dose of GeO2. Urinalysis including daily urinary protein excretion did not reveal any abnormalities in any of the groups. Urinary excretion and renal-tissue content of Ge were significantly elevated in the group of the higher dose of GeO2. Light microscopically, vacuolar degeneration and depositions of granules positive for periodic acid-Schiff in distal tubules were predominant in the higher-dose group of GeO2. The present study demonstrates that GeO2-induced nephrotoxicity develops dose dependently.

Animals↗
PubMed1991

Purpactins, new inhibitors of acyl-CoA:cholesterol acyltransferase produced by Penicillium purpurogenum. I. Production, isolation and physico-chemical and biological properties.

Penicillium purpurogenum FO-608, a soil isolate, was found to produce a series of new inhibitors of acyl-CoA:cholesterol acyltransferase (ACAT). Three active compounds, designated purpactins, A, B and C, were isolated from the fermentation broth of the producing strain by solvent extraction, silica gel column chromatography and HPLC. Purpactins inhibit ACAT activity in an enzyme assay system using rat liver microsomes with IC50 values of 121 approximately 126 microM. Purpactin A also inhibited cholesterol ester formation in J 774 macrophages, indicating the inhibition of ACAT activity in the living cells by purpactin A.

Animals↗
PubMed1991

Purpactins, new inhibitors of acyl-CoA:cholesterol acyltransferase produced by Penicillium purpurogenum. II. Structure elucidation of purpactins A, B and C.

The structure of purpactins, novel acyl-CoA:cholesterol acyltransferase (ACAT) inhibitors, was determined by spectroscopic analyses. Purpactin A was deduced to be 3-1'-acetoxy-11-hydroxy-4-methoxy-9-methyl-3'-methylbutyl-5H, 7H-dibenzo[b,g]-1,5-dioxocin-5-one, purpactin B was 5-1''-acetoxy-6'-hydroxymethyl-4-methoxy-4'-methyl-3''-methylbutyl-spiro [benzofuran-2,1'-cyclohexa-3',5'-diene]-2',3(2H)-dione and purpactin C was 5-1''-acetoxy-6'-formyl-4-methoxy-4'-methyl-3''-methylbutyl-spiro [benzofuran-2,1'-cyclohexa-3',5'-diene]-2',3(2H)-dione. Purpactin A was attributed to 1'-O-acetylpenicillide.

Benzofurans↗
PubMed1991

Purpactins, new inhibitors of acyl-CoA:cholesterol acyltransferase produced by Penicillium purpurogenum. III. Chemical modification of purpactin A.

Acylated derivatives of the C-1' and/or C-11 hydroxy group(s) of penicillide were synthesized and their inhibitory activity against acyl-CoA:cholesterol acyltransferase (ACAT) was studied. Introduction of long acyl group into either or both hydroxy residue(s) decreased the inhibitory activity. A small acyl moiety such as acetyl or n-butyryl at the C-1' hydroxy group is responsible for potent inhibitory activity against ACAT. The 1'-O-acetyl-11-O-tetrahydropyranyl derivative (11-O-2''-tetrahydropyranylpurpactin A) showed high selectivity (cytotoxic dose vs. effective dose) in a cell assay using J774 macrophages.

Animals↗
PubMed1991

Effect of different doses of aluminium hydroxide on renal deterioration and nutritional state in experimental chronic renal failure.

To investigate the effects of aluminium hydroxide (AH), a phosphate binder, on the progress of chronic renal diseases, high doses (9.6 g/kg/day, group ADR-H), moderate doses (2.4 g/kg/day, group ADR-M), and low doses (1.2 g/kg/day, group ADR-L) of the compound, were orally administered for 34 weeks to rats with Adriamycin (ADR)-induced focal glomerular sclerosis. Serum creatinine and blood urea nitrogen were significantly lower in either group ADR-H or ADR-M than in group ADR at week 34. Urinary protein excretion was significantly lower in group ADR-H than in group ADR in all observation periods and was also lower in group ADR-M than in group ADR at weeks 28 and 32. Both glomerular sclerosis and tubular change were significantly less severe in group ADR-H, while tubular change was less marked in group ADR-M than in group ADR. These results revealed that phosphate depletion was induced, and progressive renal failure was ameliorated in proportion to the dosing of AH. On the other hand, body weight was significantly smaller in group ADR-H than in group ADR in more than half of the observation period. In conclusion, a high dose of AH may adversely affect the nutritional state irrespective of having an extremely protective effect on progress of renal dysfunction. Appropriate doses of AH should be used to prevent the renal deterioration.

Administration, Oral↗