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Biomedical subjects

R Kojima

Publications and source records attributed to R Kojima.

At least 19 recordsLinked to original sources

Effect of retinoid status on alpha, beta and gamma retinoic acid receptor mRNA levels in various rat tissues.

We have investigated the effects of retinoids, vitamin D and thyroid hormone on the levels of retinoic acid receptor (RAR)alpha, RAR beta and RAR gamma mRNAs in intact animals. Although vitamin A deficiency caused no significant changes in the levels of RAR alpha and RAR gamma mRNAs, the level of RAR beta transcripts was greatly decreased in various tissues of vitamin A-deficient rats, but was restored rapidly to a normal level after administration of retinoic acid. Retinol also restored the RAR beta mRNA level, but the magnitude and kinetics of the induction differed from those by retinoic acid. The use of specific inhibitors demonstrated that this autoregulation of RAR beta gene expression in vivo occurred at the transcriptional level. In addition, from these results it was postulated that the maintenance of the normal RAR beta mRNA levels seemed to require a threshold serum retinol concentration (about 25 micrograms/dl). Moreover, we found that administration of retinol and retinoic acid to normal rats caused the overexpression of RAR beta transcripts (2-15-fold) when compared with the control levels of RAR beta mRNA, although the levels of RAR alpha and RAR gamma mRNAs were not affected. Vitamin D and thyroid hormone did not modulate the levels of RAR transcripts. These findings clearly indicate the specific ligand regulation of RAR beta gene expression in intact animals. The altered levels of RAR beta according to retinoid status may affect retinoid-inducible gene expression.

Animals

Suppression by cyclosporin A of anti-GBM nephritis in rats.

The suppressive effect of cyclosporin A (CyA) on the development of glomerulonephritis was evaluated in rats with either original- or crescentic-type anti-glomerular basement membrane (GBM) nephritis. CyA (2.5, 10 or 20 mg/kg) was given p.o. daily to original-type anti-GBM nephritic rats for 10 days from the day after the injection of anti-GBM serum. The development of the nephritis was dose-dependently suppressed by CyA before the production of specific antibody against rabbit gamma-globulin (the heterologous phase). In addition, CyA suppressed glomerular infiltration of leukocyte subsets (leukocyte with common antigen, T cell, helper T cell, suppressor/cytotoxic T cell, macrophage/monocyte). CyA was given p.o. daily to crescentic-type anti-GBM nephritic rats for 10 days from the 10th day after the injection of anti-GBM serum. CyA-administration caused a distinct suppression of the deterioration of nephritis during the autologous phase. In addition, CyA markedly suppressed the antibody production. The above data indicate that CyA has a beneficial effect on anti-GBM nephritis, and the antinephritic action of this agent may be due to the inhibition of glomerular infiltration of leukocyte subsets as well as the suppression of the antibody production.

Acetylglucosaminidase

Preventive actions of N-(3-aminopropionyl)-L-histidinato zinc (Z-103) through increases in the activities of oxygen-derived free radical scavenging enzymes in the gastric mucosa on ethanol-induced gastric mucosal damage in rats.

Z-103 at 1 to 25 mg/kg, p.o. prevented 100% ethanol-induced gastric mucosal lesions in a dose-dependent manner. Z-103 at 3 to 25 mg/kg, p.o. significantly elevated gastric mucosal superoxide dismutase (SOD)-like activity 1 hr after its administration to normal rats. In addition, Z-103 at doses (10 and 25 mg/kg, p.o.) which prevented 100% ethanol-induced gastric lesion further increased gastric mucosal SOD-like and glutathione peroxidase (GSH-px) activities elevated by 60% ethanol. Z-103 (10 and 25 mg/kg) significantly inhibited the increase in thiobarbituric acid-reactive substances in gastric mucosa injured by 60% ethanol. The combination with cycloheximide, a protein synthesis inhibitor, completely abolished the prevention of 60% ethanol-induced gastric mucosal lesions and the elevation of both free radical scavenging enzyme activities in the mucosa by Z-103 (10 mg/kg, p.o.). These results suggest that Z-103 may partly protect rat gastric mucosa against ethanol-induced damage by scavenging oxygen-derived free radicals via increases in the synthesis of SOD-like and GSH-px enzymes in the mucosa.

Administration, Oral

[Detection of ventricular late potentials comparison of 4 commercial high-resolution systems].

UNLABELLED: The purpose of this study was to evaluate the methodologic problems of noninvasive registration of ventricular late potentials. METHODS: we compared the results obtained in the same patients with four different systems which were Marquette MAC1, MAC12, ART LP101 and FUKUDA VCM 3000. Filtering was employed digital forward direction, 100-300 Hz in MAC1, digital FFT, 40-250 Hz in MAC12, digital, bidirectional, 40-250 Hz in ART and analogue, forward direction 40-300 Hz in FUKUDA VCM 3000. DEFINITION OF LATE POTENTIALS (LPs): Filtered QRS duration (FQRSD) was 120 msec or more, root mean square voltage in the last 40 msec (RMSV) was 15 microV or less in MAC12 and ART. FQRSD was 130 msec or more, RMSV was 15 microV or less in FUKUDA. FQRSD was 20 msec or more after QRS obtained from low resolution leads in MAC1. SUBJECTS: 163 patients [control 13, PVCs 23, myocardial infarction 55, others 51, IVCD (RBBB, LBBB, IVCD) 21] were included in this study. RESULTS: 17.6% of all patients (except for IVCD) showed LPs with MAC12, 20.0% with ART, 30.3% with FUKUDA, and 14.1% with MAC1. 23.1% of the control group showed LPs with MAC12 and FUKUDA, but no cases showed LPs with ART and FUKUDA. 4.3% of the PVC group showed LPs with MAC12, 13.0% with ART and FUKUDA, but no cases showed LPs with MAC1. 25.5% of the myocardial infarction group showed LPs with MAC12 and MAC1, 30.9% with ART and 36.3% with FUKUDA. All four methods gave corresponding results in 65.4% of patients, 7.0% positive and 58.4% negative findings. FQRSD of MAC12, ART and FUKUDA was 110.2 +/- 18.1 msec, 105.2 +/- 20.4 msec and 125.8 +/- 22.8 msec respectively. Correlation coefficient (r value) in FQRSD was 0.90 between ART and MAC12, 0.74 between ART and FUKUDA, and 0.75 between FUKUDA and MAC12. RMSV of MAC12, ART and FUKUDA was 49.2 +/- 30.2 microV, 43.7 +/- 37.8 microV and 22.5 +/- 10.6 microV respectively. R value in RMSV was 0.59 between ART and MAC12, 0.38 between ART and FUKUDA and 0.43 between FUKUDA and MAC12. R value in high frequency low amplitude signals duration under 40 microV of LPs positive patients in MAC1 was 0.51 between ART and MAC 12, 0.18 between MAC12 and MAC1, and 0.32 between ART and MAC1. Most of the differences result from a different interpretation of the tracings. Especially LPs far from QRS offset could be registered with neither MAC12, ART nor FUKUDA.

Action Potentials

Acute spinal cord injury: magnetic resonance imaging correlated with myelopathy.

Thirty-one patients (29 males and two females, 13-87 years of age (mean, 46.7 years] with acute spinal cord injury were studied by MR (magnetic resonance) imaging and the results were correlated with neurological findings. Magnetic resonance images were obtained with a 0.5 T superconductive MR scanner (Phillips Gyroscan S5). Initial imaging was performed within 24 hours after trauma in 13 patients, 1-7 days in 13 patients and 7-14 days in five patients. Twenty-six patients underwent follow-up examinations with MR imaging. Cord abnormalities including cord compression (23 patients), cord swelling (seven patients), and abnormal signal intensities on either T1 or T2-weighted images (26 patients) were observed on initial examination. Multivariate analysis showed that cord compression and abnormal intensities on T1-weighted images were important prognostic indicators. Hyperintensity on T2-weighted images was non-specific but correlated well with clinical recovery. Magnetic resonance imaging is useful in predicting the prognosis and for planning treatment following spinal cord injuries.

Acute Disease

Effect of dietary alpha-linolenate/linoleate balance on crescent type-anti-glomerular basement membrane nephritis in rats.

Rats were fed diets with three different ratios of alpha-linolenate (18:3 n-3) and linoleate (18:2 n-6), and then crescentic-type anti-glomerular basement membrane (GBM) nephritis was induced. The urinary protein levels and the plasma urea nitrogen levels were significantly higher, and histological abnormalities of glomeruli were seen more frequently in the high-alpha-linolenate group than in the high-linoleate group. The differences in dietary alpha-linolenate/linoleate balances were reflected in the proportions of arachidonate and eicosapentaenoate in glomerular phospholipids. Our results indicate that dietary enrichment with alpha-linolenate causes unfavorable effects in this anti-GBM nephritis model.

Animals

Spinal cord compression due to ossification of ligaments: MR imaging.

A total of 108 patients with ossification of the posterior longitudinal ligament (OPLL) (n = 92), ossification of the yellow ligament (OYL) (n = 8), or both (n = 8) were examined with magnetic resonance (MR) imaging performed with 0.5-T superconductive and 0.22-T resistive units. OPLL was demonstrated as a low-signal-intensity band between the bone marrow of the vertebral body and the dural sac on T1- and T2-weighted images. Continuous cervical OPLL was easier to diagnose than segmental cervical OPLL. T2-weighted images were more useful for detection of ossification of the ligaments. OYL was recognized as an impression on the posterior dural sac. Formation of bone marrow within an area of ossification, shown as increased or intermediate signal intensity, was observed in 56% of the cases of continuous OPLL, 11% of the cases of segmental OPLL, and none of the cases of OYL. The degree of cord compression was more severe in continuous OPLL. Degeneration of the disk was frequently associated with both types of OPLL.

Adult

Studies on the nephrotoxicity of aminoglycoside antibiotics and protection from these effects (8): Protective effect of pyridoxal-5'-phosphate against tobramycin nephrotoxicity.

We investigated the effect of pyridoxal-5'-phosphate (PALP) on tobramycin (TOB)-induced nephrotoxicity in rats. Paper electrophoretic analysis showed that in the mixture of TOB and PALP, the spot corresponding to TOB alone almost disappeared and the spot associated with TOB overlapped with that associated with PALP, although the spots of TOB alone and PALP alone were observed as single spots on the cathode and anode sides, respectively. The overlapping of both compounds indicated that TOB could directly interact with PALP in vitro. In the assay of TOB binding to renal brush border membranes (BBMs), PALP significantly inhibited the binding of TOB to BBMs by interacting with TOB outside of BBMs vesicles. Intrarenal TOB levels in rats receiving TOB and PALP were lower than those in rats given TOB alone. Combination with PALP markedly suppressed the urinary protein content, urinary N-acetyl-beta-D-glucosaminidase activity and blood urea nitrogen content elevated by TOB, and also reduced the degree of TOB-induced renal tubular cell necrosis. These results indicate that PALP protects the rat kidneys from TOB-induced nephrotoxicity and that the protective effect of PALP may be due to the reduced intrarenal TOB concentration and less binding to TOB to BBMs induced by the interaction of PALP with TOB.

Animals

Studies on the nephrotoxicity of aminoglycoside antibiotics and protection from these effects (6): A mechanism for the suppressive action of latamoxef on intrarenal tobramycin level.

The mechanism by which latamoxef (LMOX) reduces intrarenal tobramycin (TOB) levels was studied. When TOB (90 mg/kg/day, s.c.) and LMOX (500 or 2000 mg/kg/day, s.c.) were given simultaneously at separate sites to rats, 20 to 30% reductions in intrarenal TOB concentration were found on the 1st and 3rd days, as compared with the results from using TOB alone. The treatment with the reaction mixture of TOB and LMOX, which was preincubated for 3 hr at 37 degrees C to form the complex of TOB and LMOX, resulted in a greater suppression of TOB level in the kidney than administration of TOB and LMOX concomitantly at separate sites. When LMOX was given to rats 0.5 or 1.5 hr before s.c. injection of TOB, there were significant reductions in intrarenal TOB concentration. However, treatment with LMOX 5 hr before, as well as 1.5 or 5 hr after TOB injection, was ineffective in reducing the accumulation of TOB in the kidney. In the rats given both drugs simultaneously, the urinary excretion pattern of TOB almost overlapped with that of LMOX. Additionally, we detected a complex of TOB and LMOX in the urine of rats given both drugs simultaneously. These results suggest that the suppressive action of LMOX on intrarenal TOB level is due to the interaction of TOB and LMOX.

Animals

Studies on the nephrotoxicity of aminoglycoside antibiotics and protection from these effects (9): Protective effect of inositol hexasulfate against tobramycin-induced nephrotoxicity.

We examined the protective effect of inositol hexasulfate (IS6) against tobramycin (TOB)-induced nephrotoxicity. In the electrophoretic analysis, TOB alone and IS6 alone were observed as single spots on the cathode and anode sides, respectively. However, in the mixture of TOB and IS6 preincubated at 37 degrees C for 3 hr, the tailing of the spots of TOB and IS6 were observed from the origin to the cathode and the anode sides, respectively, and the overlapping of the spots of TOB and IS6 was recognized at the origin. These results indicated that TOB directly interacted with IS6 in vitro. Assay of TOB binding to rat kidney brush border membranes (BBMs) indicated that IS6 inhibited the binding of TOB to BBMs through an interaction of TOB and IS6. No significant reduction in intrarenal TOB level was observed in the rats given TOB (90 mg/kg, s.c.) and IS6 (153 or 610 mg/kg, s.c.). However, the treatment of rats with a combination of TOB and IS6 reduced the degree of necrosis of renal tubular cells and also suppressed the increases in urinary protein, urinary enzyme activities, blood urea nitrogen and plasma creatinine induced by TOB. Additionally, we detected a complex of TOB and IS6 in the urine of rats given both compounds simultaneously. These results indicate that IS6 protects against TOB-induced nephrotoxicity and that the protective action of IS6 may be due to the inhibition of TOB binding to BBMs through an interaction of TOB with IS6.

Animals

Mechanical properties of hydroxyapatite-reinforced gelatin as a model system of bone.

The elastic Young's modulus of hydroxyapatite-reinforced gelatin as a mechanical model system of bone was measured as a function of the volume fraction of hydroxyapatite, phi h. Initially, the Young's modulus gradually increased with an increase in phi h and then increased rapidly in the vicinity of phi h approximately 0.2. The phi h dependence of the Young's modulus was analysed by means of the theory of composite materials. It was found that with the increase in phi h the initial uniform stress deformation mode of the sample changed to the uniform strain deformation mode. The non-linear character in phi h dependence of the Young's modulus of this system was considered to reproduce well the novel behaviour of the mechanical properties of bone as a function of the mineral fraction. The situation was considered to be similar to a percolation problem. A preliminary analysis revealed that the critical exponent about the viscosity of the system accorded with the theoretically expected value. The result may present the evidence that the discontinuous point in mechanical properties of bone would be originated from an interaction such as a percolation of mineral particles on a matrix protein.

Biomechanical Phenomena

Preoperative computed tomography staging of rectal carcinoma.

Pelvic computed tomography (CT) was analyzed in 48 patients with rectal carcinoma. Air was insufflated into the rectum before CT scanning. The areas of tumor (T) and rectosigmoid lumen (L) were determined for T/L ratio. Changes of the perirectal fatty tissues on CT were classified into five patterns: shaggy, granular, linear, clubbed, and wavy appearances. The T/L ratio and changes of the perirectal fatty tissue were correlated with transmural tumor extension. When the T/L ratio was above 1, tumors were frequently classified as Dukes' staging B and C, whereas a T/L ratio above 2 suggested Dukes' C classification. Clubbed or wavy appearance in the perirectal fatty tissues suggested that the tumor extended beyond the submucosa involving the muscularis propria. These findings were very useful for surgery.

Adipose Tissue

Chronic cervical cord compression: clinical significance of increased signal intensity on MR images.

Magnetic resonance (MR) imaging was performed in 668 patients with chronic compressive lesions of the cervical spinal canal. High signal intensity was observed within the spinal cord on T2-weighted or proton density spin-echo images in 99 patients (14.8%). Frequency of this finding was directly proportional to severity of clinical myelopathy and degree of spinal canal compression seen on MR images. Patients with a high-signal-intensity area responded less favorably than those without to surgical or medical treatment. More than 60% of the patients had this finding when grade of myelopathy or degree of canal compression was moderate to marked. Among 10 patients who received contrast material during MR imaging, one patient had definite enhancement and another had questionable enhancement in the high-signal-intensity area. The finding disappeared after decompressive surgery and medical treatment in some cases: Three of four of the patients who underwent surgery showed good clinical improvement. High signal intensity of the spinal cord produced by compressive lesions appears to be an important indicator for predicting prognosis.

Adolescent

Effect of dietary alpha-linolenate/linoleate balance on collagen-induced platelet aggregation and serotonin release in rats.

Male Sprague-Dawley rats at 3 weeks of age were weaned to a diet supplemented either with perilla seed oil [alpha-linolenic acid (alpha-LnA)/linoleic acid (LA) = 3.66] or with safflower seed oil (alpha-LnA/LA less than 0.01) for 5-6 weeks. The eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio in platelet phospholipids was much higher in the perilla oil group than in the safflower oil group. Platelet aggregability determined turbidometrically varied greatly among individual animals, and the difference in platelet aggregability between the two dietary groups was relatively small when higher concentrations (15 and 20 micrograms/ml) of collagen were used. However, when platelet aggregability was determined as an all-or-none phenomenon at lower concentrations (7.5 and 10 micrograms/ml) of collagen, a very distinct difference was observed between the two dietary groups; aggregability was much lower in the perilla oil group than in the safflower oil group. Collagen-induced serotonin release from platelets was significantly reduced in the perilla oil group as compared with the safflower oil group. These results emphasize the importance of estimating aggregability at threshold concentrations of collagen and confirm that dietary manipulation of the essential fatty acid balance could be useful in reducing the thrombotic tendency.

Animals

Studies on the nephrotoxicity of aminoglycoside antibiotics and protection from these effects (7): Effect of latamoxef on binding of tobramycin to brush border membranes isolated from rat kidney cortex.

We investigated the effect of latamoxef (LMOX) on the binding of tobramycin (TOB) to brush border membranes (BBMs) isolated from rat kidney cortex by calcium precipitation. The simultaneous treatment with TOB (0.2 mM) and LMOX (10 and 20 mM) to the BBMs fraction (about 250 micrograms protein) significantly inhibited the binding of TOB to BBMs. The addition of the reaction mixture of TOB (0.2 mM) and LMOX (4, 10 and 20 mM) which was preincubated for 3 hr at 37 degrees C, to the BBMs fraction resulted in less binding of TOB to the membranes than that observed in the case of simultaneous treatment with both drugs. Although [14C]-labeled LMOX was taken up by BBMs temperature- and time-dependently, the pretreatment with LMOX showed no obvious differences in inhibition of the TOB binding to BBMs, as compared with the result from simultaneous treatment with both drugs. Additionally, the binding of TOB to the LMOX-treated BBMs that were resuspended in fresh medium after the pretreatment with LMOX for 10 min at 37 degrees C was similar to that of TOB to the non-treated BBMs. These results indicate that LMOX inhibits the binding of TOB to BBMs not by binding to BBMs but by interacting with TOB.

Animals

[Studies on initiation and progression of focal glomerular sclerosis in rats].

In order to clarify the mechanisms of the initiation and progression of focal glomerular sclerosis (FGS), we investigated changes in the mesangial function or qualitative changes in the extracellular matrix of mesangium in puromycin aminonucleoside (PAN)-induced FGS in rats. At first, we investigated that the relationship between the progression of FGS and mesangial function. In order to evaluate the mesangial function, rats received the i.v. injection of colloidal carbon (C. C.) (20 or 30 mg/100 g). Results obtained from this experiment suggest that the progression of glomerular sclerosis may be related to changes in mesangial function. Furthermore, results suggest that the abnormality of the extracellular matrix may lead to changes in mesangial function and the progression of glomerular sclerosis. Therefore, in the next experiment, the proteoglycans (PGs), one of the components of extracellular matrix, were analyzed by the column chromatography to clarify qualitative changes in the PGs such as the molecular size and charge density. Results obtained from this experiment indicate that the sclerotic glomeruli synthesize the PGs with different molecular size and charge density from normal glomeruli. It is concluded from these experiments that the abnormality of the mesangial function and the synthesis of PGs, the components of the extracellular matrix, may lead to the progression of FGS. Namely, the qualitatively altered PGs may cause abnormal interactions with other components of matrix, which lead to changes in mesangial function, death of mesangial cell and the progression of FGS.

Animals